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Psychosocial effects of whole-body MRI screening in adult high-risk pathogenic TP53 mutation carriers: a case-controlled study (SIGNIFY)
  1. Elizabeth K Bancroft1,2,
  2. Sibel Saya2,3,
  3. Emma Brown4,
  4. Sarah Thomas1,
  5. Natalie Taylor1,
  6. Jeanette Rothwell5,
  7. Jennifer Pope2,
  8. Anthony Chamberlain2,
  9. Elizabeth Page2,
  10. Sarah Benafif2,
  11. Helen Hanson6,
  12. Alexander Dias2,
  13. Christos Mikropoulos7,
  14. Louise Izatt8,
  15. Lucy Side9,
  16. Lisa Walker10,
  17. Alan Donaldson11,
  18. Jackie A Cook12,
  19. Julian Barwell13,
  20. Vicki Wiles14,
  21. Lauren Limb15,
  22. Diana M Eccles16,
  23. Martin O Leach17,18,
  24. Susan Shanley19,
  25. Fiona J Gilbert20,
  26. David Gallagher21,
  27. Balashanmugam Rajashanker22,23,
  28. Richard W Whitehouse22,
  29. Dow-Mu Koh17,18,
  30. S Aslam Sohaib17,
  31. D Gareth Evans5,
  32. Rosalind A Eeles1,2,
  33. Leslie G Walker24
  1. 1 Oncogenetics Team, The Royal Marsden NHS Foundation Trust, London, UK
  2. 2 Oncogenetics Team, The Institute of Cancer Research, London, UK
  3. 3 Centre for Cancer Research & Department of General Practice, University of Melbourne, Melbourne, Victoria, Australia
  4. 4 Medical Oncology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  5. 5 Clinical Genetics, Manchester University NHS Foundation Trust, Manchester, UK
  6. 6 South West Thames Regional Genetics Service, St Georges NHS Foundation Trust, London, UK
  7. 7 St Luke's Cancer Centre, Royal Surrey County Hospital, Guildford, UK
  8. 8 Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK
  9. 9 Clinical Genetics, Wessex Clinical Genetics Service, Southampton, UK
  10. 10 Clinical Genetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  11. 11 Clinical Genetics, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
  12. 12 Department of Clinical Genetics, Sheffield Children's Hospital, Sheffield, UK
  13. 13 Clinical Genetics, University Hospitals of Leicester NHS Trust, Leicester, UK
  14. 14 Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  15. 15 North West Thames Regional Genetics Service (Kennedy-Galton Centre), London North West University Healthcare NHS Trust, Harrow, UK
  16. 16 Cancer Sciences, University of Southampton Faculty of Medicine, Southampton, UK
  17. 17 Department of Diagnostic Radiology, The Royal Marsden NHS Foundation Trust, London, UK
  18. 18 Radiotherapy and Imaging, The Institute of Cancer Research, London, UK
  19. 19 Formerly at the Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  20. 20 Department of Radiology, University of Cambridge, Cambridge, UK
  21. 21 Cancer Genetics Service, Mater Hospital School, Dublin, Ireland
  22. 22 Radiology, Manchester Royal Infirmary, Manchester, UK
  23. 23 Radiology, St Mary's Hospital, Manchester, UK
  24. 24 Postgraduate Medical Studies, University of Hull, Hull, UK
  1. Correspondence to Dr Elizabeth K Bancroft, Royal Marsden NHS Foundation Trust, London, UK; elizabeth.bancroft{at}


Background Germline TP53 gene pathogenic variants (pv) cause a very high lifetime risk of developing cancer, almost 100% for women and 75% for men. In the UK, annual MRI breast screening is recommended for female TP53 pv carriers. The SIGNIFY study (Magnetic Resonance Imaging screening in Li Fraumeni syndrome: An exploratory whole body MRI) study reported outcomes of whole-body MRI (WB-MRI) in a cohort of 44 TP53 pv carriers and 44 matched population controls. The results supported the use of a baseline WB-MRI screen in all adult TP53 pv carriers. Here we report the acceptability of WB-MRI screening and effects on psychosocial functioning and health-related quality of life in the short and medium terms.

Methods Psychosocial and other assessments were carried out at study enrolment, immediately before MRI, before and after MRI results, and at 12, 26 and 52 weeks’ follow-up.

Results WB-MRI was found to be acceptable with high levels of satisfaction and low levels of psychological morbidity throughout. Although their mean levels of cancer worry were not high, carriers had significantly more cancer worry at most time-points than controls. They also reported significantly more clinically significant intrusive and avoidant thoughts about cancer than controls at all time-points. There were no clinically significant adverse psychosocial outcomes in either carriers with a history of cancer or in those requiring further investigations.

Conclusion WB-MRI screening can be implemented in TP53 pv carriers without adverse psychosocial outcomes in the short and medium terms. A previous cancer diagnosis may predict a better psychosocial outcome. Some carriers seriously underestimate their risk of cancer. Carriers of pv should have access to a clinician to help them develop adaptive strategies to cope with cancer-related concerns and respond to clinically significant depression and/or anxiety.

  • Li-Fraumeni syndrome
  • TP53 gene pathogenic variant
  • MRI
  • case controlled study
  • psychosocial

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  • Contributors LeW, EKB, EB, SiS, DGE and RAE contributed to the concept and study design. EKB, LeW and RAE wrote the manuscript. EKB, SiS, EP, AC, JP, JR, ST and DGE collected the data and analysed or interpreted the data. JR, NT, ST, HH, JP, SB, CM, ADi, ADo, JAC, JB, VW, LL, LiW, DME, MOL, SSh, FG, DG, BR, RWW, MK, SuS and DGE recruited patients and/or performed the clinical evaluation of patients. All authors revised and approved the final version. LeW and EKB are responsible for the overall content.

  • Funding This work was supported by a grant from The Annabel Evans Memorial Fund to The Royal Marsden Cancer Charity. This study represents independent research supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. This study was supported by the Clinical Research Facility at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, together with support to the CRUK Cancer Imaging Centre (C1060/A16464). DGE is supported by an NIHR research grant to the Biomedical Research Centre Manchester (IS-BRC-1215-20007). FG receives funding from the NIHR as a senior investigator.

  • Competing interests RAE: (1) GU-ASCO meeting in San Francisco, January 2016: honorarium as speaker, $500; (2) Royal Marsden NHS Foundation Trust talk (Title: Genetics and Prostate Cancer), November 2017: £1100 support from Janssen; and (3) University of Chicago invited talk, May 2018: honorarium as speaker, $1000.

  • Patient consent for publication Not required.

  • Ethics approval The SIGNIFY study was approved by the Health Research Authority NRES Committee London-Brent (12/LO/0781).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

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