Baseline Surveillance in Li-Fraumeni Syndrome Using Whole-Body Magnetic Resonance Imaging: A Meta-analysis

Abstract

Importance: Guidelines for clinical management in Li-Fraumeni syndrome, a multiple-organ cancer predisposition condition, are limited. Whole-body magnetic resonance imaging (WBMRI) may play a role in surveillance of this high-risk population.

Objective: To assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline.

Data sources: Clinical and research surveillance cohorts were identified through the Li-Fraumeni Exploration Research Consortium.

Study selection: Cohorts that incorporated WBMRI for individuals with germline TP53 mutations from January 1, 2004, through October 1, 2016, were included.

Data extraction and synthesis: Data were extracted by investigators from each cohort independently and synthesized by 2 investigators. Random-effects meta-analysis methods were used to estimate proportions.

Main outcomes and measures: The proportions of participants at baseline in whom a lesion was detected that required follow-up and in whom a new primary malignant neoplasm was detected.

Results: A total of 578 participants (376 female [65.1%] and 202 male [34.9%]; mean [SD] age, 33.2 [17.1] years) from 13 cohorts in 6 countries were included in the analysis. Two hundred twenty-five lesions requiring clinical follow-up were detected by WBMRI in 173 participants. Sixty-one lesions were diagnosed in 54 individuals as benign or malignant neoplasms. Overall, 42 cancers were identified in 39 individuals, with 35 new localized cancers treated with curative intent. The overall estimated detection rate for new, localized primary cancers was 7% (95% CI, 5%-9%).

Conclusions and relevance: These data suggest clinical utility of baseline WBMRI in TP53 germline mutation carriers and may form an integral part of baseline clinical risk management in this high-risk population.

Figure.. Flowchart of Disposition of Participants Undergoing Whole-Body Magnetic Resonance Imaging (WBMRI)

Many lesions underwent biopsies and imaging. Some participants had benign and malignant lesions. ^aDefined as those who required any intervention (eg, additional imaging or biopsy). ^bIdentified after biopsy in all but 4 cases of glioma or astrocytoma, in which the diagnosis was established with imaging alone. The total number of individuals in whom a benign or malignant neoplasm was identified includes 2 individuals in whom 2 cancers each were diagnosed, including one with 1 localized primary cancer and 1 recurrent cancer and the other with 2 new primary cancers.