Comparison of Contemporary Radiation Therapy Approaches in Combined Modality Treatment on Pediatric High-Risk Classic Hodgkin Lymphoma Study: AHOD 1331

Purpose: AHOD 1331 was a clinical trial investigating brentuximab vedotin in conjunction with chemotherapy and response adapted radiation therapy (RT) in pediatric patients with high-risk classic Hodgkin lymphoma. RT was delivered using 3-dimensional conformal RT (3D-CRT), intensity modulated RT (IMRT), or proton therapy. This analysis evaluated dosimetric and clinical outcomes for patients treated across these different RT modalities. Methods and Materials: After 5 cycles of systemic therapy, patients received 21 Gy of RT to sites including bulky mediastinal disease at diagnosis or partial metabolic responses after 2 cycles. A 9 Gy boost was delivered to sites with partial responses at the end of therapy. Clinical and dosimetric outcomes prospectively collected and were compared for 3D-CRT, IMRT, and proton therapy in a post hoc analysis. Results: Of 587 enrolled patients, 317 (54%) received protocol-directed RT: 29% with 3D-CRT, 41% with IMRT, 26% with proton therapy, and 4% with mixed modalities. Proton therapy use increased from 16% to 26% to 36% among the first, second, and third tertiles of patients irradiated (P = .045). At a median follow-up of 43 months, 3-year progression-free survival rates were equivalent across modalities (P = .77): 86.6% for 3DCRT, 87.6% for IMRT, and 87.9% for proton therapy. No significant differences were observed in acute grade 3 or higher toxicities. Proton therapy delivered significantly lower mean doses to the heart, breast, and lung compared with IMRT or 3D-CRT, whereas IMRT resulted in higher mean doses to the lungs and breasts compared with 3D-CRT. Conclusions: Selective use of RT combined with chemotherapy, including brentuximab vedotin, led to excellent outcomes for pediatric patients with high-risk Hodgkin lymphoma. Proton therapy utilization increased during the study, showing similar disease control and toxicity outcomes as 3D-CRT and IMRT. Long-term follow-up is essential to evaluate the risks of secondary malignancies and cardiac toxicity across radiation techniques.