酪氨酸激酶抑制剂联合手术治疗转移性胃肠间质瘤

Efficacy of tyrosine kinase inhibitor therapy combined with surgical resection in patients with metastatic gastrointestinal stromal tumor

目的 探讨酪氨酸激酶抑制剂（TKI）甲磺酸伊马替尼或舒尼替尼联合手术治疗晚期转移性胃肠间质瘤（GIST）的临床疗效.方法 回顾分析中山大学附属第一医院2007年6月至2009年12月接受TKI治疗后进行手术治疗的转移性GIST患者临床病理资料.结果 共计15例转移性GIST患者在TKI治疗后接受肿瘤切除手术.术前TKI治疗反应分别为疾病控制6例（40.0%）,局限性进展4例（26.7%）,全面性进展5例（33.3%）.手术相关并发症发生率20.0%.全组患者中位无进展生存期18.7个月.其中疾病控制和局限性进展组患者术后无进展中位生存期25.0个月,全面性进展组则仅为3.0个月（P＜0.01）;疾病控制和局限性进展组患者至今仍全部存活,而全面性进展组患者中位总生存期为10.5个月（P＜0.01）.结论 靶向治疗后,疾病控制或局限性进展的晚期转移性GIST患者行手术治疗安全有效,而全面性进展患者手术治疗不能改善其预后,应谨慎选择.

Objective To investigate the clinical effect of surgery following systemic targeted therapy of tyrosine kinase inhibitors （TKIs） in patients with metastatic gastrointestinal stromal tumors （GIST）. Methods From June 2007 to December 2009, data of 15 consecutive patients with metastatic GIST treated with imatinib/sunitinib followed by surgery were retrospectively analyzed. Results Disease responses to TKI treatment was categorized into controlled disease （including partial response and stable disease）（6. 40.0%）, limited progression（4, 26.7%）, and generalized progression（5, 33.3%）, respectively. Surgeries were performed after mean 12 months following TKI therapies. Gross complete resection or optimal debulking with minimal residual disease were managed to performed in 8/10 patients with disease controlled and limited progression, while optimal debulking only achieved in 2/5 patients with generalized progression. Surgical morbidity was 20.0% （3/15）. After operation, patients with disease controlled and limited progression had a median progression-free survival of 25.0 months and 2-year overall survival rate of 100%. In contrast, for patients with generalized progression, the median progression- free survival was 3 months （P 〈0.01）, and median overall survival 10.5 months. Conclusions Patients with metastatic GIST who have controlled disease or limited progression to TKI therapy can benefit from surgical resection. Surgery should be selective in patients with generalized progression since surgery hardly improves survival in these patients.