Follicular Carcinoma Follicular Carcinoma of Thyroid in QampAof Thyroid in QampA

Local seminar Local seminar Medical Oncology Medical Oncology

departmentdepartmentByBy

Salah Mabruok Salah Mabruok KhalafKhalaf

South Egypt Cancer South Egypt Cancer InstituteInstitute20122012

Case disscusionCase disscusion

A 40 years old female with excessive A 40 years old female with excessive sweating palpitation wasting with sweating palpitation wasting with polyphagia diarrheapolyphagia diarrhea

Examination thyroid swelling about Examination thyroid swelling about 2 cm firm mobile with deglutition 2 cm firm mobile with deglutition in left lobe and extend to isthmusin left lobe and extend to isthmus

Patient has a past history of RT to Patient has a past history of RT to neck for HL when aged 25 yearsneck for HL when aged 25 years

1 what the best next step1 what the best next stepATSH levelBRadioactive iodine scan CCT neck DFNACEThyroidectomy

TSH level was lower than normalTSH level was lower than normal

2 what the best next step2 what the best next stepAThyroid lobectomyBRadical thyroidectomy CRadioactive iodine scan DCT neck for stagingEFree T3 and T4

Radioactive iodine thyroid scan Radioactive iodine thyroid scan consistent with hot nodule consistent with hot nodule

Neck sonar revealed solid mass less Neck sonar revealed solid mass less than 15 cm than 15 cm

3 FNAC was indicated due to3 FNAC was indicated due to

AA Low TSH level irrespective of iodine Low TSH level irrespective of iodine scan resultscan result

BB Hot nodule on scanHot nodule on scan

CC Solid nature of the massSolid nature of the mass

DDMalignant suspicious due to previous RTMalignant suspicious due to previous RT

FNAC indicationFNAC indication

II Sonar-based criteriaSonar-based criteria Solid nodule Solid nodule

11 More than 1 cm if associated with sonographic suspious More than 1 cm if associated with sonographic suspious features features

22 More than 15 cm in absence of sonographic suspicion More than 15 cm in absence of sonographic suspicion

Mixed solid and cystic Mixed solid and cystic 11 More than 15 cm if associated with sonographic More than 15 cm if associated with sonographic

suspicious features suspicious features

22 More than 2 cm in absence of sonographic suspicion More than 2 cm in absence of sonographic suspicion

Spongiform nodule (microcystic component Spongiform nodule (microcystic component gt 50 of nodulesgt 50 of nodules

IIIIHigh risk Clinical featureHigh risk Clinical feature

RT exposure genetic RT exposure genetic predisposition predisposition

Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)

Patient was referred for FNAC and Patient was referred for FNAC and follicular neoplasia was the resultfollicular neoplasia was the result

4 4 Thyroid lobectomy or total thyroidectomy

ANo need as no evidence of malignancy with FNAC

BB Better to be done as patient has high Better to be done as patient has high risk clinical featurerisk clinical feature

CCMust be done for definite diagnosisMust be done for definite diagnosis

DDRepeat FNACRepeat FNAC

EE No need for surgery as therapy with No need for surgery as therapy with radioactive iodine is enoughradioactive iodine is enough

Lobectomy-isthmusectomy was done and revealed minimally invasive cancer then patient referred to surgeon for his opinion for further surgery5 what is the best optionACompletion of thyroidectomyBObservation with replacement therapyCPostoperative RTDAnswer A and B are valuableEPostoperative chemotherapy

Patient was maintained under Patient was maintained under surveillance with replacement therapy surveillance with replacement therapy

After 2 years of follow up the patient After 2 years of follow up the patient develop Rt cervical lymph node develop Rt cervical lymph node enlargement about 2 cm single firm enlargement about 2 cm single firm mobilemobile

6 The best next step is6 The best next step is

AA FNAC of nodeFNAC of node

BB CTMRI neckCTMRI neck

CC TSH levelTSH level

DDExcisional biopsy of node Excisional biopsy of node

CTMRI neck revealed RT thyroid CTMRI neck revealed RT thyroid lobe swelling 3 cm in diameter with lobe swelling 3 cm in diameter with increased central vascularity with Rt increased central vascularity with Rt cervical LN and FNAC revealed cervical LN and FNAC revealed follicular carcinoma follicular carcinoma

Metastatic work up revealed Metastatic work up revealed multiple lung nodules multiple lung nodules

7 The tumor of the Rt lobe is 7 The tumor of the Rt lobe is consideredconsidered

AASecond primary Second primary

BBRecurrenceRecurrence

CCBoth Both

DDNeither Neither

8 As regard follicular carcinoma after 8 As regard follicular carcinoma after RT RT AAIt is the most common of thyroid cancer It is the most common of thyroid cancer after RTafter RT

BBIt is less common than papillary carcinomaIt is less common than papillary carcinoma

CCIt has poorer prognosis than that not It has poorer prognosis than that not associated with RTassociated with RT

DDRT to can be re-adminstered if indicatedRT to can be re-adminstered if indicated

9 The following are more common in 9 The following are more common in follicular than in papillary carcinoma follicular than in papillary carcinoma EXCEPTEXCEPTAAPsammoma body Psammoma body

BBOrphan Ann nucleusOrphan Ann nucleus

CCLymph node metastasisLymph node metastasis

DDAggressiveness Aggressiveness

EENone of aboveNone of above

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Case disscusionCase disscusion

A 40 years old female with excessive A 40 years old female with excessive sweating palpitation wasting with sweating palpitation wasting with polyphagia diarrheapolyphagia diarrhea

Examination thyroid swelling about Examination thyroid swelling about 2 cm firm mobile with deglutition 2 cm firm mobile with deglutition in left lobe and extend to isthmusin left lobe and extend to isthmus

Patient has a past history of RT to Patient has a past history of RT to neck for HL when aged 25 yearsneck for HL when aged 25 years

1 what the best next step1 what the best next stepATSH levelBRadioactive iodine scan CCT neck DFNACEThyroidectomy

TSH level was lower than normalTSH level was lower than normal

2 what the best next step2 what the best next stepAThyroid lobectomyBRadical thyroidectomy CRadioactive iodine scan DCT neck for stagingEFree T3 and T4

