Pediatric blood & cancer · 2026
Feasibility and Safety of High-Dose Proton Re-Irradiation in Recurrent Pediatric Central Nervous System Tumors: A Single-Institution Retrospective Study.
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Song Jin-Ho, Baron Jonathan, Perez Carlos Chavez, Ramesh Sidharth, Minturn Jane, Desai Kavita A, Shah Amish C, Belasco Jean M, Cole Kristina A, Fisher Michael J, Storm Phillip B, Madsen Peter M, Kurtz Goldie, Lustig Robert A, Hill-Kayser Christine, LaRiviere Michael J
Аннотация
PURPOSE: Pediatric central nervous system (CNS) tumors often recur despite multimodality therapy. Although re-irradiation (re-RT) has historically been limited by concerns for severe late toxicities, modern techniques have renewed interest in this approach. Proton therapy provides dosimetric advantages that may enable curative re-treatment with reduced normal tissue exposure.
METHODS: We retrospectively reviewed 54 pediatric patients who underwent proton re-RT for recurrent CNS tumors at our institution (2010-2024). Eligible patients had received prior CNS-directed RT at ≤20 years of age. Toxicities were graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 as acute (<3 months) or late (≥3 months). Cumulative dosimetry was assessed by registering RT1 and RT2 plans and converting doses to EQD2 (α/β = 2 Gy). Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier methods.
RESULTS: Median age at re-RT was 11 years, with a median interval of 28.5 months between RT courses. The median prescribed re-RT dose was 54 Gy (range, 25-60), yielding a cumulative EQD2 of 102.6 Gy (range, 46.8-112.9). Median OS and PFS were 46.0 and 16.5 months, respectively. Among 16 ependymoma patients, all received full-dose proton re-RT (54-59.4 Gy), yielding a 1-year OS of 91.7% and PFS of 50.0%. Glioma patients had inferior outcomes (1-year OS 55.4%, PFS 41.6%) with a median re-RT EQD2 of 48.1 Gy. An RT interval of ≥12 months was associated with improved OS and PFS. Composite dosimetry in 21 patients showed a median cumulative brain D0.1cc of 109.0 Gy; only one patient developed Grade 3 radiation necrosis (RN). High-grade acute toxicity occurred in 13.0% of patients, all manageable with supportive care.
CONCLUSION: Proton re-RT for pediatric CNS tumors is feasible and associated with encouraging survival and low rates of serious late toxicity.
METHODS: We retrospectively reviewed 54 pediatric patients who underwent proton re-RT for recurrent CNS tumors at our institution (2010-2024). Eligible patients had received prior CNS-directed RT at ≤20 years of age. Toxicities were graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 as acute (<3 months) or late (≥3 months). Cumulative dosimetry was assessed by registering RT1 and RT2 plans and converting doses to EQD2 (α/β = 2 Gy). Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier methods.
RESULTS: Median age at re-RT was 11 years, with a median interval of 28.5 months between RT courses. The median prescribed re-RT dose was 54 Gy (range, 25-60), yielding a cumulative EQD2 of 102.6 Gy (range, 46.8-112.9). Median OS and PFS were 46.0 and 16.5 months, respectively. Among 16 ependymoma patients, all received full-dose proton re-RT (54-59.4 Gy), yielding a 1-year OS of 91.7% and PFS of 50.0%. Glioma patients had inferior outcomes (1-year OS 55.4%, PFS 41.6%) with a median re-RT EQD2 of 48.1 Gy. An RT interval of ≥12 months was associated with improved OS and PFS. Composite dosimetry in 21 patients showed a median cumulative brain D0.1cc of 109.0 Gy; only one patient developed Grade 3 radiation necrosis (RN). High-grade acute toxicity occurred in 13.0% of patients, all manageable with supportive care.
CONCLUSION: Proton re-RT for pediatric CNS tumors is feasible and associated with encouraging survival and low rates of serious late toxicity.