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DR:- OMAR HASHIMCANCER OF LARYNX
Anatomy of the larynx
the larynx is consists of a cartilaginous skeleton with ligaments,which carries the muscles and mostly is covered by mucous membrane .
skeleton of the larynx ;-1)Thyroid cartilage ;- consist of tow lateral
laminae which are fused in front (bow ship). At the tip of bow is a notch (Adam apple) . The superior and inferior horn arise from the posterior edge of each laminae
2) Caricoid cartilage ;-it is ship is like signet ring .it is lamina is 2-2.5 cms lies posterior .the upper edage of the lamina has tow articular surface for the arytenoid cartilage .the lateral surface on each side has articular surface for the inferior horn of the thyriod cartilage .
Arytenoid cartilage ;-pair of cartilage sited on the upper edge of the lamina of the cricoid cartilage .it has the shap of triangular pyramid .
The vocal cord are two thickened uppper end of the conus attached posterior to the vocal process of both arytenoids cartilage and interiorly to the inner surface of the angle of the thyroid cartilagecricoarytenoid muscles .
Epiglottis ;-lies against the middle of the thyroid cartilage
Laryngeal ligaments ;-is a membrane composed of a dense elastic fiber net which lies below the mucous memberane of the larynx and has different sickness in different region (conus elasticus-vocal cord –median cricothyroid ligament l-quadrangular membrane –vestibular ligament …)
Epidemiology & etiology
New case in 2009 is 12,290 with ca larynx .with men affected four time more than female .deaths from ca larynx is 3,660 . With modern care the deaths dropped from 2,97 per 100,000 to 2,24 per 100,000 .
Risk factors ;-1) Age > 55 yrs .2)Gender male to female ratio 4:13)Cigarette smoking (2-25X increase)
4) Alcohol consumption (2-6 increase ) the .The combination of cigarette and alcohol
↑(40-100) .5) Race African –American are more affected .6) Past medical history of head and neck
cancer ↑risk of ca larynx .7) Genetic factors ;- e.g fanconia anemia and
dyskeratosis congenita (condation→aplastic anemia ↑ risk of ca larynx .
8) Condition → ↓ immunity (AIDS –organ transplant ) .↑risk of ca larynx .
Pathology of the ca larynx
Ca larynx sub site
percent
supraglottic 35%
glottic 65%
subglottic 1%
The majority of ca larynx which arise from the mucosal surface is squamous cell carcinoma .
The most are well to mode differentiated .
Route of spread
spread occur by one of the three ;-A) Local extension ;- the most common ,spread
to cartilages→ sclerosis then by additional growth causes cartilage erosion → destruction and penetration of cartilages .
B) Lymph nodes met- Occur less common .the lymphatic drainage depend on the origin of the 1ry sites .
C) Distant mets- ;-the most common site of hematogenous spread is the bones then less common to the lungs .
1supr
11 111
1v v 1 11 111
1v v
1% 39% 26%
8%
5%
O%
12%
5%
3%
3%
ipsilateral nodes
contralateral nodes
lymph nodes involved in the ca larynx (supraglottic)
diagnosis Clinical presentation ;-Early presentation is hoarseness of the voice Change in the quality of the voice . While advance presentation is difficulty in the
swallowing . Cervical adenopathy . Weight loss . Throat pain . Referred pain . Air way obstruction .
Head and neck examination :- inspection of the scalp,ears,
Nose, and mouth . Palpation of the neck, mouth, tongue
Mobility, base of the tongue, and floor of mouth.Endoscope to nasal cavity,nasopharynx,oropharynx,Hypopharynx and larynx . Carefully cranial nerve
examination
Staging
Diagnosis and clinical staging depends on finding from history ,physical examination ,imaging and lab tests . Pathological staging depends on finding from surgical resection and histological examination .
