初诊手术治疗胃肠间质瘤临床病理特征及预后因素的真实世界研究

A real-world study of clinicopathological characteristics and prognostic factors of gastrointes-tinal stromal tumor with initial surgical resection

  • 摘要:
    目的 探讨初诊手术治疗胃肠间质瘤(GIST)的临床病理特征及预后因素。
    方法 采用回顾性队列研究方法。收集2011年1月至2020年12月天津医科大学肿瘤医院收治的847例初诊手术治疗GIST患者的临床病理资料;男405例,女442例;年龄为(60±10)岁。正态分布的计量资料以x±s表示,组间比较采用t检验。偏态分布的计量资料以M(范围)表示。计数资料以绝对数或百分比表示,组间比较采用χ2检验。等级资料比较采用非参数秩和检验。采用Kaplan⁃Meier法计算生存率。单因素分析采用Log⁃rank检验,多因素分析采用COX回归模型。
    结果 (1)GIST临床病理特征。847例患者中,肿瘤原发部位为胃585例、空肠和回肠142例、十二指肠76例、结直肠10例、食管3例、胃肠道外31例;合并肝转移13例,合并腹腔转移22例;肿瘤最大径为(7±5)cm,核分裂象为4(0~60)个/50高倍视野或5 mm2;美国国立卫生研究院(NIH)危险度分级为极低危31例、低危238例、中危213例、高危365例。847例患者中,CD117阳性839例,Dog-1阳性788例,CD34阳性710例;272例Ki⁃67指数 < 5%,214例为5%~9%,198例为≥10%,163例未知;R0切除814例,非R0切除33例。(2)GIST患者基因检测与术后辅助治疗。①基因检测情况:847例患者中,424例行基因检测,其中2011年、2012年、2013年、2014年、2015年、2016年、2017年、2018年、2019年、2020年基因检测率分别为1.89%(1/53)、9.76%(8/82)、8.45%(6/71)、15.66%(13/83)、50.00%(40/80)、55.26%(42/76)、73.86%(65/88)、68.27%(71/104)、80.65%(75/93)、88.03%(103/117)。424例行基因检测患者中,KIT突变338例,PDGFRA突变31例,野生型55例。②辅助治疗情况:847例患者中,253例行术后辅助治疗,其中低、中、高危患者术后辅助治疗的比例分别为8.82%(21/238)、41.78%(89/213)、39.18%(143/365)。578例中高危患者中,2011年、2012年、2013年、2014年、2015年、2016年、2017年、2018年、2019年、2020年术后辅助治疗比例分别为15.15%(5/33)、14.71%(10/68)、22.45%(11/49)、29.09%(16/55)、41.38 %(24/58)、46.15%(24/52)、32.81%(21/64)、60.00%(45/75)、60.42%(29/48)、61.84%(47/76)。253例术后辅助治疗患者中,247例接受伊马替尼治疗、6例接受舒尼替尼治疗。(3)非胃来源和胃来源GIST临床病理特征的比较。847例患者中,非胃来源和胃来源GIST分别为262例和585例,两者性别、肿瘤数目、肿瘤最大径、Ki-67指数、NIH危险度分级、R0切除比较,差异均有统计学意义(χ2=8.62、8.40、12.97、6.57,Z=-6.15,χ2=17.19,P < 0.05)。(4)GIST患者无复发生存率的影响因素分析。多因素分析结果显示:初诊年度、原发部位、肿瘤最大径、核分裂象、NIH危险度分级、R0切除、基因检测、术后辅助治疗是影响初诊手术治疗GIST患者无复发生存率的独立因素(风险比=0.58,0.61,2.00,1.71,5.81,2.56,0.65,0.38,95%可信区间为0.39~0.85,0.45~0.83,1.46~2.74,1.24~2.35,3.16~10.69,1.63~4.02,0.46~0.94,0.25~0.56,P < 0.05)。
    结论 初诊手术治疗GIST部位以胃多见,CD117和Dog-1阳性率高。GIST行基因检测和靶向治疗的人数逐年增加。非胃来源和胃来源GIST的临床病理特征及预后不同。初诊年度、原发部位、肿瘤最大径、核分裂象、NIH危险度分级、R0切除、基因检测、术后辅助治疗是影响初诊手术治疗GIST无复发生存率的独立因素。

     

