Citations

Purpose Patients with 1p/19q codeleted anaplastic oligodendroglial tumors who participated in RTOG (Radiation Therapy Oncology Group) 9402 lived much longer after chemoradiotherapy (CRT) than radiation therapy (RT) alone. However, some patients with noncodeleted tumors also benefited from CRT; survival curves separated after the median had been reached, and significantly more patients lived ≥ 10 years after CRT than RT. Thus, 1p/19q status may not identify all responders to CRT. Patients and Methods Using trial data, we inquired whether an IDH mutation or germ-line polymorphism associated with IDH-mutant gliomas identified the patients in RTOG 9402 who benefited from CRT. Results IDH status was evaluable in 210 of 291 patients; 156 (74%) had mutations. rs55705857 was evaluable in 245 patients; 76 (31%) carried the G risk allele. Both were associated with longer progression-free survival after CRT, and mutant IDH was associated with longer overall survival (9.4 v 5.7 years; hazard ratio [HR], 0.59; 95% CI, 0.40 to 0.86; P = .006). For those with wild-type tumors, CRT did not prolong median survival (1.3 v 1.8 years; HR, 1.14; 95% CI, 0.63 to 2.04; P = .67) or 10-year survival rate (CRT, 6% v RT, 4%). Patients with codeleted mutated tumors (14.7 v 6.8 years; HR, 0.49; 95% CI, 0.28 to 0.85; P = .01) and noncodeleted mutated tumors (5.5 v 3.3 years; HR, 0.56; 95% CI, 0.32 to 0.99; P < .05) lived longer after CRT than RT. Conclusion IDH mutational status identified patients with oligodendroglial tumors who did (and did not) benefit from alkylating-agent chemotherapy with RT. Although patients with codeleted tumors lived longest, patients with noncodeleted IDH-mutated tumors also lived longer after CRT.

Purpose Anaplastic oligodendrogliomas, pure (AO) and mixed (anaplastic oligoastrocytoma [AOA]), are chemosensitive, especially if codeleted for 1p/19q, but whether patients live longer after chemoradiotherapy is unknown. Patients and Methods Eligible patients with AO/AOA were randomly assigned to procarbazine, lomustine, and vincristine (PCV) plus radiotherapy (RT) versus RT alone. The primary end point was overall survival (OS). Results Two hundred ninety-one eligible patients were randomly assigned: 148 to PCV plus RT and 143 to RT. For the entire cohort, there was no difference in median survival by treatment (4.6 years for PCV plus RT v 4.7 years for RT; hazard ratio [HR] = 0.79; 95% CI, 0.60 to 1.04; P = .1). Patients with codeleted tumors lived longer than those with noncodeleted tumors (PCV plus RT: 14.7 v 2.6 years, HR = 0.36, 95% CI, 0.23 to 0.57, P < .001; RT: 7.3 v 2.7 years, HR = 0.40, 95% CI, 0.27 to 0.60, P < .001), and the median survival of those with codeleted tumors treated with PCV plus RT was twice that of patients receiving RT (14.7 v 7.3 years; HR = 0.59; 95% CI, 0.37 to 0.95; P = .03). For those with noncodeleted tumors, there was no difference in median survival by treatment arm (2.6 v 2.7 years; HR = 0.85; 95% CI, 0.58 to 1.23; P = .39). In Cox models that included codeletion status, the adjusted OS for all patients was prolonged by PCV plus RT (HR = 0.67; 95% CI, 0.50 to 0.91; P = .01). Conclusion For the subset of patients with 1p/19q codeleted AO/AOA, PCV plus RT may be an especially effective treatment, although this observation was derived from an unplanned analysis.

Purpose Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are treated with surgery and radiotherapy (RT) at diagnosis, but they also respond to procarbazine, lomustine, and vincristine (PCV), raising the possibility that early chemotherapy will improve survival. Furthermore, better outcomes in AO have been associated with 1p and 19q allelic loss. Patients and Methods Patients with AO and AOA were randomly assigned to PCV chemotherapy followed by RT versus postoperative RT alone. The primary end point was overall survival. The status of 1p and 19q alleles was assessed by fluorescence in situ hybridization. Results Two hundred eighty-nine eligible patients were randomly assigned to either PCV plus RT (n = 147) or RT alone (n = 142). At progression, 80% of patients randomly assigned to RT had chemotherapy. With 3-year follow-up on most patients, the median survival times were similar (4.9 years after PCV plus RT v 4.7 years after RT alone; hazard ratio [HR] = 0.90; 95% CI, 0.66 to 1.24; P = .26). Progression-free survival time favored PCV plus RT (2.6 years v 1.7 years for RT alone; HR = 0.69; 95% CI, 0.52 to 0.91; P = .004), but 65% of patients experienced grade 3 or 4 toxicity, and one patient died. Patients with tumors lacking 1p and 19q (46%) compared with tumors not lacking 1p and 19q had longer median survival times (> 7 v 2.8 years, respectively; P ≤ .001); longer progression-free survival was most apparent in this subset. Conclusion For patients with AO and AOA, PCV plus RT does not prolong survival. Longer progression-free survival after PCV plus RT is associated with significant toxicity. Tumors lacking 1p and 19q alleles are less aggressive or more responsive or both.