Burden of disease-specific late effects after proton beam therapy in pediatric solid and CNS tumor survivors: a single-institution survey in Japan.
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BACKGROUND: Proton beam therapy (PBT) has been increasingly adopted in pediatric oncology to reduce radiation-related toxicity; however, its long-term comorbidities remain incompletely understood. Because tumor types and treatment patterns often overlap across diagnostic groups, disease-specific evaluation may help clarify late effects following PBT. METHODS: A mailed questionnaire survey was conducted between 2015 and 2021 among 304 pediatric cancer survivors who had received PBT at the University of Tsukuba Hospital between 1984 and 2020. Responses from 110 patients diagnosed before the age of 20 years and alive at the time of the survey were analyzed. A non-PBT cohort treated between 1976 and 2013 served as a comparison group. RESULTS: The median follow-up duration was 6.3 years (range, 0.4-34.6). Thirty-six patients (33%) reported no comorbidities. Severe (grade ≥3) comorbidities occurred in 3 PBT patients (gait disturbance, renal failure requiring dialysis, and hemianopsia) and 1 non-PBT patient (secondary colorectal cancer that might have been avoided with PBT). Skeletal abnormality was the most frequent late effect, followed by hair abnormality, growth retardation, chronic skin disorders, endocrine dysfunction, dental abnormalities, and neurocognitive impairment. Skeletal abnormality was significantly associated with rhabdomyosarcoma and Ewing sarcoma family of tumors, whereas hormone replacement therapy was more common among patients with central nervous system germ cell tumors. CONCLUSIONS: This single-institution disease-specific analysis revealed distinct comorbidity patterns among childhood cancer survivors treated with PBT. Although severe late effects were rare, musculoskeletal and endocrine disorders were frequent, underscoring the need for diagnosis-tailored, long-term follow-up strategies.