A prospective study of whole-body MRI (WBMRI) as part of a multimodality screening program for individuals with Li-Fraumeni syndrome (LFS).

Abstract

10501 Background: Individuals with LFS are at risk for developing cancer in multiple organs and therefore require a multimodal cancer screening program. We assessed the performance of annual WBMRI in early cancer detection for individuals with LFS. Methods: Individuals with a germline pathogenic or likely pathogenic variant in the TP53 gene (defined as LFS) and without cancer diagnosed or treated in the preceding 6 months were eligible to undergo annual non-contrast WBMRI. Clinical findings on WBMRI, follow-up studies, and biopsies were prospectively assessed. Cancer incidence during the study period and up to 18 months after WBMRI was evaluated. Results: 162 eligible participants (pts) with LFS (127 adult, 35 pediatric) underwent a total of 477 WBMRIs; 119 (73%) underwent 3 or more. Median age at enrollment was 37 years; 75% of pts were female. Classic or Chompret diagnostic criteria for LFS were met for 66% (84/127) of adult and 77% (27/35) of pediatric pts. Follow-up studies for findings on WBMRI were pursued for 61.4% (78/127) of adult and 34.3% (12/35) of pediatric pts. Biopsies were performed without complication in 18% (29/162) of pts with 39.5% of 38 biopsies confirming a cancer diagnosis. The percentage of pts requiring follow-up studies or biopsies decreased with consecutive WBMRIs (Table 1). During the study period, 37 cancers were diagnosed in 33 pts (27 adults, 6 children); 26 of these pts were alive at the time of data cut off. Fifteen of 37 cancers (40.5%) were asymptomatic cancers diagnosed by WBMRI; 86% (13/15) of these (in 12 patients) were localized and treated with curative intent, including 3 lung cancers and 4 pelvic/abdominal sarcomas. Ten of these 12 pts remain alive at the time of last follow-up. The 22 cancers not diagnosed on WBMRI included five sarcomas, and one each of adrenocortical, lung, thyroid and renal cell carcinoma as well as cancers not likely to be detected on WBMRI (4 breast/chest wall, 3 endoluminal, 3 hematologic, and 3 metastatic recurrences). Conclusions: Annual WBMRI contributes substantially to detection of asymptomatic localized cancers among individuals with LFS but interval cancers remain common. Our study highlights limitations of WBMRI and the need for further research to enhance early detection and interception of cancer in LFS. Sequence of WB-MRI scans and timing of follow-up studies, biopsies, and cancer diagnoses. WB-MRI scan number # pts evaluated # pts with follow-up studies n (%) # pts with biopsiesn (%) # pts dx with ca by WBMRI n (%) # ca dx based on WBMRI n # pts with interval ca dxn (%) # interval ca dx by other means or symptoms (not detected on WBMRI) n 1 162 60 (37.0) 20 (12.3) 6 (3.7) 7 8 (4.9) 8 2 143 38 (26.6) 12 (8.4) 6 (4.2) 6 7 (4.9) 9 3 119 21 (17.6) 3 (2.5) 0 (0) 0 3 (2.5) 3 4 33 5 (15.2) 1 (3.0) 1 (3.0) 1 2 (6.1) 2 5 11 1 (9.1) 0 (0) 1 (9.1) 1 0 (0) 0 6 5 1 (20) 0 (0) 0 (0) 0 0 (0) 0 7 3 1 (33.3) 0 (0) 0 (0) 0 0 (0) 0 pts: participants, ca: cancer, dx: diagnosed.