3444 - Radiation-Induced Brain Necrosis Following Proton Therapy for Head and Neck Cancers near the Skull Base: Incidence and Predictive Factors
Presenter(s)
H. S. Cheng1, S. Ramesh2, N. Chadha3, S. Wang4, E. C. Dee1, Y. Wu5, C. A. Barker1, S. M. McBride1, N. Riaz1, D. Y. Gelblum1, Y. Yu1, A. Shamseddine1, Z. Abou Yehia6, W. Wong7, A. Ho5, R. J. Wong8, I. Ganly8, R. J. Young5, K. Tam9, V. S. Tabar5, M. Cohen8, and N. Y. Lee1; 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 2Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, 3Weill Cornell Medical College, New York, NY, 4weifang medical university, weifang, China, 5Memorial Sloan Kettering Cancer Center, New York, NY, 6mskcc, Houston, TX, 7Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 8Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 9Memorial Sloan Kettering, New York, NY
Purpose/Objective(s): To determine the incidence and risk factors of radiation-induced brain necrosis (RIBN) in head and neck cancer patients with disease near the skull base treated with curative-intent proton therapy.
Materials/Methods: We retrospectively reviewed the medical records of 251 consecutive patients treated with curative-intent proton therapy between March 2014 and June 2025, including both upfront and re-irradiation (re-RT) cases, to determine the incidence of radiation therapy–induced brain necrosis (RIBN). Eligible patients had tumors involving the sinonasal tract, nasopharynx, orbit, or lacrimal gland. Patients with primary central nervous system tumors, those treated with palliative intent, or those with less than 6 months of follow-up were excluded. The incidence rate of RIBN was evaluated using the CTCAE v5.0 grading criteria. Risk factors were evaluated using univariate log-rank testing and multivariable Cox proportional hazards regression modeling.
Results: A total of 251 patients were included in this study, comprising 235 patients treated upfront with a median follow-up of 33 months (range, 6–139) and 16 patients who underwent re-RT with a median follow-up of 32.5 months (range, 10–72). Primary sites included the sinonasal tract (54.2%), nasopharynx (27.9%), orbit (15.5%), and the others (2.4%). The median proton dose was 7000 cGy (range, 4500–8612) in the upfront cohort and 7000 cGy (range, 6000–7200) in the re-RT cohort. RIBN developed in 12.3% (29/235) of upfront patients (8.5% grade 1–2; 3.8% grade 3), with a median time to onset of 24 months (range, 2–62), compared with 37.5% (6/16) in the re-RT cohort (25.0% grade 1–2; 12.5% grade 3), with a median time to onset of 10.5 months (range, 6–49).The 2-year cumulative incidence was 6.9% in the upfront cohort and 25.5% in the re-RT cohort. On univariate analysis, significant risk factors for RIBN included T3–4 disease (HR 4.41, 95% CI 1.56–12.51, p=0.0052), re-RT (HR 4.31, 95% CI 1.78–10.47, p=0.0012), and concurrent chemotherapy (HR 4.21, 95% CI 1.45–11.70, p=0.0079). On multivariate analysis, T3–4 disease (HR 3.31, 95% CI 1.15–9.52, p=0.0263), re-RT (HR 2.88, 95% CI 1.18–7.05, p=0.0205), and concurrent chemotherapy (HR 3.00, 95% CI 1.04–8.66, p=0.0421) remained independently associated with RIBN.
Conclusion: RIBN is a late complication following proton therapy for head and neck cancers involving the skull base. The incidence was 12.3% (including 3.8% grade 3) in patients receiving upfront proton therapy and 37.5% (including 12.5% grade 3) in those undergoing proton re-RT. Advanced tumor stage, re-RT and concurrent chemotherapy were identified as significant risk factors. Strategies to mitigate this risk are warranted to improve the therapeutic ratio.