    Abstract:
    Objective To investigate the clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumor (GIST) with initial surgical resection.
    Methods The retro-spective cohort study was conducted. The clinicopathological data of 847 GIST patients who under-went initial surgical resection in Tianjin Medical University Cancer Institute & Hospital from January 2011 to December 2020 were collected. There were 405 males and 442 females, aged (60±10)years. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the nonparameter rank sum test. The Kaplan-Meier method was used to calculate survival rates. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX regression model.
    Results (1) Clinicopatholo-gical characteristics. Of 847 patients, the tumor primary location was stomach in 585 cases, jejunum and ileum in 142 cases, duodenum in 76 cases, colorectum in 10 cases, esophagus in 3 cases, and extra-gastrointestinal in 31 cases. There were 13 cases with liver metastasis and 22 cases with abdominal metastasis. The tumor maximum diameter was (7±5)cm, and the number of nuclear divisions was 4(range, 0-60) cells/50 high-power field or 5 mm2. According to risk classification of National Institutes of Health (NIH), 31 cases were of extremely low risk, 238 cases were of low risk, 213 cases were of moderate risk, 365 cases were of high risk. There were 839 of 847 patients positive for CD117, 788 cases positive for Dog-1, 710 cases positive for CD34, respectively. There were 272 cases with Ki-67 < 5%, 214 cases with Ki-67 of 5%- 9%, 198 cases with Ki-67 ≥10%, 163 cases with missing data. R0 resection was in 814 cases and non-R0 resection was in 33 cases. (2) Gene testing and postoperative adjuvant therapy of GIST patients. ① Gene testing. Of 847 patients, 424 underwent genetic testing. The proportion of genetic testing was 1.89%(1/53) in 2011, 9.76%(8/82) in 2012, 8.45%(6/71) in 2013, 15.66%(13/83) in 2014, 50.00%(40/80) in 2015, 55.26%(42/76) in 2016, 73.86%(65/88) in 2017, 68.27%(71/104) in 2018, 80.65%(75/93) in 2019, 88.03%(103/117) in 2020, respectively. Of 424 with genetic testing, 338 cases had KIT mutation, 31 cases had PDGFRA mutation, 55 cases were wild type. ② Adjuvant therapy. Of 847 patients, 253 patients underwent postoperative adjuvant therapy. The proportions of postoperative adjuvant therapy were 8.82%(21/238), 41.78%(89/213), 39.18%(143/365) in patients of low risk, moderate risk, high risk. Of 578 patients with moderate to high risk, the proportion of postoperative adjuvant therapy was 15.15%(5/33) in 2011, 14.71%(10/68)in 2012, 22.45%(11/49) in 2013, 29.09%(16/55) in 2014, 41.38%(24/58) in 2015, 46.15%(24/52) in 2016, 32.81%(21/64)in 2017, 60.00%(45/75) in 2018, 60.42%(29/48) in 2019, 61.84%(47/76) in 2020, respectively. Of 253 patients underwent postoperative adjuvant therapy, 247 cases received imatinib had 6 cases received sunitinib. (3) Comparison of clinicopathological characteristics of GIST with non-gastric origin and gastric origin. Of 847 patients, 262 cases had non-gastric origin and 585 cases had gastric origin. There were significant differences in gender, the number of tumor, tumor maximum diameter, Ki⁃67 index, risk classification of NIH, and R0 resection between the two groups (χ2=8.62, 8.40, 12.97, 6.57, Z=-6.15, χ2=17.19, P < 0.05). (4) Analysis of influencing factors for recurrence-free survival rate in GIST patients. Results of multivariate analysis showed that the year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classification of NIH, R0 resection, genetic testing and postoperative adjuvant therapy were independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection (hazard ratio=0.58, 0.61, 2.00, 1.71, 5.81, 2.56, 0.65, 0.38, 95% confidence interval as 0.39-0.85, 0.45-0.83, 1.46-2.74, 1.24-2.35, 3.16-10.69, 1.63-4.02, 0.46-0.94, 0.25-0.56, P < 0.05).
    Conclusions GIST with initial surgical resection is common located in stomach, with high positive rate in CD117 and Dog-1. The number of people undergoing genetic testing and targeted therapy for GIST is increasing year by year. There are significant differ-ences in clinicopathological characteristics between GIST with non-gastric origin and gastric origin. The year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classifica-tion of NIH, R0 resection, genetic testing and postoperative adjuvant therapy are independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection.

     

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