Background

The past 20 years have seen advances in colorectal cancer management. We sought to determine whether survival in patients undergoing resection of colorectal liver metastases (CLM) has improved in association with three landmark advances: introduction of irinotecan- and/or oxaliplatin-containing regimens, molecular targeted therapy, and multigene alteration testing.

Methods

Patients undergoing CLM resection during 1998–2014 were identified and grouped by resection year. The influence of alterations in RAS, TP53, and SMAD4 was evaluated and validated in an external cohort including patients with unresectable metastatic colorectal cancer.

Results

Of 1961 patients, 1599 met the inclusion criteria. Irinotecan- and/or oxaliplatin-containing regimens and molecular targeted therapy were used for more than 50% of patients starting in 2001 and starting in 2006, respectively, so patients were grouped as undergoing resection during 1998–2000, 2001–2005, or 2006–2014. Liver resectability indications expanded over time. The 5-year overall survival (OS) rate was significantly better in 2006–2014, vs. 2001–2005 (56.5% vs. 44.1%, P < 0.001). RAS alteration was associated with worse 5-year OS than RAS wild-type (44.8% vs. 63.3%, P < 0.001). However, OS did not differ significantly between patients with RAS alteration and wild-type TP53 and SMAD4 and patients with RAS wild-type in our cohort (P = 0.899) or the external cohort (P = 0.932). Of 312 patients with genetic sequencing data, 178 (57.1%) had clinically actionable alterations.

Conclusion

OS after CLM resection has improved with advances in medical therapy and surgical technique. Multigene alteration testing is useful for prognostication and identification of potential therapeutic targets.

中文翻译：

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随着时间的推移，结肠直肠肝转移切除术后生存率的提高以及多基因改变测试对转移性结肠直肠癌患者的临床影响

背景

在过去的 20 年里，结直肠癌的治疗取得了进展。我们试图确定接受结肠直肠肝转移 (CLM) 切除术的患者的生存率是否因三个里程碑式的进展而有所改善：引入含伊立替康和/或奥沙利铂的方案、分子靶向治疗和多基因改变测试。

方法

确定 1998-2014 年期间接受 CLM 切除的患者并按切除年份分组。RAS、TP53和SMAD4改变的影响在包括不可切除的转移性结直肠癌患者在内的外部队列中进行了评估和验证。

结果

在 1961 名患者中，1599 名符合纳入标准。从 2001 年和 2006 年开始，分别有超过 50% 的患者使用了含伊立替康和/或奥沙利铂的方案和分子靶向治疗，因此将患者分组为 1998-2000、2001-2005 或 2006 年期间接受切除的患者–2014。肝脏可切除性适应症随着时间的推移而扩大。2006-2014 年的 5 年总生存率 (OS) 明显优于 2001-2005 年（56.5% 对 44.1%，P  < 0.001）。与RAS野生型相比，RAS改变与更差的 5 年 OS 相关（44.8% 对 63.3%，P  < 0.001）。然而，RAS变异患者和野生型TP53患者的 OS 没有显着差异和SMAD4和患者RAS野生型在我们的队列（P  = 0.899）或外部队列（P  = 0.932）。在拥有基因测序数据的 312 名患者中，178 名 (57.1%) 具有临床上可行的改变。

结论

随着药物治疗和手术技术的进步，CLM 切除术后的 OS 有所改善。多基因改变测试可用于预测和识别潜在的治疗靶点。