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Role of FDG PET(/CT) in Assessing Response to Treatment of Lymphoma , Breast and Lung Cancers

Role of FDG PET(/CT) in Assessing Response to Treatment of Lymphoma , Breast and Lung Cancers. Niraj R. Patel, M.D. September 1, 2011. Why this Topic?. Cancer management can be improved FDG PET/CT provides different data than conventional imaging Detects changes earlier

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Role of FDG PET(/CT) in Assessing Response to Treatment of Lymphoma , Breast and Lung Cancers

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  1. Role of FDG PET(/CT) in Assessing Response to Treatment of Lymphoma, Breast and Lung Cancers Niraj R. Patel, M.D. September 1, 2011

  2. Why this Topic? • Cancer management can be improved • FDG PET/CT provides different data than conventional imaging • Detects changes earlier • Detecting changes earlier can help improve cancer management

  3. PET/CT’s Value in Cancer Management • FDG PET is more Sensitive & sometimes more Specific in detecting metastases • CT was 70% Sn & 69% Sp whereas PET/CT was 85% Sn & 84% Sp for nodal staging of NSCLC (Shim Radiology 2005) • CT was 88% Sn & 86% Sp whereas PET/CT was 100% Sn & 90% Sp for lymphoma (Schaefer Radiology 2004) • CT was 68% Sn & 69% Sp whereas PET/CT was 87% Sn & 62% Sp for breast cancermetastases (Tatsumi EJNMMI 2006) • PET scans accurately show whether cancer is responding to therapy before CI does • Visual assessment is sufficient (Lowe JNM 1994)

  4. Problems with PET • SUV not wholly objective • Partial-volume averaging affects SUV • SUV not consistent between different PET cameras • SUV sometimes not consistent using same PET camera (eg, patient becomes emaciated) • Although qualitative comparison may help • Cannot detect small volume tumors • No clear guidelines on ideal interval to rescan • Radiotx introduces confounding factors

  5. Problems with PET

  6. Basics on FDG PET

  7. Basics on FDG PET

  8. Basics on FDG PET Cherry SR and Gambhir SS. “Use of Positron Emission Tomography in Animal Research.” ILAR Journal V42(3) 2001.

  9. Hot (Abnormal) or Not (Physiologic) North Texas Clinical PET Institute. “Lymphoma - 53-year-old female.” PETNET Solutions. 2011.

  10. Hot (Abnormal) or Not (Physiologic) North Texas Clinical PET Institute. “Lymphoma - 53-year-old female.” PETNET Solutions. 2011.

  11. Hot (Abnormal) or Not (Physiologic) North Texas Clinical PET Institute. “Lymphoma - 53-year-old female.” PETNET Solutions. 2011.

  12. Modern Medicine vs. Cancers • Survival rates doubled over 60 years for some cancers • Breast • Colorectal • Cervical • Survival rates remain “abysmally” low for other cancers • Lung • Gastric • Pancreatic • Many cancer drugs are not effective Ben-Haim S and Ell P. “18F-FDG PET and PET/CT in the Evaluation of Cancer Treatment Response.” JNM 2009; 50(1):88-99.

  13. Modern Medicine vs. Cancers “The problem of giving drugs to people who don’t benefit from them is huge… Diagnostic tests don’t yet exist to distinguish who does and who does not respond to these medications, but these statistics show the great need for such tests.” X Aspinall MG and Hamermesh RG. “Realizing the Promise of Personalized Medicine.” Harvard Business Review. 01 Oct 2007.

  14. Importance of Assessing Response • Knowing whether somebody is a Responder makes a difference • If patient is a Responder • Reduces patient & medical team’s anxieties • Saves money & resources (eg, less additional lab/imaging) • If Non-responder (ie, resistant to therapy) • Prompts change in management, may be beneficial • Reduces morbidity and shifts focus to palliation • Saves money & resources

  15. Changing Role of PET in Cancer • Conventional role of PET/CT is staging –baseline, surveillance and after clinical evidence of recurrence • Emerging role of PET/CT is assessing response to therapy • Metabolic changes convey response to therapy earlier than anatomy changes (by CT, U/S or MRI) • Can change management earlier in the course

  16. RECIST: Complete Response • Complete Response (CR) • All target lesions must have disappeared • Any pathological lymph nodes (target or non-target) must have reduced in short axis to < 10 mm • Disappearance of all non-target lesions and normalization of tumor marker level Khan O and Protheroe A. “Testis cancer.” Postgrad Med J 2007;83:624-632. Eisenhauer EA et al. “New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1).” European Journal of Cancer 2009; 45:228-247.

  17. RECIST: Progressive Disease • New lesion • Substantial worsening in non-target disease (even if Stable or Partial Response of target disease) • If measurable disease is absent, change in non-measurable disease • ie, ↑ pleural effusion from ‘trace’ to ‘large’, ↑ in lymphangitic disease from localized to widespread Eisenhauer EA et al. “New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1).” European Journal of Cancer 2009; 45:228-247.

