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Corinne Haioun Unité Hémopathies Lymphoides Hôpital Henri Mondor Créteil, France PET and Lymphoma
[object Object],[object Object],[object Object],[object Object],Need for an accurate and sensitive tool  to detect residual disease  PET and Lymphoma  : Background
PET and Hodgkin Lymphoma  : Background  ,[object Object],[object Object],[object Object]
HD prognostic score: clinical variables Hasenclever d. NEJM 1998; 339:1506
HD prognostic score: 7y-FFP and OS  Hasenclever d. NEJM 1988; 339:1506 7% of the patients
[object Object],According to PET-2 (+vs.-) and IPS (0-2 vs 3-7)  HL prognosis: from IPS to PET  Intergruppo   Italiano Linfomi
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
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
The situation in Diffuse Large B-Cell Lymphoma Weber W: J.Nucl. Med 2007: 48: 1580-82.
Current questions for DLBCL patients ,[object Object],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
[object Object],[object Object],[object Object],[object Object],Early (after 2 cycles) PET treatment evaluation with visual analysis Haioun, Blood 2005; 106: 1376-1381
Early treatment evaluation Before treatment At 2 cycles At 4 cycles FDG-PET2 (+) Haioun C, et al. Blood 2005; 106(4): 1376–81
Early treatment evaluation FDG-PET2 (-) Before treatment At 2 cycles At 4 cycles Haioun C, et al. Blood 2005; 106(4): 1376–81
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)
(High negative predictive value): NPV=  TN TN +FN (Low  positive predictive value): PPV=  TP TP +FP FN FP FDG-PET in DLBCL
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%
 =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
Lin C.: J. Nucl. Med 2007; 48, 1626-1632 ,[object Object],[object Object],[object Object],[object Object]
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%
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.
MSKCC 01-142-DLBCL: Risk Adapted Therapy Transplant-eligible,   CS IIX, III or IV  age-adjusted IPI 1, 2, or 3 Risk Factors ,[object Object],[object Object],[object Object],[object Object],[object Object],Moskowitz et al., Blood 108: Abstract 532, 2006
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
Outcome based upon Interim  Restaging PET scan ,[object Object],Moskowitz et al., Blood 108: Abstract 532, 2006
Optimize PET interpretation ,[object Object],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
LNH07-3B ,[object Object],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
Acknowledgements  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

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Pet And Lymphoma

  • 1. Corinne Haioun Unité Hémopathies Lymphoides Hôpital Henri Mondor Créteil, France PET and Lymphoma
  • 2.
  • 3.
  • 4. HD prognostic score: clinical variables Hasenclever d. NEJM 1998; 339:1506
  • 5. HD prognostic score: 7y-FFP and OS Hasenclever d. NEJM 1988; 339:1506 7% of the patients
  • 6.
  • 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. 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. The situation in Diffuse Large B-Cell Lymphoma Weber W: J.Nucl. Med 2007: 48: 1580-82.
  • 10.
  • 11.
  • 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 FDG-PET2 (-) Before treatment At 2 cycles At 4 cycles Haioun C, et al. Blood 2005; 106(4): 1376–81
  • 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. (High negative predictive value): NPV= TN TN +FN (Low positive predictive value): PPV= TP TP +FP FN FP FDG-PET in DLBCL
  • 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.  =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.
  • 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. 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.
  • 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.
  • 24.
  • 25.
  • 26.