Page 241 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Summary, discussion and future perspectives
and it gives important background information for part a. Chapter 6a shows that both interim [18F]FDG PET and age-adjusted international prognostic index are independent response biomarkers [15]. The negative predictive value for 2-year progression-free survival of patients with a low/low-intermediate age-adjusted IPI and ∆SUVmax>70% was 93%. The positive predictive value for patients with a high-intermediate/high age-adjusted IPI and ∆SUVmax≤70% was 65%. Besides that, the external validation of semi-quantitative ∆SUVmax criterion outperformed the Deauville 5-point scale in the 2-year progression-free survival prediction (positive predictive value of 53% versus 38%, respectively).
In Chapter 7 the results of the clinical phase II study HOVON-130 of 82 MYC positive aggressive B-cell lymphoma patients (a subgroup of DLBCL patients with worse prognosis) treated with a combination of R-CHOP and lenalidomide are described [16]. In this study both interim [18F]FDG PET and end-of-treatment [18F]FDG PET scans were performed. The complete metabolic response rate at end-of-treatment was 67% and was comparable (no official head to head comparison possible) to studies applying more intensive chemotherapy regimens. The positive and negative predictive value of the end-of-treatment scan for relapse within 12 months were 81% and 93%, respectively. The observational analysis of interim [18F]FDG PET showed a positive and negative predictive value for the end-of-treatment [18F]FDG PET result of 60% and 79%, respectively. These results do not support the use of interim [18F]FDG PET in this specific patient subgroup.
Chapter 8 contains the main results of the PETRA interim [18F]FDG PET project (KWF/Alpe d’Huzes grant VU 2012-5848) with individual patient data meta-analyses from 1692 DLBCL patients from 8 international studies [17]. Deauville score and ∆SUVmax criteria were compared at different timing of the interim [18F]FDG PET after 2 and after 4 cycles. ∆SUVmax criteria had a higher discriminative power and predictive value for 2-year progression-free survival than the Deauville 5-point scale (with a positivity cut-off for DS 4 and 5). However, the optimal timing and response criteria may vary depending on the clinical context of the study. In general, hazard ratios increased for later timing of the interim [18F]FDG PET scan, i.e. improved patient stratification. The negative predictive values were high (above 80%) for all criteria, for both interim [18F]FDG PET after 2 and after 4 cycles. Generally, the positive predictive values are rather low
239
9