Mutation Predicts Benefit From Alkylating Chemotherapy in Oligodendroglial Tumors

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Patients in the Radiation Therapy Oncology Group (RTOG) 9402 study with 1p/19q codeleted anaplastic oligodendroglial tumors had markedly prolonged overall survival after chemoradiotherapy (with procarbazine, lomustine, and vincristine) compared with radiation therapy alone. Some patients with noncodeleted tumors also benefited from chemoradiotherapy. In a study reported in the Journal of Clinical Oncology, Cairncross and colleagues examined whether IDH mutation or germ-line polymorphism associated with IDH-mutant gliomas (rs55705857) identified the patients in RTOG 9402 who benefited from chemoradiotherapy.

IDH status could be ascertained in 210 of 291 patients, with 156 (74%) having mutations; rs55705857 was evaluable in 245 patients, with 76 (31%) carrying the G risk allele. Both alterations were associated with prolonged progression-free survival after chemoradiotherapy, and mutant IDH was associated with significantly prolonged overall survival (9.4 vs 5.7 years, hazard ratio [HR] = 0.59, P = .006).

Chemoradiotherapy vs radiotherapy did not prolong median overall survival (1.3 vs 1.8 years, HR = 1.14, P = .67) or 10-year overall survival (6% vs 4%) in patients with wild-type tumors. Median overall survival was significantly prolonged for chemoradiotherapy vs radiotherapy in patients with codeleted IDH-mutated tumors (14.7 vs 6.8 years, HR = 0.49, P = .01) and those with noncodeleted IDH-mutated tumors (5.5 vs 3.3 years, HR = 0.56, P < .05).

The investigators concluded, “IDH mutational status identified patients with oligodendroglial tumors who did (and did not) benefit from alkylating-agent chemotherapy with [radiotherapy]. Although patients with codeleted tumors lived longest, patients with noncodeleted IDH-mutated tumors also lived longer after [chemoradiotherapy].” ■

Cairncross JG, et al: J Clin Oncol. February 10, 2014 (early release online).




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