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结直肠肝转移切除后的无复发生存条件:RAS 和 TP53 共突变持续存在有害关联。

Conditional Recurrence-Free Survival after Resection of Colorectal Liver Metastases: Persistent Deleterious Association with RAS and TP53 Co-Mutation.

机构信息

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

出版信息

J Am Coll Surg. 2019 Sep;229(3):286-294.e1. doi: 10.1016/j.jamcollsurg.2019.04.027. Epub 2019 May 2.


DOI:10.1016/j.jamcollsurg.2019.04.027
PMID:31054911
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6703951/
Abstract

BACKGROUND: Conditional recurrence-free survival (RFS) probability, that is, the probability of remaining recurrence-free after a given interval without recurrence, has not been reported after resection of colorectal liver metastases (CLMs). We aimed to estimate conditional RFS and identify factors affecting conditional RFS. STUDY DESIGN: Patients undergoing initial resection of CLMs during 2000-2016 with mutation data were identified. The RFS and risk factors for recurrence were evaluated at the time of resection for all patients and at 1 year and 2 years after resection for patients who remained recurrence-free. RESULTS: Of 2,118 patients, 485 met the inclusion criteria, of which 225 were recurrence-free at 1 year and 109 were recurrence-free at 2 years. The 5-year RFS rates were 17.3%, 36.8%, and 70.7% for all patients and the 1-year and 2-year recurrence-free groups, respectively, when assessed from the time of initial CLM resection. RAS/TP53 co-mutation was the only factor independently associated with increased risk of recurrence for all groups (all patients, hazard ratio 1.47; 95% CI 1.19 to 1.82; p < 0.001; 1-year recurrence-free, hazard ratio 1.69; 95% CI 1.17 to 2.43; p = 0.005; 2-year recurrence-free, hazard ratio 2.41; 95% CI 1.12 to 5.17; p = 0.024). T category, extrahepatic disease, multiple CLMs, largest CLM diameter, and surgical margin status were risk factors for recurrence in all patients and/or the 1-year recurrence-free group, but not the 2-year recurrence-free group. Median RFS was lower for patients with RAS/TP53 co-mutation than for those with RAS/TP53 wild-type in the 1-year (1.5 vs 2.8 years; p = 0.006) and 2-year recurrence-free groups (3.0 vs 5.9 years; p = 0.024). CONCLUSIONS: Conditional RFS is useful for updating prognosis after a given time interval without recurrence after CLM resection. Importantly, RAS/TP53 co-mutation has a persistent deleterious association with recurrence.

摘要

背景:在结直肠肝转移瘤(CLM)切除术后,尚未报道有条件无复发生存率(RFS),即给定时间间隔内无复发的生存概率。我们旨在评估有条件的 RFS 并确定影响有条件 RFS 的因素。

研究设计:确定了 2000-2016 年间接受初始 CLM 切除术且有突变数据的患者。对所有患者在切除时以及在无复发的患者在切除后 1 年和 2 年时评估 RFS 和复发风险因素。

结果:在 2118 名患者中,有 485 名符合纳入标准,其中 225 名在 1 年内无复发,109 名在 2 年内无复发。所有患者、1 年无复发组和 2 年无复发组的 5 年 RFS 率分别为 17.3%、36.8%和 70.7%,从初始 CLM 切除时开始评估。RAS/TP53 共突变是所有组中唯一与复发风险增加相关的因素(所有患者,风险比 1.47;95%CI 1.19 至 1.82;p<0.001;1 年无复发,风险比 1.69;95%CI 1.17 至 2.43;p=0.005;2 年无复发,风险比 2.41;95%CI 1.12 至 5.17;p=0.024)。T 分期、肝外疾病、多个 CLM、最大 CLM 直径和手术切缘状态是所有患者和/或 1 年无复发组的复发风险因素,但不是 2 年无复发组的复发风险因素。在 1 年(1.5 年与 2.8 年;p=0.006)和 2 年无复发组(3.0 年与 5.9 年;p=0.024)中,RAS/TP53 共突变患者的中位 RFS 低于 RAS/TP53 野生型患者。

结论:在 CLM 切除术后无复发的特定时间间隔后,有条件的 RFS 有助于更新预后。重要的是,RAS/TP53 共突变与复发具有持续的有害关联。

相似文献

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[6]
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[7]
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[7]
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[8]
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本文引用的文献

[1]
Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases: A Multi-institutional, International Analysis of 1099 Patients.

Ann Surg. 2019-6

[2]
Deleterious Effect of RAS and Evolutionary High-risk TP53 Double Mutation in Colorectal Liver Metastases.

Ann Surg. 2019-5

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CA Cancer J Clin. 2017-3-1

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CA Cancer J Clin. 2017-1-17

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Factors influencing recurrence following initial hepatectomy for colorectal liver metastases.

Br J Surg. 2016-6-16

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Impact of KRAS, BRAF, PIK3CA, TP53 status and intraindividual mutation heterogeneity on outcome after liver resection for colorectal cancer metastases.

Int J Cancer. 2016-8-1

[7]
Predictors of early recurrence after resection of colorectal liver metastases.

World J Surg Oncol. 2015-4-1

[8]
KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases.

Cancer. 2014-8-25

[9]
Getting more out of survival data by using the hazard function.

Clin Cancer Res. 2014-2-5

[10]
Early recurrence after liver resection for colorectal metastases: risk factors, prognosis, and treatment. A LiverMetSurvey-based study of 6,025 patients.

Ann Surg Oncol. 2014-4

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