Weldon Christopher B, Madenci Arin L, Boikos Sosipatros A, Janeway Katherine A, George Suzanne, von Mehren Margaret, Pappo Alberto S, Schiffman Joshua D, Wright Jennifer, Trent Jonathan C, Pacak Karel, Stratakis Constantine A, Helman Lee J, La Quaglia Michael P
Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
J Clin Oncol. 2017 Feb 10;35(5):523-528. doi: 10.1200/JCO.2016.68.6733. Epub 2016 Dec 28.
Purpose Wild-type gastrointestinal stromal tumors (WT-GISTs) that lack KIT or PDGFRA mutations represent a unique subtype of GIST that predominantly affects children. We sought to determine the effect on event-free survival (EFS) of staging variables, extent of resection, and repeat resection of tumors. Methods In 2008, a WT-GIST clinic was established at the National Cancer Institute, allowing the development of a large clinical database. We included participants who underwent resection of WT-GIST. Associations with EFS (ie, freedom from disease progression or recurrence) were evaluated using the Kaplan-Meier method and Cox proportional hazards modeling. Results Among 76 participants with WT-GISTs, the median follow-up was 4.1 years. Overall EFS (± SE) was 72.6 ± 5.4% at 1 year, 57.6 ± 6.2% at 2 years, 23.7 ± 6.0% at 5 years, and 16.3 ± 5.5% at 10 years postoperatively. Hazard of disease progression or recurrence was significantly increased for patients with metastatic disease (adjusted hazard ratio [AHR], 2.3; 95% CI, 1.0 to 5.1; P = .04) and > 5 mitoses per 50 high-power fields (AHR, 2.5; 95% CI, 1.1 to 6.0; P = .03), whereas there was no significant effect of negative microscopic resection margins (AHR, 0.9; 95% CI, 0.4 to 2.2; P = 0.86). There was no association between type of gastric resection (ie, anatomic v partial/wedge) and EFS ( P = .67). Repeated resection after the initial resection was significantly associated with decreasing postoperative EFS ( P < .01). Five patients (6%) died after initial enrollment in 2008. Conclusion WT-GIST is an indolent disease, and most patients survive with disease progression. We found no improvement in EFS with more extensive or serial resections. Disease progression or recurrence may be more closely related to tumor biology than surgical management. These data suggest that resections for WT-GISTs be restricted to the initial procedure and that subsequent resections be performed only to address symptoms such as obstruction or bleeding.
目的 缺乏KIT或PDGFRA突变的野生型胃肠道间质瘤(WT-GISTs)是GIST的一种独特亚型,主要影响儿童。我们试图确定分期变量、切除范围和肿瘤重复切除对无事件生存期(EFS)的影响。方法 2008年,美国国立癌症研究所设立了WT-GIST诊所,从而建立了一个大型临床数据库。我们纳入了接受WT-GIST切除的参与者。使用Kaplan-Meier方法和Cox比例风险模型评估与EFS(即无疾病进展或复发)的相关性。结果 在76例WT-GIST患者中,中位随访时间为4.1年。术后1年的总体EFS(±标准误)为72.6±5.4%,2年时为57.6±6.2%,5年时为23.7±6.0%,10年时为16.3±5.5%。转移性疾病患者疾病进展或复发的风险显著增加(调整后的风险比[AHR],2.3;95%可信区间[CI],1.0至5.1;P = 0.04),每50个高倍视野有>5个有丝分裂象的患者也是如此(AHR,2.5;95%CI,1.1至6.0;P = 0.03),而显微镜下切除切缘阴性无显著影响(AHR,0.9;95%CI,0.4至2.2;P = 0.86)。胃切除类型(即解剖性切除与部分/楔形切除)与EFS之间无相关性(P = 0.67)。初次切除后重复切除与术后EFS降低显著相关(P < 0.01)。5例患者(6%)在2008年初次入组后死亡。结论 WT-GIST是一种惰性疾病,大多数患者在疾病进展的情况下存活。我们发现更广泛或系列切除并不能改善EFS。疾病进展或复发可能与肿瘤生物学关系比手术管理更为密切。这些数据表明,WT-GIST的切除应限于初次手术,后续切除仅在处理诸如梗阻或出血等症状时进行。