Definitive Reirradiation of Intracranial Neoplasms With Intensity-Modulated Proton Therapy: Early Outcomes and Toxicities

Abstract

Management of recurrent or new primary intracranial tumors in a previously irradiated area presents a significant challenge. For inoperable patients, reirradiation (re-RT) may provide the best chance for prolonged disease control. However, given concerns for excessive morbidity, re-RT with definitive doses (≥ 45 Gy) is not commonly prescribed. Given its dosimetric advantages over photon-based techniques, we hypothesize that intensity-modulated proton therapy (IMPT) may permit safer dose escalation in the re-RT setting. This study examined feasibility of definitive brain re-RT in a cohort of patients treated with IMPT.The electronic medical record of a pencil beam scanning-only proton center was queried for adult patients who developed in-field recurrence or new primary tumor for which they subsequently received definitive-dose (≥ 45 Gy) re-RT. Dosimetric and clinical characteristics were collected. Survival was examined using the Kaplan-Meier method. Toxicities were assessed using the Common Terminology Criteria for Adverse Events v.5.0.Between August 2019 and February 2021, 62 consecutive patients received intracranial re-RT with IMPT. Twelve (18%) were treated to ≥ 45 Gy and were included for analysis. Median age at the time of re-RT was 51.5 years, and 83% of patients had an Eastern Cooperative Oncology Group score of 0. The most common histologies were oligodendroglioma (n = 4), astrocytoma (n = 3), and meningioma (n = 3). Median time from prior radiation course to IMPT was 9.4 years (range, 3.6 - 42.0 years). IMPT was delivered with conventional fractionation in 92% and hypofractionation in 8% of cases. Median equivalent dose in 2 Gy fractions (EQD2) for initial course was 53.1 Gy. Median EQD2 for the re-RT course was 54.0 Gy. The entire re-RT course was completed as planned by 83% of patients. Patients received concurrent temozolomide (66%) or temozolomide plus bevacizumab plus nivolumab (8%). Dosimetric data from the initial course were available for 58% of patients. The median cumulative (initial radiation and re-RT combined) maximum EQD2 doses were 116.8 Gy to brain, 66.2 Gy to brainstem, 67.7 Gy to chiasm, 72.0 Gy to ipsilateral optic nerve, and 54.5 Gy to contralateral optic nerve. At a median follow-up of 5.4 months, 58.3% (n = 7) of patients developed grade 2 toxicities including fatigue (n = 6) and alopecia (n = 5). No grade ≥3 neurotoxicities were documented. Median progression free survival was 7 months; median overall survival was not reached.Early results of our single-institution experience suggest a potential for safe intracranial re-RT with definitive-dose IMPT for select patients. Based on these findings, we are activating a prospective study to identify subsets of patients who are best fit for IMPT re-RT and formulate optimal dose regimens and normal tissue composite dose constraints.L. Maillie: None. S. Sharma: None. J.T. Yang: None. N. Ohri: Consultant; Merck, AstraZeneca. I.J. Choi: Employee; New York Proton Center. Travel Expenses; Varian; National Association of Proton Therapy, Proton Collaborative Group. Oversee and provide guidance for new and existing research protocols, ensure best practices for organization research endeavors.; Proton Collaborative Group. B.K. Yeh: None. R.H. Press: None. A. Chhabra: None. M.K. Garg: None. Y. Yamada: Consultant; University of Wollongong. Speaker's Bureau; Varian Medical Systems, BrainLab. Medical advisor; Chordoma Foundation. C.B. Simone: Employee; New York Proton Center. Honoraria; Varian Medical System, Novocure. Travel Expenses; Varian Medical System; Proton Collaborative Group (PCG), Annals of Palliative Medicine, American Society for Radiation Oncology. S. Lazarev: None.