Radioactive iodine thyroid scan Radioactive iodine thyroid scan consistent with hot nodule consistent with hot nodule

Neck sonar revealed solid mass less Neck sonar revealed solid mass less than 15 cm than 15 cm

3 FNAC was indicated due to3 FNAC was indicated due to

AA Low TSH level irrespective of iodine Low TSH level irrespective of iodine scan resultscan result

BB Hot nodule on scanHot nodule on scan

CC Solid nature of the massSolid nature of the mass

DDMalignant suspicious due to previous RTMalignant suspicious due to previous RT

FNAC indicationFNAC indication

II Sonar-based criteriaSonar-based criteria Solid nodule Solid nodule

11 More than 1 cm if associated with sonographic suspious More than 1 cm if associated with sonographic suspious features features

22 More than 15 cm in absence of sonographic suspicion More than 15 cm in absence of sonographic suspicion

Mixed solid and cystic Mixed solid and cystic 11 More than 15 cm if associated with sonographic More than 15 cm if associated with sonographic

suspicious features suspicious features

22 More than 2 cm in absence of sonographic suspicion More than 2 cm in absence of sonographic suspicion

Spongiform nodule (microcystic component Spongiform nodule (microcystic component gt 50 of nodulesgt 50 of nodules

IIIIHigh risk Clinical featureHigh risk Clinical feature

RT exposure genetic RT exposure genetic predisposition predisposition

Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)

Patient was referred for FNAC and Patient was referred for FNAC and follicular neoplasia was the resultfollicular neoplasia was the result

4 4 Thyroid lobectomy or total thyroidectomy

ANo need as no evidence of malignancy with FNAC

BB Better to be done as patient has high Better to be done as patient has high risk clinical featurerisk clinical feature

CCMust be done for definite diagnosisMust be done for definite diagnosis

DDRepeat FNACRepeat FNAC

EE No need for surgery as therapy with No need for surgery as therapy with radioactive iodine is enoughradioactive iodine is enough

Lobectomy-isthmusectomy was done and revealed minimally invasive cancer then patient referred to surgeon for his opinion for further surgery5 what is the best optionACompletion of thyroidectomyBObservation with replacement therapyCPostoperative RTDAnswer A and B are valuableEPostoperative chemotherapy

Patient was maintained under Patient was maintained under surveillance with replacement therapy surveillance with replacement therapy

After 2 years of follow up the patient After 2 years of follow up the patient develop Rt cervical lymph node develop Rt cervical lymph node enlargement about 2 cm single firm enlargement about 2 cm single firm mobilemobile

6 The best next step is6 The best next step is

AA FNAC of nodeFNAC of node

BB CTMRI neckCTMRI neck

CC TSH levelTSH level

DDExcisional biopsy of node Excisional biopsy of node

CTMRI neck revealed RT thyroid CTMRI neck revealed RT thyroid lobe swelling 3 cm in diameter with lobe swelling 3 cm in diameter with increased central vascularity with Rt increased central vascularity with Rt cervical LN and FNAC revealed cervical LN and FNAC revealed follicular carcinoma follicular carcinoma

Metastatic work up revealed Metastatic work up revealed multiple lung nodules multiple lung nodules

7 The tumor of the Rt lobe is 7 The tumor of the Rt lobe is consideredconsidered

AASecond primary Second primary

BBRecurrenceRecurrence

CCBoth Both

DDNeither Neither

8 As regard follicular carcinoma after 8 As regard follicular carcinoma after RT RT AAIt is the most common of thyroid cancer It is the most common of thyroid cancer after RTafter RT

BBIt is less common than papillary carcinomaIt is less common than papillary carcinoma

CCIt has poorer prognosis than that not It has poorer prognosis than that not associated with RTassociated with RT

DDRT to can be re-adminstered if indicatedRT to can be re-adminstered if indicated

9 The following are more common in 9 The following are more common in follicular than in papillary carcinoma follicular than in papillary carcinoma EXCEPTEXCEPTAAPsammoma body Psammoma body

BBOrphan Ann nucleusOrphan Ann nucleus

CCLymph node metastasisLymph node metastasis

DDAggressiveness Aggressiveness

EENone of aboveNone of above

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

1 what the best next step1 what the best next stepATSH levelBRadioactive iodine scan CCT neck DFNACEThyroidectomy

TSH level was lower than normalTSH level was lower than normal

2 what the best next step2 what the best next stepAThyroid lobectomyBRadical thyroidectomy CRadioactive iodine scan DCT neck for stagingEFree T3 and T4

Radioactive iodine thyroid scan Radioactive iodine thyroid scan consistent with hot nodule consistent with hot nodule

Neck sonar revealed solid mass less Neck sonar revealed solid mass less than 15 cm than 15 cm

3 FNAC was indicated due to3 FNAC was indicated due to

AA Low TSH level irrespective of iodine Low TSH level irrespective of iodine scan resultscan result

BB Hot nodule on scanHot nodule on scan

CC Solid nature of the massSolid nature of the mass

DDMalignant suspicious due to previous RTMalignant suspicious due to previous RT

FNAC indicationFNAC indication

II Sonar-based criteriaSonar-based criteria Solid nodule Solid nodule

11 More than 1 cm if associated with sonographic suspious More than 1 cm if associated with sonographic suspious features features

22 More than 15 cm in absence of sonographic suspicion More than 15 cm in absence of sonographic suspicion

Mixed solid and cystic Mixed solid and cystic 11 More than 15 cm if associated with sonographic More than 15 cm if associated with sonographic

suspicious features suspicious features

22 More than 2 cm in absence of sonographic suspicion More than 2 cm in absence of sonographic suspicion

Spongiform nodule (microcystic component Spongiform nodule (microcystic component gt 50 of nodulesgt 50 of nodules

IIIIHigh risk Clinical featureHigh risk Clinical feature

RT exposure genetic RT exposure genetic predisposition predisposition

Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)

Patient was referred for FNAC and Patient was referred for FNAC and follicular neoplasia was the resultfollicular neoplasia was the result

