摘要
目的分析和探索中国胃肠间质瘤(GIST)的疾病特征以及诊断和治疗的历史变迁。方法中国胃肠间质瘤研究组(CN-GIST)选取国内4家大容量的医疗中心,收集并检索自1998年1月1日至2015年12月31日18年期间所收治的GIST患者的临床病理资料并进行回顾性分析。采用Kaplan—Meier法绘制生存曲线,采用Life Table计算累计生存率,生存率组间比较采用Logrank检验。结果4家医疗中心18年期间共收治2610例GIST患者,其中广州中山大学肿瘤防治中心667例(25.6%),武汉华中科技大学附属协和医院754例(28.9%),广州南方医科大学南方医院692例(26.5%),广东省人民医院497例(19.0%)。男性1394例,女性1216例,男女比例1.15:1.00,年龄18~95(中位数58.0)岁。按照每3年为一个时间段,将18年分为6个时间段,新接收患者病例数量逐渐增长,分别为1998-2000年13例(0.5%);2001-2003年68例(2.6%);2004-2006年256例(9.8%);2007-2009年517例(19.8%);2010-2012年814例(31.2%);2013-2015年942例(36.1%)。肿瘤原发部位位于食管50例(1.9%),胃1686例(64.6%),十二指肠206例(7.9%),空肠和回肠446例(17.1%),结直肠133例(5.1%),胃肠道外GIST89例(3.4%)。就诊时肿瘤局限于原发部位者2404例(92.1%),复发转移206例(7.9%);复发转移的患者中,肝转移126例(61.2%),腹腔和(或)盆腔转移64例(31.1%),肝转移加腹腔和(或)盆腔转移12例(5.8%),其他部位转移4例(1.9%)。全组有352例患者进行了基因检测,其中2004-2006年只有1例(0.4%,1/256).2007-2009年有7例(1.4%,7/517),2010-2012年有150例(18.4%,150/814),2013-2015年有194例(20.6%,194/942);原发突变位点位于c-Kit外显子9者占8.5%(30/352),外显子11者占68.8%(242/352),外显子13者占1.1%(4/352),外显子17者占0.6%(2/352);PDGFRA外显子12突变者占0.9%(3/352),外显子18突变者占5.7%(20/352);有51例(14.5%)c-Kit及PDGFRA检测均未发现突变。全组共有2202例接受手术治疗,其中根治性切除2038例(92.6%),姑息性切除164例(7.4%)。根治性切除患者的NIH危险度分期构成:极低危450例(22.1%),低危593例(29.1%),中危283例(13.9%),高危712例(34.9%)。995例NIH危险度分级为中高危患者中有550例(55.3%)术后接受了伊马替尼辅助治疗,接受辅助治疗患者的比例按本研究划分的6个时间段分别为0、42.8%(12/28)、19.8%(20/101)、9.8%(21/215)、65.7%(176/268)和85.6%(321/375)。复发转移的206例GIST患者中,200例(97.1%)接受了伊马替尼一线治疗,22例(10.7%)接受了舒尼替尼二线治疗。具有完整随访资料的患者共计1743例(66.8%),中位随访时间35.9(0.1~173.8)月。极低危、低危、中危及高危患者其5年总体生存率分别为100%、97%、95%和78%。结论本研究为国内GIST研究提供了最大宗数据资料,揭示了中国在过去的18年间GIST疾病特征和诊断治疗的历史变迁,为进一步前瞻性研究提供了可靠的基础数据。
Objective To elucidate the historic and current diagnosis and treatment status of gastrointestinal stromal tumor (GIST) in the Chinese population based on four high volume databases. Methods Clinicopathological data of GIST patients with follow-up information between January 1998 and December 2015 from Sun Yat-sen University Cancer Center, Union Hospital of Huazhong University of Science and Technology, Southern Medical University Nanfang Hospital and Guangdong General Hospital were retrospectively analyzed. Kaplan-Meire method was used to draw survival curve. The accumulative survival rate was calculated by life table method. Comparison of survival rate among groups was examined by Log-rank test. Results A total of 2 610 cases were enrolled into the study, including 667(25.6%) cases from Sun Yat-sen University Cancer Center, 754(28.9%) cases from Union Hospital of Huazhong University of Science and Technology, 692 (26.5%) cases from Southern Medical University Nanfang Hospital and 497 (19.0%) cases from Guangdong General Hospital. There were 1 394 male and 1 216 female cases with the ratio of 1.15 to 1.00. The age of patients was from 18 to 95 (median 58.0) years old. Three-year was used as a time stage, then 18 years were divided into 6 stages. New GIST patients increased gradually year