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Corinne HaiounUnité Hémopathies Lymphoides
Hôpital Henri MondorCréteil, France
PET and Lymphoma
First and only rule: to cure the patient with first-line treatment
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
PET and 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%.
PET and Hodgkin Lymphoma : Background
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
According to IPS 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
3210
Years after diagnosis
1.0
0.8
0.6
0.4
0.2
0.0
Pro
gre
ssio
n-f
ree s
urv
ival p
rob
ab
ilit
y
Gallamini: Hematologica 2006; 91, 475-81
Gallamini: JCO 2007; 25, 3743-52
Hutchings: Blood 2006; 107, 52-59Kostakoglu: Cancer 2006; 107:2678-87
H10 TrialH10 Trial
Ran
do
mis
ation
FDG-PET
1 cycle ABVDIN-RT 30 Gy(+boost 6 Gy
résiduals)
whatever
Favourable Group F
UnfavourableGroup U
Ran
do
mis
ation
ABVD 2 cycles
ABVD 2 cycles
ABVD 2 cycles
ABVD 2 cycles
FDG-PET
FDG-PET
FDG-PET
ABVD 2 cycles
BEACOPP2 cycles
esca
IN-RT 30 Gy(+ boost 6 Gy)
ABVD 4 cycles
2 cycles BEACOPPesca
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
HodgkinLymphoma
Stage I/II
The situation in Diffuse Large B-Cell
Lymphoma
Weber W: J.Nucl. Med 2007: 48: 1580-82.
Current questions for DLBCL patients
Role of PET to individualize treatment ?
PET– (n = 54)
PET+ (n = 36)Pro
bab
ilit
y
p < 0.0001
Years after randomisation
Event-free survival
p = 0.006
Overall survival
100 100
0 1 2 3 0 1 2 3Years after randomisation
Pp
rob
abil
ity 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
• 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
Early (after 2 cycles) PET treatment evaluation with visual analysis
Before treatment At 2 cycles At 4 cycles
FDG-PET2 (+)
Early treatment evaluation
Haioun C, et al. Blood 2005; 106(4): 1376–81
FDG-PET2 (-)
Before treatment At 2 cycles At 4 cycles
Early treatment evaluation
Haioun C, et al. Blood 2005; 106(4): 1376–81
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)
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
Current questions for DLBCL patients
Role of PET to individualize treatment ?
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4Years
% survival
(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)Pro
bab
ilit
y o
f E
FS
p < 0.0001
Years after randomisation
Event-free survival
p = 0.006
median f/u: 2 years
Overall survival100 100
0 1 2 3 0 1 2 3
Years after randomisation
pro
ba
bil
ity
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%
(Bq/g)
Activité injectéePoids du corps
C*totale =
(Bq/g)
Activité mesurée
Volume du foyerC*tissulaire =
C*tissulaire
C*totale
SUV =
Si distribution homogène, SUV = 1
=1g/cm3
SUV=Ci*()
dose/poids
Lin C.: J. Nucl. Med 2007; 48, 1626-1632
•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
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%
Months After Randomization
> 65.7%
65.7%
SUV max Reduction
P < .0001
Pro
babili
ty o
f EFS
(%
)
Visual Analysis
PET (-)
PET (+)
P = .009
Visual Analysis versus SUV-based Assessment
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
• 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
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
Interim PET does not predict EFS
Moskowitz et al., Blood 108: Abstract 532, 2006
Optimize PET interpretation
PET data sent over the internet via a dedicatedserver to 3 readers: review in 48 hours
Medical Gateway
AnonymizationDouble
encryption
Time : 10 mn
3 Readers
Time : 10 mn
Current questions for DLBCL patients
Role of PET to individualize treatment ?
LNH07-3BDLBCL ; <60 yearsaa-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 + ASCTMTX iv
MTX iv AraCR- IFM / VP16
Salvage : CORAL
PETPET
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
Role of PET to individualize treatment ?
Acknowledgements
• 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