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.

Figure 1

The figure illustrates one example of a tumor showing classic features of oligodendroglioma (A,B) and one example in which the classic features of oligodendroglioma were not present (C,D).

Figure 2

Kaplan–Meier estimates of overall survival by histopathology (CFO and NCFO), with and without presence of necrosis. Pair‐wise comparisons and P‐values are tabulated below the graphic. CFO = tumor with features classic for oligodendroglioma; NCFO = tumor with features not classic for oligodendroglioma.

Figure 3

Kaplan–Meier estimates of progression‐free survival by histopathology (CFO and NCFO), with and without presence of necrosis. Pair‐wise comparisons and P‐values are tabulated below the graphic. CFO = tumor with features classic for oligodendroglioma; NCFO = tumor with features not classic for oligodendroglioma.

Figure 4

The figure illustrates an example of a CFO tumor which did not show 1p 19q deletion (panel A) and one example of a NCFO tumor with 1p 19q deletion (panel B). CFO = tumor with features classic for oligodendroglioma; NCFO = tumor with features not classic for oligodendroglioma.

Figure 5

Kaplan‐Meier estimates of overall survival by histopathology (CFO and NCFO) and genotype (1p 19q deletion status). Pair‐wise comparisons and P‐values are tabulated below the graphic. CFO = tumor with features classic for oligodendroglioma; NCFO = tumor with features not classic for oligodendroglioma.

Figure 6

Kaplan‐Meier estimates of overall survival by histopathology (CFO and NCFO) and treatment (PCV‐RT and RT only). Pair‐wise comparisons and p‐values are tabulated below the graphic. CFO = tumor with features classic for oligodendroglioma; NCFO = tumor with features not classic for oligodendroglioma; PCV = procarbazine, lomustine and vincristine; RT = radiotherapy.

Figure 7

Kaplan‐Meier estimates of progression‐free survival by histopathology (CFO and NCFO) and treatment (PCV‐RT and RT only). Pair‐wise comparisons and p‐values are tabulated below the graphic. CFO = tumor with features classic for oligodendroglioma; NCFO = tumor with features not classic for oligodendroglioma; PCV = procarbazine, lomustine and vincristine; RT = radiotherapy.