In contrast, the Radiation Therapy Oncology Group (RTOG) trial (RTOG-9402 [NCT00002569]) demonstrated no differences in median survival by treatment arm between an 8-week, intensive PCV chemotherapy regimen followed by immediate involved-field-plus-radiation therapy and radiation therapy alone. However, in an unplanned subgroup analysis, patients with 1p/19q codeleted anaplastic oligodendroglioma and mixed anaplastic astrocytoma demonstrated a median survival of 14.7 years versus 7.3 years (HR, 0.59; 95% CI, 0.37–0.95; P = .03). For patients with noncodeleted tumors, there was no difference in median survival by treatment arm (2.6 vs. 2.7 years; HR, 0.85; 95% CI, 0.58–1.23; P = .39).[Level of evidence: 1iiA]
Based on these data, CODEL, a study that randomly assigned patients to radiation therapy alone (control arm), radiation therapy with temozolomide, and temozolomide alone (exploratory arm), was halted because radiation therapy alone was no longer considered adequate treatment in patients with anaplastic oligodendroglioma with 1p/19q codeletion. A comparison between temozolomide and PCV chemotherapy in anaplastic oligodendroglioma has not been done, although in the setting of grade 3 anaplastic gliomas, no survival difference was seen between PCV chemotherapy and temozolomide.[2,8]
Anaplastic oligodendrogliomas (WHO grade III) have a low cure rate with standard local treatment, but their prognosis is generally better than that of anaplastic astrocytomas. Since anaplastic oligodendrogliomas are uncommon, phase III randomized trials restricted to them are not practical. They are generally managed with the following:
- Postoperative radiation therapy (PORT) alone, with chemotherapy at progression.
- Postoperative chemotherapy with radiation at progression.
- PORT plus chemotherapy, even though the combination of radiation plus chemotherapy is not known to be superior in outcome to sequential modality therapy.
PORT alone has been compared with postoperative chemotherapy alone in patients with anaplastic gliomas (i.e., 144 astrocytomas, 91 oligoastrocytomas, and 39 oligodendrogliomas) with crossover to the other modality at the time of tumor progression. Of the 139 patients randomly assigned to radiation therapy, 135 were randomly assigned to chemotherapy with a 32-week course of either PCV or single-agent temozolomide (2:1:1 randomization). The order of the modalities did not affect TTF or OS.[Levels of evidence: 1iiA and 1iiD]. Neither TTF nor OS differed across the treatment arms.