4 4 Thyroid lobectomy or total thyroidectomy

ANo need as no evidence of malignancy with FNAC

BB Better to be done as patient has high Better to be done as patient has high risk clinical featurerisk clinical feature

CCMust be done for definite diagnosisMust be done for definite diagnosis

DDRepeat FNACRepeat FNAC

EE No need for surgery as therapy with No need for surgery as therapy with radioactive iodine is enoughradioactive iodine is enough

Lobectomy-isthmusectomy was done and revealed minimally invasive cancer then patient referred to surgeon for his opinion for further surgery5 what is the best optionACompletion of thyroidectomyBObservation with replacement therapyCPostoperative RTDAnswer A and B are valuableEPostoperative chemotherapy

Patient was maintained under Patient was maintained under surveillance with replacement therapy surveillance with replacement therapy

After 2 years of follow up the patient After 2 years of follow up the patient develop Rt cervical lymph node develop Rt cervical lymph node enlargement about 2 cm single firm enlargement about 2 cm single firm mobilemobile

6 The best next step is6 The best next step is

AA FNAC of nodeFNAC of node

BB CTMRI neckCTMRI neck

CC TSH levelTSH level

DDExcisional biopsy of node Excisional biopsy of node

CTMRI neck revealed RT thyroid CTMRI neck revealed RT thyroid lobe swelling 3 cm in diameter with lobe swelling 3 cm in diameter with increased central vascularity with Rt increased central vascularity with Rt cervical LN and FNAC revealed cervical LN and FNAC revealed follicular carcinoma follicular carcinoma

Metastatic work up revealed Metastatic work up revealed multiple lung nodules multiple lung nodules

7 The tumor of the Rt lobe is 7 The tumor of the Rt lobe is consideredconsidered

AASecond primary Second primary

BBRecurrenceRecurrence

CCBoth Both

DDNeither Neither

8 As regard follicular carcinoma after 8 As regard follicular carcinoma after RT RT AAIt is the most common of thyroid cancer It is the most common of thyroid cancer after RTafter RT

BBIt is less common than papillary carcinomaIt is less common than papillary carcinoma

CCIt has poorer prognosis than that not It has poorer prognosis than that not associated with RTassociated with RT

DDRT to can be re-adminstered if indicatedRT to can be re-adminstered if indicated

9 The following are more common in 9 The following are more common in follicular than in papillary carcinoma follicular than in papillary carcinoma EXCEPTEXCEPTAAPsammoma body Psammoma body

BBOrphan Ann nucleusOrphan Ann nucleus

CCLymph node metastasisLymph node metastasis

DDAggressiveness Aggressiveness

EENone of aboveNone of above

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

TSH level was lower than normalTSH level was lower than normal

2 what the best next step2 what the best next stepAThyroid lobectomyBRadical thyroidectomy CRadioactive iodine scan DCT neck for stagingEFree T3 and T4

Radioactive iodine thyroid scan Radioactive iodine thyroid scan consistent with hot nodule consistent with hot nodule

Neck sonar revealed solid mass less Neck sonar revealed solid mass less than 15 cm than 15 cm

3 FNAC was indicated due to3 FNAC was indicated due to

AA Low TSH level irrespective of iodine Low TSH level irrespective of iodine scan resultscan result

BB Hot nodule on scanHot nodule on scan

CC Solid nature of the massSolid nature of the mass

DDMalignant suspicious due to previous RTMalignant suspicious due to previous RT

FNAC indicationFNAC indication

II Sonar-based criteriaSonar-based criteria Solid nodule Solid nodule

11 More than 1 cm if associated with sonographic suspious More than 1 cm if associated with sonographic suspious features features

22 More than 15 cm in absence of sonographic suspicion More than 15 cm in absence of sonographic suspicion

Mixed solid and cystic Mixed solid and cystic 11 More than 15 cm if associated with sonographic More than 15 cm if associated with sonographic

suspicious features suspicious features

22 More than 2 cm in absence of sonographic suspicion More than 2 cm in absence of sonographic suspicion

Spongiform nodule (microcystic component Spongiform nodule (microcystic component gt 50 of nodulesgt 50 of nodules

IIIIHigh risk Clinical featureHigh risk Clinical feature

RT exposure genetic RT exposure genetic predisposition predisposition

Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)

Patient was referred for FNAC and Patient was referred for FNAC and follicular neoplasia was the resultfollicular neoplasia was the result

4 4 Thyroid lobectomy or total thyroidectomy

ANo need as no evidence of malignancy with FNAC

BB Better to be done as patient has high Better to be done as patient has high risk clinical featurerisk clinical feature

CCMust be done for definite diagnosisMust be done for definite diagnosis

DDRepeat FNACRepeat FNAC

EE No need for surgery as therapy with No need for surgery as therapy with radioactive iodine is enoughradioactive iodine is enough

Lobectomy-isthmusectomy was done and revealed minimally invasive cancer then patient referred to surgeon for his opinion for further surgery5 what is the best optionACompletion of thyroidectomyBObservation with replacement therapyCPostoperative RTDAnswer A and B are valuableEPostoperative chemotherapy

Patient was maintained under Patient was maintained under surveillance with replacement therapy surveillance with replacement therapy

After 2 years of follow up the patient After 2 years of follow up the patient develop Rt cervical lymph node develop Rt cervical lymph node enlargement about 2 cm single firm enlargement about 2 cm single firm mobilemobile

6 The best next step is6 The best next step is

AA FNAC of nodeFNAC of node

BB CTMRI neckCTMRI neck

CC TSH levelTSH level

DDExcisional biopsy of node Excisional biopsy of node

CTMRI neck revealed RT thyroid CTMRI neck revealed RT thyroid lobe swelling 3 cm in diameter with lobe swelling 3 cm in diameter with increased central vascularity with Rt increased central vascularity with Rt cervical LN and FNAC revealed cervical LN and FNAC revealed follicular carcinoma follicular carcinoma

Metastatic work up revealed Metastatic work up revealed multiple lung nodules multiple lung nodules

