FACET - European Journal of Cancer Care

FACET - European Journal of Cancer CareSeptember 2005

slides available at: www.blackwellpublishing.com/journals/ecc

PET in oncology: An oncologist’s view

Mikhaeel, N.G.1

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*Click on “View”; “Notes Page” for explanatory notes

An oncologist’s view

• The cancer journey from diagnosis to treatment

• The role of PET in oncology

• Specific cancers

• The future



PET in oncology: An oncologist’s view (continued)

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Cancer journey

• Diagnosis

• Staging

• Choice of therapy

• Assessment of response

• Follow-up, detection and treatment of recurrence



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Treatment decisions

Cancer treatment depends largely on its EXTENT (=

stage)

• Radical versus palliative

• Operability (and extent of surgery)

• Radical radiotherapy (and its extent)

• Need for adjuvant systemic treatment

• Combination treatment



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Late toxicity

In successfully treated cancers, LATE TOXICITY is important

• example: early Hodgkin’s Lymphoma (HL)

• A plateau has been reached in cure rates

• Death from treatment toxicity exceeds death from HL >10-15 years

• Current research is to improve the Therapeutic Index



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Improving therapeutic index

(1) Tailoring the treatment to individual’s prognosis: e.g.

• Prognostic indices

• Radiotherapy planning

(2) Response-adapted therapy – the oncologist needs:

• accurate staging

• accurate response assessment


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The role of PET (1)

(1) Diagnosis: limited use

• FDG uptake in inflammatory tissue

• ? SUV

Examples

• Indeterminate solitary pulmonary nodules

• Cerebral pathology in HIV+ patients

• ? Guiding biopsy in suspected malignancy


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The role of PET (2)

(2) Staging: TNM

T:

• Primary size (e.g. breast, lung)

• Depth of wall infiltration (e.g. gastro intestinal (GI), bladder)

• Extent of organ involvement (e.g. prostate)

• Infiltration of surrounding tissues (e.g. head & neck, uterine cervix)


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The role of PET (3)

N:

• Size

• normal v abnormal

• size determines N stage (head & neck)

• Number (colorectal cancer)

• Anatomical extent (lung)

M:• Liver, lung, bone, brain


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The role of PET (4)Where PET may help

T:

• Difficult areas on cross-sectional imaging; e.g. lung, head & neck

N:

• Normal size nodes with disease

• Enlarged but reactive nodes

M:

• One whole body staging test (except brain)

• May be useful in special situations e.g. liver resection of CRC metastases


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The role of PET (5)

(3) Therapy

Clinical implication of change in stage:

• Prognosis

• Choice of therapy


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The role of PET (6)

(4) Response Assessment

Context

• Radical:

– Complete response (CR) is the aim

– ? salvage treatment

– prognosis

• Palliative:

– quantitative measurement

– continue, stop or change treatment


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The role of PET (7)

• CT: the Gold Standard (quantitative)

Problems with measurements

• inter (15%) and intra (6%) -observer variability

• 1D v 2D v 3D measurement

• large mass smaller nodes

• Tumours shrink at different rates (even same disease e.g. HL)

• Residual masses / abnormalities


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The role of PET (8)

• Response criteria by CT:

– Objective Response Criteria

– RECIST (Response Evaluation Criteria In Solid Tumors )

4 categories of response: CR, PR, SD & PD

• CRu (unconfirmed / uncertain)

• What QUANTITATIVE criteria to use in PET?


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The role of PET (9)

• CT has the clear advantage of size measurement (palliative treatment, trials)

• PET has the clear advantage of accurately assessing CR (radical treatment)

• PET has the clear advantage of assessing early response in highly sensitive tumours e.g lymphomas, ? solid tumours

• ? CT/PET


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The role of PET (10)

(5) Follow-up & detection of relapse:

PET for routine FU? Limited by:

• Possibility of false positive

• Availability and cost

May be useful:

• selected cases with suspicion of relapse

• resolve equivocal findings on other tests


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The role of PET in lung cancer


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The role of PET in colorectal cancers

Coronal

Transaxial


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The role of PET in breast, CNS and

head & neck cancers

• Breast cancer – limited role although it is established in diagnosing brachial plexopathy and differentiating between local recurrence and radiation damage.

