Magnetic Resonance Imaging Screening in Li Fraumeni Syndrome (SIGNIFY)

Magnetic Resonance Imaging Screening In Li Fraumeni Syndrome: An Exploratory Whole Body MRI Study

This study is aimed at exploring the use of whole body MRI for early cancer detection in TP53 mutation carriers and population controls, with the hypothesis that more cancers will be detected in the TP53 mutation carrier group. A secondary end-point will be the number of incidental findings detected and subsequent investigations required. A series of questionnaires will be used to assess the psychological impact of screening on both the study and control group.

Study Overview

• Status: Completed
• Conditions: Li-Fraumeni Syndrome
• Intervention / Treatment: Other: Whole body MRI; Other: Psychological questionnaires

• Study Type: Observational
• Enrollment (Actual): 88

Contacts and Locations

Study Locations

• United Kingdom
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Cancer Genetics Unit, Royal Marsden Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The TP53 mutation carriers will be recruited from genetics clinics and through advertising.

The population controls will be recruited through advertising

Description

Inclusion Criteria:

• Carrier of germline TP53 mutation which, in the view of the geneticist, is not known to be low penetrance OR non-related individual with no personal history of malignancy and no first degree relatives diagnosed with malignancy under the age of 50 years
• Please note, TP53 carrier cohort is complete and no longer open to recruitment
• Age between 18 and 60
• Able to give informed consent

Exclusion Criteria:

• Individual with low penetrance TP53 mutation
• Individual with TP53 variant of unknown significance.
• Previous malignancy diagnosed < 5 years ago in TP53 carriers (except non-melanomatous skin cancer or cervical CIS) Previous history of malignancy in non-related controls (except non-melanomatous skin cancer or cervical CIS)
• Current symptoms suggestive of malignancy
• Contraindication to MRI (such as non-MR compatible metal implants) as specified by the standard MR safety checklist
• Claustrophobia
• ECOG performance status >2

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TP53 mutation carriers; Carriers of TP53 mutation not known to be low penetrance	Other: Whole body MRI; Individuals will undergo whole body and brain MRI; Other: Psychological questionnaires; All recruits will complete questionnaires at 6 time points to assess psychological impact
Population controls; Population controls will be sex and aged matched (+/- 5 years) to the TP53 mutation carrier group, with no personal history of cancer and no family history of cancer diagnosed under 50 years	Other: Whole body MRI; Individuals will undergo whole body and brain MRI; Other: Psychological questionnaires; All recruits will complete questionnaires at 6 time points to assess psychological impact

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis of malignant disease	Following MRI scan further investigations may be required to diagnose malignancy	Within 12 months of MRI scan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis of relevant non-malignant disease	Further investigations may be required following the MRI to characterise such findings.	12 months following MRI scan
Diagnosis of non-relevant disease, number and type of investigations required		12 months following MRI
Psychological impact of MRI screening	Psychological questionnaires to be completed at intervals up till 12 months post scan	12 months following MRI screening

Collaborators and Investigators

• Sponsor: Institute of Cancer Research, United Kingdom
• Collaborators: Cancer Research UK; National Institute for Health Research, United Kingdom
• Investigators: Principal Investigator: Rosalind Eeles, PhD, Institute of Cancer Research, Surrey, UK

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: November 27, 2012
• First Submitted That Met QC Criteria: November 27, 2012
• First Posted (Estimate): November 29, 2012

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: TP53; Li-Fraumeni Syndrome; Whole Body Magnetic Resonance Imaging; Psychological Impact
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Neoplasms; Disease; Genetic Diseases, Inborn; Neoplastic Syndromes, Hereditary; DNA Repair-Deficiency Disorders; Syndrome; Li-Fraumeni Syndrome
• Other Study ID Numbers: CCR3802

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymised data can be applied for via the Steering Committee