KRAS 突变型结直肠癌肝转移患者行解剖性肝切除可改善无病生存。

Anatomical Resections Improve Disease-free Survival in Patients With KRAS-mutated Colorectal Liver Metastases.

机构信息

*Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD †Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, the Netherlands ‡Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH §Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX.

出版信息

Ann Surg. 2017 Oct;266(4):641-649. doi: 10.1097/SLA.0000000000002367.

DOI:10.1097/SLA.0000000000002367

PMID:28657938

Abstract

OBJECTIVE

To investigate the potential clinical advantage of anatomical resection versus nonanatomical resection for colorectal liver metastases, according to KRAS mutational status.

BACKGROUND

KRAS-mutated colorectal liver metastases (CRLM) are known to be more aggressive than KRAS wild-type tumors. Although nonanatomical liver resections have been demonstrated as a viable approach for CRLM patients with similar oncologic outcomes to anatomical resections, this may not be the case for the subset of KRAS-mutated CRLM.

METHODS

389 patients who underwent hepatic resection of CRLM with known KRAS mutational status were identified. Survival estimates were calculated using the Kaplan-Meier method, and multivariable analysis was conducted using the Cox proportional hazards regression model.

RESULTS

In this study, 165 patients (42.4%) underwent nonanatomical resections and 140 (36.0%) presented with KRAS-mutated CRLM. Median disease-free survival (DFS) in the entire cohort was 21.3 months, whereas 1-, 3-, and 5-year DFS was 67.3%, 34.9%, and 31.5% respectively. Although there was no difference in DFS between anatomical and nonanatomical resections in patients with KRAS wild-type tumors (P = 0.142), a significant difference in favor of anatomical resection was observed in patients with a KRAS mutation (10.5 vs. 33.8 months; P < 0.001). Five-year DFS was only 14.4% in the nonanatomically resected group, versus 46.4% in the anatomically resected group. This observation persisted in multivariable analysis (hazard ratio: 0.45; 95% confidence interval: 0.27-0.74; P = 0.002), when corrected for number of tumors, bilobar disease, and intraoperative ablations.

CONCLUSIONS

Nonanatomical tissue-sparing hepatectomies are associated with worse DFS in patients with KRAS-mutated tumors. Because of the aggressive nature of KRAS-mutated CRLM, more extensive anatomical hepatectomies may be warranted.

摘要

目的

根据 KRAS 突变状态，探讨解剖性肝切除术与非解剖性肝切除术治疗结直肠肝转移的潜在临床优势。

背景

KRAS 突变型结直肠肝转移（CRLM）的侵袭性高于 KRAS 野生型肿瘤。虽然非解剖性肝切除术已被证明是一种可行的方法，可获得与解剖性肝切除术相似的肿瘤学结果，但对于 KRAS 突变型 CRLM 的亚组患者，情况可能并非如此。

方法

共确定了 389 例接受 KRAS 突变状态已知的结直肠肝转移肝切除术的患者。使用 Kaplan-Meier 法计算生存估计值，采用 Cox 比例风险回归模型进行多变量分析。

结果

在这项研究中，165 例（42.4%）患者行非解剖性肝切除术，140 例（36.0%）患者为 KRAS 突变型 CRLM。全队列的中位无病生存（DFS）为 21.3 个月，1、3 和 5 年的 DFS 分别为 67.3%、34.9%和 31.5%。在 KRAS 野生型肿瘤患者中，解剖性与非解剖性肝切除术之间的 DFS 无差异（P = 0.142），但在 KRAS 突变型患者中，解剖性肝切除术具有显著优势（10.5 与 33.8 个月；P < 0.001）。非解剖性肝切除组 5 年 DFS 仅为 14.4%，而解剖性肝切除组为 46.4%。这一观察结果在多变量分析中仍然存在（风险比：0.45；95%置信区间：0.27-0.74；P = 0.002），在校正肿瘤数量、双侧疾病和术中消融后仍然成立。