Clinical Outcomes of Reirradiation in IDH-Mutant Astrocytomas and 1p/19q Codeleted Oligodendrogliomas

Abstract

Recent data has demonstrated that IDH-mutant gliomas (IMGs) have a favorable prognosis as compared to IDH wild type gliomas. While primary fractionated radiation therapy (RT) is part of standard of care for IMGs, clinical outcomes and optimal technique of reirradiation for relapsed IMGs after primary RT are not well defined. This study aims to analyze the clinical outcomes and toxicity of reirradiation for recurrent IMGs. Recurrent IMG patients including IDH-mutant astrocytomas and 1p/19q codeleted oligodendrogliomas who received reirradiation at our institution were retrospectively reviewed. Reirradiation techniques included stereotactic radiosurgery (SRS) or external beam RT (EBRT). Local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated from start of reirradiation and compared using Kaplan-Meier analysis. Biologically equivalent dose in 2Gy fractions (EQD2) for brain were estimated for each course of RT using the linear-quadratic model and α/β of 3. Radiation necrosis (RN) was evaluated based on all available clinical, radiographic and pathological data. From 2001-2017, 23 recurrent IMGs were reirradiated (74% oligodendrogliomas, 26% astrocytomas). All tumors were initially diagnosed as grade II (65%) or III (35%) before primary RT. In 21 patients who had surgery for relapsed disease, 62% had increased tumor grade. Median follow up after reirradiation was 20 months (range 1 - 105). Median time between RT courses was 13.2 years (0.4 – 26.2). Fifteen patients (65%) were treated with EBRT (53% Intensity-modulated RT, 47% proton therapy); 8 patients (35%) were treated with SRS (87% single-fraction, 13% multi-fraction). Median EQD2 of reirradiation was 51.8 Gy (25.2 – 92), and cumulative EQD2 of combined RT courses was 102.5 Gy (85 – 148). Sixteen (70%) patients received concurrent or adjuvant chemotherapy.For the entire cohort, 2-year LC was 79%, 2-year PFS was 58%, and 2-year OS was 65%. LC, PFS, and OS were not significantly different between oligodendrogliomas and astrocytomas (all P > 0.05). Two-year LC for EBRT and SRS were 80% for both groups (P= 0.35), and 2-year PFS for EBRT and SRS were 60% and 57%, respectively (P=0.60). Radiation necrosis occurred in 5 patients (22%). Reirradiation appears to show promising activity for radiation-relapsed IMGs with moderate risk of RN. Future investigation with longer follow-up and larger cohort is warranted.