Department of Medicine, Yale University, New Haven, Connecticut, USA.
Department of Pathology, Yale University, New Haven, Connecticut, USA.
J Med Genet. 2023 Jun;60(6):533-539. doi: 10.1136/jmg-2022-108770. Epub 2022 Sep 17.
Guidelines recommend universal mismatch repair (MMR) tumour testing of colorectal adenocarcinomas (CRCs) to screen for Lynch syndrome (LS). However, its implementation remains disjointed and referral for genetic testing dismal, particularly among minorities. We aimed to increase referral, cancer genetic testing and eventually LS diagnosis by developing the CLEAR LS (Closed Loop Enhanced Assessment and Referral for Lynch Syndrome) intervention, a systems approach which in the second phase was automated.
This is a cohort study of all patients diagnosed with CRC at an academic centre between 1 January 2012, when implementation of universal CRC testing began, and 31 January 2021. The original cohort spanned through 31 May 2015. Tumour testing included MMR immunohistochemistry, followed by V600E/ promoter methylation testing when indicated. The intervention included a manual phase (1 June 2015 through 31 July 2018), which systematised pathology screening and cancer genetics (CG) referral mechanisms, and an automated phase (1 August 2018 through 31 January 2021) using computer programming.
A total of 249/1541 CRC (17.38%) had MMR loss of expression and 129 (8.37%) qualified for CG evaluation. Referral was 27.58% in the original cohort and 92.1% in the intervention (p<0.001). Patients seen by CG among referred were 27.58% in the original cohort and 74.3% in the intervention (p two-sided<0.001). The distribution of race/ethnicity among patients qualifying and referred for CG evaluation was not significantly different across cohorts. LS diagnosis increased from 0.56% (original cohort) to 1.43% (intervention). Cost per new diagnosis of LS decreased from US$173 675 to $87 960 from original cohort to intervention.
Implementation of systematic case identification and referral support mechanisms significantly increased the proportion of patients undergoing genetic testing and doubled the percentage of patients diagnosed with LS with no referral differences across racial/ethnic groups.
指南建议对结直肠腺癌（CRC）进行普遍的错配修复（MMR）肿瘤检测，以筛查林奇综合征（LS）。然而，其实施仍然脱节，遗传检测的转诊率仍然很低，尤其是在少数族裔中。我们旨在通过开发 CLEAR LS（闭环增强评估和林奇综合征转诊）干预措施来增加转诊、癌症基因检测，并最终诊断 LS，这是一种系统方法，在第二阶段实现了自动化。
这是一项对 2012 年 1 月 1 日（开始实施普遍 CRC 检测）至 2021 年 1 月 31 日期间在学术中心诊断为 CRC 的所有患者的队列研究。原始队列涵盖至 2015 年 5 月 31 日。肿瘤检测包括 MMR 免疫组织化学，然后在需要时进行 V600E/启动子甲基化检测。干预措施包括手动阶段（2015 年 6 月 1 日至 2018 年 7 月 31 日），该阶段使病理学筛查和癌症遗传学（CG）转诊机制系统化，以及自动阶段（2018 年 8 月 1 日至 2021 年 1 月 31 日），使用计算机编程。
共有 249/1541 例 CRC（17.38%）出现 MMR 表达缺失，129 例（8.37%）符合 CG 评估条件。在原始队列中，转诊率为 27.58%，干预组为 92.1%（p<0.001）。在转诊患者中，CG 就诊的患者在原始队列中为 27.58%，在干预组中为 74.3%（p 双侧<0.001）。在符合 CG 评估条件和转诊的患者中，种族/族裔分布在两个队列中没有显著差异。LS 诊断率从 0.56%（原始队列）增加到 1.43%（干预组）。LS 新诊断的每个病例成本从原始队列的 173675 美元降至干预组的 87960 美元。
系统的病例识别和转诊支持机制的实施显著提高了接受基因检测的患者比例，并将 LS 诊断率提高了一倍，且在不同种族/族裔群体中没有转诊差异。
