周彩存晚期非小细胞肺癌内科治疗个体化.pptVIP

晚期非小细胞肺癌内科治疗的个体化 同济大学附属上海市肺科医院 周彩存 晚期非小细胞肺癌的治疗现状 Platinum-based doublets improve overall survival Prolonged chemotherapy more than 3-4 cycles could not further improve efficacy Doublets plus avastin or cetuximab improve overall survival compared with doublets Chemotherapy could improve disease-related symptoms Chemotherapy has toxicities Advanced lung cancer could not be cured and our aim is to make it chronic disease 个体化治疗 Definition - 4R: Right agent, right dose, right patients and right timing - Biomarkers：predictive, prognostic - Purpose: improvement of efficacy of therapy Advantages？ -Informative treatment strategy -Better treatment outcome -Less risk of toxicities -Decrease in cost 我院开展的晚期NSCLC药物基因组学个体化研究 ERCC1 RRM1 BRCA1 SNP of DNA repair genes ERCC1和XRCC3基因多态性在晚期接受含铂方案化疗病人中的疗效预测作用 Published in JJCO 研究方案及流程 Taqman探针结合实时荧光PCR方法与直接测序法一致 基线特征及SNP分布 Genotyping Male Female Age Adeno Squam St IIIB St IV Total 56.9% 43.1% 61 62.3% 37.7% 30.8% 69.2% ERCC1 118 C/C 53.6% 46.4% 61 57.1% 42.9% 28.9% 71.1% 118 C/T+ T/T 63.0% 37% 60 71.7% 28.3% 34.8% 65.2% XRCC3 241 C/C 56.8% 43.2% 61 59.5% 40.5% 34.2% 65.8% 241 C/T+T/T 52.6% 47.4% 60 78.9% 21.1% 10.5% 89.5% Adeno=adenocarcinoma, Squam=squamous cell carcinoma, St= Stage SNP与化疗疗效的关系 Genotyping Number PR SD PD Total 130 20% 65.4% 14.6% ERCC1 Wild-type 84 19% 65.5% 15.5% Mutant 46 21.7% 65.3% 13.0% XRCC3 Wild-type 111 19.8% 64% 16.2% Mutant 19 21.1% 77.6% 5.3% 多因素回归分析 ERCC1 mRNA表达水平对NSCLC一线接受含铂双药治