title: Baseline results from the UK SIGNIFY study: a whole-body MRI screening study in TP53 mutation carriers and matched controls.
abstract: In the United Kingdom, current screening guidelines for TP53 germline mutation carriers solely recommends annual breast MRI, despite the wide spectrum of malignancies typically seen in this group. This study sought to investigate the role of one-off non-contrast whole-body MRI (WB MRI) in the screening of asymptomatic TP53 mutation carriers. 44 TP53 mutation carriers and 44 population controls were recruited. Scans were read by radiologists blinded to participant carrier status. The incidence of malignancies diagnosed in TP53 mutation carriers against general population controls was calculated. The incidences of non-malignant relevant disease and irrelevant disease were measured, as well as the number of investigations required to determine relevance of findings. In TP53 mutation carriers, 6 of 44 (13.6, 95% CI 5.2-27.4%) participants were diagnosed with cancer during the study, all of which would be considered life threatening if untreated. Two were found to have two primary cancers. Two participants with cancer had abnormalities on the MRI which were initially thought to be benign (a pericardial cyst and a uterine fibroid) but transpired to be sarcomas. No controls were diagnosed with cancer. Fifteen carriers (34.1, 95% CI 20.5-49.9%) and seven controls (15.9, 95% CI 6.7-30.1%) underwent further investigations following the WB MRI for abnormalities that transpired to be benign (p = 0.049). The cancer detection rate in this group justifies a minimum baseline non-contrast WB MRI in germline TP53 mutation carriers. This should be adopted into national guidelines for management of adult TP53 mutation carriers in addition to the current practice of contrast enhanced breast MRI imaging.
authors.affiliation: The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, London, UK.
authors.forename: Sibel
authors.initials: S
authors.lastname: Saya
authors.affiliation: The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, London, UK.|University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Killick
authors.affiliation: Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Taylor
authors.affiliation: Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Bancroft
authors.affiliation: Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Rothwell
authors.affiliation: The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Benafif
authors.affiliation: The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, London, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dias
authors.affiliation: The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, London, UK.|Cancer Unit, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, UK.
authors.forename: Christos
authors.initials: C
authors.lastname: Mikropoulos
authors.affiliation: The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, London, UK.
authors.forename: Jenny
authors.initials: J
authors.lastname: Pope
authors.affiliation: The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, London, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Chamberlain
authors.affiliation: Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Ranga
authors.initials: R
authors.lastname: Gunapala
authors.affiliation: Guys and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Izatt
authors.affiliation: Great Ormond Street Hospital & UCL Institute for Women's Health, London, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Side
authors.affiliation: Oxford University Hospitals, Oxford, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Walker
authors.affiliation: University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Tomkins
authors.affiliation: Sheffield Children's NHS Foundation Trust, Sheffield, UK.
authors.forename: Jackie
authors.initials: J
authors.lastname: Cook
authors.affiliation: University of Leicester, Leicester, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Barwell
authors.affiliation: University of Cambridge, Cambridge, UK.
authors.forename: Vicki
authors.initials: V
authors.lastname: Wiles
authors.affiliation: Northwick Park Hospital, London, UK.
authors.forename: Lauren
authors.initials: L
authors.lastname: Limb
authors.affiliation: University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Eccles
authors.affiliation: The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, London, UK.|Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Leach
authors.affiliation: Royal Marsden NHS Foundation Trust, London, UK.|Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Shanley
authors.affiliation: University of Cambridge, Cambridge, UK.
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Gilbert
authors.affiliation: St Georges Hospital, London, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Hanson
authors.affiliation: Mater Hospital, Dublin, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Gallagher
authors.affiliation: Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: Bala
authors.initials: B
authors.lastname: Rajashanker
authors.affiliation: Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Whitehouse
authors.affiliation: The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, London, UK.|Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Dow-Mu
authors.initials: DM
authors.lastname: Koh
authors.affiliation: Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: S Aslam
authors.initials: SA
authors.lastname: Sohaib
authors.affiliation: Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.affiliation: The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, London, UK. rosalind.eeles@icr.ac.uk.|Royal Marsden NHS Foundation Trust, London, UK. rosalind.eeles@icr.ac.uk.
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
mesh_terms: D000328:Adult; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D006113:United Kingdom; D051598:Whole Body Imaging / Q000379:methods; D055815:Young Adult
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Controls; Li Fraumeni syndrome; Screening; TP53 mutation carriers; Whole body MRI