Page 130 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation
P. 130
Chapter 6a
In the HOVON-84 study (Hemato-Oncologie voor Volwassenen Nederland [Haemato Oncology Foundation for Adults in the Netherlands]), DLBCL patients were randomized between R-CHOP14 and RR-CHOP14 (R-CHOP14 with intensified rituximab in the first 4 cycles) [12]. In both arms, observational I-PET was performed after 4 cycles (I-PET4). To our knowledge, this was the first DLBCL randomized clinical trial in which I-PET4 results did not lead to treatment modification, which enables examination of its predictive value.
Our primary objective was to use prespecified cutoffs and methodologies from previous DLBCL studies to validate the potential added predictive value of baseline MTV and I-PET4 response to baseline clinical characteristics (aaIPI) for 2-y PFS in DLBCL in an independent study. A secondary objective was to determine the optimal I-PET4 response criteria.
Materials and methods
Study population
Newly diagnosed DLBCL patients included in the HOVON-84 NHL study (EudraCT2006-005174-42, NTR1014) with I-PET4 were eligible. For this analysis, we combined the R-CHOP14 and RR-CHOP14 study arms, as there were no statistically significant outcome differences between the arms [12]. Randomization was stratified for aaIPI score. The main eligibility criteria of the clinical study are described elsewhere [12,13]. The HOVON-84 study was approved by the institutional review board of all centers, and participants signed an informed consent form.
Study design
Patients at least 66 y old received 6 cycles of R-CHOP14 followed by 2 additional doses of rituximab; patients aged 65 y or less received 8 cycles of R-CHOP14. Baseline PET was highly recommended but not mandatory. I-PET was performed after 4 cycles R-CHOP14 or RR-CHOP14 (without treatment modifications, I-PET4).
Qualitative and quantitative image analysis
Baseline PET scans were analyzed with the semiautomatic ACCURATE tool [14] (Fig. 1) to obtain MTV using a fixed SUV of at least 4.0 [15,16]. Continuous
128
