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

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.