Targeted Radiotherapy for Early-Stage Low-Risk Pediatric Hodgkin Lymphoma Slow Early Responders: A COG AHOD0431 Analysis.

Children's Oncology Group trial AHOD0431 reduced systemic therapy and used response-adapted involved-field radiotherapy (IFRT) in early-stage pediatric classical Hodgkin lymphoma. We investigated the impact of PET response after 1 cycle (PET1) and IFRT on outcomes and relapse pattern. Patients on AHOD 0431 underwent PET1 response assessment after AVPC (doxorubicin, vincristine, prednisone, and cyclophosphamide). "Rapid early responders" (RER) had a negative PET1; "slow early responders" (SER) had a positive PET1. Patients with a partial response (PR) by CT and functional imaging following 3 chemotherapy cycles received 21-Gy IFRT, while complete responders (CR) had no IFRT. Progression-free survival (PFS) was evaluated for RER and SER patients treated with or without IFRT. Recurrence sites were initial, new, or both. Relapses involving initial sites were characterized as "within PET1+ site" or "initially involved but outside PET1+ site". Median follow-up was 118 months. The 10-year PFS rate among RER patients was 96.6% with IFRT and 84.1% without IFRT (p=.10), while SER patients were 80.9% with IFRT and 64.0% without IFRT (p=.03). Among 90 RER patients who did not receive IFRT, all 14 relapses included an initial site. Among 45 SER patients receiving no IFRT, 14/16 relapses were in the initial site (9 PET1+ site only). Among 58 patients receiving IFRT, 5/10 relapses were in the PET1+ site. Following 3 cycles of AVPC alone, RER patients experienced favorable results. Conversely, SER patients experienced unfavorable outcomes with AVPC alone, although they improved with 21-Gy IFRT. Radiotherapy remains an important component of treatment for patients who are SER. Trial Registration: Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients with Newly Diagnosed Hodgkin's' Lymphoma; https://clinicaltrials.gov/ct2/show/NCT00302003; NCT00302003.