Oligodendroglioma Patients with 1p/19q Co-deletion Treated with Early or Delayed Radiation Therapy over the Last Two Decades: A Multi-institutional Report

Abstract

To evaluate the patterns of care and clinical outcomes of irradiated oligodendroglioma patients using a pooled analysis of a multi-institutional cohort. Oligodendroglioma patients with confirmed 1p/19q co-deletion who were treated with radiation therapy (RT) with or without chemotherapy from 2000-2017 at four tertiary academic cancer centers were retrospectively reviewed. PFS and OS rates were determined with Kaplan-Meier analyses. Logistic regression analysis was used to identify factors associated with delayed use of RT. Cox regression analysis was used to identify factors associated with worse progression free survival (PFS) and overall survival (OS). Progression was defined as progression after RT, whether RT was delivered adjuvantly or in a delayed fashion. All times to progression or death were determined from the time of initial surgery. One hundred eighty-eight patients were identified: 122 (65%) received early RT (within 6 months of surgery, median: 1.2 months, range: 0.03-5.6 months), and 67 (35%) received delayed RT (more than 6 months from surgery, median: 50 months, range: 6.3-213 months). Most patients were treated with intensity-modulated RT (65%) followed by 3D conformal RT (23%) and proton therapy (12%). Median age and follow up was 43 years (range 20-80) and 69 months (range 2-242), respectively. For patients who were treated with early RT, 70% were treated with RT and temozolomide (TMZ), and 15% were treated with RT and procarbazine/lomustine/vincristine (PCV), and 15% were treated with RT alone. For patients who were treated with delayed RT, 36% patient were treated with initial chemotherapy and then salvage RT later, 46% were treated with RT +TMZ, 13% were treated with RT+PCV, and 5% were treated with RT alone. Ten-year PFS for early RT and delayed RT were 63% vs. 74%, respectively (P=0.02); ten-year OS for early RT and delayed RT were 67% vs. 91%, respectively (P=0.02). Younger age (OR = 1.04, 95% CI 1.02-1.07) and grade 2 histology (OR = 7.0, 95% CI 3.4 -14.2) were associated with delayed RT. Gliomatosis (HR = 46, 95% CI 5.1-422) and grade 3 histology (HR = 2.2, 95% CI 1.3-3.9) were significantly associated with worse PFS after RT. Older age (HR = 1.06, 95% CI 1.03-1.09), lower performance status (HR = 1.04, 95% CI 1.01-1.08), gliomatosis (HR = 42.7, 95% CI 4.5-401), and early RT (HR = 2.4, 95% CI 1.03-5.6) were associated with worse OS. In this large multi-institutional cohort with treatment spanning over two decades, oligodendroglioma patients had favorable prognosis regardless whether treated with early or delayed RT. Young age and grade 2 histology were more likely to receive delayed RT, which was not associated with significantly worse PFS or OS. Among this molecularly homogenous oligodendroglioma population with 1p/19q co-deletion, grade 3 histology was prognostic for PFS after RT but not OS. When chemotherapy was chosen to combine with either early or delayed RT, TMZ was preferentially chosen over PCV.