Page 242 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 9
for all criteria, probably due to the prevalence of progression of 22% in our data. However, positive predictive values were somewhat higher at interim [18F]FDG PET after 4 cycles compared to 2 cycles (∆SUVmax 57% vs 46% and Deauville 4-5 43% vs 31%) and were higher for ∆SUVmax compared to the Deauville 4-5 positivity cut-off. A Deauville score of 5 selected the patients with the worst response (about 5% of patients) and can be identified at interim [18F]FDG PET after 2 cycles, with similar positive- and negative predictive values compared to 4 cycles. In the multivariable analyses both IPI score and interim [18F]FDG PET scan (all criteria) were independent predictors of outcome. We concluded that good response (defined as ∆SUVmax ≥66%) after 2 cycles of R-CHOP treatment may qualify for randomized trials evaluating de-escalation of therapy regimens. Poor response (defined as ∆SUVmax <70%) after 4 cycles of R-CHOP treatment may qualify for evaluating new therapies in a randomized trial.
The 3 chapters of this final part of the thesis comprised the clinical validation of interim [18F]FDG PET in 2 HOVON studies and the individual patient data meta-analysis of studies included in the PETRA database. It can be concluded that interim [18F]FDG PET indeed has predictive value for 2-year progression- free survival, 2-year overall survival and 2-year time to progression. These results can be used for future trial designs and power calculations of clinical studies with de-escalation strategies or new therapy regimens for DLBCL patients. However, this is not the case for the subgroup of DLBCL patients with a MYC translocation. A recent study demonstrated that MYC positive patients have more frequent progression during treatment after negative interim [18F]FDG PET assessment and new lesion at sites that were not initially involved compared to MYC negative patients [18]. This is probably due to the aggressive disease characteristics of double (MYC with BCL2 or BCL6) and triple hit (MYC, BCL2 and BCL6) lymphoma patients. Currently, a fluorescent in situ hybridization (FISH) analysis is recommended in all DLBCL patients in the Netherlands in order to detect double or triple hit lymphoma patients and change treatment to DA-EPOCH-R with CNS prophylaxis instead of R-CHOP.
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