Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
J Clin Oncol. 2014 May 20;32(15):1563-70. doi: 10.1200/JCO.2013.51.2046. Epub 2014 Mar 17.
The ACOSOG (American College of Surgeons Oncology Group) Z9001 (Alliance) study, a randomized, placebo-controlled trial, demonstrated that 1 year of adjuvant imatinib prolonged recurrence-free survival (RFS) after resection of primary GI stromal tumor (GIST). We sought to determine the pathologic and molecular factors associated with patient outcome.
There were 328 patients assigned to the placebo arm and 317 to the imatinib arm. Median patient follow-up was 74 months. There were 645 tumor specimens available for mitotic rate or mutation analysis.
RFS remained superior in the imatinib arm (hazard ratio, 0.6; 95% CI, 0.43 to 0.75; Cox model-adjusted P < .001). On multivariable analysis of patients in the placebo arm, large tumor size, small bowel location, and high mitotic rate were associated with lower RFS, whereas tumor genotype was not significantly associated with RFS. Multivariable analysis of patients in the imatinib arm yielded similar findings. When comparing the two arms, imatinib therapy was associated with higher RFS in patients with a KIT exon 11 deletion of any type, but not a KIT exon 11 insertion or point mutation, KIT exon 9 mutation, PDGFRA mutation, or wild-type tumor, although some of these patient groups were small. Adjuvant imatinib did not seem to alter overall survival.
Our findings show that tumor size, location, and mitotic rate, but not tumor genotype, are associated with the natural history of GIST. Patients with KIT exon 11 deletions assigned to 1 year of adjuvant imatinib had a longer RFS.
ACOSOG（美国外科医师学院肿瘤学组）Z9001（联盟）研究是一项随机、安慰剂对照试验，证明了原发性胃肠道间质瘤（GIST）切除术后 1 年接受辅助伊马替尼治疗可延长无复发生存期（RFS）。我们试图确定与患者结局相关的病理和分子因素。
328 例患者被分配到安慰剂组，317 例患者被分配到伊马替尼组。中位患者随访时间为 74 个月。有 645 个肿瘤标本可用于有丝分裂率或突变分析。
伊马替尼组的 RFS 仍然较好（风险比，0.6；95%CI，0.43 至 0.75；Cox 模型调整的 P <.001）。在安慰剂组患者的多变量分析中，大肿瘤大小、小肠位置和高有丝分裂率与较低的 RFS 相关，而肿瘤基因型与 RFS 无显著相关性。伊马替尼组患者的多变量分析得出了类似的结果。当比较两组时，伊马替尼治疗与任何类型的 KIT 外显子 11 缺失的患者的 RFS 较高相关，但与 KIT 外显子 11 插入或点突变、KIT 外显子 9 突变、PDGFRA 突变或野生型肿瘤无关，尽管这些患者群体中的一些较小。辅助伊马替尼似乎并未改变总生存期。
我们的发现表明，肿瘤大小、位置和有丝分裂率，但不是肿瘤基因型，与 GIST 的自然史相关。接受 1 年辅助伊马替尼治疗的 KIT 外显子 11 缺失患者的 RFS 更长。
