Corredor Jessica L, Dodd-Eaton Elissa B, Woodman-Ross Jacynda, Woodson Ashley, Nguyen Nam H, Peng Gang, Green Sierra, Gutierrez Angelica M, Arun Banu K, Wang Wenyi
medRxiv. 2024 Jul 10:2024.07.09.24310095. doi: 10.1101/2024.07.09.24310095.
Current clinical guidelines for genetic testing for Li-Fraumeni Syndrome (LFS) have many limitations, primarily the criteria don't consider detailed personal and family history information and may miss many individuals with LFS. A personalized risk assessment tool, LFSPRO, was created to estimate a proband's risk for LFS based on personal and family history information. The purpose of this study is to compare LFSPRO to existing clinical criteria to determine if LFSPRO can outperform these tools. Additionally, we gauged genetic counselors' (GCs) experience using LFSPRO for their patients.
Between December 2021 and March 2024, GCs identified patients concerning for LFS based on the patients' personal and family history information. This information was entered into LFSPRO to predict the risk to have a pathogenic/pathogenic (LP/P) germline variant. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) was compared between LFSPRO and Chompret criteria. Select GCs were asked to fill out surveys regarding their experience using LFSPRO following their genetic counseling appointments.
LFSPRO's sensitivity and specificity were 0.529 and 0.781 compared to Chompret's respective 0.235 and 0.677. Additionally, LFSPRO had a positive predictive value (PPV) of 0.30 compared to Chompret's 0.114. LFSPRO's risk prediction was concordant with genetic testing results in 75% of probands. Eighty-one percent of GC surveys reported LFSPRO being concordant with the GC's expectations and 75% would feel comfortable sharing the results with patients.
LFSPRO showed improved sensitivity and specificity compared to Chompret criteria and GCs report a positive experience with LFSPRO. LFSPRO can be used to increase access to genetic testing for patients at risk for LFS and could help healthcare providers give more direct risk assessments regarding LFS testing and management for patients.
目前关于李-弗劳梅尼综合征（LFS）基因检测的临床指南存在许多局限性，主要是其标准未考虑详细的个人和家族病史信息，可能会遗漏许多LFS患者。创建了一种个性化风险评估工具LFSPRO，以根据个人和家族病史信息估计先证者患LFS的风险。本研究的目的是将LFSPRO与现有临床标准进行比较，以确定LFSPRO是否能优于这些工具。此外，我们评估了遗传咨询师（GCs）使用LFSPRO为患者服务的经验。
在2021年12月至2024年3月期间，GCs根据患者的个人和家族病史信息识别出疑似LFS的患者。将这些信息输入LFSPRO，以预测携带致病性/可能致病性（LP/P）种系变异的风险。比较了LFSPRO和乔普雷标准之间的敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）。部分GCs被要求在遗传咨询预约后填写关于他们使用LFSPRO经验的调查问卷。
与乔普雷标准（分别为0.235和0.677）相比，LFSPRO的敏感性和特异性分别为0.529和0.781。此外，LFSPRO的阳性预测值（PPV）为0.30，而乔普雷标准为0.114。LFSPRO的风险预测与75%的先证者的基因检测结果一致。81%的GC调查问卷报告称LFSPRO与GCs的预期一致，75%的GCs会放心地与患者分享结果。
与乔普雷标准相比，LFSPRO的敏感性和特异性有所提高，GCs报告使用LFSPRO的体验良好。LFSPRO可用于增加有LFS风险患者的基因检测机会，并有助于医疗保健提供者对患者的LFS检测和管理进行更直接的风险评估。
