Genomic alterations associated with early-stage disease and early recurrence in patients with colorectal cancer.

IF 4.8 2区医学 Q1 ONCOLOGY

Oncologist Pub Date : 2024-11-12 DOI:10.1093/oncolo/oyae269

Leontios Pappas, Julia C F Quintanilha, Richard S P Huang, Aparna R Parikh

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引用次数: 0

Abstract

Background: The molecular characterization of early-stage (1-3) colorectal cancer (CRC) remains incomplete, as opposed to metastatic disease, where comprehensive genomic profiling (CGP) is routinely performed. This study aimed to characterize the genomics of stages 1-3 versus IV CRC, and the genomics of patients recurring within 1 year of diagnosis.

Patients and methods: Patients from a de-identified CRC clinico-genomic database who received Foundation Medicine testing (FoundationOne/FoundationOne CDx) during routine clinical care at approximately 280 US cancer clinics between March 2014 and June 2023 were included. Genomic alterations (GA) were compared by Fisher's exact test.

Results: A total of 4702 patients were included; 1902 with stages 1-3 and 2800 with stage 4 disease. Among patients with stages 1-3 disease, 546 recurred within 1 year. Patients staged 1-3 had higher prevalence of microsatellite instability (MSI-H, 11.4% vs 4.5%, P < .001), tumor mutational burden (TMB) ≥ 10 Mut/Mb (14.6% vs 6.8%, P < .001), GA in RNF43 (11.2% vs 5.7%, P < .001), MSH6 (3.9% vs 1.7%, P < .001), MLH1 (2.3% vs 0.7%, P < .001), and MSH2 (1.5% vs 0.6%, P < .01) compared to those with stage 4 disease. Patients who recurred within 1 year had higher prevalence of MSI-H (13.2% vs 4.4%, P < .001), TMB ≥ 10 Mut/Mb (16.2% vs 6.9%, P < .001), BRAF V600E (17.2% vs 7.9%, P < .003), GA in RNF43 (13.7% vs 5.3%, P < .001), MSH6 (4.2% vs 1.6%, P = .035), and BRCA1/2 (6.2% vs 3.0%, P = .030). On recurrence, more patients received targeted therapy when CGP was performed before versus after first-line therapy (43% vs 19%, P < .001).

Conclusions: Early-stage CRC patients can have distinct genomic profiles and CGP in this population can help expand access to targeted therapies.

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与结直肠癌患者早期疾病和早期复发相关的基因组变化。

背景：早期（1-3 期）结直肠癌（CRC）的分子特征描述仍不完整，而转移性疾病则常规进行全面的基因组分析（CGP）。这项研究旨在描述1-3期与IV期CRC的基因组学特征，以及诊断后1年内复发患者的基因组学特征：研究纳入了2014年3月至2023年6月期间在约280家美国癌症诊所的常规临床治疗中接受基础医学检测（FoundationOne/FoundationOne CDx）的去身份化CRC临床基因组数据库中的患者。基因组改变（GA）通过费雪精确检验进行比较：结果：共纳入 4702 例患者，其中 1902 例为 1-3 期患者，2800 例为 4 期患者。1-3期患者中有546人在1年内复发。1-3期患者的微卫星不稳定性（MSI-H，11.4% 对 4.5%，P）发生率较高：早期 CRC 患者可能有不同的基因组特征，在这一人群中开展 CGP 有助于扩大靶向治疗的可及性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncologist 医学-肿瘤学

CiteScore

10.40

自引率

3.40%

发文量

309

审稿时长

3-8 weeks

期刊介绍： The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.