INTERIM PET IN DLBCL - 2011
CON …. Anton Anton Hagenbeek, Hagenbeek, M.D., M.D., Ph.D. Ph.D. Academic Academic Medical Medical Center Center Department Department of of Hematology Hematology University University of of Amsterdam Amsterdam Amsterdam, Amsterdam, The The Netherlands Netherlands
[email protected] [email protected]
““In In the absence of effective therapies, criteria to measure response are irrelevant ” irrelevant” Cheson, Cheson, 2008 2008
Or: The indication/application of a (new) imaging modality is justified by its impact on patient management
PREDICTIVE VALUE OF INTERIM PET EARLY TREATMENT EVALUATION 2 years Study
DLBCL
n
PET after . . .
PET-
PET+
Jerusalem , 2000
28
3 cycles
62% (PFS)
0% (PFS)
Spaepen, 2002
43
3-4 cycles
85% (PFS)
4% (PFS)
Kostakoglu, 2002
24
1 cycle
85% (PFS)
> 70% 70% ≤≤ 70% 70%
83% 83% 40% 40%
94% 94% 50% 50%
NB: NB:
Outcomes Outcomes did did not not differ differ significantly significantly whether whether PET2 PET2 and and PET4 PET4 were were visually visually positive positive or or negative negative (IHP (IHP or or Beauville Beauville criteria) criteria) Casasnovas -43, 2011 Casasnovas et et al., al., Blood Blood 118, 118, 37 37-43, 2011
VISUAL ANALYSIS PET2 AND PET4: POOR PREDICTIVE VALUE FOR PFS AND OS
78% 78% of of PET2 PET2 positive positive and and 80%* 80%* of of PET4 PET4 positive positive patients patients had had aa ∆ ∆ SUV SUV max max above above the the cut cut off off value value (PFS (PFS at at 22 years: years: 77% 77% and and 83%, 83%, respectively) respectively) Thus, Thus, patients patients classified classified as as poor poor responders -chemo according responders to to R R-chemo according to to visual visual analysis analysis were were good good responders responders as as identified identified by by ∆ ∆ SUV SUV max max analysis analysis ** 85% 85% false false positive positive PET4 PET4 –– visual visual analysis! analysis! (Moskowitz (Moskowitz et et al., al., 2010) 2010)
CAN THE SUV VALUE OF INTERIM PET BE USED TO DETERMINE THE NEED FOR RESIDUAL MASS BIOPSY IN DLBCL? (Juweid, Smith, Itti and Meignan, JCO 28, e719-720, 2010: comments to Moskowitz data) ““A A cut cut off off SUV SUV at at interim interim PET PET of of ≤≤ 3.5 3.5 was was associated associated with with aa very very low low likelyhood ” likelyhood of of aa positive positive biopsy biopsy” positive positive biopsy biopsy (NHL+) (NHL+) Interim Interim SUV SUV at at biopsy biopsy site site (n=36) (n=36)
≤≤ 3.5 3.5
1/20 1/20
(5%; -24.9%) (5%; 0.1 0.1-24.9%)
>> 3.5 3.5
4/16 4/16
(25%; -52.4%) (25%; 7.3 7.3-52.4%)
““The The cut cut off off SUV SUV value value of of 3.5 3.5 would would have have spared spared more more than than half half of of the the patients ield of patients (20/36) (20/36) with with positive positive interim interim PET PET aa biopsy biopsy with with aa low low yyield of finding ” finding NHL NHL (1/20 (1/20 == 5%) 5%)”
CONCLUSIONS 1. The PET/CT scan at the end of treatment is – so far – the most powerful predictor of outcome 2. Interim scanning has not been shown to improve survival and thus should be restricted to clinical trials!
THE PETAL TRIAL IN DLBCL 6x -CHOP 6x R R-CHOP 22 X -CHOP: PET XR R-CHOP: PET ++ → →® ® 66 blocks -ALL protocol blocks B B-ALL protocol
NB: NB:
-- 33 week week interval interval chemo chemo → → PET PET -- no no hematopoietic hematopoietic growth growth factors factors -- SUV SUV based based interim interim PET PET assessment assessment
ANSWERS TO QUESTIONS FROM OUR CHAIRMAN …
Q1: Is there any evidence that early PET has a prognostic role in DLBCL?
A1: Yes, there is ““any any evidence ”evidence” needs confirmation in large trials
Q2: Should we report early interim PET in DLBCL qualitatively or quantitatively? A2: Most probably quantitatively – ∆ SUV max … Need more data NB: majority of interim PET(+) pts are primarily refractory (IVS)
Q3: Is histological confirmation the ““gold” gold” standard reference for patients with mid -treatment mid-treatment positive PET? (e.g. after 4 cycles ) A3: According to Itti et al. (2009) and Casasnovas (2011) – based on SUV analysis – probably not … ….. or: not below a certain SUV value … ….. (Moskowitz, 2010)
Q4: Is interim PET feasible in multicenter clinical trials?
A4: Yes!
Q5: Are there sufficient data to support change in treatment based on interim PET results?
A5: No! Results from PETAL trial? (currently 700 patients enrolled)
