Toxicity, Disease Control, and Survival Following Proton Therapy-Fractionated Re-Irradiation for Recurrent Intracranial Meningioma Not Amenable to Radiosurgery

Abstract

Listen

Translate article

With its finite range and sharper lateral penumbrae, proton therapy provides unique dosimetric advantages for fractionated re-irradiation of recurrent intracranial meningioma not amenable to radiosurgery due to either bulky tumor size or adjacent organs-at-risk. This analysis features the largest such clinical series to date and seeks to determine whether these dosimetric advantages translate into favorable clinical outcomes. Patients who received fractionated proton therapy re-irradiation for recurrent intracranial meningioma not amenable to radiosurgery were included. Toxicity was assessed using the NCI’s Cancer Treatment Common Terminology for Adverse Events (CTCAE) version 5.0. Local control (LC, defined as tumor control within the re-irradiated region), intracranial progression-free survival (PFS, including progression within and outside the re-irradiated region) and overall survival (OS) rates were estimated using the Kaplan-Meier method. 30 patients with follow-up ≥90 days were identified at a single institution. Median age was 65 years (range: 32 – 87). Median target volume was 61.57cc (range: 5.59 – 325.48), with 24 patients having >25cc target volume. Median follow-up for living patients was 26 months (interquartile range: 9-35 months). Prior to re-irradiation, patients received a median of 1 radiotherapy treatment (range: 1 – 5). 69% of prior treatments were radiosurgery and 31% were fractionated radiotherapy. Median time from prior radiotherapy to re-irradiation was 57 months (range: 11 – 278). Median re-irradiation dose was 54.1 CGE (range: 48.7 – 60.3). At the time of re-treatment, 16 patients had a surgically confirmed WHO grade, with 6, 9, and 1 being WHO grade III, II, and I, respectively. For the overall cohort, median PFS was 12.3 months, median OS was not reached, and one-year local control was 52.3%. For surgically confirmed WHO grade III tumors, median PFS was 11 months, median OS was 17 months, and one-year local control was 41.7%. For surgically confirmed WHO grade II tumors, median PFS was 16 months, median OS was not reached, and one-year local control was 74.1%. Acute toxicity included grade 1 fatigue, radiation dermatitis, and alopecia in 43%, 47%, and 70% of patients, respectively. Radiation-related intracranial edema occurred in 23% of patients and in every case resolved with dexamethasone. Late toxicity included 3 cases of grade 1 radiation necrosis (RN), 1 case of grade 2 RN requiring bevacizumab, and no cases of grade 3 RN. Proton therapy fractionated re-irradiation for recurrent intracranial meningioma not amenable to radiosurgery leads to favorable tumor control and survival with limited RN risk, including in high-risk tumors for which salvage therapy options remain limited.