Interim FDG-PET analysis to identify patients with aggressive non-Hodgkin lymphoma who benefit from treatment intensification: a post-hoc analysis of the PETAL trial

The randomized PETAL trial failed to demonstrate a benefit of interim FDG-PET (iPET)-based treatment intensification over continued standard therapy with CHOP (plus rituximab (R) in CD20-positive lymphomas). We hypothesized that PET analysis of all lymphoma manifestations may identify patients who benefitted from treatment intensification. A previously developed neural network was employed for iPET analysis to identify the highest pathological FDG uptake (max-SUV_AI) and the mean FDG uptake of all lymphoma manifestations (mean-SUV_AI). High mean-SUV_AI uptake was determined separately for iPET-positive and iPET-negative patients. The endpoint was time-to-progression (TTP). There was a significant interaction of additional rituximab and mean-SUV_AI in the iPET-negative group (HR = 0.6, p < 0.05). Patients with high mean-SUV_AI had significantly prolonged TTP when treated with 6xR-CHOP + 2 R (not reached versus 52 months, p < 0.05), whereas max-SUV_manual failed to show an impact of additional rituximab. In the iPET-positive group, patients with high mean-SUV_AI had a significantly longer TTP with (R-)CHOP than with the Burkitt protocol (14 versus 4 months, p < 0.01). Comprehensive iPET evaluation may provide new prognosticators in aggressive lymphoma. Additional application of rituximab was associated with prolonged TTP in iPET-negative patients with high mean-SUV_AI. Comprehensive iPET interpretation could identify high-risk patients who benefit from study-specific interventions.