Long-Term Outcome of Molecularly Defined Oligodendrogliomas: Comparison of Grade 2 and 3 Tumors

Background and Objectives – Molecularly defined oligodendrogliomas are rare tumors whose prognosis has improved over time because of more effective treatments. However, several aspects of management are still controversial, and studies with long-term follow-up are needed. The main aim of this study was to analyze and compare the natural history and management of patients with OG2 and OG3 and define which factors have the strongest effect on outcome.Methods – We reviewed an institutional retrospective cohort (1996–2024) of patients with molecularly defined OG2 and OG3 according to World Health Organization 2021. We retrieved information on baseline clinical features, MRI characteristics (i.e., presence and pattern of contrast enhancement), extent of resection, initial treatment modalities after surgery, and management at progression. The relationships of these factors with progression-free survival (PFS) and overall survival (OS) were studied with univariate and multivariate analyses.Results – Among 240 patients with IDH-mutant 1p/19q-codeleted oligodendrogliomas, grade 2 tumors were 149 (62.1%) and grade 3 were 91 (37.9%) with a median age of 42 and 44 years, respectively. Male/female ratio was 73/76 (49%/51%). Among patients with OG3, 70/91 (77%) exhibited a diffuse grade 3 histology (OG3d), whereas 21/91 (23%) had focal grade 3 areas only (OG3f). Overall, patients with OG2 and OG3 had similar median PFS (57.6 months, CI 53.2–61.9, vs 59.8 months, CI 41.9–77.6, p = 0.25), and prolonged median OS (274 months vs not reached). However, patients with OG3 exhibited a shorter time to radiotherapy at progression and their survival probability declined more rapidly within the first decade after surgery. The extent of resection was the only factor that significantly affected both PFS and OS in a multivariate analysis (for PFS, hazard ratio [HR] 0.90, 0.62–0.99, p = 0.026; for OS, HR 0.29, 0.13–0.79, p = 0.016), whereas tumor grade did not. Temozolomide alone as initial treatment of high-risk OG2 and OG3 with large residual tumor after surgery was not detrimental for survival. The same was true for observation in a small group of young patients with nonenhancing OG3 who have undergone complete resection and with only focal areas of malignancy (OG3f).Discussion – This large retrospective cohort of IDH-mutant 1p/19q-codeleted oligodendrogliomas receiving standard treatments could serve as a benchmark for comparison with new IDH inhibitors in future clinical studies.