Abstract BACKGROUND Grade 3 IDH-mutant 1p/19q-codeleted oligodendrogliomas (OG3) are considered at higher risk of progression and poorer survival compared to Grade 2 (OG2). Standard treatments for OG3 include maximal safe resection followed by adjuvant radio-chemotherapy (PCV or temozolomide). However, since the adoption of molecular classifications, the prognostic relevance of histological grading has been questioned. We compared clinical characteristics, treatment responses, and outcomes of molecularly defined OG2 and OG3 patients in a long-term observational study. PATIENTS AND METHODS We reviewed a dataset of patients with a diagnosis of IDH1/2-mutant 1p19q-codeleted OG3 and OG2 treated from 1996 to 2024. RESULTS We included 240 patients (OG2: 149, 62.1%; OG3: 91, 37.9%). Median age was 42 and 44 years for OG2 and OG3. OG2 and OG3 had a similar incidence of seizures at onset (116/149, 77.9% vs 73/91, 80.2%). Gross-total resection (GTR) non-significantly prevailed among OG2 vs OG3 (68/149, 58.6% vs 48/91, 41.4%, p=0.285). After surgery, treatment modalities for OG2 were observation in low-risk patients (97/149, 65.1%) and upfront temozolomide (TMZ) in high-risk (48/149, 32.2%), whereas in OG3 were upfront TMZ in 44/91 (48.4%), chemoradiation (RT + TMZ) in 35/91 (38.5%) and observation in 12/91 (13.2%) patients with focal grade 3 areas after GTR. Median follow-up was 110.8 months. Overall, OG2 and OG3 patients had a similar mPFS (57.6 months vs 59.8 months, p=0.251). Among OG3 patients, those who received RT+TMZ showed a slightly longer PFS (76.4 months) compared to those who were treated with TMZ upfront (64.4 months) or observed after surgery (47.9 months) (p=0.440). Both OG2 and OG3 had long mOS (274 months vs not reached), although survival probability at 12 months was higher for OG2 (90% vs 69%, p=0.019). Interestingly, mOS did not significantly differ among OG3 patients who received TMZ upfront + delayed RT at recurrence vs those who were treated with early RT+TMZ after surgery (both not reached, p=0.665). Finally, in a multivariable analysis, histological grading did not significantly affect PFS or OS. CONCLUSIONS In our cohort, OG3 patients showed survival outcomes comparable to OG2. TMZ upfront with delayed RT appeared as effective as early RT+TMZ in OG3. Novel therapies, such as IDH inhibitors, may further enhance future treatment strategies.
Pronello et al. (Wed,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: