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FACET - European Journal of Cancer Care

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  • Notes
    In this presentation, I will start by discussing what the oncologist needs from imaging.
    I will review the current evidence to assess where Positron Emission Tomography (PET) may meet these needs and where it is currently used in clinical practice.
    I will discuss a specific clinical example (lymphomas) and finally a brief overview of the future.
  • Notes
    The cancer journey starts by diagnosis.
    Following that, some additional tests are usually performed to decide on the extent of the cancer, which is expressed as stage.
    The appropriate treatment is then chosen according to the type and site of cancer and its stage.
    The response to treatment is very often assessed by imaging.
    The patient then is followed up for the detection of recurrent cancer which may be treated again.
  • Notes
    With few exceptions, wide spread cancer can not be cured and the aim of treatment becomes palliative.
    Surgery is usually indicated and possible in localised cancer.
    Curative radiotherapy is indicated only in localised disease.
    In some cases, the addition of chemotherapy, following primary cancer treatment, can increase the chances of cure by eradicating microscopic metastatic disease.
  • Notes
    Current research in the treatment of early Hodgkin’s Lymphoma is aiming to minimise late treatment toxicity, while maintaining the current cure rate. This concept is known as optimising the therapeutic index (balance of benefit and risks of a treatment).
  • Notes
    Improving the therapeutic index can be achieved by two strategies:
    Tailoring the treatment to the prognosis of the individual patient. An example is using prognostic indices to predict the prognosis and hence intensity of treatment. Another example is to tailor the irradiation volume to the individual patient according to extent of cancer.
    Using the concept of “Response-adapted Therapy” where response to treatment is assessed and ineffective therapy is stopped / changed early. Also the intensity / duration of therapy can be adjusted to response (more intensive therapy if poor response, less therapy for excellent response).
    To do this, the oncologist needs accurate staging and accurate and early assessment of response.
  • Notes
    The most commonly used tracer in oncology is FDG (fluouro-deoxy-glucose). It is not a specific tracer for cancer. It also accumulates in areas of infection or inflammation. However, FDG accumulation can be useful in certain specific clinical situations as the examples given above.
    The degree of uptake (as measured by SUV [standard uptake value], which relates the uptake in an area of interest to the administered dose) can help in some situations to differentiate between malignant and benign processes (e.g. indeterminate solitary pulmonary nodule).
  • Notes
    The TNM (Tumour, Node, Metastases) system is widely used in staging solid tumours.
    However, the criteria defining each category varies from one tumour to the other. For example, T stage depends on size in breast cancer, but on depth of wall infiltration in bowel cancer. In prostate cancer, it depends on the extent of cancer within the prostate and in uterine cervix cancer, it depends on the degree of local infiltration of surrounding tissues.
    In some cancers, the accurate T staging can only be determined on histological examination after surgery.
     
  • Notes
    The N (lymph node) stage also varies according to the specific cancer.
    Radiological (e.g. CT, MRI or US) nodal status (malignant versus benign) is determined by size of lymph nodes.
    The number of lymph nodes determines the N stage in colorectal cancer (CRC) but the size, number and bilaterality of lymph nodes determines N stage in head and neck cancer.
    The M stage depends on the presence or absence of distant spread. The commonest organs are liver, lung , bone and brain.
  • Notes
    FDG-PET may help the staging of difficult areas on cross-sectional imaging.
    An example is lung cancer, where the extent of the primary tumour may not be obvious when adjacent to / within areas of collapse or consolidation. PET has also been shown to be more accurate than CT in staging the hilar/mediastinal lymph nodes in lung cancer.
    PET can result in both upstaging and downstaging of lung cancer.
    The advantage of FDG-PET in cancer staging also includes the ability to stage the whole body in one test.
    In some situations, PET offers more information on the extent of metastatic disease than CT/MRI. For example, potentially resectable liver secondaries from colorectal cancer (CRC).
  • Notes
    The change of stage can result in a change in the prognosis and also the choice of therapy. Very occasionally the change in stage does not have any significant implication.
    This is a list of examples from clinical practice where information from PET can help the choice of therapy:
    Operability (lung cancer, liver metastases from CRC)
    Extent of surgery (head and neck, lung)
    Neoadjuvant treatment (lung, CRC)
    Chemo / radiotherapy combinations (lymphoma)
    Extent of radiotherapy (lung, lymphoma).
  • Notes
    The response to treatment is assessed in two different contexts with different aims and implications.
    In the radical/curative context, the aim of treatment is to achieve complete response (CR). Cure is only possible following complete eradication of the tumour. Failure to achieve CR usually results in the initiation of salvage treatment.
    In the palliative/non-curative context, CR is not always possible and may not be necessary. However, the response to treatment is usually assessed to ensure that the treatment is working or otherwise it will be stopped or changed. The degree of response sometimes has a prognostic implication.
    Therefore, in radical treatment it is important to confirm CR status while in the palliative context, a quantitative measurement of the volume of cancer is usually required.
    .
  • Notes
    The gold standard imaging modality in cancer has been computed tomography(CT) which offers three dimensional measurement.
    However, there is inter and intra-observer variability and occasional difficulty when a large nodal mass breaks down into smaller nodes.
    Also, different tumours are made of different proportions of malignant and stromal components. In some cancers, the stromal/ fibrotic component may form the majority of the tumour bulk (e.g. Nodular sclerosing Hodgkin’s Lymphoma and Mediastinal sclerosing Bcell Lymphoma). In these cases, the tumour may respond well to treatment but the reduction in size could be slow.
    Another common problem (e.g. in treatment of lymphomas and testicular tumours) is the presence of residual masses at the end of treatment, where CT is unable to differentiate between residual active tumour and a fibrotic/necrotic mass.
  • Notes
    When CT is used to assess response, different response criteria, based on size measurement, can be used.
    However, there is no established criteria as yet to determine response on PET. PET is able though to confirm CR (i.e. complete disappearance of all abnormal uptake), where CT is limited.
    CR = complete response
    PR = partial response
    SD = stable disease
    PD = progressive disease
    CRu = complete response, unconfirmed / uncertain
  • Notes
    This slide summarises the relative advantage of PET and CT in response assessment.
    The combination of PET/CT may lead in the future to developing a combined response criteria.
    .
  • Notes
    Follow up has a value where the following criteria applies:
    high likelihood of relapse
    ability to detect relapse early
    availability of salvage treatment
    advantage to early treatment of relapse
    However, conventional imaging has not been shown to be cost effective in most cancers.
    The use of PET in routine follow-up is limited by the non-specificity of FDG for cancer and the current limited availability and expense of PET.
    However, PET is usually helpful in assessing selected cases with suspected relapse or resolve equivocal findings on other tests. Two examples are:
    brachial plexopathy after breast cancer treatment
    colorectal cancer: Rising markers with no obvious recurrence.

