Pet And Lymphoma

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Pet And Lymphoma

  1. 1. Corinne Haioun Unité Hémopathies Lymphoides Hôpital Henri Mondor Créteil, France PET and Lymphoma
  2. 2. <ul><li>First and only rule: to cure the patient with first-line treatment </li></ul><ul><li>Residual masses at the end of therapy are frequent (70% HL, 50% NHL) but only a minority of patients relapse (<20% HL, 25% NHL) </li></ul><ul><li>Patients in apparent complete remission also relapse </li></ul><ul><li>Early treatment of residual activedisease may improve survival </li></ul>Need for an accurate and sensitive tool to detect residual disease PET and Lymphoma : Background
  3. 3. PET and Hodgkin Lymphoma : Background <ul><li>Hodgkin Lymphoma is a curable disease, with more than 75% of the patients free of disease 10 years or more after standard treatment. </li></ul><ul><li>However, nearly 15-20% of the patients treated with ABVD fail therapy either for progression or relapse. </li></ul><ul><li>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%. </li></ul>
  4. 4. HD prognostic score: clinical variables Hasenclever d. NEJM 1998; 339:1506
  5. 5. HD prognostic score: 7y-FFP and OS Hasenclever d. NEJM 1988; 339:1506 7% of the patients
  6. 6. <ul><li>According to IPS </li></ul>According to PET-2 (+vs.-) and IPS (0-2 vs 3-7) HL prognosis: from IPS to PET Intergruppo Italiano Linfomi
  7. 7. PET-0: 25.03.04 PET-2: 30.06.04 PET-6: 08.11.04 Gallamini: Hematologica 2006; 91, 475-81 Gallamini: JCO 2007; 25, 3743-52 Hutchings: Blood 2006; 107, 52-59 Kostakoglu: Cancer 2006; 107:2678-87
  8. 8. H10 Trial Randomisation Favourable Group F Unfavourable Group U Randomisation ABVD 2 cycles ABVD 2 cycles ABVD 2 cycles ABVD 2 cycles FDG- PET FDG- PET FDG- PET ABVD 2 cycles BEACOPP 2 cycles esca IN-RT 30 Gy (+ boost 6 Gy) ABVD 4 cycles 2 cycles BEACOPP esca IN-RT 30 Gy (+ boost 6 Gy) ABVD 2 cycles IN-RT 30 Gy (+boost 6 Gy résiduels) négative positive negative positive The results whatever The results Second registration First registration Hodgkin Lymphoma Stage I/II FDG- PET 1 cycle ABVD IN-RT 30 Gy (+boost 6 Gy résiduals) whatever
  9. 9. The situation in Diffuse Large B-Cell Lymphoma Weber W: J.Nucl. Med 2007: 48: 1580-82.
  10. 10. Current questions for DLBCL patients <ul><li>Role of PET to individualize treatment ? </li></ul>PET– (n = 54) PET+ (n = 36) Probability p < 0.0001 Years after randomisation Event-free survival p = 0.006 Overall survival 100 100 0 1 2 3 0 1 2 3 Years after randomisation Pprobability 80 60 40 20 0 80 60 40 20 0 PET– (n = 54) PET+ (n = 36) Interim PET after 2 cycles may help stratify patients ? Haioun C, et al. Blood 2005
  11. 11. <ul><li>All the sites of FDG uptake are scored in PET-0 and PET-2. </li></ul><ul><li>Each FDG uptake focus is quantified according to a score graded 1-3 (1 low, 2 moderate, 3 high) for extension and intensity </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul>Early (after 2 cycles) PET treatment evaluation with visual analysis Haioun, Blood 2005; 106: 1376-1381
  12. 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. 13. Early treatment evaluation FDG-PET2 (-) Before treatment At 2 cycles At 4 cycles Haioun C, et al. Blood 2005; 106(4): 1376–81
  14. 14. Current questions for DLBCL patients 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 Role of PET to individualize treatment ? 2-year outcome Study n PET after . . . PET- PET+ Jerusalem 2000 28 median: 3 cycles 62% (PFS) 0% (PFS) Spaepen 2002 70 median: 3 cycles 85% (PFS) 4% (PFS) Kostakoglu 2002 30 1 cycle 85% (PFS) <15% (PFS) Haioun 2005 90 2 cycles 82% (EFS) 43% (EFS) Michaël 2005 121 median: 2 cycles 87% (PFS) 34% (PFS)
  15. 15. (High negative predictive value): NPV= TN TN +FN (Low positive predictive value): PPV= TP TP +FP FN FP FDG-PET in DLBCL
