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PET and Lymphoma

PET and Lymphoma. Corinne Haioun Unité Hémopathies Lymphoides Hôpital Henri Mondor Créteil, France. First and only rule: to cure the patient with first-line treatment. PET and Lymphoma : Background.

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PET and Lymphoma

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  1. PET and Lymphoma Corinne Haioun Unité Hémopathies Lymphoides Hôpital Henri Mondor Créteil, France

  2. First and only rule: to cure the patient with first-line treatment PET and Lymphoma : Background • Residual masses at the end of therapy are frequent(70% HL, 50% NHL) but only a minority of patients relapse (<20% HL, 25% NHL) • Patients in apparent complete remission also relapse • Early treatment of residual activedisease may improve survival Need for an accurate and sensitive tool to detect residual disease

  3. PET and Hodgkin Lymphoma : Background • Hodgkin Lymphoma is a curable disease, with more than 75% of the patients free of disease 10 years or more after standard treatment. • However, nearly 15-20% of the patients treated with ABVD fail therapy either for progression or relapse. • FDG-PET scan could be a surrogate test for chemosensitivity, due to its ability to predict treatment outcome with an overall accuracy of 90-95%.

  4. HD prognostic score: clinical variables Hasenclever d. NEJM 1998; 339:1506

  5. HD prognostic score: 7y-FFP and OS 7% of the patients Hasenclever d. NEJM 1988; 339:1506

  6. HL prognosis: from IPS to PET IntergruppoItaliano Linfomi According to IPS According to PET-2 (+vs.-) and IPS (0-2 vs 3-7)

  7. PET-0: 25.03.04 PET-2: 30.06.04 Gallamini: Hematologica 2006; 91, 475-81 Gallamini: JCO 2007; 25, 3743-52 PET-6: 08.11.04 Hutchings: Blood 2006; 107, 52-59 Kostakoglu: Cancer 2006; 107:2678-87

  8. 1 cycle ABVD IN-RT 30 Gy (+boost 6 Gy résiduals) whatever FDG- PET H10 Trial ABVD 2 cycles The results Favourable Group F Randomisation ABVD 2 cycles négative BEACOPP 2 cycles esca IN-RT 30 Gy (+ boost 6 Gy) FDG- PET ABVD 2 cycles Hodgkin Lymphoma Stage I/II positive whatever ABVD 2 cycles IN-RT 30 Gy (+boost 6 Gy résiduels) FDG- PET ABVD 2 cycles The results Unfavourable Group U Randomisation negative ABVD 4 cycles 2 cycles BEACOPPesca IN-RT 30 Gy (+ boost 6 Gy) FDG- PET ABVD 2 cycles positive First registration Second registration

  9. The situation in Diffuse Large B-Cell Lymphoma Weber W: J.Nucl. Med 2007: 48: 1580-82.

  10. Current questions for DLBCL patients Role of PET to individualize treatment ? Interim PET after 2 cycles may help stratify patients ? Event-free survival Overall survival 100 100 PET– (n = 54) 80 80 PET– (n = 54) 60 60 Pprobability Probability PET+ (n = 36) 40 40 PET+ (n = 36) 20 20 p < 0.0001 p = 0.006 0 0 0 1 2 3 0 1 2 3 Years after randomisation Years after randomisation Haioun C, et al. Blood 2005

  11. Early (after 2 cycles) PET treatment evaluation with visual analysis • All the sites of FDG uptake are scored in PET-0 and PET-2. • Each FDG uptake focus is quantified according to a score graded 1-3 (1 low, 2 moderate, 3 high) for extension and intensity • PET-2 negative: Negative was defined as having no residual abnormal uptake or as having a unique residual site (with an extent score of 1) associated with an intensity score of 1, whereas all the other previously hypermetabolic sites were extinguished. • PET-2 positive: Positive was defined as having at least one residual site (with an extent score of 1) associated with an intensity score of 2, or as having 2 or more residual sites with any extent and intensity scores. Haioun, Blood 2005; 106: 1376-1381

  12. Early treatment evaluation Before treatment At 2 cycles At 4 cycles FDG-PET2 (+) Haioun C, et al. Blood 2005; 106(4): 1376–81

  13. Early treatment evaluation Before treatment At 2 cycles At 4 cycles FDG-PET2 (-) Haioun C, et al. Blood 2005; 106(4): 1376–81

