Anaplastic oligodendroglial tumors: refining the correlation among histopathology, 1p 19q deletion and clinical outcome in Intergroup Radiation Therapy Oncology Group Trial 9402.

ABSTRACT

Intergroup Radiation Therapy Oncology Group Trial 9402 study, a phase III trial of chemotherapy plus radiotherapy (PCV-plus-RT) vs. radiotherapy alone for pure and mixed anaplastic oligodendroglioma confirmed the prognostic significance of 1p 19q deletion and showed that only progression-free survival (PFS) was prolonged in PCV-plus-RT-treated patients and only in association with 1p 19q deletion. We reviewed tumor histopathology, separating 115 tumors deemed to be classic for oligodendroglioma (CFO) from 132 lacking classic features of oligodendroglioma (NCFO) and evaluated the relationship of histopathology and 1p 19q status to treatment and outcome. The study disclosed (i) overall survival (OS) of patients with CFO was significantly longer than for patients with NCFO (P < 0.0001) and was not affected by necrosis. Median OS for CFO patients with and without necrosis was 6.6 and 6.3 years (OS log-rank P = not significant), respectively, in contrast to NCFO showing 1.9 and 3.3 years respectively (OS log-rank P = 0.014). (ii) Classic oligodendroglial morphology was highly associated with 1p 19q deletion, present in 80% of CFO and only in 13% of NCFO. (iii) On multivariate analysis, both classic oligodendroglial morphology and 1p 19q deletion remained significantly associated with PFS and OS. (iv) Patients with CFO treated with PCV-plus-RT showed a trend toward increased survival compared with CFO treated with RT (P = 0.08). Median OS was not reached in the PCV-plus-RT group and was 6.3 years in RT group. These findings suggest that classic oligodendroglial morphology combined with 1p 19q deletion may in the future be predictive of chemotherapeutic response and survival.