Presenter(s)
J. T. Lucas Jr1, H. Worrall2, J. Becksfort2, T. T. Patni2, V. T. Groben2, E. Burghen2, H. T. Ruleman2, M. Marker2, C. H. Hua2, N. D. Sabin2, S. Kaste2, O. Ates2, A. J. Boria2, C. C. Chen2, G. T. Armstrong2, M. M. Hudson2, Y. Li2, C. L. Tinkle1, M. Krasin2, K. E. Nichols2, and T. E. Merchant2; 1Department of Radiation Oncology, St. Jude Children’s Research Hospital, Memphis, TN, 2St. Jude Children's Research Hospital, Memphis, TN
Purpose/Objective(s): Survivors of pediatric cancer treated with radiation therapy remain at risk for developing subsequent neoplasms. The Phase IV trial prospectively evaluates the safety profile of pencil-beam scanning proton therapy (PBS-PT) in children. We report the incidence, characteristics, and attribution of subsequent tumors observed during long-term follow-up.
Materials/Methods: From 2017–2022, 995 children were enrolled on trial and underwent systematic toxicity surveillance. Subsequent tumor events were abstracted from structured CTCAE/SJLIFE-modified CTCAE assessments, radiology reports, and pathology-confirmed diagnoses. Each event was categorized by histology, timing, relation to irradiated fields, and treating-physician attribution (excluded ? certain). Medical, procedural, and surgical interventions were recorded.
Results: Across the cohort, subsequent tumors were uncommon, with events including benign neoplasms (osteochondroma, focal nodular hyperplasia, retention cysts, desmoid fibromatosis), thyroid neoplasms (papillary and follicular carcinomas), low-grade gliomas, meningiomas, and rare high-grade secondary malignancies (e.g., osteosarcoma, high-grade glioma, AML) at a median follow-up of 5 years (3.17-9.77). The 5-year cumulative incidence rate for subsequent neoplasms (benign and malignant) was 1.6% (95% CI: 0.7–3.0) and 1.2% (95% CI: 0.3-3.3) in CNS and Non-CNS patients. Most events were CTCAE Grade 1, asymptomatic, and discovered through surveillance imaging. A subset of events demonstrated clear predisposing risk factors, including cancer predisposition syndromes (e.g., DICER1, Li-Fraumeni, Cowden) and prior chemotherapy exposures. Surgical excision was the most frequent intervention; medical or procedural therapies were uncommon. No pattern suggested clustering within high-dose proton regions. 5 of 38 patients with a documented subsequent tumor succumbed to disease (13.2% (95% CI 5.8–27.3).
Conclusion: In this large prospective cohort, subsequent tumors following PBS-PT were infrequent and predominantly benign, with most events unrelated to proton therapy. Although rare secondary malignancies occurred, many were attributable to underlying genetic syndromes or systemic therapies rather than PBS-PT. These findings support the long-term safety of PBS-PT, while underscoring the importance of extended surveillance to characterize very late risks (NCT03223766).