  16. 16. Event-free survival and overall survival according to response at 2 cycles on the basis of PET (n = 90) PET– (n = 54) PET+ (n = 36) Probability of EFS p < 0.0001 Years after randomisation Event-free survival p = 0.006 median f/u: 2 years Overall survival 100 100 0 1 2 3 0 1 2 3 Years after randomisation probability of OS 80 60 40 20 0 80 60 40 20 0 Haioun C, et al. Blood 2005; 106(4): 1376–81 PET– (n = 54) PET+ (n = 36) PPV 50 % NPV 74 % Accuracy 68.5%
  17. 17.  =1g/cm 3 (Bq/g) Activité injectée Poids du corps C* totale = (Bq/g) Activité mesurée Volume du foyer C* tissulaire = C* tissulaire C* totale SUV = Si distribution homogène, SUV = 1 SUV= Ci*(  ) dose/poids
  18. 18. Lin C.: J. Nucl. Med 2007; 48, 1626-1632 <ul><li>92 patients </li></ul><ul><li>PET baseline and after 2 courses of CT </li></ul><ul><li>IPI 0-1: 38; IPI 2-3: 54 </li></ul><ul><li>Therapy: CHOP, R-CHOP, ACVPB/ACE, R-ACVBP </li></ul>
  19. 19. SUV-based Assessment versus Visual Analysis SUV and EFS : Optimal cut-off point of SUVmax reduction: 65.7% (ROC analysis) Lin C, Itti E. JNM 2007; 48:1626-32. PPV 81.3% NPV 75.0% Accuracy 76.1%
  20. 20. Visual Analysis versus SUV-based Assessment Months After Randomization > 65.7%  65.7% SUV max Reduction P < .0001 Probability of EFS (%) Visual Analysis PET (-) PET (+) P = .009 n=34 n=58 n=76 n=16 Linh C, Itti E. JNM 2007; 48:1626-32.
  21. 21. MSKCC 01-142-DLBCL: Risk Adapted Therapy Transplant-eligible, CS IIX, III or IV age-adjusted IPI 1, 2, or 3 Risk Factors <ul><li>Therapy interval-2 weeks with peg-filgrastim support </li></ul><ul><li>PET 10-14 days post cycle 4 </li></ul><ul><li>Treatment is adapted by biopsy, not PET </li></ul><ul><li>No radiation therapy permitted except for testicular disease </li></ul><ul><li>IT methotrexate for aaHR, paranasal sinus, testis, BM </li></ul>Moskowitz et al., Blood 108: Abstract 532, 2006
  22. 22. Moskowitz et al., Blood 108: Abstract 532, 2006 MSKCC 01-142-DLBCL: Risk Adapted Therapy Transplant-eligible, CS IIX, III or IV age-adjusted IPI 1, 2, or 3 Risk Factors
  23. 23. Outcome based upon Interim Restaging PET scan <ul><li>Interim PET does not predict EFS </li></ul>Moskowitz et al., Blood 108: Abstract 532, 2006
  24. 24. Optimize PET interpretation <ul><li>Role of PET to individualize treatment ? </li></ul>PET data sent over the internet via a dedicated server to 3 readers: review in 48 hours Medical Gateway Anonymization Double encryption Time : 10 mn 3 Readers Time : 10 mn Current questions for DLBCL patients
  25. 25. LNH07-3B <ul><li>Role of PET to individualize treatment ? </li></ul>DLBCL ; <60 years aa-IPI = 2-3 PET 4 PET Results Arm A A1 A2 B2 B1 R R-ACVBP14 + MTX IT + G-CSF PET 2 PET 4 R-CHOP14 + MTX IT + G-CSF Z-BEAM + ASCT MTX iv MTX iv AraC R- IFM / VP16 Salvage : CORAL PET PET 4+ PET Results Salvage : CORAL Arm B A1 A2 B2 B1 2- /4 - 2+ /4 - 2- /4 - 4+ PET 0 PET 4 PET Final R-CHOP14 + G-CSF
  26. 26. Acknowledgements <ul><li>Lymphoma Unit </li></ul><ul><ul><li>Karim Belhadj </li></ul></ul><ul><ul><li>Taoufik El Gnaoui </li></ul></ul><ul><ul><li>Isabelle Gaillard </li></ul></ul><ul><ul><li>Jehan Dupuis </li></ul></ul><ul><ul><li>Frederique Kuhnowski </li></ul></ul><ul><li>Radiology </li></ul><ul><ul><li>Alain Luciani </li></ul></ul><ul><ul><li>Alain Rahmouni </li></ul></ul><ul><li>Biostatistics </li></ul><ul><ul><li>François Hémery </li></ul></ul><ul><ul><li>Eric Lepage </li></ul></ul><ul><li>Nuclear Medicine </li></ul><ul><ul><li>Emmanuel Itti </li></ul></ul><ul><ul><li>Eva Evangelista </li></ul></ul><ul><ul><li>Sophie Lin </li></ul></ul><ul><ul><li>Michel Meignan </li></ul></ul><ul><li>Hematopathology </li></ul><ul><ul><li>Christiane Copie </li></ul></ul><ul><ul><li>Karen Leroy </li></ul></ul><ul><ul><li>Philippe Gaulard </li></ul></ul>

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