The Evolution of Radiation Therapy in Children's Oncology Group Trials, From 1998 to 2025

Significant advancements in external beam radiation therapy (RT) over the past 20+ years have occurred with evolution from 2-dimensional techniques based on plain film x rays to 3-dimensional conformal and intensity modulated photon techniques. Likewise, proton radiation therapy (PRT) was also introduced and has become more widely available. Each advance in radiation technique improves targeting and has the potential to mitigate late effects associated with RT. In this study, we use metadata from past and present Children's Oncology Group trials that included RT to describe the evolution of different RT modalities across time and disease sites.

Imaging and Radiation Oncology Core database was queried for protocols with at least 1 patient receiving RT from 1998 to 2025. Protocol metadata, including primary disease site, study timeline, and quality assurance , was extracted, as were nonidentifiable patient-level variables including age, institution, year of enrollment, and RT modality used. Descriptive statistics were used for downstream analysis.

The study population comprised 8898 patients, including 7881 from the United States and 1017 from other countries. The median age at enrollment was 9 years; California, Texas, Florida, and New York were among the top contributing states. Of the 83 included Children's Oncology Group trials, 48 included at least 1 patient receiving PRT. The number of trials allowing PRT peaked in 2010 with 17 protocols. Trials involving central nervous system tumors and rhabdomyosarcoma/soft tissue sarcomas dominated both in the number of trials and enrollment. They were also among the earliest to incorporate PRT into treatment protocols. From 1998 to 2025, 3-dimensional photon-based treatments declined from 73% to 15%, whereas intensity modulated radiation therapy/volumetric modulated arc therapy usage rose from 26% to 89% over the same interval. The use of PRT increased from 2% pre-2000 to nearly 40% in 2021, which has since stabilized. Quality assurance review demonstrated >90% protocol compliance across all RT modalities both nationally and internationally.

Over 25 years of Children's Oncology Group experience, photon therapy has transitioned from 3-dimensional conformal to intensity modulated radiation therapy/volumetric modulated arc therapy, whereas PRT use has continued to expand, particularly in central nervous system and rhabdomyosarcoma/soft tissue sarcomas trials. These trends highlight how pediatric cooperative group studies continue to shape national standards and underscore the need for future work linking modality adoption with toxicity, survivorship, and access across diverse treatment settings.