复发或转移胃肠间质瘤再次手术患者的临床特点及预后因素分析

Analysis of clinical features and prognostic factors on reoperation patients with postoperative recurrence or metastasis of gastrointestinal stromal tumor

目的探讨复发或转移胃肠间质瘤(GIST)再次手术患者的临床特点和预后影响因素。方法回顾性收集上海交通大学医学院附属瑞金医院2003年2月至2016年1月首次手术后出现复发或转移,并行再次或多次手术的31例GIST患者的临床资料进行回顾性病例对照研究。分析本组患者的临床特点,并采用Kaplan-Meier生存曲线计算生存率,采用Cox单因素和多因素回归模型进行预后分析。结果本组患者首次手术年龄35~78(中位数49)岁,其中男性17例(54.8%),女性14例(45.2%),肿瘤位于小肠21例(67.7%)、胃2例(6.5%)、结直肠4例(12.9%)以及其他部位4例(12.9%)。根据NIH标准进行风险程度评估:高度风险26例(83.9%),中度风险3例(9.7%),低风险2例(6.5%)。首次手术后全组患者中有15例按NCCN指南规范服用靶向药物伊马替尼,1O例患者不规律服药,6例患者未服药。R0切除29例(93.5%),R1或R2切除2例(6.5%)。首次术后出现复发时间中位数为32.3(5.2-117.6)个月,复发患者中位年龄56岁。28例(90_3%)复发部位位于肝脏及原部位,1例(3.2%)复发于大网膜,2例(6.5%)位于盆腔。复发后二次手术肿瘤直径中位数为6.5cm,R0切除23例(74.2%),R1或R2切除8例(25.8%)。20例(64.5%)发现复发后直接手术,11例(35.5%)行伊马替尼或舒尼替尼治疗后再行手术。全组患者中有29例(93.5%)成功随访,随访时间为7.3~160.3(中位数49.5)个月。二次手术后全组患者无复发生存期为3.2~148.6(中位数29.7)个月。至随访日期,全组患者有9例患者因肿瘤复发而死亡,20例存活患者中有8例患者带瘤生存,1例患者行第3次手术;全组患者总生存时间为6.2-160.3(中位数38.4)个月。首次手术后进行规律靶向治疗的15例患者5年无复发生存率和5年总生存率分别为73.4%和81.7%,均明显高于未进行规范靶向治疗16例患者的37.6%和38.9%,两者差异均有统计意义(分别为P=0.015,P=0.023);复发肝转移或合并肝转移的11例患者其5年无复发生存率和5年总生存率分别为29.8%和33.2%,均明显低于未合并肝转移20例患者的79.1%和88.1%,两者差异均有统计意义(均P<0.001)。将以上因素纳入Cox模型中进行总体生存的多因素分析,结果显示,首次术后进行规律靶向治疗(HR=0.362,95%CI:0.210~1.074,P=0.089)以及存在肝转移(HR:5.342,95%CI:0.902~12.580,P=0.057)均不是影响预后的独立因素。结论复发或转移胃肠间质瘤首次术后规范靶向药物治疗能提高复发后再次手术患者的预后;若患者首次术后出现肝转移,则预后较差。

Objective To investigate the clinical characteristics and prognostic factors of reoperation patients with postoperative recurrence or metastasis of gastrointestinal stromal tumor (GIST). Methods A retrospective case-control study was performed on the clinical data of 31 patients with GIST who had recurrence or metastasis after the first surgery and underwent one or more operations again from February 2003 to January 2016 at Ruijin Hospital, Shanghai Jiaotong University School of Medicine. The clinical characteristics of these patients were analyzed. Kaplan-Meier survival curve was used to calculate the survival rate, Cox univariate and multivariate regression model was applied to prognosis analysis. Results Age of these 31 patients at the first operation was 35-78 (median 49) years, including 17 males (54.8%) and 14 females (45.2%). The tumors of 21 cases located in small intestines (67.7%), 2 cases in stomach (6.5%), 4 cases (12.9% ) in colorectum and of 4 cases (12.9%) in other sites. According to NIH criteria, risk assessment indicated 26 cases were (83.8%) with high risk, 3 cases (9.7%) with moderate risk, and 2 cases (6.5%) with low risk. After the first operation, 15 cases received the IM (imatinib) therapy regularly based on NCCN guideline,10 cases received the therapy irregularly, and the other 6 cases did not receive the therapy. R0 resection was performed in 29 cases (93.5%) and R1/R2 resection was performed in 2 cases (6.5%). The median interval between the first operation to the recurrence was 32.3 (5.2-117.6) months and the median age of recurrence was 56 years old. Refer to the recurrent location, 28 cases (90.3%) were found in the same location or liver, 1 case in greater omentum, and 2 cases in pelvic cavity. The median diameter of the tumor in reoperation was 6.5 cm. Twenty-three cases (74.2%) received R0 excision and the other 8 cases(25.8%) received R1/R2 excision. At diagnosis of tumor recurrence, 20 cases (64.5%) received the second surgery immediately and the other 11 cases received surgery after imatinib or sunitinib treatment. Twenty-nine (93.5%) patients were followed up for 7.3 to 160.3 (median 49.5) months. After the second surgery, the relapse-free survival (RFS) of the whole group was 3.2 to 148.6(median: 29.7) months. Till the end of follow-up, 9 cases died of recurrence. Among 20 alive cases, 8 cases were living with the tumor, 1 case received the third surgery. The median overall survival (OS) time was 38.4 (6.2-160.3) months. The 5-year RFS and the 5-year OS of 15 cases who received regular targeted therapy after the first operation were 73.4% and 81.7% respectively, significantly higher than those of the other 16 cases who received irregular or no targeted therapy(37.6%, P=0.015 and 38.9%,P=0.023, respectively). The 5-year RFS rate and the 5-year OS rate of the 11 patients who were diagnosed or complicated with liver metastasis were 29.8% and 32.2% respectively, which were significantly lower than those of the 20 patients without liver metastasis (79.1% and 88.1% respectively, both P<0.001). Cox model for OS, the results showed that regular targeted therapy after first surgery (HR=0.362, 95%CI:0.210-1.074, P=0.089) and the liver metastasis (HR=5.342, 95%CI: 0.902-12.580, P=0.057) were not the independent risk factors. Conclusions Regular targeted therapy according to the guideline after the first operation for GIST patients with recurrence or metastasis may improve the prognosis. Prognosis of GIST patients with postoperative liver metastasis is poor.