Oligodendroglial tumors: from biology to a better patient care
Review, 15 - 20Tag this article
Oligodendroglial tumors (pure oligodendrogliomas and oligoastrocytomas) are heterogenous in terms of molecular profile and outcome. Genetics has accomplished significant advances improving our knowledge and helping clinical management of oligodendroglioma patients: three prognostic subgroups are defined, in both grade II and grade III, based on the 1p19q codeletion and IDH1/2 mutation status: (i) 1p/19q codeleted (most of them are CIC mutated and all are IDH1/IDH2 and TERT promoter mutated) which have the best outcome, (ii) non 1p19q co-deleted and IDHmutated (which have the ATRX mutation instead of TERT promoter mutation) with intermediate outcome and (iii) double negative with the poorest outcome. These subgroups have distinct natural history and the 1p19q codeletion is also associated with a better response to alkylating chemotherapy: recently, two trials (RTOG 9402 and EORTC 26951) have shown unambiguously near-doubling of median survival times (14.7 y vs 7.3 y in the RTOG study) of patients with 1p19q codeleted grade III gliomas treated with chemotherapy (PCV) and radiation therapy (RT) vs RT alone, whereas patient without codeletion have a poorer survival with marginal, no significant benefit of adjuvant chemotherapy. Based on these results, assessment of 1p/19q status is required in patients with grade III oligodendroglial tumor in order to deliver the right treatment. The recently identified molecular alterations (IDH1/2, CIC, FUBP1 and TERT promoter mutations) are attractive candidates to new molecular targeted agents, but further studies and better understanding are needed.
KEY WORDS: oligodendroglioma; IDH1; 1p19q codeletion; prognostic markers; adjuvant chemotherapy; PCV.