Hassan Imran, You Y Nancy, Shyyan Roman, Dozois Eric J, Smyrk Thomas C, Okuno Scott H, Schleck Cathy D, Hodge David O, Donohue John H
Division of Colon and Rectal Surgery, SIU School of Medicine, 701 N Rutledge, PO Box 19638, Springfield, IL, 67308, USA,
Ann Surg Oncol. 2008 Jan;15(1):52-9. doi: 10.1245/s10434-007-9633-z. Epub 2007 Nov 14.
Tyrosine kinase inhibitors have been shown to have marked clinical efficacy in patients with unresectable or metastatic gastrointestinal stromal tumors (GIST). We performed a comparative and prognostic analysis of our experience with surgically managed GIST to determine factors associated with adverse oncologic outcomes.
Oncologic outcomes of 191 patients with primary GIST surgically managed between 1978 and 2004 at a single institution were reviewed. Prognostic factors were analyzed by Cox analysis (hazard ratio [HR] and 95% confidence interval [95% CI]) and included age, sex, disease presentation (asymptomatic vs. symptomatic), tumor site (stomach, small bowel, colorectal), disease extent (localized vs. metastatic) and risk levels (high, intermediate, low, very-low) assigned on the basis of size and number of mitoses according to current National Institutes of Health recommendations. Primary end points were disease-free survival (DFS) and disease-specific survival (DSS).
A total of 186 patients (97%) had c-kit-positive GIST. There were 54% high, 22% intermediate, 18% low, and 8% very low risk GIST originating from the stomach (54%), small bowel (36%), and colon and rectum (10%). Median patient age was 65 (range, 13-91) years, and 108 subjects (57%) were male. Seventy-two percent of patients had symptomatic local disease, and 21% patients had synchronous metastases. Most (95%) underwent R0 resections of their primary tumor. Among 146 patients (76%) with localized disease at presentation undergoing R0 resection, the 5-year DFS was 65%. High-risk GIST (HR 12, 95% CI, 5-32, P < .0001), symptomatic presentation (HR 2.5, 95% CI, 1.1-6, P = .04), and GIST in the small bowel (HR 2.8, 95% CI, 1-5, P = .003) were independently associated with decreased DFS. After a median follow-up of 63 months among survivors, the 5-year DSS was 68%. High-risk disease (HR 14.3, 95% CI, 5-41, P < .0001), symptomatic presentation (HR 3.1, 95% CI, 1.2-7.9, P = .02), and GIST in the small bowel (2.6,3 95% CI, 1-5, P = .006) were independently associated with decreased DSS.
High-risk GIST are associated with increased disease recurrence and decreased survival despite complete surgical resection. These patients should receive adjuvant therapy in the form of tyrosine kinase inhibitors.
酪氨酸激酶抑制剂已被证明在不可切除或转移性胃肠道间质瘤(GIST)患者中具有显著的临床疗效。我们对手术治疗GIST的经验进行了比较和预后分析,以确定与不良肿瘤学结局相关的因素。
回顾了1978年至2004年在单一机构接受手术治疗的191例原发性GIST患者的肿瘤学结局。通过Cox分析(风险比[HR]和95%置信区间[95%CI])分析预后因素,包括年龄、性别、疾病表现(无症状与有症状)、肿瘤部位(胃、小肠、结直肠)、疾病范围(局限性与转移性)以及根据美国国立卫生研究院当前建议基于大小和有丝分裂数指定的风险水平(高、中、低、极低)。主要终点为无病生存期(DFS)和疾病特异性生存期(DSS)。
共有186例患者(97%)为c-kit阳性GIST。高风险GIST占54%,中风险占22%,低风险占18%,极低风险占8%,起源于胃(54%)、小肠(36%)以及结肠和直肠(10%)。患者中位年龄为65岁(范围13 - 91岁),108例受试者(57%)为男性。72%的患者有症状性局部疾病,21%的患者有同步转移。大多数(95%)患者对其原发性肿瘤进行了R0切除。在146例(76%)初诊为局限性疾病并接受R0切除的患者中,5年DFS为65%。高风险GIST(HR 12,95%CI,5 - 32,P <.0001)、有症状表现(HR 2.5,95%CI,1.1 - 6,P =.04)以及小肠GIST(HR 2.8,95%CI,1 - 5,P =.003)与DFS降低独立相关。在幸存者中进行中位63个月的随访后,5年DSS为68%。高风险疾病(HR 14.3,95%CI,5 - 41,P <.0001)、有症状表现(HR 3.1,95%CI,1.2 - 7.9,P =.02)以及小肠GIST(HR 2.6,95%CI,1 - 5,P =.006)与DSS降低独立相关。
尽管进行了完整的手术切除,但高风险GIST与疾病复发增加和生存率降低相关。这些患者应以酪氨酸激酶抑制剂的形式接受辅助治疗。