胃肠道间质瘤伊马替尼继发耐药的基因状况和治疗策略.docVIP

  胃肠道间质瘤伊马替尼继发耐药的基因状 况和治疗策略 杜春燕* 5 10 15 20 25 30 35 40 45 （复旦大学附属肿瘤医院胃及软组织外科，上海 200032） 摘要：目的 探索伊马替尼继发耐药胃肠道间质瘤的突变规律和治疗策略。 方法 回顾性分 析复旦大学附属肿瘤医院 2003-2011 年共 14 例复发转移伊马替尼继发耐药的晚期胃肠道间 质瘤病例的临床资料，通过测序分析继发耐药病例的 KIT/PDGFRa 基因突变状态。 结果 本 组 14 病例均在手术完整切除原发病灶后，出现复发转移，经伊马替尼治疗后产生继发耐药， 经基因突变分析，采用手术联合靶向治疗等综合治疗方案，多能获得长期带瘤生存（死亡 3 例，生存 11 例，平均生存时间 76.9 月）。本组中检测到二次突变 9 例，二次突变率 64.3% （9/14）。结论 复发转移胃肠道间质瘤伊马替尼治疗后继发耐药多由基因二次突变产生， 根据肿瘤基因突变方式，采取个体化综合治疗，疗效较好。 关键词：胃肠道间质瘤；伊马替尼；继发耐药；二次突变 中图分类号：R6 The study of gene mutations and treatment in the patients with advanced gastrointestinal stromal tumors acquired resistance to imatinib Du Chunyan (Department of Gastric cancer and soft tissue surgery, Cancer hospital, Fudan University, ShangHai 200032) Abstract: Objective To explore the gene mutation and treatment strategy for advanced gastrointestinal stromal tumors (GIST) acquired resistance to imatinib. Methods The clinical data of 14 cases of recurrent and metastatic advanced GIST acquired resistance to imatinib admitted between 2003 and 2011 at Cancer Hospital of Fudan University were analyzed retrospectively, including the data of gene mutation analysis. Results All cases were performed complete resection of primary tumors. Imatinib was taken after tumor recurrence and/or metastasis. All cases got acquired resistance to imatinib. A comprehensive treatment of surgical resection combined with molecularly targeted therapy was employed with considerably effectiveness in all cases. Three case died of tumor progress and the rest 11 cases survived for 76.9 months of the mean existing survival time. In the arm, 9 cases (9/14) were detected the secondary mutation in the KIT and PDGFRa gene. Conclusion For recurrent and metastatic advanced GIST acquired resistance to imatinib, secondary mutation is one of the most important mechanisms. A multidisciplinary approach is an effective treatment strategy which can offer a better prognosis. Keywords: gastrointestinal stromal tumors; imaitnib; imatinib; acquir