Efficacy of initial temozolomide for high-risk low grade gliomas in a phase II AINO (Italian Association for Neuro-Oncology) study: a post-hoc analysis within molecular subgroups of WHO 2016

J Neurooncol. 2019 Oct;145(1):115-123. doi: 10.1007/s11060-019-03277-x. Epub 2019 Sep 25.

Abstract

Introduction: The optimal management of high risk WHO grade II gliomas after surgery is debated including the role of initial temozolomide to delay radiotherapy and risk of cognitive defects.

Methods: A post-hoc analysis of a phase II multicenter study on high risk WHO grade II gliomas, receiving initial temozolomide alone, has re-evaluated the long-term results within the molecular subgroups of WHO 2016. The primary endpoint of the study was response according to RANO, being seizure response, PFS and OS secondary endpoints.

Results: Response rate among oligodendrogliomas IDH-mutant and 1p/19q codeleted (76%) was significantly higher than that among diffuse astrocytomas either mutant (55%) or wild-type (36%). A reduction of seizure frequency > 50% was observed in 87% of patients and a seizure freedom in 72%. The probability of seizure reduction > 50% was significantly associated with the presence of an IDH mutation. Median PFS, PFS at 5 and 10 years, median OS and OS at 5 and 10 years were significantly longer in oligodendrogliomas IDH-mutant and 1p/19q codeleted. Sixty-seven percent of patients with oligodendroglioma IDH mutant and 1p/19q codeleted did not recur with a median follow up of 9.3 years, while 59% did not receive radiotherapy at recurrence with a median follow up of 8.2 years.

Conclusions: The beneficial effects of initial temozolomide prevail in oligodendrogliomas IDH-mutant and 1p/19q codeleted: thus, these tumors, when incompletely resected or progressive after surgery alone, or with intractable seizures, should receive temozolomide as initial treatment with salvage radiotherapy and/o reoperation and/or second-line chemotherapy at recurrence.

Keywords: Grade II gliomas; Oligodendrogliomas IDH-mutant and 1p/19q codeleted; Response; Survival; Temozolomide; WHO 2016.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Brain Neoplasms / classification
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Glioma / classification
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Survival Rate
  • Temozolomide / therapeutic use*
  • World Health Organization

Substances

  • Antineoplastic Agents, Alkylating
  • Temozolomide