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结直肠癌肝转移灶切除术：肿瘤负荷与KRAS突变状态对预后的影响

Resection of Colorectal Liver Metastasis: Prognostic Impact of Tumor Burden vs KRAS Mutational Status.

作者信息

Tsilimigras Diamantis I, Hyer J Madison, Bagante Fabio, Guglielmi Alfredo, Ruzzenente Andrea, Alexandrescu Sorin, Poultsides George, Sasaki Kazunari, Aucejo Federico, Pawlik Timothy M

机构信息

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH.

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH; University of Verona, Verona, Italy.

出版信息

J Am Coll Surg. 2021 Apr;232(4):590-598. doi: 10.1016/j.jamcollsurg.2020.11.023. Epub 2020 Dec 28.

DOI:10.1016/j.jamcollsurg.2020.11.023

PMID:33383214

Abstract

BACKGROUND

The prognostic impact of colorectal liver metastasis (CRLM) morphologic characteristics relative to KRAS mutational status after hepatic resection remains ill defined.

STUDY DESIGN

Patients undergoing hepatectomy for CRLM between 2001 and 2018 were identified using an international multi-institutional database. Tumor burden score (TBS) was defined as distance from origin on a Cartesian plane that incorporated maximum tumor size (x-axis) and number of lesions (y-axis). Impact of TBS on overall survival (OS) relative to KRAS status (wild type [wtKRAS] vs mutated [mutKRAS]) was assessed.

RESULTS

Among 1,361 patients, the median number of metastatic lesions was 2 (interquartile range [IQR] 1-3), and median size of the largest metastatic lesion was 3.0 cm (IQR 2.0-5.0 cm), resulting in a median TBS of 4.1 (IQR 2.8-6.1); KRAS status was wtKRAS (n = 420, 30.9%), mutKRAS (n = 251, 18.4%), and unknown (n = 690, 50.7%). Overall median and 5-year OS were 49.5 months (95%CI 45.2-53.8) and 43.2%, respectively. In examining the entire cohort, TBS was associated with long-term prognosis (5-year OS, low TBS: 49.4% vs high TBS: 36.7%), as was KRAS mutational status (5-year OS, wtKRAS: 48.2% vs mutKRAS: 31.1%; unknown KRAS: 44.0%)(both p < 0.01). Among patients with wtKRAS tumors, TBS was strongly associated with improved OS (5-year OS, low TBS: 59.1% vs high TBS: 38.4%, p = 0.002); however, TBS failed to discriminate long-term prognosis among patients with mutKRAS tumors (5-year OS, low TBS: 37.4% vs high TBS: 26.7%, p = 0.19). In fact, patients with high TBS/wtKRAS CRLM had comparable outcomes to patients with low TBS/mutKRAS tumors (5-year OS, 38.4% vs 37.4%, respectively; p = 0.59). On multivariable analysis, while TBS was associated with OS among patients with wtKRAS CRLM (hazard ratio 1.43, 95%CI 1.02-2.00; p = 0.03), TBS was not an independent predictor of survival among patients with mutKRAS CRLM (HR 1.36, 95%CI 0.92-1.99; p = 0.12).

CONCLUSIONS

While TBS was associated with survival among patients with wtKRAS tumors, CRLM morphology was not predictive of long-term outcomes among patients with mutKRAS CRLM.

摘要

背景

肝切除术后，结直肠癌肝转移（CRLM）的形态学特征相对于KRAS突变状态的预后影响仍不明确。

研究设计

利用国际多机构数据库确定2001年至2018年间接受CRLM肝切除术的患者。肿瘤负荷评分（TBS）定义为笛卡尔平面上距原点的距离，该平面纳入了最大肿瘤大小（x轴）和病灶数量（y轴）。评估TBS相对于KRAS状态（野生型[wtKRAS]与突变型[mutKRAS]）对总生存期（OS）的影响。

结果

在1361例患者中，转移病灶的中位数为2个（四分位间距[IQR]1 - 3），最大转移病灶的中位数大小为3.0 cm（IQR 2.0 - 5.0 cm），导致TBS的中位数为4.1（IQR 2.8 - 6.1）；KRAS状态为wtKRAS（n = 420，30.9%）、mutKRAS（n = 251，18.4%）和未知（n = 690，50.7%）。总体中位生存期和5年总生存率分别为49.5个月（95%CI 45.2 - 53.8）和43.2%。在检查整个队列时，TBS与长期预后相关（5年总生存率，低TBS：49.4% vs高TBS：36.7%），KRAS突变状态也是如此（5年总生存率，wtKRAS：48.2% vs mutKRAS：31.1%；KRAS未知：44.0%）（两者p < 0.01）。在wtKRAS肿瘤患者中，TBS与改善的总生存期密切相关（5年总生存率，低TBS：59.1% vs高TBS：38.4%，p = 0.002）；然而，TBS未能区分mutKRAS肿瘤患者的长期预后（5年总生存率，低TBS：37.4% vs高TBS：26.7%，p = 0.19）。事实上，高TBS/wtKRAS CRLM患者的结局与低TBS/mutKRAS肿瘤患者相当（5年总生存率分别为38.4%和37.4%；p = 0.59）。在多变量分析中，虽然TBS与wtKRAS CRLM患者的总生存期相关（风险比1.43，95%CI 1.02 - 2.00；p = 0.03），但TBS不是mutKRAS CRLM患者生存的独立预测因素（HR 1.36，95%CI 0.92 - 1.99；p = 0.12）。