Evaluation of whole-body MRI for cancer early detection in Li-Fraumeni syndrome

Abstract

Li-Fraumeni syndrome (LFS) is a high-risk hereditary cancer predisposition syndrome affecting 1 in 5000 individuals. Current standard of care in adults includes annual whole-body MRI (WB-MRI) and MRI brain (MRB) surveillance to enable early cancer detection. We performed a retrospective single-centre study of adults with TP53 pathogenic germline variants or proven somatic mosaicism undergoing annual WB-MRI surveillance between January 2012 and January 2024, and MRB surveillance between August 2017 and January 2024. 325 WB-MRI scans were performed in 75 individuals. 17 cancers were diagnosed in 16 individuals. Nine out of 17 cancers were WB-MRI detected (7/9 had stage 1/2 disease). Benign incidental findings were identified in 89/325 (27.4%) of WB-MRI scans, prompting 53 additional investigations. As a stand-alone surveillance tool, WB-MRI demonstrated a pan-cohort specificity of 95.5%, negative predictive value of 97.4% and sensitivity of 42.9%. 32 individuals underwent 53 MRB scans detecting one cancer. We report the findings from the longest and largest single-centre experience of WB-MRI surveillance for cancer early detection in adults with LFS, demonstrating a high and acceptable level of cancer exclusion but modest sensitivity with WB-MRI prompting a significant number of additional investigations.

Keywords: Early Diagnosis; Heredity.