  18. PERCIST: Progressive Disease • PERCIST incorporates PET • Negative PET at baseline  Positive PET at follow-up is Progressive Disease (because it’s a new lesion) • No baseline PET, but Positive PET at follow-up • If follow-up Positive PET corresponds to new disease on CT, Progressive Disease • If follow-up Positive PET not confirmed on CT as new site, additional follow-up CT scan needed to determine if true progression • If follow-up Positive PET corresponds to pre-existing site of disease on CT that is not progressing on anatomic imaging, not Progressive Disease Wahl RL et al. “From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors.” JNM 2009; 50:5(Suppl).

  19. PERCIST: Progressive Disease Wahl RL et al. “From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors.” JNM 2009; 50:5(Suppl).

  20. PERCIST: Partial Response Wahl RL et al. “From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors.” JNM 2009; 50:5(Suppl).

  21. Hot (Abnormal) or Not (Physiologic) Thompson Cancer Survival Center “Lung Cancer - 64-year-old male” PETNET Solutions. 2011.

  22. Hot (Abnormal) or Not (Physiologic) • Thompson Cancer Survival Center “Lung Cancer - 64-year-old male” PETNET Solutions. 2011.

  23. Lymphoma Winslow T. “Stages of Adult Non-Hodgkin Lymphoma.” NCI. 2009.

  24. Lymphoma • Hodgkins Disease • Non-HodgkinsLympoma(15 per 100K) • DLBC (~30%) & Follicular (~20%) • International Workshop Criteria (1999) • Complete remission and Stable disease is self-explanatory • Progressive disease: > 50% ↑ in any lesion, or new lesion • Why PET data is helpful • Lymph node size unreliable indicator of disease state • Change in size is reliable, but lack of change is not Sp • Change in metabolic activity more Sn

  25. PET/CT Recommended in Lymphoma • International Harmonization Project (which Juweid et al proposed in 2005) • Lymphoma recommendations incorporating PET data • After chemotx or immunotx, repeat PET/CT in 6-8 weeks after starting therapy • But if radiotherapy, repeat PET/CT in 8-12 weeks after finishing XRT • Visual assessment sufficient to determine if positive PET post-completion of therapy • PET monitoring warranted only if clinical trial or prospective registry, otherwise be judicious

  26. PET/CT Recommended in Lymphoma Ben-Haim S and Ell P. “18F-FDG PET and PET/CT in the Evaluation of Cancer Treatment Response.” JNM 2009; 50(1):88-99.

  27. PET Predicts Response in Lymphoma • Using visual assessment, Kostakoglu’s Cornell team focused on 30 aggressive lymphoma patients (13 HD, 17 NHL) who got PET scans after 1 chemotx cycle • After 1 cycle of chemotx, FDG-positive PET patients had median Progression Free Survival of 5 months • Patients with FDG-negative PET had PFS for entire follow-up period (median of 1½ years)

  28. FDG PET Better than CT in Residual Lymphoma • Before PET, residual lymphoma on follow-up CT scans often considered positive (unless proven otherwise) • Poor Sp for relapse/active disease • Jerusalem’s team in U. of Liège (Belgium) focused on 92 patients (19 with HD, 35 with intermediate/high-grade NHL) • All got CT (but not all got FDG PET) at baseline • All got CT and FDG PET 1-3 months after therapy Jerusalem G et al. “Whole-Body PET Using 18F-Fluorodeoxyglucose for Posttreatment Evaluation in Hodgkin's Disease and Non-Hodgkin’s Lymphoma Has Higher Diagnostic and Prognostic Value Than Classical Computed Tomography Scan Imaging.” Blood 1999; 94(2): 429-433.

  29. FDG PET Better than CT in Residual Lymphoma • 24 of 54 had residual mass on CT • 13 of 19 HD, 11 of 35 NHL • 5 of 24 with residual mass had FDG-positive post-therapy PET • 1 of 30 with no residual was FDG-positive on PET • Relapses • All 6FDG-positive pts (100%) • 5 of 19 (26%) pts with FDG-negative residual mass • 3 of 29 (10%) pts with negative CT and PET scans Juweid ME et al. “Use of Positron Emission Tomography for Response Assessment of Lymphoma: Consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma.” JCO 2007; 25,(5): 571-578. Jerusalem G et al. “Whole-Body PET Using 18F-Fluorodeoxyglucose for Posttreatment Evaluation in Hodgkin's Disease and Non-Hodgkin’s Lymphoma Has Higher Diagnostic and Prognostic Value Than Classical Computed Tomography Scan Imaging.” Blood 1999; 94(2): 429-433.