There are American joint committee on cancer (AJCC)
And Tumor, Node, and Metastasis .(TNM)
Tx primary tumor can not be assessed T0 No evidence of primary tumor T is Carcinoma insitu
AJCC ,TNM classification of carcinoma
Primary tumor ;-
T1 Tumor limited to 1 sub site of supraglottis ,with normal vocal cord mobility
T2 Tumor in more than 1 adjacent sub site of the supraglottis or glottis .with out fixation of the larynx
T3 tumor limited to larynx with vocal cord fixation, or invades following postcricoid area preepiglottic spaceOr inner cortex of thyroid cartilage
T4a
Moderate advanced local disease, tumor invade thyroid cartilage or pre -larynx tissues
T4b
Very advanced local disease ,tumor invade prevertedral space,carotid artery,or invades mediastinal structure
supraglottis ;-
T1 Tumor limited to 1 vocal cord with normal mobility
T1b Tumor involve both vocal cord with normal mobility
T2 Tumor extends to supraglottis or subglottis with impaired vocal cord mobility.
T3 Tumor limited to the larynx with vocal cord fixation Or involve paraglottic space ,or inner cortex of thyroid cartilage .
T4a Moderately advanced local disease ,outer cortex of thyroid cartilage or tissues surrounding the larynx
T4b Very advanced local disease prevertebral space or mediastinal structures .
Glottis
T1 tumor limited to the subglottis
T2 Tumor extend to vocal cord with normal or impaired mobility
T3 Tumor limited to the larynx with vocal cord fixation
T4 Moderately advanced local disease .invading of the cricoid or thyroid cartilage or tissue around the larynx .
T4b
Very advanced local disease ,invading the prevertebral space ,cartoid artery ,meditational structure .
Sub glottis ;-
Nx Can not be assessed
N0 no lymph nodes metastasis
N1 metastasis in the ipsilateral lymph nodes≤3 cm (greater dimension)
N2a Metastasis in single ipsilateral lymph nodes>3cm but≤6cm in greater dimension
N2b Metastasis in multiple ipsilateral lymph nodes none >6 cm
N2c Metastasis in bilateral or contra lateral lymph nodes none > 6cm
N3 Metastasis in lymph nodes >6cm in greater dimension
Regional lymph nodes ;-
Ca larynx suspected
Complete history & physical exam
Endoscopy and biopsy
imaging
study
Labstudy interven
tion
Lesion incapable of regional
met-GLOTTIC
T1-2N0M0
LESION CAPABLE
OF REGIONAL
*Mets-
Advanced lesion
suitable for organ conservati
on**
Advanced lesion
beyond organ
conservation ***
Prognosis ;-
The out come of treatment of ca larynx is varies substantially, from excellent to poor. The most important prognostic factors include extent/stage at diagnosis, the exact site of origin of disease and patient’s performance status /ability to tolerate the desired therapy
Treatment
Localized lesion incapable of regional metastasis ; this include the SCC of glottis (T1 or T2, N0 ) .this treated by radiation therapy to the primary site only . Surgery is second option but radiation is preferable due to subsequent voice quality .
Radiation therapy ;- is indicated for all early stage . The techniques ;- small opposed portals (e.g. 5x5 or 6x6 cm ) treating the primary tumor only .the dose is 63 Gy in 28 fr/ 2.25 CGY/day in 5.6 weeks .
Usually the portals extend from hyoid bone to the bottom of the cricoids cartilage (upper/lower) and from the flash of the skin to the anterior aspect of the vertebral body (anterior/posterior) .
Usually we use tow parallel opposed 4-6 MV photon
Beam field .In recent years arandomized study done
concurring the fraction schaclat for T1N0M0 glottic cancer were treated either with 2,0 or 2.25 Gy ,the 5yrs local control rate favored the group that received 2.25 Gy
(92 versus 77%) . But the cause specific survival rate were similar (100 and 97%) .
Localized lesion capable of regional metastasisLimited extent SCC of the supraglottic larynx (T1N0-smallN1 and most T2N0 . In treatment of
the these type of the lesion the tow type of the treatment can be done radiation and surgery but the radiation is preferable due to less morbid .
Radiation ;- suitable for all case . Specially if the extend of the disease required total laryngectomy to repair the surgery .
