Limited efficacy of temozolomide alone for astrocytoma, IDH-mutant, CNS WHO grades 2 or 3

J Neurooncol. 2022 Oct;160(1):149-158. doi: 10.1007/s11060-022-04128-y. Epub 2022 Sep 16.


Purpose: The role of temozolomide chemotherapy alone in isocitrate dehydrogenase (IDH)-mutant astrocytomas has not been conclusively determined. Radiotherapy might be superior to temozolomide. Recent studies have linked temozolomide with induction of hypermutation and poor clinical course in some IDH-mutant gliomas.

Methods: In this retrospective study, 183 patients with astrocytoma, IDH-mutant, CNS WHO grade 2 or 3 and diagnosed between 2001 and 2019 were included. Patients initially monitored by wait-and-scan strategies or treated with radiotherapy or temozolomide alone were studied. Patient data were correlated with outcome. Matched pair and subgroup analyses were conducted.

Results: Radiotherapy was associated with longer progression-free survival than temozolomide (6.2 vs 3.4 years, p = 0.02) and wait-and-scan strategies (6.2 vs 4 years, p = 0.03). Patients treated with radiotherapy lived longer than patients treated with temozolomide (14.4 vs 10.7 years, p = 0.02). Survival was longer in the wait-and-scan cohort than in the temozolomide cohort (not reached vs 10.7 years, p < 0.01). Patients from the wait-and-scan cohort receiving temozolomide at first progression had significantly shorter survival times than patients treated with any other therapy at first progression (p < 0.01). Post-surgical T2 tumor volume, contrast enhancement on MRI and WHO grade were associated with overall survival in univariate analyses (p < 0.01).

Conclusion: The results suggest superiority of radiotherapy over temozolomide and wait-and-scan strategies regarding progression-free survival and superiority of radiotherapy over temozolomide regarding overall survival. Our results are consistent with the notion that early temozolomide might compromise outcome in some patients.

Keywords: Astrocytoma; Hypermutation; Radiotherapy; Temozolomide.

MeSH terms

  • Antineoplastic Agents, Alkylating / therapeutic use
  • Astrocytoma* / pathology
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Dacarbazine / therapeutic use
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Mutation
  • Retrospective Studies
  • Temozolomide / therapeutic use
  • World Health Organization


  • Temozolomide
  • Isocitrate Dehydrogenase
  • Dacarbazine
  • Antineoplastic Agents, Alkylating