Impact of 1p/19q codeletion and histology on outcomes of anaplastic gliomas treated with radiation therapy and temozolomide

Int J Radiat Oncol Biol Phys. 2015 Feb 1;91(2):268-76. doi: 10.1016/j.ijrobp.2014.10.027.

Abstract

Purpose: Anaplastic gliomas represent a heterogeneous group of primary high-grade brain tumors, and the optimal postoperative treatment remains controversial. In this report, we present our institutional data on the clinical outcomes of radiation therapy (RT) plus temozolomide (RT + TMZ) for anaplastic gliomas, stratified by histology and 1p/19q codeletion.

Methods and materials: A single-institution retrospective review was conducted of patients with supratentorial anaplastic oligodendroglioma (AO), mixed anaplastic oligoastrocytoma (AOA), and anaplastic astrocytoma (AA). After surgery, RT was delivered at a median total dose of 60 Gy (range, 31.6-63 Gy) in daily fractions. All patients received standard concurrent TMZ, with or without adjuvant TMZ. Histological/molecular subtypes were defined as codeleted AO/AOA, non-codeleted AO/AOA, and AA.

Results: From 2000 to 2012, 111 cases met study criteria and were evaluable. Codeleted AO/AOA had superior overall survival (OS) to non-codeleted AO/AOA (91% vs 68% at 5 years, respectively, P=.02), whereas progression-free survival (PFS) was not significantly different (70% vs 46% at 5 years, respectively, P=.10). AA had inferior OS to non-codeleted AO/AOA (37% vs 68% at 5 years, respectively, P=.007) and inferior PFS (27% vs 46%, respectively, P=.03). On multivariate analysis, age, performance status, and histological or molecular subtype were independent predictors for both PFS and OS. Compared to historical controls, RT + TMZ provided comparable OS to RT with procarbazine, lomustine, and vincristine (RT + PCV) for codeleted AO/AOA, superior OS to RT alone for non-codeleted AO/AOA, and similar OS to RT alone for AA.

Conclusions: RT + TMZ may be a promising treatment for both codeleted and non-codeleted AO/AOA, but its role for AA remains unclear.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Chemoradiotherapy
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 1 / genetics*
  • Chromosomes, Human, Pair 19 / genetics*
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Female
  • Gene Deletion
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Glioma / genetics*
  • Glioma / mortality
  • Glioma / pathology
  • Glioma / therapy*
  • Humans
  • Male
  • Middle Aged
  • Missouri / epidemiology
  • Prevalence
  • Radiotherapy Dosage
  • Retrospective Studies
  • Risk Factors
  • Survival Rate
  • Temozolomide
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Temozolomide