作者
Wei Yuan,Wen Huang,Lili Ren,H Y Liang,Xihao Du,Min Fu,Chenyue Xu,Fang Yu,Kangjie Shen,Ying Hou
摘要
Objective: To investigate the clinicopathological features, treatment and prognosis of gastric intermediate-risk gastrointestinal stromal tumor (GIST), so as to provide a reference for clinical management and further research. Methods: A retrospective observational study of patients with gastric intermediate-risk GIST, who underwent surgical resection between January 1996 and December 2019 at Zhongshan Hospital of Fudan University, was carried out. Results: Totally, 360 patients with a median age of 59 years were included. There were 190 males and 170 females with median tumor diameter of 5.9 cm. Routine genetic testing was performed in 247 cases (68.6%, 247/360), and 198 cases (80.2%) showed KIT mutation, 26 cases (10.5%) showed PDGFRA mutation, and 23 cases were wild-type GIST. According to "Zhongshan Method"(including 12 parameters), there were 121 malignant and 239 non-malignant cases. Complete follow-up data were available in 241 patients; 55 patients (22.8%) received imatinib therapy, 10 patients (4.1%) experienced tumor progression, and one patient (PDGFRA mutation, 0.4%) died. Disease-free survival (DFS) and overall survival rate at 5 years was 96.0% and 99.6%, respectively. Among the intermediate-risk GIST, there was no difference in DFS between the overall population, KIT mutation, PDGFRA mutation, wild-type, non-malignant and malignant subgroups (all P>0.05). However, the non-malignancy/malignancy analysis showed that there were significant differences in DFS among the overall population (P<0.01), imatinib treatment group (P=0.044) and no imatinib treatment group (P<0.01). Adjuvant imatinib resulted in potential survival benefit for KIT mutated malignant and intermediate-risk GIST in DFS (P=0.241). Conclusions: Gastric intermediate-risk GIST shows a heterogeneous biologic behavior spectrum from benign to highly malignant. It can be further classified into benign and malignant, mainly nonmalignant and low-grade malignant. The overall disease progression rate after surgical resection is low, and real-world data show that there is no significant benefit from imatinib treatment after surgery. However, adjuvant imatinib potentially improves DFS of intermediate-risk patients with tumors harboring KIT mutation in the malignant group. Therefore, a comprehensive analysis of gene mutations in benign/malignant GIST will facilitate improvements in therapeutic decision-making.目的: 探讨真实世界中外科手术切除胃中危胃肠间质瘤(gastrointestinal stromal tumor,GIST)的临床病理特征、治疗过程和预后,为今后临床实践的决策和研究提供参考。 方法: 收集复旦大学附属中山医院1996年1月至2019年12月间诊断为胃中危GIST病例,记录临床病理特征、治疗经过和结局。 结果: 360例胃中危GIST,男性190例,女性170例;平均年龄59岁;平均最大径5.9 cm;247例行基因检测(247/360,68.6%),其中KIT突变198例(80.2%)、PDGFRA突变26例(10.5%)、KIT/PDGFRA野生型23例(9.3%);按照12项指标的中山方法,非恶性239例,恶性121例(低度恶性103例,中度恶性15例,高度恶性3例)。获访241例,55例(22.8%)接受伊马替尼辅助治疗。10例进展(进展率4.1%),1例死亡(为PDGFRA突变,病死率0.4%),5年无瘤生存率96.0%,5年总生存率99.6%。此组胃中危GIST中,有无伊马替尼辅助治疗,在总体人群、KIT突变组、PDGFRA突变组、野生型组、非恶性组以及恶性组,无瘤生存率差异均无统计学意义(P>0.05)。但恶性组与非恶性组相比,在总体人群(P<0.01)、伊马替尼治疗组(P=0.044)、无伊马替尼治疗组(P<0.01)无瘤生存率差异均有统计学意义。KIT突变恶性患者,伊马替尼辅助治疗,无瘤生存率潜在获益(P=0.241)。 结论: 胃中危GIST涵盖从良性到高度恶性的异质性生物学行为谱系,不能视为同一危险度的疾病,可进一步良恶性分层,以非恶性和低度恶性为主。外科手术切除总体疾病进展率低,真实世界数据显示术后现有伊马替尼治疗方案无明显获益。KIT基因突变恶性患者辅助治疗潜在延长无瘤生存率,GIST良恶性和基因突变综合分析对临床决策更有帮助。.