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15 年以上经手术切除的早发性和筛查期结直肠癌伴肝转移患者的基因组图谱与生存的相关性研究。

Association of genomic profiles and survival in early onset and screening-age colorectal cancer patients with liver metastases resected over 15 years.

机构信息

Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

Department of Surgery, Stanford University School of Medicine, Stanford, California, USA.

出版信息

J Surg Oncol. 2022 Apr;125(5):880-888. doi: 10.1002/jso.26797. Epub 2022 Jan 23.

Abstract

BACKGROUND

This study explores whether genomic profiles of colorectal liver metastasis (CRLM) patients with early onset (EO, < 50 years old) and screening age (SA) primary diagnosis are associated with overall survival (OS).

METHODS

All patients undergoing hepatectomy between 2002 and 2017 were identified and tumor specimens with next-generation sequencing data were cataloged. Gene and signaling-level alterations were checked for association with OS from primary diagnosis accommodating for left-truncated survival.

RESULTS

Of 1822 patients, 333 were sequenced-127 (38%) EO-CRLM and 206 (62%) SA-CRLM patients. More aggressive features presented in EO-CRLM patients-synchronous metastatic presentation (83% vs. 75%, p < 0.001) and primary node-positive disease (71% vs. 61%, p < 0.001). The median OS from primary diagnosis was 11.8 years (95% confidence interval = 7.94-NA). Five-year OS did not differ by age (p = 0.702). On multivariable analysis, altered APC (EO-CRLM: [hazard ratio [HR] = 0.37, p = 0.018] vs. SA-CRLM:[HR = 0.61, p = 0.260]), BRAF (EO-CRLM:[HR = 4.38, p = 0.007] vs. SA-CRLM:[HR = 4.78, p = 0.032]), and RAS-TP53 (EO-CRLM:[HR = 2.82, p = 0.011] vs. SA-CRLM:[HR = 2.35, p = 0.003]) associated with OS.

CONCLUSIONS

Despite bearing more aggressive features, EO-CRLM patients had similar genomic profiles and survival as SA-CRLM patients. Better performance status in younger patients leading to increased treatment tolerance may partly explain this. As screening and treatment strategies from older patients are applied to younger patients, genomic predictors of biology identified historically in older cohorts could apply to EO patients.

摘要

背景

本研究旨在探讨结直肠癌肝转移(CRLM)患者中早发(EO,<50 岁)和筛查年龄(SA)初诊患者的基因组谱是否与总生存期(OS)相关。

方法

确定了 2002 年至 2017 年间接受肝切除术的所有患者,并对具有下一代测序数据的肿瘤标本进行了编目。从初诊时考虑到左截断生存,检查基因和信号级别的改变与 OS 的关联。

结果

在 1822 名患者中,有 333 名患者进行了测序-127 名(38%)EO-CRLM 和 206 名(62%)SA-CRLM 患者。EO-CRLM 患者表现出更具侵袭性的特征-同步转移表现(83%比 75%,p<0.001)和原发性淋巴结阳性疾病(71%比 61%,p<0.001)。初诊时的中位 OS 为 11.8 年(95%置信区间=7.94-NA)。年龄不同,5 年 OS 无差异(p=0.702)。多变量分析显示,APC 改变(EO-CRLM:[风险比[HR] = 0.37,p=0.018] vs. SA-CRLM:[HR=0.61,p=0.260]),BRAF(EO-CRLM:[HR=4.38,p=0.007] vs. SA-CRLM:[HR=4.78,p=0.032])和 RAS-TP53(EO-CRLM:[HR=2.82,p=0.011] vs. SA-CRLM:[HR=2.35,p=0.003])与 OS 相关。

结论

尽管 EO-CRLM 患者具有更具侵袭性的特征,但他们的基因组谱和生存情况与 SA-CRLM 患者相似。年轻患者更好的身体状况导致更高的治疗耐受性可能部分解释了这一点。随着 older 患者的筛查和治疗策略应用于年轻患者,历史上在 older 队列中确定的生物学的基因组预测因子可能适用于 EO 患者。

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