• Central nervous system (CNS)

• Head & neck


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The role of PET in other solid tumours


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Role of PET in lymphomas

• Staging

• Early response assessment

• Assessment of remission after treatment

• Evaluation of residual masses

• Follow-up and early detection of relapse

Pre-treatment scan demonstrating FDG uptake by lymphoma is essential


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N Stage Stage Treatment

change

Bangerter 1998 44 5 (11%) 1 (2%) 6 (14%)

Weidman 1999 20 3 (15%) 0 -

Partridge 2000 44 18 (41%)

3 (7%) 11 (25%)

Hueltenschmidt 2001

25 3 (12%) 7 (28%) -

Jerusalem 2001 33 4 (12%) 3 (9%) 1 (3%)

Welhrauch 2002

22 4 (18%) 5 (23%) 4 (18%)

Menzel 2002 28 4 (14%) 2 (7%) -

Studies for staging of Hodgkin’s

Lymphoma (HL)


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PET in staging early Follicular Lymphoma

Sagittal

Transaxial

Coronal

PET showed stage 4 with lumbar spine & spleen uptake.

L2


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A very novel use of PET in the

management of lymphomas is the use in early assessment of

response

• In high-grade NHL a large proportion of patients is not cured with primary treatment

• Salvage high dose chemotherapy is effective but toxic

• Selecting patients unlikely to be cured by primary chemotherapy is becoming possible with PET


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High grade NHL: Progression-free

survival

Progression-free survival

Interim PET positive

Minimal residual uptake

Interim PET negative

2-year survival

30.3 %

(CI 16.6-44.1)

59.3 %

(CI 35.5-82.9)

93.0 %

(CI 85.4-100)

5-year survival

16.2 %

(CI 3.5-28.8)

59.3 %

(CI 35.5-82.9)

88.8 %

(CI 77.9-99.7)

Mikhaeel et al, Ann Oncol 2005


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The future (1)

Technology:

• CT/PET

• New tracers e.g. 11C, 18F, peptides, Abs

Studies:

• protocols defining optimal use; timing, place in management algorithms etc.

• studies of clinical impact on patient management

• cost effectiveness

• response criteria


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The future (2)

Research:

• Drug pharmacokinetics

• Gene expression

• Cell proliferation (e.g. 18F fluoro-thymidine)

• In vivo imaging of apoptosis, hypoxia & receptor expression in the individual patient

Availability


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References • Bangerter M., Moog F., Buchmann I.,

Kotzerke J., Griesshammer M., Hafner M., Elsner K., Frickhofen N., Reske F.N., Bergmann L.. (1998) Whole-body 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for accurate staging of Hodgkin's disease. Annals of Oncology 9(10):1117-22.

• Hueltenschmidt B., Sautter-Bihl M.L., Lang O., Maul F.D., Fischer J., Mergenthaler H.G. & Bihl H. (2001) Whole body positron emission tomography in the treatment of Hodgkin disease. Cancer 91 (2):302-10.

• Jerusalem G., Beguin Y., Fassotte M.F., Najjar F., Paulus P., Rigo P., Fillet G. (2001) Whole-body positron emission tomography using 18F-fluorodeoxyglucose compared to standard procedures for staging patients with Hodgkin’s disease. Haematologica 86:266–73.


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References (continued)• Menzel C., Dobert N., Mitrou P., Mose S.,

Diehl M., Berner U. & Grunwald F.F. (2002) Positron emission tomography for the staging of Hodgkin's lymphoma-increasing the body of evidence in favor of the method. Acta Oncologica 41(5):430-6.

• Mikhaeel N.G., Hutchings M., Fields P.A., O’Doherty M.J., Timothy A.R. (2005) FDG-PET after two to three cycles of chemotherapy predicts progression-free and overall survival in high-grade non-Hodgkin lymphoma Annals of Oncology Advance Access published online on June 24, 2005

• Partridge S, Timothy A, O’Doherty MJ, Hain S.F., Rankin S., Mickhaeel G. (2000) 2-Fluorine-18-fluoro-2-deoxy-d-glucose positron emission tomography in the pretreatment staging of Hodgkin’s disease: influence on patient management in a single institution. Annals of Oncology11:1273–9.


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References (continued)• Weihrauch M.R, Re D, Bischoff S, Dietlein

M., Scheidhauer K., Krug B., Textoris F., Ansen S., Franklin J., Bohlen H., Wolf J., Schicha H., Diehl V., Tesch H. (2002) Whole-body positron emission tomography using 18F-fluorodeoxyglucose for initial staging of patients with Hodgkin’s disease. Annals of Hematology 81:20–5.

• Wiedmann E., Baican B., Hertel A., Baum R.P., Chow K.U. Knupp B. Adams S., Hor G., Hoelzer D. Mitrou P.S. (1999) Positron emission tomography (PET) for staging and evaluation of response to treatment in patients with Hodgkin’s disease. Leukaemia and Lymphoma 1999;34:545–51.

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