Abstract：
BACKGROUND: Genetic evaluation is essential in assessing colorectal cancer (CRC) and colorectal liver metastasis (CRLM). The aim of this study was to determine the pragmatic value of KRAS on oncological outcomes after CRLM according to the ESMO recommendations and to query whether it is necessary to request KRAS testing in each situation.
METHODS: A retrospective cohort of 126 patients who underwent surgery for hepatic resection for CRLM between 2009 and 2020 were reviewed. The patients were divided into three categories: wild-type KRAS, mutated KRAS and impractical KRAS according to their oncological variables. The impractical (not tested) KRAS group included patients with metachronous tumours and negative lymph nodes harvested. Disease-free survival (DFS), overall survival (OS) and hepatic recurrence-free survival (HRFS) were calculated by the Kaplan-Meier method, and a multivariable analysis was conducted using the Cox proportional hazards regression model.
RESULTS: Of the 108 patients identified, 35 cases had KRAS wild-type, 50 cases had a KRAS mutation and the remaining 23 were classified as impractical KRAS. Significantly longer medians for OS, HRFS and DFS were found in the impractical KRAS group. In the multivariable analyses, the KRAS mutational gene was the only variable that was maintained through OS, HRFS and DFS. For HRFS (HR: 13.63; 95% confidence interval (CI): 1.35-100.62; p = 0.010 for KRAS), for DFS (HR: 10.06; 95% CI: 2.40-42.17; p = 0.002 for KRAS) and for OS (HR: 4.55%; 95% CI: 1.37-15.10; p = 0.013).
CONCLUSIONS: Our study considers the possibility of unnecessary KRAS testing in patients with metachronous tumours and negative lymph nodes harvested. Combining the genetic mutational profile (i.e., KRAS in specific cases) with tumour characteristics helps patient selection and achieves the best prognosis after CRLM resection.
METHODS: A retrospective cohort of 126 patients who underwent surgery for hepatic resection for CRLM between 2009 and 2020 were reviewed. The patients were divided into three categories: wild-type KRAS, mutated KRAS and impractical KRAS according to their oncological variables. The impractical (not tested) KRAS group included patients with metachronous tumours and negative lymph nodes harvested. Disease-free survival (DFS), overall survival (OS) and hepatic recurrence-free survival (HRFS) were calculated by the Kaplan-Meier method, and a multivariable analysis was conducted using the Cox proportional hazards regression model.
RESULTS: Of the 108 patients identified, 35 cases had KRAS wild-type, 50 cases had a KRAS mutation and the remaining 23 were classified as impractical KRAS. Significantly longer medians for OS, HRFS and DFS were found in the impractical KRAS group. In the multivariable analyses, the KRAS mutational gene was the only variable that was maintained through OS, HRFS and DFS. For HRFS (HR: 13.63; 95% confidence interval (CI): 1.35-100.62; p = 0.010 for KRAS), for DFS (HR: 10.06; 95% CI: 2.40-42.17; p = 0.002 for KRAS) and for OS (HR: 4.55%; 95% CI: 1.37-15.10; p = 0.013).
CONCLUSIONS: Our study considers the possibility of unnecessary KRAS testing in patients with metachronous tumours and negative lymph nodes harvested. Combining the genetic mutational profile (i.e., KRAS in specific cases) with tumour characteristics helps patient selection and achieves the best prognosis after CRLM resection.
摘要：
背景：遗传评估对于评估结直肠癌（CRC）和结直肠肝转移（CRLM）至关重要。这项研究的目的是根据ESMO建议确定KRAS对CRLM后肿瘤结局的实用价值，并询问是否有必要在每种情况下要求KRAS测试。
方法：回顾了2009年至2020年期间126例接受CRLM肝切除术的患者的回顾性队列。患者分为三类：野生型KRAS，根据肿瘤变量突变KRAS和不切实际的KRAS。不切实际（未经测试）的KRAS组包括异时性肿瘤和淋巴结阴性的患者。无病生存率（DFS），通过Kaplan-Meier法计算总生存期（OS）和无肝复发生存期（HRFS），采用Cox比例风险回归模型进行多变量分析。
结果：在确定的108名患者中，35例KRAS野生型，50例具有KRAS突变，其余23例被归类为不切实际的KRAS。OS的中位数明显更长，在不切实际的KRAS组中发现了HRFS和DFS。在多变量分析中，KRAS突变基因是唯一通过OS维持的变量，HRFS和DFS。对于HRFS（HR：13.63；95％置信区间（CI）：1.35-100.62；KRAS的p=0.010），对于DFS(HR:10.06;95%CI:2.40-42.17;KRASp=0.002)和OS(HR:4.55%;95%CI:1.37-15.10;p=0.013)。
结论：我们的研究考虑了在异时性肿瘤和淋巴结阴性患者中进行不必要的KRAS检测的可能性。结合基因突变谱(即，在特定情况下，具有肿瘤特征的KRAS）有助于患者选择并在CRLM切除后达到最佳预后。
方法：回顾了2009年至2020年期间126例接受CRLM肝切除术的患者的回顾性队列。患者分为三类：野生型KRAS，根据肿瘤变量突变KRAS和不切实际的KRAS。不切实际（未经测试）的KRAS组包括异时性肿瘤和淋巴结阴性的患者。无病生存率（DFS），通过Kaplan-Meier法计算总生存期（OS）和无肝复发生存期（HRFS），采用Cox比例风险回归模型进行多变量分析。
结果：在确定的108名患者中，35例KRAS野生型，50例具有KRAS突变，其余23例被归类为不切实际的KRAS。OS的中位数明显更长，在不切实际的KRAS组中发现了HRFS和DFS。在多变量分析中，KRAS突变基因是唯一通过OS维持的变量，HRFS和DFS。对于HRFS（HR：13.63；95％置信区间（CI）：1.35-100.62；KRAS的p=0.010），对于DFS(HR:10.06;95%CI:2.40-42.17;KRASp=0.002)和OS(HR:4.55%;95%CI:1.37-15.10;p=0.013)。
结论：我们的研究考虑了在异时性肿瘤和淋巴结阴性患者中进行不必要的KRAS检测的可能性。结合基因突变谱(即，在特定情况下，具有肿瘤特征的KRAS）有助于患者选择并在CRLM切除后达到最佳预后。
