Temozolomide for low-grade gliomas - Predictive impact of 1p/19q loss on response and outcome

Objective: To evaluate the predictive impact of chromosome 1p/19q deletions on the response and outcome of progressive low-grade gliomas (LGG) treated with up-front temozolomide (TMZ) chemotherapy. Methods: Adult patients with measurable, progressive LGG ( WHO grade II) treated with TMZ delivered at the conventional schedule (200 mg/m2/day for 5 consecutive days, repeated every 28 days) were retrospectively evaluated for response by central review of MRI-s. Chromosome 1p and 19q deletions were detected by the loss of the heterozygosity technique (LOH). Results: A total of 149 consecutive patients were included in this retrospective, single center observational study. The median number of TMZ cycles delivered was 14 (range 2 to 30). Seventy-seven patients (53%) experienced an objective response (including 22 [15%] cases of partial response and 55 [38%] cases of minor response), 55 (37%) patients had stable disease, and 14 (10%) had a progressive disease. The median time to maximum tumor response was 12 months ( range 3 to 30 months). The median progression-free survival (PFS) was 28 months (95% CI: 23.4 to 32.6). Material for genotyping was available for 86 patients. Combined 1p/19q LOH was present in42% of the cases and was significantly associated with a higher rate ( p = 0.02) and longer objective response to chemotherapy (p = 0.017), and both longer PFS (p = 4.10(-5)) and overall survival (p = 0.04). Conclusion: Low-grade gliomas respond to temozolomide and loss of chromosome 1p/19q predicts both a durable chemosensitivity and a favorable outcome.