Safety and Efficacy of Photon Re-Irradiation with Whole-Brain Radiotherapy or Craniospinal Irradiation for Recurrent Pediatric Central Nervous System Malignancies

Background: Limited data exist regarding the safety and efficacy of photon re-irradiation with whole-brain radiotherapy (WBRT) or craniospinal irradiation (CSI) in children with recurrent or second primary CNS tumors. Materials and methods: In this retrospective single-institution study, 23 patients < 21 years who underwent photon re-irradiation with WBRT (n = 9) or CSI (n = 14) for CNS tumors between 2013 and 2026 were included. Clinical and treatment characteristics were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Toxicities were graded using CTCAE v5.0. Results: In our cohort, the median age at diagnosis was 8.5 years (range: 0.2–19.7 years), and medulloblastoma was the most common histology (30%). Median time to the first relapse after initial irradiation was 12.0 months (range: 0.9–92.5 months). Median re-irradiation dose to the whole brain or craniospinal axis was 24.0 Gy (range: 20.0–36.0 Gy). For 15 patients who received involved field boosts, median total dose was 30.6 Gy (range: 20.0–54.0 Gy). With median follow-up after re-RT of 12.2 months (range: 1.0–106.8), 12-month PFS and OS were 24.2% and 67.0%, respectively. Four patients who received curative-intent re-CSI remain alive with median follow-up of 20.4 months (range: 5.8–106.8). The crude rate of grade >2 CNS toxicity was 8.7%. Of 10 patients with new neurologic symptoms before re-irradiation, 7 (70%) had symptomatic improvement after treatment. Conclusions: Photon re-irradiation with WBRT or CSI was feasible and achieved disease control in a subset of patients and meaningful symptom palliation with acceptable acute toxicity. Careful attention to cumulative dose constraints is essential, and longer follow-up is needed to assess durability and late effects.