SIGNIFIED: whole-body MRI screening in Li-Fraumeni syndrome in the UK

Li-Fraumeni syndrome (LFS), caused by a pathogenic germline variant of the TP53 tumour suppressor gene, is an autosomal dominant condition that predisposes affected individuals to multiple cancers at a young age. International guidelines recommend yearly screening to identify cancers: in addition to annual breast magnetic resonance imaging (MRI) in female patients and full dermatological skin check, patients should undergo whole-body imaging. Whole-body MRI (WB-MRI) can image from vertex to toes in a single examination, without the use of ionising radiation. We aimed to assess the utility of WB-MRI in detecting malignancies in LFS patients.

SIGNIFIED was a prospective, exploratory and observational study. Patients with LFS were identified and invited to undergo two WB-MRIs 12 months apart. WB-MRI was carried out at 1.5 T from vertex to toes without contrast, including axial T1-, T2- and diffusion-weighted imaging. Images were reviewed independently by two experienced oncological radiologists. Suspicious lesions and incidental findings were discussed in a multidisciplinary meeting, with further investigation and management carried out on a case-by-case basis.

Between July 2022 and August 2023, 54 individuals (14 males, 40 females) with LFS underwent a baseline WB-MRI within the study. Fifty patients had a second scan ∼12 months later. Following the first WB-MRI, nine patients underwent biopsy/excision (16.7%), and four cancers were diagnosed (7.4%). Five patients developed interval cancer between the first and second WB-MRI. These were either outside of the initial WB-MRI field of view (i.e. upper limb sarcoma, breast carcinoma) or had developed clinically since the initial scan. Six patients (12%) were diagnosed with a cancer following the second WB-MRI. Seven (70%) out of the 10 cancers detected overall by both scans were in an early stage, and the remaining 3 (30%) were locally advanced or metastatic.

WB-MRI can identify early cancers in the high-risk setting of LFS screening, with cancers detected at both baseline and 12-month follow-up screenings. The burden of additional investigations for incidental findings decreases with repeat imaging.