Transcript

  • 1. FACET - European Journal of Cancer Care September 2005 slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view Mikhaeel, N.G.1 SlideOne *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
  • 2. FACET - European Journal of Cancer Care September 2005 slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) SlideTwo *Click on “View”; “Notes Page” for explanatory notes Cancer journey • Diagnosis • Staging • Choice of therapy • Assessment of response • Follow-up, detection and treatment of recurrence
  • 3. FACET - European Journal of Cancer Care September 2005 slides available at: www.blackwellpublishing.com/journals/ecc SlideThree *Click on “View”; “Notes Page” for explanatory notes PET in oncology: An oncologist’s view (continued) 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
  • 4. FACET - European Journal of Cancer Care September 2005 slides available at: www.blackwellpublishing.com/journals/ecc SlideFour *Click on “View”; “Notes Page” for explanatory notes PET in oncology: An oncologist’s view (continued) 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
  • 5. FACET - European Journal of Cancer Care September 2005 slides available at: www.blackwellpublishing.com/journals/ecc SlideFive *Click on “View”; “Notes Page” for explanatory notes PET in oncology: An oncologist’s view (continued) 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
  • 6. FACET - European Journal of Cancer Care September 2005 SlideSix *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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
  • 7. FACET - European Journal of Cancer Care September 2005 SlideSeven *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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)
  • 8. FACET - European Journal of Cancer Care September 2005 SlideEight *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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
  • 9. FACET - European Journal of Cancer Care September 2005 SlideNine *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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
  • 10. FACET - European Journal of Cancer Care September 2005 SlideTen *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) The role of PET (5) (3) Therapy Clinical implication of change in stage: • Prognosis • Choice of therapy
  • 11. FACET - European Journal of Cancer Care September 2005 SlideEleven *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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
  • 12. FACET - European Journal of Cancer Care September 2005 SlideTwelve *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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
  • 13. FACET - European Journal of Cancer Care September 2005 SlideThirteen *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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?
  • 14. FACET - European Journal of Cancer Care September 2005 SlideFourteen *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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
  • 15. FACET - European Journal of Cancer Care September 2005 SlideFifteen *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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
  • 16. FACET - European Journal of Cancer Care September 2005 SlideSixteen *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) The role of PET in lung cancer
  • 17. FACET - European Journal of Cancer Care September 2005 SlideSeventeen *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) The role of PET in colorectal cancers Coronal Transaxial
  • 18. FACET - European Journal of Cancer Care September 2005 SlideEighteen *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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
  • 19. FACET - European Journal of Cancer Care September 2005 SlideNineteen *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) The role of PET in other solid tumours
  • 20. FACET - European Journal of Cancer Care September 2005 SlideTwenty *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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
  • 21. FACET - European Journal of Cancer Care September 2005 SlideTwentyOne *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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)
  • 22. FACET - European Journal of Cancer Care September 2005 SlideTwentyTwo *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) PET in staging early Follicular Lymphoma Sagittal Transaxial Coronal PET showed stage 4 with lumbar spine & spleen uptake. L2
  • 23. FACET - European Journal of Cancer Care September 2005 SlideTwentyThree *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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
  • 24. FACET - European Journal of Cancer Care September 2005 SlideTwentyFour *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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
  • 25. FACET - European Journal of Cancer Care September 2005 SlideTwentyFive *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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
  • 26. FACET - European Journal of Cancer Care September 2005 SlideTwentySix *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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
  • 27. FACET - European Journal of Cancer Care September 2005 SlideTwentySeven *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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.
  • 28. FACET - European Journal of Cancer Care September 2005 SlideTwentyEight *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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.
  • 29. FACET - European Journal of Cancer Care September 2005 SlideTwentyNine *Click on “View”; “Notes Page” for explanatory notes slides available at: www.blackwellpublishing.com/journals/ecc PET in oncology: An oncologist’s view (continued) 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.