Kaloshi G, Benouaich-Amiel A, Diakite F, Taillibert S, Lejeune J, Laigle-Donadey F, Renard M-A, Iraqi W, Idbaih A, Paris S, Capelle L, Duffau H, Cornu P, Simon J-M, Mokhtari K, Polivka M, Omuro A, Carpentier A, Sanson M, Delattre J-Y, Hoang-Xuan K
Service de Neurologie Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris Cedex 13, France.
Neurology. 2007 May 22;68(21):1831-6. doi: 10.1212/01.wnl.0000262034.26310.a2.
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.
Adult patients with measurable, progressive LGG (WHO grade II) treated with TMZ delivered at the conventional schedule (200 mg/m(2)/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).
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 in 42% 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).
Low-grade gliomas respond to temozolomide and loss of chromosome 1p/19q predicts both a durable chemosensitivity and a favorable outcome.
评估1p/19q染色体缺失对初治替莫唑胺（TMZ）化疗的进展性低级别胶质瘤（LGG）的反应和预后的预测影响。
回顾性评估按常规方案（200mg/m²/天，连续5天，每28天重复）接受TMZ治疗的可测量、进展性LGG（世界卫生组织二级）成年患者的MRI，通过中心审查评估反应。采用杂合性缺失技术（LOH）检测1p和19q染色体缺失。
本回顾性单中心观察性研究共纳入149例连续患者。TMZ化疗周期的中位数为14个（范围2至30个）。77例患者（53%）出现客观反应（包括22例[15%]部分缓解和55例[38%]轻微反应），55例（37%）患者疾病稳定，14例（10%）患者疾病进展。达到最大肿瘤反应的中位时间为12个月（范围3至30个月）。中位无进展生存期（PFS）为28个月（95%CI：23.4至32.6）。86例患者有基因分型材料。42%的病例存在1p/19q联合LOH，且与更高的化疗客观反应率（p = 0.02）、更长的化疗客观反应时间（p = 从0.017）、更长的PFS（p = 4.10(-5)）和总生存期（p = 0.04）显著相关。
低级别胶质瘤对替莫唑胺有反应，1p/19q染色体缺失预示着持久的化疗敏感性和良好的预后。