by year. There were 13 (0.5%) cases during 1998 to 2000, 68(2.6%) cases during 2001 to 2003, 256(9.8%) cases during 2004 to 2006, 517 (19.8%) cases during 2007 to 2009, 814 (31.2%) cases during 2010 to 2012, and 942 (36.1%) cases during 2013 to 2015. Primary GIST sites were esophagus in 50 (1.9%) cases, stomach in 1 686 (64.6%) cases, duodenum in 206 (7.9%) cases, jejunum and ileum in 446 (17.1%) cases, colon and rectum in 133 (5.1%) cases, and non-gastrointestinal tract in 89 (3.4%) cases. GIST lesions of 2 404(92.1%) cases located in the primary sites and relapse/metastasis occurred in 206 cases when consulting. Among 206 relapse/metastasis cases, liver metastasis was found in 126 (61.2%) cases, abdominal cavity/ pelvic cavity metastasis in 64 (31.1%) cases, liver plus abdominal cavity/pelvic cavity metastasis in 12 (5.8%) cases, and other site metastasis in 4 (1.9%) cases. Among all the patients, 352 received gene detection, including 1 (0.4%) during 2004 to 2006, 7 (1.4%) during 2007 to 2009, 150 (18.4%) during 2010 to 2012, and 194 (20.6%) during 2013 to 2015. Most of the primary oncogenic mutational site occurred in c-Kit, including 30 (8.5%) cases in exon 9, 242 (68.8%) eases in exon 11, 4 (1.1%) cases in exon 13, 2 (0.6%) cases in exon 17, while 3 (0.9%) cases in PDGFRA exon 12 and 20 (5.7%) cases in PDGFRA 18, besides, no mutations of KIT and PDGFRA were detected in 51 (14.5%) cases. A total of 2 202 cases underwent operation, including 2 038 (92.6%) of radical resection and 164 (7.4%) of palliative resection. Among 2 038 patients undergoing radical resection, 450 (22.1%) cases were very low risk, 593 (29.1%) cases were low risk, 283 (13.9%) eases were moderate risk and 712 (34.9%) cases were high risk according to NIH risk classification. Of 995 patients with moderate and high risk, 550 (55.3%) cases received postoperative imatinib adjuvanttherapy, whose ratio in above 6 time stages was as follows: O, 42.8% (12/28), 19.8% (20/101), 9.8% (21/215), 65.7% (176/268) and 85.6% (321/375). Of 206 relapse/metastasis patients, 200 (97.1%) cases received imatinib as the first-line therapy, and 22 (10.7%) received sunitinib as the second-line therapy. A total of 1 743 patients had complete follow-up data and median follow-up time was 35.9 (0.1 to 173.8) months. The 5-year overall survival rates in very low, low, moderate and high risk patients were 100%, 97%, 95% and 78% respectively. Conclusion This retrospective study provides the largest data of GIST and indicates the historic changes of clinicopathological characteristics, diagnosis and treatment of GIST for further domestic GIST research.
出处
《中华胃肠外科杂志》
CAS
CSCD
北大核心
2016年第11期1265-1270,共6页
Chinese Journal of Gastrointestinal Surgery
基金
国家自然科学基金(81372474,81602061)
广州市科技计划(2014J4100179)
关键词
胃肠间质瘤
肿瘤分期
诊断
治疗
预后
Gastrointestinal stromal tumor
Staging
Diagnosis
Treatment
Prognosis