7 The tumor of the Rt lobe is 7 The tumor of the Rt lobe is consideredconsidered

AASecond primary Second primary

BBRecurrenceRecurrence

CCBoth Both

DDNeither Neither

8 As regard follicular carcinoma after 8 As regard follicular carcinoma after RT RT AAIt is the most common of thyroid cancer It is the most common of thyroid cancer after RTafter RT

BBIt is less common than papillary carcinomaIt is less common than papillary carcinoma

CCIt has poorer prognosis than that not It has poorer prognosis than that not associated with RTassociated with RT

DDRT to can be re-adminstered if indicatedRT to can be re-adminstered if indicated

9 The following are more common in 9 The following are more common in follicular than in papillary carcinoma follicular than in papillary carcinoma EXCEPTEXCEPTAAPsammoma body Psammoma body

BBOrphan Ann nucleusOrphan Ann nucleus

CCLymph node metastasisLymph node metastasis

DDAggressiveness Aggressiveness

EENone of aboveNone of above

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Radioactive iodine thyroid scan Radioactive iodine thyroid scan consistent with hot nodule consistent with hot nodule

Neck sonar revealed solid mass less Neck sonar revealed solid mass less than 15 cm than 15 cm

3 FNAC was indicated due to3 FNAC was indicated due to

AA Low TSH level irrespective of iodine Low TSH level irrespective of iodine scan resultscan result

BB Hot nodule on scanHot nodule on scan

CC Solid nature of the massSolid nature of the mass

DDMalignant suspicious due to previous RTMalignant suspicious due to previous RT

FNAC indicationFNAC indication

II Sonar-based criteriaSonar-based criteria Solid nodule Solid nodule

11 More than 1 cm if associated with sonographic suspious More than 1 cm if associated with sonographic suspious features features

22 More than 15 cm in absence of sonographic suspicion More than 15 cm in absence of sonographic suspicion

Mixed solid and cystic Mixed solid and cystic 11 More than 15 cm if associated with sonographic More than 15 cm if associated with sonographic

suspicious features suspicious features

22 More than 2 cm in absence of sonographic suspicion More than 2 cm in absence of sonographic suspicion

Spongiform nodule (microcystic component Spongiform nodule (microcystic component gt 50 of nodulesgt 50 of nodules

IIIIHigh risk Clinical featureHigh risk Clinical feature

RT exposure genetic RT exposure genetic predisposition predisposition

Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)

Patient was referred for FNAC and Patient was referred for FNAC and follicular neoplasia was the resultfollicular neoplasia was the result

4 4 Thyroid lobectomy or total thyroidectomy

ANo need as no evidence of malignancy with FNAC

BB Better to be done as patient has high Better to be done as patient has high risk clinical featurerisk clinical feature

CCMust be done for definite diagnosisMust be done for definite diagnosis

DDRepeat FNACRepeat FNAC

EE No need for surgery as therapy with No need for surgery as therapy with radioactive iodine is enoughradioactive iodine is enough

Lobectomy-isthmusectomy was done and revealed minimally invasive cancer then patient referred to surgeon for his opinion for further surgery5 what is the best optionACompletion of thyroidectomyBObservation with replacement therapyCPostoperative RTDAnswer A and B are valuableEPostoperative chemotherapy

Patient was maintained under Patient was maintained under surveillance with replacement therapy surveillance with replacement therapy

After 2 years of follow up the patient After 2 years of follow up the patient develop Rt cervical lymph node develop Rt cervical lymph node enlargement about 2 cm single firm enlargement about 2 cm single firm mobilemobile

6 The best next step is6 The best next step is

AA FNAC of nodeFNAC of node

BB CTMRI neckCTMRI neck

CC TSH levelTSH level

DDExcisional biopsy of node Excisional biopsy of node

CTMRI neck revealed RT thyroid CTMRI neck revealed RT thyroid lobe swelling 3 cm in diameter with lobe swelling 3 cm in diameter with increased central vascularity with Rt increased central vascularity with Rt cervical LN and FNAC revealed cervical LN and FNAC revealed follicular carcinoma follicular carcinoma

Metastatic work up revealed Metastatic work up revealed multiple lung nodules multiple lung nodules

7 The tumor of the Rt lobe is 7 The tumor of the Rt lobe is consideredconsidered

AASecond primary Second primary

BBRecurrenceRecurrence

CCBoth Both

DDNeither Neither

8 As regard follicular carcinoma after 8 As regard follicular carcinoma after RT RT AAIt is the most common of thyroid cancer It is the most common of thyroid cancer after RTafter RT

BBIt is less common than papillary carcinomaIt is less common than papillary carcinoma

CCIt has poorer prognosis than that not It has poorer prognosis than that not associated with RTassociated with RT

DDRT to can be re-adminstered if indicatedRT to can be re-adminstered if indicated

9 The following are more common in 9 The following are more common in follicular than in papillary carcinoma follicular than in papillary carcinoma EXCEPTEXCEPTAAPsammoma body Psammoma body

BBOrphan Ann nucleusOrphan Ann nucleus

CCLymph node metastasisLymph node metastasis

DDAggressiveness Aggressiveness

EENone of aboveNone of above

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

FNAC indicationFNAC indication

II Sonar-based criteriaSonar-based criteria Solid nodule Solid nodule

11 More than 1 cm if associated with sonographic suspious More than 1 cm if associated with sonographic suspious features features

22 More than 15 cm in absence of sonographic suspicion More than 15 cm in absence of sonographic suspicion

Mixed solid and cystic Mixed solid and cystic 11 More than 15 cm if associated with sonographic More than 15 cm if associated with sonographic

suspicious features suspicious features

22 More than 2 cm in absence of sonographic suspicion More than 2 cm in absence of sonographic suspicion

Spongiform nodule (microcystic component Spongiform nodule (microcystic component gt 50 of nodulesgt 50 of nodules

IIIIHigh risk Clinical featureHigh risk Clinical feature

RT exposure genetic RT exposure genetic predisposition predisposition

Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)

Patient was referred for FNAC and Patient was referred for FNAC and follicular neoplasia was the resultfollicular neoplasia was the result

