Abstract

Abstract BACKGROUND IDH-mutant gliomas are a diverse group of gliomas possessing a mutation in the isocitrate dehydrogenase enzyme. The treatment for both oligodendroglioma (1p/19q co-deleted) and astrocytoma includes resection followed by radiation therapy and chemotherapy. However, there is debate over the optimal timing of adjuvant treatment after surgery. An initial observation approach is sometimes pursued, particularly after gross total resection in young adults. We sought to examine the impact of timing of treatment in order to inform clinical decision-making. METHODS We identified 286 biopsied or resected glial tumors treated at MD Anderson Cancer Center from July 2015 to June 2022. Tumors were categorized using available molecular data based on the WHO 2021 diagnostic criteria. Progression-free survival was analyzed using Kaplan-Meier estimates. RESULTS Of 286 tumors, 232 had identified IDH-mutation, of which 89 were 1p/19q co-deleted and 143 were non-co-deleted. Of oligodendroglioma patients, 71 received either upfront chemotherapy, radiation or both and 18 received treatment upon progression; of astrocytoma patients, 96 were treated upfront and 47 received treatment at progression. Among oligodendroglioma patients, there were no significant differences in PFS between treatment timing groups (75.6 vs 66.7 months, P = 0.18). There was additionally no difference between oligodendroglioma patients treated initially with PC or PCV regimens vs temozolomide (not reached vs 75.4 months, P = 0.24). Among astrocytoma patients, upfront treatment was associated with longer PFS (93.8 vs 45.2 months, P < 0.01). Patients with low-risk grade 2 gliomas (age <40 and gross total resection) also showed longer PFS with upfront treatment (138.0 vs 45.2 months, P = 0.03). CONCLUSION Overall, the results in this molecularly defined cohort suggest a progression-free survival benefit from upfront treatment in IDH-mutant lower grade gliomas, including in low-risk gliomas. The optimal timing and nature of adjuvant treatment for lower grade gliomas remains a matter of debate.

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