  14. Current questions for DLBCL patients Role of PET to individualize treatment ? Jerusalem et al. Haematologica, 85(6): 613-8   2000; Spaepen et al. Ann Oncol, 13(9): 1356-63   2002; Kostakoglu et al. J Nucl Med, 43(8): 1018-27   2002; Haioun C et al. Blood 2005; 106(4): 1376–81; Mickaeel et al. 2005

  15. FDG-PET in DLBCL TN TN +FN (High negative predictive value): NPV= FN TP TP +FP FP (Low positive predictive value): PPV=

  16. Event-free survival and overall survival according to response at 2 cycles onthe basis of PET (n = 90) Overall survival Event-free survival 100 100 PET– (n = 54) 80 PPV 50 % NPV 74 % Accuracy 68.5% 80 PET– (n = 54) 60 60 PET+ (n = 36) probability of OS Probability of EFS 40 40 median f/u: 2 years PET+ (n = 36) 20 20 p < 0.0001 p = 0.006 0 0 0 1 2 3 0 1 2 3 Years after randomisation Years after randomisation Haioun C, et al. Blood 2005; 106(4): 1376–81

  17. Activité mesurée C*tissulaire = Volume du foyer (Bq/g) Ci*() SUV= dose/poids Activité injectée C*tissulaire C*totale = Poids du corps SUV = C*totale (Bq/g) Si distribution homogène, SUV = 1 =1g/cm3

  18. 92 patients • PET baseline and after 2 courses of CT • IPI 0-1: 38; IPI 2-3: 54 • Therapy: CHOP, R-CHOP, ACVPB/ACE, R-ACVBP Lin C.: J. Nucl. Med 2007; 48, 1626-1632

  19. SUV-based Assessment versus Visual Analysis SUV and EFS: Optimal cut-off point of SUVmax reduction: 65.7%(ROC analysis) PPV 81.3% NPV 75.0% Accuracy 76.1% Lin C, Itti E. JNM 2007; 48:1626-32.

  20. Visual Analysis versus SUV-based Assessment SUV max Reduction Visual Analysis Probability of EFS (%) n=58 PET (-) n=76 > 65.7% n=34 PET (+) P < .0001 n=16 P = .009 65.7% Months After Randomization Linh C, Itti E. JNM 2007; 48:1626-32.

  21. MSKCC 01-142-DLBCL: Risk Adapted TherapyTransplant-eligible,CS IIX, III or IV age-adjusted IPI 1, 2, or 3 Risk Factors • Therapy interval-2 weeks with peg-filgrastim support • PET 10-14 days post cycle 4 • Treatment is adapted by biopsy, not PET • No radiation therapy permitted except for testicular disease • IT methotrexate for aaHR, paranasal sinus, testis, BM Moskowitz et al., Blood 108: Abstract 532, 2006

  22. MSKCC 01-142-DLBCL: Risk Adapted TherapyTransplant-eligible,CS IIX, III or IV age-adjusted IPI 1, 2, or 3 Risk Factors Moskowitz et al., Blood 108: Abstract 532, 2006

  23. Outcome based upon Interim Restaging PET scan Interim PET does not predict EFS Moskowitz et al., Blood 108: Abstract 532, 2006

  24. Current questions for DLBCL patients Optimize PET interpretation Role of PET to individualize treatment ? 3 Readers Anonymization Double encryption Time : 10 mn Time : 10 mn Medical Gateway PET data sent over the internet via a dedicated server to 3 readers: review in 48 hours

  25. PET Results PET Results Salvage : CORAL 4+ R-ACVBP14 + MTX IT + G-CSF MTX iv R- IFM / VP16 AraC A1 A1 2- /4 - Arm A A2 A2 MTX iv Z-BEAM + ASCT PET 0 PET 2 PET 4 R PET Final 2+ /4 - PET PET PET 4 PET 4 B2 B2 Arm B 2- /4 - B1 B1 R-CHOP14 + MTX IT + G-CSF R-CHOP14 + G-CSF 4+ Salvage : CORAL LNH07-3B DLBCL ; <60 years aa-IPI = 2-3 Role of PET to individualize treatment ?

  26. Lymphoma Unit Karim Belhadj Taoufik El Gnaoui Isabelle Gaillard Jehan Dupuis Frederique Kuhnowski Radiology Alain Luciani Alain Rahmouni Biostatistics François Hémery Eric Lepage Nuclear Medicine Emmanuel Itti Eva Evangelista Sophie Lin Michel Meignan Hematopathology Christiane Copie Karen Leroy Philippe Gaulard Acknowledgements

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