4 4 Thyroid lobectomy or total thyroidectomy

ANo need as no evidence of malignancy with FNAC

BB Better to be done as patient has high Better to be done as patient has high risk clinical featurerisk clinical feature

CCMust be done for definite diagnosisMust be done for definite diagnosis

DDRepeat FNACRepeat FNAC

EE No need for surgery as therapy with No need for surgery as therapy with radioactive iodine is enoughradioactive iodine is enough

Lobectomy-isthmusectomy was done and revealed minimally invasive cancer then patient referred to surgeon for his opinion for further surgery5 what is the best optionACompletion of thyroidectomyBObservation with replacement therapyCPostoperative RTDAnswer A and B are valuableEPostoperative chemotherapy

Patient was maintained under Patient was maintained under surveillance with replacement therapy surveillance with replacement therapy

After 2 years of follow up the patient After 2 years of follow up the patient develop Rt cervical lymph node develop Rt cervical lymph node enlargement about 2 cm single firm enlargement about 2 cm single firm mobilemobile

6 The best next step is6 The best next step is

AA FNAC of nodeFNAC of node

BB CTMRI neckCTMRI neck

CC TSH levelTSH level

DDExcisional biopsy of node Excisional biopsy of node

CTMRI neck revealed RT thyroid CTMRI neck revealed RT thyroid lobe swelling 3 cm in diameter with lobe swelling 3 cm in diameter with increased central vascularity with Rt increased central vascularity with Rt cervical LN and FNAC revealed cervical LN and FNAC revealed follicular carcinoma follicular carcinoma

Metastatic work up revealed Metastatic work up revealed multiple lung nodules multiple lung nodules

7 The tumor of the Rt lobe is 7 The tumor of the Rt lobe is consideredconsidered

AASecond primary Second primary

BBRecurrenceRecurrence

CCBoth Both

DDNeither Neither

8 As regard follicular carcinoma after 8 As regard follicular carcinoma after RT RT AAIt is the most common of thyroid cancer It is the most common of thyroid cancer after RTafter RT

BBIt is less common than papillary carcinomaIt is less common than papillary carcinoma

CCIt has poorer prognosis than that not It has poorer prognosis than that not associated with RTassociated with RT

DDRT to can be re-adminstered if indicatedRT to can be re-adminstered if indicated

9 The following are more common in 9 The following are more common in follicular than in papillary carcinoma follicular than in papillary carcinoma EXCEPTEXCEPTAAPsammoma body Psammoma body

BBOrphan Ann nucleusOrphan Ann nucleus

CCLymph node metastasisLymph node metastasis

DDAggressiveness Aggressiveness

EENone of aboveNone of above

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Patient was referred for FNAC and Patient was referred for FNAC and follicular neoplasia was the resultfollicular neoplasia was the result

4 4 Thyroid lobectomy or total thyroidectomy

ANo need as no evidence of malignancy with FNAC

BB Better to be done as patient has high Better to be done as patient has high risk clinical featurerisk clinical feature

CCMust be done for definite diagnosisMust be done for definite diagnosis

DDRepeat FNACRepeat FNAC

EE No need for surgery as therapy with No need for surgery as therapy with radioactive iodine is enoughradioactive iodine is enough

Lobectomy-isthmusectomy was done and revealed minimally invasive cancer then patient referred to surgeon for his opinion for further surgery5 what is the best optionACompletion of thyroidectomyBObservation with replacement therapyCPostoperative RTDAnswer A and B are valuableEPostoperative chemotherapy

Patient was maintained under Patient was maintained under surveillance with replacement therapy surveillance with replacement therapy

After 2 years of follow up the patient After 2 years of follow up the patient develop Rt cervical lymph node develop Rt cervical lymph node enlargement about 2 cm single firm enlargement about 2 cm single firm mobilemobile

6 The best next step is6 The best next step is

AA FNAC of nodeFNAC of node

BB CTMRI neckCTMRI neck

CC TSH levelTSH level

DDExcisional biopsy of node Excisional biopsy of node

CTMRI neck revealed RT thyroid CTMRI neck revealed RT thyroid lobe swelling 3 cm in diameter with lobe swelling 3 cm in diameter with increased central vascularity with Rt increased central vascularity with Rt cervical LN and FNAC revealed cervical LN and FNAC revealed follicular carcinoma follicular carcinoma

Metastatic work up revealed Metastatic work up revealed multiple lung nodules multiple lung nodules

7 The tumor of the Rt lobe is 7 The tumor of the Rt lobe is consideredconsidered

AASecond primary Second primary

BBRecurrenceRecurrence

CCBoth Both

DDNeither Neither

8 As regard follicular carcinoma after 8 As regard follicular carcinoma after RT RT AAIt is the most common of thyroid cancer It is the most common of thyroid cancer after RTafter RT

BBIt is less common than papillary carcinomaIt is less common than papillary carcinoma

CCIt has poorer prognosis than that not It has poorer prognosis than that not associated with RTassociated with RT

DDRT to can be re-adminstered if indicatedRT to can be re-adminstered if indicated

9 The following are more common in 9 The following are more common in follicular than in papillary carcinoma follicular than in papillary carcinoma EXCEPTEXCEPTAAPsammoma body Psammoma body

BBOrphan Ann nucleusOrphan Ann nucleus

CCLymph node metastasisLymph node metastasis

DDAggressiveness Aggressiveness

EENone of aboveNone of above

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Lobectomy-isthmusectomy was done and revealed minimally invasive cancer then patient referred to surgeon for his opinion for further surgery5 what is the best optionACompletion of thyroidectomyBObservation with replacement therapyCPostoperative RTDAnswer A and B are valuableEPostoperative chemotherapy

Patient was maintained under Patient was maintained under surveillance with replacement therapy surveillance with replacement therapy

After 2 years of follow up the patient After 2 years of follow up the patient develop Rt cervical lymph node develop Rt cervical lymph node enlargement about 2 cm single firm enlargement about 2 cm single firm mobilemobile

