Reappraisal of prognostic factors in CNS WHO grade 3 oligodendrogliomas IDH-mutant and 1p/19q co-deleted: Lessons from the French POLA cohort

Background: In the POLA cohort, 3 pathological groups of CNS WHO grade 3 oligodendroglioma IDH-mutant and 1p/19q co-deleted have been described: group 1 (high mitotic count only), group 2 (microvascular proliferation MVP and no necrosis), and group 3 (MVP and necrosis). Methods: 494 patients from the POLA cohort, with a median follow-up of 96 months were included. To identify the impact of the pathological groups and contrast enhancement (CE) in group 1 on overall survival (OS) or progression-free survival (PFS), survival curves were obtained (Kaplan-Meier method) and compared (log-rank test). The prognostic value of clinical factors and CDKN2A homozygous deletion HD were also tested. Multivariate analysis was performed. Results: Survival analysis demonstrated that the pathological groups were associated with both progression-free survival (PFS P = .01) and overall survival (OS P = .001). In group 1, patients with CE (1CE+) had a poorer prognosis compared to those without (OS P = .028, PFS P = .006). Further stratification into group 1CE-, group 1CE+, group 2, and group 3 provided clearer prognostic distinctions (OS P = .002, PFS P < .0001). Other prognostic factors included age (OS P < .0001, PFS P = .002), extent of surgical resection (OS P = .001, PFS P = .003), KPS (OS P < .0001, PFS P = 0.002), postoperative treatment (OS P = .007, PFS P < .0001), and CDKN2A HD (OS and PFS P < .0001). The pathological groups remained of prognostic significance for PFS in multivariate analysis. Conclusions: Necrosis and CDKN2A HD are adverse prognostic factors of WHO grade 3 oligodendrogliomas, IDH-mutant, and 1p/19q co-deleted. Besides, in group 1 patients, lack of CE is a factor of better prognosis.