Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors characterized byKITorPDGFRAmutations. Over three decades, significant changes in drug discovery and loco-regional (LR) procedures have impacted treatment strategies. We assessed the evolution of treatment strategies for metastatic GIST patients treated in the three national coordinating centers of NetSarc, the French network of sarcoma referral centers endorsed by the National Institute of Cancers, from 1990 to 2018. The primary objective was to describe the clinical and biological profiles as well as the treatment modalities of patients with metastatic GIST in a real-life setting, including access to clinical trials and LR procedures in the metastatic setting. Secondary objectives were to assess (1) patients’ outcome in terms of time to next treatment (TNT) for each line of systemic treatment, (2) patients’ overall survival (OS), (3) evolution of patients’ treatment modalities and OS according to treatment access: <2002 (pre-imatinib approval), 2002–2006 (pre-sunitinib approval), 2006–2014 (pre-regorafenib approval), post 2014, and (4) the impact of clinical trials and LR procedures on TNT and OS in the metastatic setting. 1038 patients with a diagnosis of GIST made in one of the three participating centers between 1990 and 2018 were included in the national prospective database. Among them, 492 patients presented metastasis, either synchronous or metachronous. The median number of therapy lines in the metastatic setting was 3 (range 0–15). More than half of the patients (55%) participated in a clinical trial during the course of their metastatic disease and half (51%) underwent additional LR procedures on metastatic sites. The median OS in the metastatic setting was 83.4 months (95%CI [72.7; 97.9]). The median TNT was 26.7 months (95%CI [23.4; 32.3]) in first-line, 10.2 months (95%CI [8.6; 11.8]) in second line, 6.7 months (95%CI [5.3; 8.5]) in third line, and 5.5 months (95%CI [4.3; 6.7]) in fourth line, respectively. There was no statistical difference in OS in the metastatic setting between the four therapeutic periods (log rank,p= 0.18). In multivariate analysis, age, AFIP Miettinen classification, mutational status, surgery of the primary tumor, participation in a clinical trial in the first line and LR procedure to metastatic sites were associated with longer TNT in the first line, whereas age, mitotic index, mutational status, surgery of the primary tumor and LR procedure to metastatic sites were associated with longer OS. This real-life study advocates for early reference of metastatic GIST patients to expert centers to orchestrate the best access to future innovative clinical trials together with LR strategies and further improve GIST patients’ survival.
胃肠道间质瘤（GIST）是一种罕见的间叶源性肿瘤，其特征为KIT或PDGFRA基因突变。过去三十年间，药物研发和局部区域（LR）治疗手段的重大进展深刻影响了治疗策略。本研究评估了1990年至2018年间，在法国国家癌症研究所认证的肉瘤转诊中心网络（NetSarc）的三个国家级协调中心接受治疗的转移性GIST患者治疗策略的演变。主要目的是在真实世界环境中描述转移性GIST患者的临床和生物学特征以及治疗模式，包括在转移性背景下参与临床试验和接受LR治疗的机会。次要目标包括评估：（1）各线系统治疗中至下次治疗时间（TNT）的患者结局；（2）患者总生存期（OS）；（3）根据治疗可及性时期（2002年前[伊马替尼获批前]、2002-2006年[舒尼替尼获批前]、2006-2014年[瑞戈非尼获批前]及2014年后）分析患者治疗模式和OS的演变；（4）临床试验和LR治疗对转移性背景下TNT和OS的影响。 研究纳入了1990年至2018年间在三个参与中心之一确诊的1038例GIST患者，数据来源于国家前瞻性数据库。其中492例患者存在同步或异时性转移。转移性背景下治疗线数的中位数为3线（范围0-15线）。超过半数患者（55%）在转移性疾病过程中参与了临床试验，半数患者（51%）对转移灶接受了额外的LR治疗。转移性背景下的中位OS为83.4个月（95%CI [72.7; 97.9]）。各线治疗的中位TNT分别为：一线治疗26.7个月（95%CI [23.4; 32.3]）、二线治疗10.2个月（95%CI [8.6; 11.8]）、三线治疗6.7个月（95%CI [5.3; 8.5]）、四线治疗5.5个月（95%CI [4.3; 6.7]）。四个治疗时期之间的转移性背景OS无统计学差异（对数秩检验，p=0.18）。多变量分析显示，年龄、AFIP Miettinen分级、突变状态、原发肿瘤手术、一线参与临床试验以及对转移灶的LR治疗与更长的一线TNT相关；而年龄、核分裂指数、突变状态、原发肿瘤手术以及对转移灶的LR治疗与更长的OS相关。 这项真实世界研究主张，应尽早将转移性GIST患者转诊至专业中心，以统筹规划未来创新性临床试验的最佳参与途径，结合LR治疗策略，从而进一步提升GIST患者的生存预后。
肿瘤(癌症)患者之家