FDG PET then response-adapted chemotherapy

RATHL (Response-Adapted Therapy in advanced Hodgkin Lymphoma; NCT00678327; Johnson et al., NEJM 2016) enrolled 1214 patients (1119 evaluable) with stage IIB-IV or bulky IIA classical Hodgkin lymphoma. All patients received two cycles of ABVD chemotherapy and then an interim FDG PET-CT scan (PET2). Patients with a negative PET2 (Deauville score 1-3; 83.7% of scanned patients) were randomised to continue ABVD or to drop bleomycin (AVD) for the remaining four cycles; those with a positive PET2 were escalated to BEACOPP-14 or escalated BEACOPP, with no randomisation in that arm.

At a median follow-up of 41 months, 3-year progression-free survival in PET2-negative patients was 85.7% with continued ABVD versus 84.4% with AVD (absolute difference 1.6 percentage points, within the prespecified non-inferiority margin), while overall survival was around 97% in both arms; the trial's practical conclusion was that bleomycin can be safely omitted after a negative interim scan, reducing pulmonary toxicity with an estimated treatment-failure risk of only 1.6%. PET2-positive patients who were escalated to BEACOPP reached a 3-year progression-free survival of 67.5%, which the investigators judged better than historical rates of continuing ABVD alone in PET2-positive disease (previously reported in the 15-45% range). Long-term follow-up (Blood 2022; JCO 2024) confirmed durability of both the de-escalation and escalation strategies.

RATHL is the paradigm case for FDG-PET-guided, response-adapted treatment and sits alongside other PET2-adapted trials (Italian GITIL/FIL HD0607, US Intergroup S0816) that validated the same principle: interim FDG-PET response predicts outcome and can be used prospectively to tailor chemotherapy intensity. The same logic (imaging mid-treatment to decide whether to change systemic therapy) generalises to other FDG-avid cancers, for example the germ-cell tumour and lymphoma literature more broadly, though the specific numbers above are for classical Hodgkin lymphoma.