P11.51.B Initial temozolomide monotherapy without radiotherapy might be of limited benefit in the treatment of astrocytoma, IDH-mutant, CNS WHO grade 2 and 3

Abstract Background The role of temozolomide chemotherapy alone in isocitrate dehydrogenase (IDH-) mutant astrocytomas has not been conclusively determined. Radiotherapy might be superior to temozolomide alone. Recent studies have linked temozolomide therapy with poor clinical course and induction of hypermutation in IDH-mutant gliomas. Material and Methods In this retrospective, single-center study, 183 patients with astrocytoma, IDH-mutant, CNS WHO grade 2 or 3 according to WHO 2021 and diagnosed between 2000 and 2019 were included. Patients initially monitored by means of a wait-and-scan strategy, or treated with radiotherapy alone, or receiving temozolomide alone after histological sampling through biopsy or tumor resection were studied. Patient-related, clinical and imaging data were correlated with progression-free and overall survival. A matched-pair analysis accounting for post-surgical tumor volume was conducted. Results No significant differences in median age and clinical status at diagnosis was seen. WHO grades were balanced between patients treated with radiotherapy and temozolomide, but the proportion of WHO grade 2 gliomas was higher in the wait-and-scan cohort. Radiotherapy was associated with significantly longer overall survival than temozolomide (in years, 14.4 vs 10.7; p=0.02) and longer progression-free survival than temozolomide (in years, 6.2 vs 3.4, p=0.02) and wait-and-scan strategies (in years, 6.2 vs 4; p=0.03). Comparing wait-and-scan with temozolomide, survival was significantly longer in the wait-and-scan cohort (in years, not reached vs 10.7, p<0.0001). An analysis of WHO grade 2 astrocytomas only also showed superior survival in the wait-and-scan cohort as compared to temozolomide (p=0.02). Of note PFS was similar overall and in WHO grade 2 astrocytomas. Conclusion The results suggest superiority of radiotherapy alone over temozolomide alone or wait-and-scan strategies in IDH-mutant WHO grade 2 and 3. Recent study results indicating that temozolomide might compromise prognosis in some IDH-mutant gliomas might be supported by our data, although caution in interpretation of retrospective data is required. The potential negative effects may only be apparent in the long-term.