6 The best next step is6 The best next step is

AA FNAC of nodeFNAC of node

BB CTMRI neckCTMRI neck

CC TSH levelTSH level

DDExcisional biopsy of node Excisional biopsy of node

CTMRI neck revealed RT thyroid CTMRI neck revealed RT thyroid lobe swelling 3 cm in diameter with lobe swelling 3 cm in diameter with increased central vascularity with Rt increased central vascularity with Rt cervical LN and FNAC revealed cervical LN and FNAC revealed follicular carcinoma follicular carcinoma

Metastatic work up revealed Metastatic work up revealed multiple lung nodules multiple lung nodules

7 The tumor of the Rt lobe is 7 The tumor of the Rt lobe is consideredconsidered

AASecond primary Second primary

BBRecurrenceRecurrence

CCBoth Both

DDNeither Neither

8 As regard follicular carcinoma after 8 As regard follicular carcinoma after RT RT AAIt is the most common of thyroid cancer It is the most common of thyroid cancer after RTafter RT

BBIt is less common than papillary carcinomaIt is less common than papillary carcinoma

CCIt has poorer prognosis than that not It has poorer prognosis than that not associated with RTassociated with RT

DDRT to can be re-adminstered if indicatedRT to can be re-adminstered if indicated

9 The following are more common in 9 The following are more common in follicular than in papillary carcinoma follicular than in papillary carcinoma EXCEPTEXCEPTAAPsammoma body Psammoma body

BBOrphan Ann nucleusOrphan Ann nucleus

CCLymph node metastasisLymph node metastasis

DDAggressiveness Aggressiveness

EENone of aboveNone of above

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Patient was maintained under Patient was maintained under surveillance with replacement therapy surveillance with replacement therapy

After 2 years of follow up the patient After 2 years of follow up the patient develop Rt cervical lymph node develop Rt cervical lymph node enlargement about 2 cm single firm enlargement about 2 cm single firm mobilemobile

6 The best next step is6 The best next step is

AA FNAC of nodeFNAC of node

BB CTMRI neckCTMRI neck

CC TSH levelTSH level

DDExcisional biopsy of node Excisional biopsy of node

CTMRI neck revealed RT thyroid CTMRI neck revealed RT thyroid lobe swelling 3 cm in diameter with lobe swelling 3 cm in diameter with increased central vascularity with Rt increased central vascularity with Rt cervical LN and FNAC revealed cervical LN and FNAC revealed follicular carcinoma follicular carcinoma

Metastatic work up revealed Metastatic work up revealed multiple lung nodules multiple lung nodules

7 The tumor of the Rt lobe is 7 The tumor of the Rt lobe is consideredconsidered

AASecond primary Second primary

BBRecurrenceRecurrence

CCBoth Both

DDNeither Neither

8 As regard follicular carcinoma after 8 As regard follicular carcinoma after RT RT AAIt is the most common of thyroid cancer It is the most common of thyroid cancer after RTafter RT

BBIt is less common than papillary carcinomaIt is less common than papillary carcinoma

CCIt has poorer prognosis than that not It has poorer prognosis than that not associated with RTassociated with RT

DDRT to can be re-adminstered if indicatedRT to can be re-adminstered if indicated

9 The following are more common in 9 The following are more common in follicular than in papillary carcinoma follicular than in papillary carcinoma EXCEPTEXCEPTAAPsammoma body Psammoma body

BBOrphan Ann nucleusOrphan Ann nucleus

CCLymph node metastasisLymph node metastasis

DDAggressiveness Aggressiveness

EENone of aboveNone of above

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

CTMRI neck revealed RT thyroid CTMRI neck revealed RT thyroid lobe swelling 3 cm in diameter with lobe swelling 3 cm in diameter with increased central vascularity with Rt increased central vascularity with Rt cervical LN and FNAC revealed cervical LN and FNAC revealed follicular carcinoma follicular carcinoma

Metastatic work up revealed Metastatic work up revealed multiple lung nodules multiple lung nodules

7 The tumor of the Rt lobe is 7 The tumor of the Rt lobe is consideredconsidered

AASecond primary Second primary

BBRecurrenceRecurrence

CCBoth Both

DDNeither Neither

8 As regard follicular carcinoma after 8 As regard follicular carcinoma after RT RT AAIt is the most common of thyroid cancer It is the most common of thyroid cancer after RTafter RT

BBIt is less common than papillary carcinomaIt is less common than papillary carcinoma

CCIt has poorer prognosis than that not It has poorer prognosis than that not associated with RTassociated with RT

DDRT to can be re-adminstered if indicatedRT to can be re-adminstered if indicated

9 The following are more common in 9 The following are more common in follicular than in papillary carcinoma follicular than in papillary carcinoma EXCEPTEXCEPTAAPsammoma body Psammoma body

BBOrphan Ann nucleusOrphan Ann nucleus

CCLymph node metastasisLymph node metastasis

DDAggressiveness Aggressiveness

EENone of aboveNone of above

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

7 The tumor of the Rt lobe is 7 The tumor of the Rt lobe is consideredconsidered

AASecond primary Second primary

BBRecurrenceRecurrence

CCBoth Both

DDNeither Neither

8 As regard follicular carcinoma after 8 As regard follicular carcinoma after RT RT AAIt is the most common of thyroid cancer It is the most common of thyroid cancer after RTafter RT

BBIt is less common than papillary carcinomaIt is less common than papillary carcinoma

CCIt has poorer prognosis than that not It has poorer prognosis than that not associated with RTassociated with RT

DDRT to can be re-adminstered if indicatedRT to can be re-adminstered if indicated

9 The following are more common in 9 The following are more common in follicular than in papillary carcinoma follicular than in papillary carcinoma EXCEPTEXCEPTAAPsammoma body Psammoma body

BBOrphan Ann nucleusOrphan Ann nucleus

CCLymph node metastasisLymph node metastasis

DDAggressiveness Aggressiveness

EENone of aboveNone of above

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

8 As regard follicular carcinoma after 8 As regard follicular carcinoma after RT RT AAIt is the most common of thyroid cancer It is the most common of thyroid cancer after RTafter RT

BBIt is less common than papillary carcinomaIt is less common than papillary carcinoma

CCIt has poorer prognosis than that not It has poorer prognosis than that not associated with RTassociated with RT

