Analysis of brain necrosis and secondary cancers after proton beam therapy for pediatric intracranial tumors: A single-center retrospective study

Masashi Mizumoto^1*Hiroko Fukushima²Yoshiko Oshiro³Takashi Saito¹Ai Muroi⁴Yuni Yamaki²Sho Hosaka²Masako Inaba²Toshitaka Ishiguro⁵Masahiko Harada¹Hikaru Niitsu¹Toshiki Ishida¹Taisuke Sumiya¹Keiichiro Baba¹Masatoshi Nakamura^1,6Haruko Numajiri¹Kei Nakai⁶Hideyuki Sakurai⁶

• ¹Radiation Oncology, University of Tsukuba, Tsukuba, Japan
• ²Pediatrics, University of Tsukuba, Tsukuba, Japan
• ³Tsukuba Medical Center Byoin, Tsukuba, Japan
• ⁴neurosurgery, University of Tsukuba, Tsukuba, Japan
• ⁵Radiology, University of Tsukuba, Tsukuba, Japan
• ⁶Tsukuba Daigaku Fuzoku Byoin, Tsukuba, Japan

Background: Proton beam therapy (PBT) is increasingly used for pediatric intracranial tumors due to lower long-term radiation-associated toxicities. However, data on late adverse effects, particularly brain necrosis and intracranial secondary cancer, remain limited. The aim of this study is to evaluate the incidence of these events following PBT in pediatric patients treated at a single center.Procedure: We retrospectively reviewed the medical records of 189 patients under 20 years of age who received PBT for intracranial tumors between 1991 and 2023. Clinical information, irradiation parameters, concurrent chemotherapy, and follow-up outcomes were collected. Brain necrosis and intracranial secondary cancers were assessed based on events presenting with grade ≥2 clinical symptoms.Results: Among 151 patients with sufficient follow-up data (median follow-up: 41.7 months), two cases of brain necrosis (1.3%) and two cases of intracranial secondary cancer (1.3%) were identified. The 5-year cumulative incidence was 2.3% (95% CI: 0-5.4%) for brain necrosis and 2.7% (95% CI: 0-6.4%) for intracranial secondary cancer. These respective incidence rates were similar for patients followed for more than two years (n=94), and slightly higher at 2.7% and 3.1% for those receiving a total dose >50 Gy (n=134). Among patients treated with PBT alone (n=125), the incidence was 1.7% for brain necrosis and 3.6% for secondary malignancy.Conclusions: This single-center retrospective study shows a low incidence of brain necrosis and secondary malignancy following PBT for pediatric patients with intracranial tumors. These findings indicate a favorable long-term safety profile of PBT in this population.