  30. Juweid ME et al. “Use of Positron Emission Tomography for Response Assessment of Lymphoma: Consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma.” JCO 2007; 25,(5): 571-578.

  31. 2 months after the above PET/CT 4 months after the above PET/CT Juweid ME et al. “Use of Positron Emission Tomography for Response Assessment of Lymphoma: Consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma.” JCO 2007; 25,(5): 571-578.

  32. FDG PET Improves on CT in Residual Lymphoma • If there was a residual mass on CT, progression-free survival at 1 year was 62%, and 77% of these patients survived 1 year • PFS was 88% if no residual mass, and 95% of these patients survived 1 year • If patient was FDG PET-positive, PFS at 1-year was 0%, and 50% of these patients survived 1 year • PFS was 86% if FDG-negative, and 92% of these patients survived 1 year Jerusalem G et al. “Whole-Body PET Using 18F-Fluorodeoxyglucose for Posttreatment Evaluation in Hodgkin's Disease and Non-Hodgkin’s Lymphoma Has Higher Diagnostic and Prognostic Value Than Classical Computed Tomography Scan Imaging.” Blood 1999; 94(2): 429-433.

  33. FDG PET Better than CT in Residual Lymphoma • Guay’s team in Quebec focused on 48 HD patients getting FDG PET after therapy (median ~2 months after) • 34 patients were disease free for 1.7 years, 14 patients relapsed within ½ year • FDG PET was 79% Sn and 97% Sp for predicting relapse, and both PPV and NPV was 92% • CT was 83% Sn and 40% Sp for predicting relapse, with PPV of 45% and NPV of 80% Jerusalem G et al. “Whole-Body PET Using 18F-Fluorodeoxyglucose for Posttreatment Evaluation in Hodgkin's Disease and Non-Hodgkin’s Lymphoma Has Higher Diagnostic and Prognostic Value Than Classical Computed Tomography Scan Imaging.” Blood 1999; 94(2): 429-433. Guay C et al. “Prognostic Value of PET Using 18F-FDG in Hodgkin’s Disease for Posttreatment Evaluation.” JNM 2003; 44:1225–1231.

  34. PET Predicts Lymphoma Response Mid-Therapy • Lin’s team in Paris hospital focused on 92 patients with newly dx’d DLBCL • CT and FDG PET scan 2 weeks before & after chemotherapy • Median follow-up was 3.5 years • PPV for relapse of residual mass was 42% on CT showing residual disease • PPV for relapse was 100% on FDG-positive PET Lin C et al. “Early 18F-FDG PET for Prediction of Prognosis in Patients with Diffuse Large B-Cell Lymphoma: SUV-Based Assessment Versus Visual Analysis.” JNM 2007; 48:1626–1632.

  35. PET Predicts Lymphoma Response Mid-Therapy Lin C et al. “Early 18F-FDG PET for Prediction of Prognosis in Patients with Diffuse Large B-Cell Lymphoma: SUV-Based Assessment Versus Visual Analysis.” JNM 2007; 48:1626–1632.

  36. PET Predicts Lymphoma Response Mid-Therapy • Substantial ↓ (≥ 65.7%) in SUVmaxfrom hottest lesion on 1st to hottest lesion on 2nd PET had an accuracy of 76% in predicting event-free survival at 2 years • In 32 patients who progressed or died, mean ↓ in SUVmax was 61% • In 60 patients with EFS, mean ↓ in SUVmax was 78% • Perhaps an objective marker is better • 14 patients considered ‘positive’ on visually-assessed 2nd PET turned out to be negative (Responders) using very reduced SUVmax on 2nd PET Lin C et al. “Early 18F-FDG PET for Prediction of Prognosis in Patients with Diffuse Large B-Cell Lymphoma: SUV-Based Assessment Versus Visual Analysis.” JNM 2007; 48:1626–1632.

  37. PET Predicts Lymphoma Response Mid-Therapy EFS on visual assessment EFS on ΔSUVmax Lin C et al. “Early 18F-FDG PET for Prediction of Prognosis in Patients with Diffuse Large B-Cell Lymphoma: SUV-Based Assessment Versus Visual Analysis.” JNM 2007; 48:1626–1632.

  38. Hot (Abnormal) or Not (Physiologic) Northern California P.E.T. Imaging Center. “Thyroid Cancer - Patient with history of papillary thyroid cancer.” PETNET Solutions. 2011.

  39. Hot (Abnormal) or Not (Physiologic) Northern California P.E.T. Imaging Center. “Thyroid Cancer - Patient with history of papillary thyroid cancer.” PETNET Solutions. 2011.

