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Comparative Study
. 2025 Nov 15;123(4):972-979.
doi: 10.1016/j.ijrobp.2025.06.3876. Epub 2025 Jun 28.

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

Bradford S Hoppe  1 , Raymond B Mailhot-Vega  2 , Lindsay A Renfro  3 , Qinglin Pei  4 , Anne-Marie Charpentier  5 , Rahul R Parikh  6 , Kenneth B Roberts  7 , Frank G Keller  8 , Angela Punnett  9 , Susan Parsons  10 , Stephan D Voss  11 , Adina Alzaraki  12 , Kathleen M McCarten  13 , Stella Flampouri  14 , Sandy Kessel  13 , Yue Wu  15 , Stephen Y Cho  16 , Kara M Kelly  17 , Sharon M Castellino  8 , David C Hodgson  18
Affiliations
Comparative Study

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

Bradford S Hoppe et al. Int J Radiat Oncol Biol Phys. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest: BSH holds a leadership role (Co-Chair) NRG Hematologic Malignancies Working Group. RRP received payment/honoraria for a speakers bureau from Mevion Medical Systems. FGK participates on Aflac’s Data Safety Monitoring Board. SP received consulting fees from Seagen for stakeholder survey development and analysis and is a member of the Dana-Farber/Harvard Cancer Center Data Safety Monitoring Board. SF is a member of the Proton Collaborative Group (PCG) Data and Safety Monitoring Board; Chair of Task Group No. 427 Technical Guidelines for the Use of Proton Therapy in Clinical Trials, American Association of Physicists in Medicine (AAPM); and Co-Chair of the Lymphoma Sub-Committee, Particle Therapy Co-Operative Group (PTCOG). KMK has a grant from National Cancer Institute and subcontracts with Emory University, Washington University, Hospital for Sick Kids in Toronto, and COG/PHI (all paid to her institution); received an honoraria from the American Society of Hematology for educational events; received travel support from the Lymphoma Research Foundation and American Society of Hematology; is a member of the Bristol Meyers Squibb Data Safety Monitoring Board; holds an unpaid leadership role on the Lymphoma Research Foundation Scientific Advisory Board; holds a leadership role on the Children’s Oncology Group Scientific Council (payment to her institution from an NCI subcontract); and received drugs from Pfizer/Seagen and Bristol Meyers Squibb for NCI-sponsored NCTN clinical trial. SMC received grants from Seattle Genetics (now Pfizer)- Pediatric Advisory Board and Bristol Meyers Squibb (Pediatric Advisory Board); received payment for lectures from the St. Jude Children’s Hospital - Scientific Symposium; received travel support from the Lymphoma Research Foundation - Sci Ad Board; and holds unpaid leadership roles on the Leukemia and Lymphoma Society Board of Directors and Lymphoma Research Foundation Scientific Advisory Board. DCH has stock in Immvue Therapeutics and is the Vice-Chair of Research for the Faculty of Radiation Oncology, University of Toronto. The other authors have nothing to disclose.

References

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