晚期肠源性间质瘤临床特征和伊马替尼疗效分析

Clinical features and efficacy of imatinib in patients with advanced gastrointestinal stromal tumors

目的 探讨肠源性间质瘤的临床特征及伊马替尼治疗的疗效和预后因素。方法 回顾性分析肠源间质瘤85例,根据原发部位将全组病例分为十二指肠组12例,小肠组64例,结直肠组9例。均行起始剂量400mg·d^-1的甲磺酸伊马替尼口服治疗。客观疗效用Logistic回归分析,生存分析用Kaplan-Meier法,预后多因素分析用Cox回归模型。结果 患者的性别、年龄和ECOG评分等因素对三组基线水平的影响差异无统计学意义。全组中共75例可评价疗效,其中CR10例（13.3%）、PR44例（58.7%）、SD16例（21.3%）、PD5例（6.7%）,RR为72.0%,DCR为90.3%。三组RR和DCR的差异无统计学意义。Logistic回归分析显示患者性别差异能够影响伊马替尼的疗效,女性患者应用伊马替尼能够取得更好的临床效果。全组患者的中位PFS为51.5个月,中位OS为62.0个月。1、2、3、5年生存率分别为93.8%、83.4%、79.2%和54.1%。十二指肠组、小肠组和结直肠组的中位PFS分别为23.0、51.5和58.5个月,中位OS分别为59.5、63.5和62.5个月。十二指肠组的PFS显著低于其余两组（P=0.034）,但三组的OS差异无统计学意义（P=0.643）。肿瘤来源于十二指肠、肝转移、年龄〈65岁和获RR是影响PFS的独立因素;单纯肝转移是影响OS的独立因素。三组患者接受伊马替尼治疗后出现的主要不良反应主要为水肿、白细胞减少、腹泻、皮肤反应等。不良反应多为1-2级,3-4级少见,患者耐受性良好。各组不良反应仅呕吐和肾功能存在差异,其他均差异无统计学意义。结论 接受伊马替尼治疗可显著改善晚期肠源GIST患者的OS和PFS,十二指肠来源GIST的PFS明显低于小肠和结直肠来源GIST,肿瘤的原发部位、年龄和是否肝转移是影响患者生存的主要因素。

Objective To investigate the clinical features of gastrointestinal stromal tumors（GIST）,and to analyze the related charac-teristics of the curative effect of imatinib treatment and the prognostic factors.Methods Data of 85 advanced GIST patients were ret-rospectively analyzed,who were treated at The First Affiliated Hospital of Anhui Medical University,and The Second Affiliated Hospi-tal of Anhui Medical University from January 2004 to January 2016.,According to the primary sites,patients were assigned into 3 groups：duodenum group（n =12）,small intestine group（n =64）and colon group（n =9）.All patients were given imatinib mesylate orally with an initial dose of 400 mg per day.The efficacy,survival and prognosis were analyzed with Logistic regression model,Kap-lan-Meier method and Cox regression model,respectively.Results There were no significant differences in the influence of gender, age and ECOG score on baseline patients’characteristics among the three groups.Totally 75 cases were evaluated for curative effect, of which 10 cases（13.3%）achieved CR,44 cases（58.7%）PR,16 cases（21.3%）SD,and 5 cases（6.7%）PD.RR and DCR were 72.0% and 90.3%,respectively.There were no statistical differences in RR and DCR among the 3 groups.According to the Logistic regression model analysis,the gender differences could affect the clinical efficacy of imatinib,and the female patients treated with imatinib could achieve a better clinical outcome.The median progression-free survival（PFS）and median overall survival（OS） of all patients were 51.5 months and 62.0 months,respectively.The 1-year,2-year,3-year and 5-year survival rates were 93.8%, 83.4%,79.2% and 54.1%,respectively.The PFS of duodenum group,small intestine group and colon group were 23.0,51.5 and 58.5 months,respectively.The median OS of duodenum group,small intestine group and colon group were 59.5,63.5 and 62.5 months,respectively.However,the PFS in duodenum group was significantly lower than that in the other two groups（P =0.034）. There was no statistical difference in the OS among the three groups（P =0.643）.According to the Cox proportional hazards regres-sion model analysis,GIST originated from the duodenum,the liver metastasis,the age under 65 and RR were the independent factors affecting the PFS.The liver metastasis was the independent factor affecting the OS.The main adverse reactions of three groups of pa-tients after receiving imatinib therapy were edema,leukopenia,diarrhea,and skin reaction.The adverse reactions were mainly 1 -2 grade,and 3 to 4 grades were rare and well tolerated.There were no statistical differences in adverse reactions among the 3 groups ex-cept for in vomiting and renal function.Conclusions The OS and PFS can be significantly prolonged after imatinib mesylate therapy in advanced gastrointestinal stromal tumor patients.The PFS in duodenum group is significantly lower than that in small intestine group and colon group.The original location of GIST,age,and liver metastasis are the main factors affecting the survival of GIST pa-tients.