  40. Breast Cancers Unknown artist. “General Information on Breast Cancer.” NCI. 2009.

  41. Breast Cancers • Annual age-adjusted incidence of 126 per 100K women in U.S. • Highest incidence in 40-55 age group • More than 7 in 10 new breast cancers are invasive ductal carcinoma • Worst prognosis • Commonly spreads to regional LN • Extent of LN involvement predicts recurrence

  42. PET/CT in Breast Cancer (IDC) • Limited value in initial diagnosis/staging • Primary tumors small • Axillarylymphadenopathy addressed surgically • 99mTc MDP bone scan as Sn as 18F FDG PET • When infiltration evident, PET is useful • Internal mammary, mediastinal, and distant mets • Better accuracy (90%) than conventional imaging for assessing recurrence • Changes management in ½ of recurrent patients

  43. PET/CT for Response in Breast Cancer • In chemotherapy-only patients, PPV for response was 93% for PET/CT , NPV 84% • Conventional imaging PPV was 85% and NPV 59% • Radiotherapy ↓ accuracy • ↓ FDG uptake preceded Δ in tumor size and predicted response to treatment Avril Net al. “Response to Therapy in Breast Cancer.” JNM 2009; 50:55S–63S.

  44. PET Predicts Breast Cancer Response • Vranjesevic’s team at UCLA focused on 61 breast cancer patients (74% with IDC) who were treated • 31% had NCED and 62% had evidence of recurrence • FDG PET blindly re-interpreted • CI not reinterpreted (CT, MRI, MM, U/S, MDP scan) • FDG PET better at prognosticating recurrence • PET was 84% Sp while CI was 68% Sp • PPV of 93% (39 TP out of 42 positive PET scans) • Conventional imaging PPV of 85% (33 TP of 39 positive CI scans) Vranjesevic D et al. “Whole-Body 18F-FDG PET and Conventional Imaging for Predicting Outcome in Previously Treated Breast Cancer Patients.” JNM 2002; 43:325–329.

  45. PET Predicts Breast Cancer Response • FDG PET better at prognosticating no disease (gold standard was clinical follow-up of ~2 years after PET ± 1 year) • PET was 93% Snwhile CI was 79% Sn • NPV of 84% (16 TN of 19 negative PET scans) • Conventional imaging NPV of 59% (13 TN of 19 negative CI scans) Vranjesevic D et al. “Whole-Body 18F-FDG PET and Conventional Imaging for Predicting Outcome in Previously Treated Breast Cancer Patients.” JNM 2002; 43:325–329.

  46. PET Predicts Breast Cancer Response What about discordant findings? Vranjesevic D et al. “Whole-Body 18F-FDG PET and Conventional Imaging for Predicting Outcome in Previously Treated Breast Cancer Patients.” JNM 2002; 43:325–329.

  47. PET Predicts Breast Cancer Response • PET and Conventional Imagingdiscordant in 25% of patients • 9 PET-positive but negative on CI • 6 positive on CI but PET-negative • PET correct in 80% (12 of 15) discordant cases • 6 of 9 positive PET (and negative CI)  True Positive • 6 of 6 negative PET(and positive CI)  True Negative • CI correct in 3 discordant cases (20%), which were false-positive PET scans Vranjesevic D et al. “Whole-Body 18F-FDG PET and Conventional Imaging for Predicting Outcome in Previously Treated Breast Cancer Patients.” JNM 2002; 43:325–329.

  48. PET/CT for Response in Breast Cancer • Significant ↓ in SUV after 1st and 2nd cycle of chemotherapy (mean 72% and 53% ↓ from baseline) in Responders • In Non-responders, no significant change in SUV • Best outcome were in patients with ↓ ≥ 60% in SUV Vranjesevic D et al. “Whole-Body 18F-FDG PET and Conventional Imaging for Predicting Outcome in Previously Treated Breast Cancer Patients.” JNM 2002; 43:325–329.

  49. PET Predicts Breast Cancer Response • Rousseau’s French team focused on 64 patients with neoadjuvant therapy for stage 2 and 3 breast cancer Rousseau C et al. “Monitoring of Early Response to Neoadjuvant Chemotherapy in Stage II and III Breast Cancer by [18F]Fluorodeoxyglucose Positron Emission Tomography.” JCO 2006;24:5366-5372.

  50. PET Predicts Breast Cancer Response • SUV of primary breast tumor ↓ to background in 94% (34 of 36) Responders • No significant variance in all 28 non-responders • Using cutoff of ≥ 60% ↓ in SUV between baseline and next PET scan • Sn 61%, Sp 96%, and NPV 68% after 1 course • Sn 89%, Sp 95%, and NPV 85% after 2 courses • For U/S, Sn 64%, Sp 43%, and NPV 55% • For Mammography, Sn 31%, Sp 56%, and NPV 45% Rousseau C et al. “Monitoring of Early Response to Neoadjuvant Chemotherapy in Stage II and III Breast Cancer by [18F]Fluorodeoxyglucose Positron Emission Tomography.” JCO 2006;24:5366-5372.

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