Salvage Treatment for Recurrent IDH-mutant Diffuse Gliomas after Radiation Therapy

Abstract

Optimal management of patients diagnosed with recurrent IDH-mutant gliomas (IMGs) who relapse after prior radiation therapy (RT) is not well defined. This study evaluates the patterns of care and outcomes of our institutional experience with recurrent IMGs. Recurrent IMG patients including IDH-mutant astrocytomas (AC) and 1p/19q codeleted oligodendrogliomas (OD) from 1997-2019 were retrospectively reviewed at our institution. Recurrence was defined as progressive disease after initial RT with/without chemotherapy. IDH-mutation was confirmed using either immunohistochemistry or sequencing on either initial or recurrent tissue. Overall survival (OS) was calculated from the date of first recurrence and compared using Kaplan-Meier analysis. From 1997-2019, 100 patients with IMGs received salvage treatment after recurrence (49% OD, 51% AC). Tumor grade at recurrence was classified as: II (29%), III (55%) or IV (16%). First-line salvage therapies included: surgery alone (9%), chemotherapy alone (70%), RT alone (4%), and chemoradiotherapy (17%). Across all recurrences, 94% received chemotherapy (90% for OD and 98% for AC); 67% had surgery (71% for OD and 63% for AC); 40% had re-irradiation (41% for OD and 39% for AC). The median dose of re-irradiation was 36 Gy or GyRBE, and the most common technique was proton beam therapy (30%). After a median follow up of 21 months (range 1 – 256), OS was 63% at 2 years and 47% at 5 years. Patients with OD had significantly better OS than patients with AC: 74% vs 50% at 2 years, 56% vs 38% at 5 years, respectively, p=0.02. Among the OD patients, those treated with re-irradiation had higher but not statistically different OS than chemotherapy alone: 84% vs 65% at 2 years, respectively, p=0.62; a similar trend was also observed for the AC patients: 70% vs 37% at 2 years, respectively, p=0.31. Although chemotherapy was the most common salvage treatment for recurrent IDH-mutant OD and AC, local therapies such as surgery and re-irradiation were frequently used. The incorporation of re-irradiation with chemotherapy may warrant further investigation.