2167 - Radiation Necrosis after Pencil Beam Scanning Proton Therapy for CNS Tumors: Incidence and Timing

Purpose/Objective(s):

Cranial radiation therapy (RT) remains a cornerstone in the management of central nervous system (CNS) neoplasms. However, radiation necrosis (RN) is a significant toxicity that may develop months to years after treatment. Although proton RT offers potential dosimetric and biologic advantages over photon RT, data on RN after pencil beam scanning (PBS) proton RT is limited and constrained by small cohorts and incomplete dosimetric analyses. In this study, we aim to characterize the incidence, timing, and severity of RN after PBS proton RT.

Materials/Methods: We retrospectively reviewed consecutive patients with primary intracranial CNS tumors treated with PBS proton RT from a single institution between December 2019 and July 2025. Patients with prior cranial RT or treated with doses <45 Gy were excluded. Baseline characteristics, comorbidities, dosimetric parameters, and RN incidence were analyzed.

Results: Seventy-nine patients were included. Median age was 43 years (range, 18-81), 23% had smoking history, and 33% had comorbidities, most commonly hypertension (32%) and diabetes (14%). Histologies included high grade glioma in 28%, low grade meningioma in 20%, high grade meningioma in 18%, and low grade glioma in 15%, with frontal lobe being the most frequent tumor location. Treatment consisted of surgery followed by RT in 34%, RT alone in 25%, and surgery followed by chemoRT in 33%. Median prescribed dose was 57.6 GyRBE (IQR, 54-59.7 GyRBE) in 30 fractions, with a median CTV of 86.7 cm³ (IQR, 40.7-164.9). A boost was delivered in 42% of patients, with a median volume of 49.5 cm³. Median Dmax doses to organs at risk were 51.1 Gy to optic chiasm, 52.5 Gy to right optic nerve, 20.9 Gy to left optic nerve, and 57.4 Gy to brain. Median mean doses were 33.7 Gy to right cochlea, 7.4 Gy to left cochlea, and 8.8 Gy to brain. At a median follow up 34 months, 12 patients (15%) developed grade =1 RN. The majority were low grade: 6 (8%) patients had grade 1 toxicity and 3 (4%) had grade 2. Three patients (4%) developed grade =3 RN, with one grade 4 event. Three patients were treated with Boswellia, and 3 required surgical intervention. Median time to RN onset was 124 days (range, 28-779) following RT.

Conclusion:

In this cohort, clinically significant high-grade RN was uncommon and comparable to rates reported in historical photon series. However, time to RN onset appeared relatively early. Overall, PBS proton RT demonstrated an acceptable safety profile for CNS tumors.