DDRT to can be re-adminstered if indicatedRT to can be re-adminstered if indicated

9 The following are more common in 9 The following are more common in follicular than in papillary carcinoma follicular than in papillary carcinoma EXCEPTEXCEPTAAPsammoma body Psammoma body

BBOrphan Ann nucleusOrphan Ann nucleus

CCLymph node metastasisLymph node metastasis

DDAggressiveness Aggressiveness

EENone of aboveNone of above

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

9 The following are more common in 9 The following are more common in follicular than in papillary carcinoma follicular than in papillary carcinoma EXCEPTEXCEPTAAPsammoma body Psammoma body

BBOrphan Ann nucleusOrphan Ann nucleus

CCLymph node metastasisLymph node metastasis

DDAggressiveness Aggressiveness

EENone of aboveNone of above

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Papillary Cancer1048708 Histologic Psammoma bodies

intranuclear groves and cytoplasmic inclusions

Orphan Ann nucleus1048708 Multicentric 30-501048708 Spread via Lymphatics-

propensity for cervical node involvement1048708 Invasion of adjacent

structures and distant mets uncommon

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

FOLLICULAR THYROID CANCER 15-20 Of Thyroid Cancers ldquoWell Differentiatedrdquo Usually Encapsulated More Common Among Older Patients Woman gt Man More Aggressive amp Less Curable Than Papillary Blood Spread (lung and bone) 60 10 Year Survival Types Overtly Vs Minimally Invasive Hurthle

Cell Rarely associated with radiation exposure Invasion into blood vessels (veins and arteries)

within the thyroid gland is common

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

10 Stage of the tumor of that patient 10 Stage of the tumor of that patient according to TNM staging according to TNM staging AAII

BBIIII

CCIIIIIIII

DDIVIV

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

STAGING OFTHYROID CANCER

In differentiated thyroid carcinoma several classification and staging systems have been introduced However no clear consensus has emerged favoring any one method over another

1048708 AMES systemAGES SystemGAMES system

1048708 TNM system 1048708 MACIS system 1048708 University of Chicago system 1048708 Ohio State University system 1048708 National Thyroid Cancer Treatment

Cooperative Study (NTCTCS)

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

TNM Staging TNM Staging Primary tumor (T)Primary tumor (T) (All categories may be subdivided into (a) solitary tumor or (b) multifocal (All categories may be subdivided into (a) solitary tumor or (b) multifocal

tumor)tumor)

TXTX Primary tumor cannot be assessed Primary tumor cannot be assessed T0T0 No evidence of primary tumor No evidence of primary tumor T1T1 Tumor 2 cm or less in greatest dimension Tumor 2 cm or less in greatest dimension

limited to the thyroid limited to the thyroid T2T2 Tumor larger than 2 cm but 4 cm or Tumor larger than 2 cm but 4 cm or

smaller in greatest dimension limited to the smaller in greatest dimension limited to the thyroid thyroid

T3T3 Tumor larger than 4 cm in greatest Tumor larger than 4 cm in greatest dimension limited to the thyroid or any dimension limited to the thyroid or any tumor with minimal extrathyroid extension tumor with minimal extrathyroid extension (eg extension to sternothyroid muscle or (eg extension to sternothyroid muscle or perithyroid soft tissues) perithyroid soft tissues)

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

T4aT4a Tumor of any size extending Tumor of any size extending beyond the thyroid capsule to invade beyond the thyroid capsule to invade subcutaneous soft tissues larynx subcutaneous soft tissues larynx trachea esophagus or recurrent trachea esophagus or recurrent laryngeal nerve laryngeal nerve

T4bT4b Tumor invades prevertebral Tumor invades prevertebral fascia or encases carotid artery or fascia or encases carotid artery or mediastinal vessels mediastinal vessels

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Regional lymph nodes (N)Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and (Regional lymph nodes are the central compartment lateral cervical and

upper mediastinal lNs)upper mediastinal lNs)

NXNX Regional lymph nodes cannot be Regional lymph nodes cannot be assessed assessed

N0N0 No regional lymph node metastasis No regional lymph node metastasis N1N1 Regional lymph node metastasis Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) the cricothyroid membrane (precricoid) lymph nodes) lymph nodes)

N1b Metastasis to unilateral or bilateral N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes cervical or superior mediastinal lymph nodes

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Distant metastases (M) Distant metastases (M) MXMX Distant metastasis cannot be Distant metastasis cannot be

assessed assessed M0M0 No distant metastasis No distant metastasis M1M1 Distant metastasis Distant metastasis

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

AJCC Stage Groupings AJCC Stage Groupings Papillary or follicular thyroid cancerPapillary or follicular thyroid cancer

Younger than 45 yearsYounger than 45 years Stage I Stage I

Any T any N M0 Any T any N M0 Stage II Stage II

Any T any N M1 Any T any N M1

Age 45 years and olderAge 45 years and older Stage I Stage I

T1 N0 M0T1 N0 M0 Stage II Stage II

T2 N0 M0 T2 N0 M0 Stage III Stage III

T3 N0 M0 T3 N0 M0 T1 N1a M0 T1 N1a M0 T2 N1a M0 T2 N1a M0 T3 N1a M0T3 N1a M0

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Papillary or follicular thyroid cancer Papillary or follicular thyroid cancer ((Age 45 years Age 45 years and older)and older)

Stage IVA Stage IVA T4a N0 M0 T4a N0 M0 T4a N1a M0 T4a N1a M0 T1 N1b M0 T1 N1b M0 T3 N1b M0 T3 N1b M0 T2 N1b M0 T2 N1b M0 T4a N1b M0T4a N1b M0

Stage IVB Stage IVB T4b any N M0T4b any N M0

Stage IVC Stage IVC Any T any N M1Any T any N M1

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

1048708 University of Chicago system Class Imdashdisease limited to the

thyroid gland Class IImdashlymph node involvement Class IIImdashextrathyroidal invasion Class IVmdashdistant metastases

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

1048708 The NTCTCS created a staging approach that was applied prospectively to a registry of patients drawn from 14 cooperating institutions

