The Prognostic Impact of Primary Tumor Site Differs According to the KRAS Mutational Status A Study By the International Genetic Consortium for Colorectal Liver Metastasis
The Prognostic Impact of Primary Tumor Site Differs According to the KRAS Mutational Status A Study By the International Genetic Consortium for Colorectal Liver Metastasis
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DOI：
10.1097/sla.0000000000003504
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发表时间：
2021-06-01
影响因子：
9
通讯作者：
Weiss, Matthew J.
中科院分区：
文献类型：
--
作者：
Margonis, Georgios Antonios;Amini, Neda;Weiss, Matthew J.
目的：探讨Kirsten大鼠肉瘤2病毒癌基因同源物（KRAS）突变状态对结肠癌肝转移（CLM）患者肿瘤侧边性的影响。背景：虽然一些研究表明，右侧（RS）原发肿瘤的CLM患者的预后更差，但其他研究发现，左侧（LS）原发肿瘤的CLM患者与RS的CLM患者的预后模棱两可。重要的是，最近来自不可切除的转移性结直肠癌的证据表明，肿瘤的侧边仅在野生型肿瘤中影响预后。方法：排除直肠或横结肠肿瘤患者及KRAS突变状态未知的患者。RS与LS原发性CRC的预后影响是在KRAS突变状态分层后确定的。结果：RS 277例（38.6%），LS 441例（61.4%）。大约三分之一的肿瘤（28.1%）携带KRAS突变。在整个队列中，与LS相比，RS与更差的5年总生存率（OS）相关（39.4% vs 50.8%, P = 0.03），并且在多变量分析中仍与更差的OS显著相关（风险比1.45,P = 0.04）。在野生型患者中，与RS肿瘤相关的更差的5年OS在单变量分析中明显（43.7%比55.5%,P = 0.02），在多变量分析中持续存在（风险比1.49,P = 0.01）。相比之下，KRAS突变肿瘤患者中，即使在单变量分析中，肿瘤侧边性对5年OS也没有影响（32.8% vs 34.0%, P = 0.38）。结论：本研究首次证明了KRAS突变状态对原发肿瘤侧预后的影响是不同的。RS肿瘤仅在野生型肿瘤患者中与较差的生存相关。
Objective: To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status.Background: Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivocal outcomes of patients with CLM with RS versus left-sided (LS) primary tumors. Importantly, recent evidence from unresectable metastatic CRC suggests that tumor laterality impacts prognosis only in those with wild-type tumors.Methods: Patients with rectal or transverse colon tumors and those with unknown KRAS mutational status were excluded from analysis. The prognostic impact of RS versus LS primary CRC was determined after stratifying by KRAS mutational status.Results: 277 patients had a RS (38.6%) and 441 (61.4%) had a LS tumor. Approximately one-third of tumors (28.1%) harbored KRAS mutations. In the entire cohort, RS was associated with worse 5-year overall survival (OS) compared with LS (39.4% vs 50.8%, P = 0.03) and remained significantly associated with worse OS in the multivariable analysis (hazard ratio 1.45, P = 0.04). In wild-type patients, a worse 5-year OS associated with a RS tumor was evident in univariable analysis (43.7% vs 55.5%, P = 0.02) and persisted in multivariable analysis (hazard ratio 1.49, P = 0.01). In contrast, among patients with KRAS mutated tumors, tumor laterality had no impact on 5-year OS, even in the univariable analysis (32.8% vs 34.0%, P = 0.38).Conclusions: This study demonstrated, for the first time, that the prognostic impact of primary tumor side differs according to KRAS mutational status. RS tumors were associated with worse survival only in patients with wild-type tumors.