The techniques ;- For small supraglottic include the primary lesion pulse
the upper and mid cervical (level1&11) .For more extensive supraglottic lesion also include
low, anterior cervical (level1v) nodes .If N1 anterior cervical disease the posterior cervical
(level 5) should be treated .Radiation technique ;-usually lateral and parallels op-Posed fields are used . For T1 supraglottic lesion a dose
of 66 GY in 33fr 2fr/day .for T2 supraglottic 70 GY in35 fr .
Advanced lesion suitable for organ preservationT3 –T4 ;- this lesion traditionally treated by
laryngectomy(with or without pharyngectomy) .now these is larynx sparing therapy these is no deferent in the cervival between surgery and the larynx sparing therapy .but not all lesion are suitable for organ preservation therapy (unreliable patients,pts contuse smoking during treatment ,hypertensive,pts who cannot tolerate discomfort
of the surgery)
The treatment modal which used for organ preservation;-
Indicated for advanced lesion that have not penetrated cartilage .(cord fixation is not contra-
Indication).Techniques ;-the primary tumor and clinical
involvedNodes should receive 70 GY in 35 frs .All anterior and posterior cervical
andsupraclavicular clinically uninvolved are at risk for sub clinical involvement and need to receive minimum of 50 GY
The chemotherapy ;- include cisplatin I.V on day 1,22 &43 of radiotherapy .
Clinical evidence ;-Randomized trials ;-
Department of veteran affairs larynx
pts number= 332 ( stage 111 or 1v ca larynx ). Median fallow up 33 monthsCompared 3 cycles of indication cisplatin + flurouracil chemotherapy Versus laryngectomy postoperative radiation.The survival rate is equal in both arm for 2 yrs =68% ( p=0.098) .there were More local recurrence (p=0.005)and fewer distant metastases (p=0.016)In the chemotherapy group than in the other group
EORTC24891 b
Randomized of patent number202 with ca larynx of the pyriform sinus stage 11-1v follow up to 51 months .Compared cycles of inducation cisplatin chemotherapy and thenradiotherapy verus larngectomy and postoperative radiotherapy median cervival was 44months in inducation chemotherapy arm and 25 months in surgery arm .Local and regional recurrence was similar in both arm
RTOG Randomized care of 520 patients who wise Required laryngectomy . Comparing inducation cisplatin plus fluoro-Uracil and then radiotherapy versus radiotherapy with concurrent administration of cisplatin versus radiotherapy alone .The primary end point of preservation of the larynx significantly favored concurrentTherapy 2yrs-88% while inducation chemo-75% and the radiotherapy 70%.2nd end point of loco regional control significantly Favored concurrent therapy 78% while with inducation chemo-61% and 56% with radiotherapyAlone .overall survival was similar in all groups
Resectable advanced lesions not suitable for organPreservation ;-the important part in preservation is the preservation of the function .once function is Irreparably lost , these is little benefit to preserving The anatomy .in other cases concurrent chemo-may be
toxic due to other diseases or refuse stop smoking /co-morbidities /unreliable who cutting medication /patients who emotionally would prefer
Surgery / cartilage destroyed or extracapssular extension. 2studies show that stage111 loco regional
Control improved by adding cisplatin concurrent with
Radiation therapy tech- ;-the fields include the primary site (tumor +ve LNs) +subclinical LNS
The upper border includes the nodes in the upper jugular region. both the ipsilateral and contra lateral
Posterior are include in the treatment portals if anterior chain +ve.
The primary site &area with↑risk(dissected and has
Altered vascular supply)60-66GY 33fr .While area of low risk(not dissected) will receive50-54 fr .
unresectable advanced lesion not suitable for organ
Preservation ;- in unresectable patients with good general condition with no heamatogenus spread can be approached with curative- intent chemotherapy-enhanced radiation therapy . In very
Fit patients inducation chemotherapy succeeded by
Chemo—enhanced radiation therapy .for patient with
Already distant metastasis role will be palliation
Post-operative radiation therapy .Radiation is indicated for all lesion extent Tech – 60-66 GY to operative bed and
drainageNodes .Chemo- ;-indicated for microscopically
involved mucosal margin /extra capsular extension of nodal
Disease . Tech- I-V ;-cisplatin 1 on day 1 ,22 and 43 of
radiotherapy treatment .