Clinical pathologic staging was based upon 1048708 patient age at diagnosis 1048708 tumor histology 1048708 tumor size 1048708 intrathyroidal multifocality 1048708 extraglandular invasion 1048708 metastases 1048708 tumor differentiation

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

MAICS Scoring 1048708 Developed by the Mayo Clinic for staging 1048708 It is known to be the most accurate

predictor of a patients outcome with papillary thyroid cancer

(M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)

MAICS Score 20 year Survival lt6 = 99 6-7 = 89 7-8 = 56 gt8 = 24

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

11 The best next step is- 11 The best next step is- AA Thyroidectomy with neck dissection aloneThyroidectomy with neck dissection alone

BB RAI aloneRAI alone

CC Neck RTNeck RT

DD Both A and B are correctBoth A and B are correct

EE Both A and C are correctBoth A and C are correct

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Radical Thyoidectomy without Radical Thyoidectomy without residual was doneresidual was done

12 The patient should be planned for12 The patient should be planned forAA Pre-therapy iodine scanPre-therapy iodine scan

BB RAIRAI

CC Chemoradiation Chemoradiation

DD Postoperative RTPostoperative RT

EE Close follow up with maintaining TSH lowClose follow up with maintaining TSH low

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

I131I131 a postoperative course of a postoperative course of therapeutic (ablative) doses of Itherapeutic (ablative) doses of I131131 results in a decreased recurrence rate results in a decreased recurrence rate among among high-risk patientshigh-risk patients with with follicular carcinomasfollicular carcinomas

WHEN= indicationsWHEN= indications (any present) Age lt 15 y or gt 45 y Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor gt 4 cm in diameter Cervical lymph node metastases Aggressive variant

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Pretherpy IPretherpy I123123 scan was positive and scan was positive and RAI in a 30 mCi was taken one week RAI in a 30 mCi was taken one week after radioactive scanning with poor after radioactive scanning with poor responseresponse

13 The reason for poor response may 13 The reason for poor response may be due tobe due to

ASublethal radiation stunningBLow TSH levelCHigh grade tumorD Low-dose iodine ablation EAll of above

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Pretherapy whole body iodine scanIf performed a pretherapy scan should use a low dose of 131I (1 to 5 mCi) or 123I

To detect residual thyroid tissue thyroid cancer and metastatic foci

To reduce the potential for sublethal radiation stunning of thyroid tissue that prevents optimal uptake of future 131I therapy

Stunning is defined as a reduction in uptake of the 131I therapy dose induced by a pretreatment diagnostic dose

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Need high TSH level 131I may be given either when the patient

demonstrates biochemical evidence of hypothyroidism (feedback increased endogenous TSH) or after treating the patient with recombinant human TSH (exogenous TSH)

Both methods are based on the principle that TSH stimulates 131I uptake in both residual thyroid tissue and residual carcinoma and that it permits ablation of both

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Dose of RAIThe dosing of 131I for ablation is somewhat controversial Low-dose ablation with less than 30 mCi administered on an outpatient basis

For low-risk young patients

High-dose ablation with100 to 200 mCi For high-risk patients

300 mCi For all patients with metastatic disease that

treated with repeated therapeutic doses of 131I

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

14 The best management of this 14 The best management of this patient ispatient is

AASystemic chemotherapySystemic chemotherapy

BBPalliative RTPalliative RT

CCTarget therapy with bevacizumabTarget therapy with bevacizumab

DDAll of aboveAll of above

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Stage IV Follicular Stage IV Follicular

The most common sites of metastases are lymph nodes The most common sites of metastases are lymph nodes lung and bone lung and bone

Treatment of lymph node metastases alone is often Treatment of lymph node metastases alone is often curativecurative

Standard treatment optionsStandard treatment options 1)1) I131I131 Metastases that demonstrate uptake of this Metastases that demonstrate uptake of this

isotopeisotope2)2) RadiationRadiation therapy for localized lesions unresponsive to therapy for localized lesions unresponsive to

I131I1313)3) Resection Resection of limited metastases dont uptake of I131of limited metastases dont uptake of I1314)4) Thyroid-stimulating hormone suppressionThyroid-stimulating hormone suppression with with

thyroxine is also effective in many lesions not sensitive thyroxine is also effective in many lesions not sensitive to I131to I131

5)5) ChemotherapyChemotherapy has been reported to produce occasional has been reported to produce occasional complete responses of long durationcomplete responses of long duration

6)6) Patients unresponsive to I131 should also be Patients unresponsive to I131 should also be considered candidates for considered candidates for clinical trialsclinical trials testing new testing new approaches to this diseaseapproaches to this disease

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Systemic chemotherapySystemic chemotherapy

doxorubicin alone doxorubicin alone cisplatin and of doxorubicin (better)cisplatin and of doxorubicin (better) Combined chemotherapy with Combined chemotherapy with

bleomycin adriamycin and bleomycin adriamycin and platinum in advanced thyroid platinum in advanced thyroid cancercancer

Several histologic types of thyroid Several histologic types of thyroid carcinoma responded but the best carcinoma responded but the best responses were observed in medullary responses were observed in medullary and anaplastic giant-cell carcinomasand anaplastic giant-cell carcinomas

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy

Sorafenib TosylateSorafenib Tosylate in Patients With in Patients With Metastatic or Unresectable Iodine Non-Metastatic or Unresectable Iodine Non-Avid Resistant Avid Resistant Thyroid CancerThyroid Cancer

Pazopanib HydrochloridePazopanib Hydrochloride in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

Sorafenib (Nexavar)Sorafenib (Nexavar) in Patients With in Patients With Advanced Advanced Thyroid CancerThyroid Cancer

LenalidomideLenalidomide in Patients With Radioiodine- in Patients With Radioiodine-Unresponsive Unresectable Metastatic Unresponsive Unresectable Metastatic Papillary or FollicularPapillary or Follicular Thyroid Carcinoma Thyroid Carcinoma

BortezomibBortezomib in Patients With Metastatic in Patients With Metastatic Papillary or FollicularPapillary or Follicular Thyroid Cancer Thyroid Cancer Unresponsive to Prior Radioiodine TherapyUnresponsive to Prior Radioiodine Therapy