Whole-Body MRI Surveillance-Baseline Findings in the Swedish Multicentre Hereditary TP53-Related Cancer Syndrome Study (SWEP53)

Abstract

A surveillance strategy of the heritable TP53-related cancer syndrome (hTP53rc), commonly referred to as the Li-Fraumeni syndrome (LFS), is studied in a prospective observational nationwide multi-centre study in Sweden (SWEP53). The aim of this sub-study is to evaluate whole-body MRI (WB-MRI) regarding the rate of malignant, indeterminate, and benign imaging findings and the associated further workup generated by the baseline examination. Individuals with hTP53rc were enrolled in a surveillance program including annual whole-body MRI (WB-MRI), brain-MRI, and in female carriers, dedicated breast MRI. A total of 68 adults ≥18 years old have been enrolled to date. Of these, 61 fulfilled the inclusion criteria for the baseline MRI scan. In total, 42 showed a normal scan, while 19 (31%) needed further workup, of whom three individuals (3/19 = 16%) were diagnosed with asymptomatic malignant tumours (thyroid cancer, disseminated upper GI cancer, and liver metastasis from a previous breast cancer). Forty-three participants were women, of whom 21 had performed risk-reducing mastectomy prior to inclusion. The remaining were monitored with breast MRI, and no breast tumours were detected on baseline MRI. WB-MRI has the potential to identify asymptomatic tumours in individuals with hTP53rc syndrome. The challenge is to adequately and efficiently investigate all indeterminate findings. Thus, a multidisciplinary team should be considered in surveillance programs for individuals with hTP53rc syndrome.

Keywords: Li–Fraumeni; MRI screening; cancer; cancer prevention; clinically actionable TP53 variant; germline TP53; hTP53rc syndrome; hereditary breast cancer; hereditary cancer syndrome; surveillance program; whole-body MRI.

Figure 1

Display protocol of MR-imaging pulse sequences as specified in the SWEP53 study (female). Coronal stitched reformatted whole-body images with (a) T2-weighted (b) T1-weighted Dixon-based gradient-echo sequence with fat and water. (c) Opposed-phase (water and fat images no shown), echo-planar-based diffusion weighted images with b-values of (d) 50 s/mm² and (e) 800 s/mm². A 30 mm paravertebral thoracic lesion was found (d,e), yellow arrows, regarded as a schwannoma. Note the incomplete coverage of the distal part of the extremities on the whole-body images, in this case due to the individual’s size. The performed breast and brain MRI are not shown.

Figure 2

Flowchart of included individuals in SWEP53 and their imaging outcomes. * Two patients were not eligible for WB-MRI due to recurrent disease/new cancer diagnosis; two participants had not yet undergone WB-MRI. One person could not perform MRI due to pain; one withdrew consent for the study; one pending result. ** Normal scans = do not require any further workup. *** Lesions requiring further workup (imaging, fine needle aspiration cytology, biopsy, or referrals).

Figure 3

Anatomical distribution of baseline WB-MRI findings. Green indicating benign lesion, yellow indeterminate, and red indicating malignant findings. Image created with BioRender.com (accessed on 7 December 2021).