The volume delineation ;- The primary tumor site,all nodal beds at risk
of subclinical disease and operative bed . The upper border include the nodes in jugular region .the high
Risk region→ 60-66 GY .low risk→50-54 GY .
RTOG 9501
459 patients . Who ,after definitive surgery , had histologic invasionOf tow or more regional LNs/extra capsular extension of nodal diseaseOr mucosal resection margin.Randomized to radiotherapy alone o(60-66GY) versus identical treatment+concurrent cisplatin on day 1 ,22 &43 .The primary end point of loco regional control favored concurrent chemotherapy at 2 yrs 82% ( with chemotherapy ) versus 72% (no chemotherapy ).The secondary end point of disease free survival also favored concurrentTherapy ( p=0.04) but over all survival not different
Supporting clinical evidence
EORTC22931
Patients number 334 ,who after definitive surgery had histological Evidence of extra nodal spread , + ve margin , per neural involvementOr vascular tumor embolism (median fallow up 60 months )Randomized to radiotherapy alone (66 GY in 33 fr) versus identical treatment +concurrent cisplatin in day 1, 22 &43 .The primary end point of disease free survival favored concurrent therapyAt 5 yr s4% with chemotherapy verus36% (no chemotherapy) p=o.o4Second end point of overall survival(p=0.02) and loco regional control(p=0.007) both significantly favored concurrent therapy
schedule frequency
First follow up 2weeks after radiation →for acute reaction
Yrear0-1 Every month
Year 1-2 Every 2 months
Year2-3 Every 3 months
Year 3+ Every 6 months
From the previous data of RTOG 9501and EORTC 22931
Which concurring the benefit of chemotherapy.
Were the ECE (extra capsular extenation) or +ve SM.
Involvement of2 more LNs by tumor is not predict
Benefit from chemotherapy .
Palliation treatmentThe emis is to controlling thedistressing loco-Regional signs or symptoms of disease for during the
patient remaining alive .For who have one or tow non life threatening
lesion .with good response to chemotherapy ,the radiation
Therapy that approaches the intensity of definitive Treatment. With more advanced metastatic disease The author tends to favor asplit-course( eg;-30GY in
2weeks the tow weeks rest ,followed by another30 GY in 2weeksto smaller field never over lap the
spinal cord.for patient live more we can do quadShot technique
For M0tumor
Multi-institutional phase 111 trial includeing 295 patient with unresectableNondisseminated ,head and neck cancer.Randomized to stander radiation therapy alone (70YG in 30 fr ) versusIdentical radiation +concurrent bolus cisplatin on day 1 ,22 ,34 versus Split-course radiation therapy + bolus cisplatin and continuous –infusionFluorourcil . The with concurrent cisplatin is associated with improve of The survival,at the cost increase the toxicity .the 3yrs overall survival37% .
Supporting clinical evidence ;-
For M0 tumor
166 patients with locally advanced ( 74% operable and 26% unoperable)laryngeal and hypophyaryngealcancer .Randomized to to treatment with docetaxel (taxotere) ,cisplatin And 5-fluorourcil inducation then chemoradiotherapy versus Cisplatin and fluorourcil (pf) then chemoradiotherapy .For inoperable 2 yrs overall survival was 55% with TPF AND 41% In the PF . for inoperable tumor ,the 2 yrs progression free survival was 42%In TPF and 30% in the PF .
For MI TUMOR
30 patients who had advanced head and neck nearly stage 1v With performance score of 2-3 .Quad shot =14 GY in 4fr given twice a day at least 6hours apartOver 2 consecutive days ahd repeated up to twice more every4 weeks .53% objective reponse rate ( complete reponse,2, partial response,4.) .Median progression free survival3,1 months . Median overall survival 57 months .44% patients had measurable improvement in the quality of life
Organ at risk
Dose limitation (GY)
spinal cord 45
brachial plexus
60
mandible 70
posterior neck
<35 (astrip of normal tissue should be left to facilitateDrainge )
Dose limitation gude line in the ca larynx