Corinne Haioun Unité Hémopathies Lymphoides Hôpital Henri Mondor Créteil, France PET and Lymphoma
Jan 18, 2016
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