Magnetic Resonance Imaging Screening in Li Fraumeni Syndrome

Study Overview
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Brief Summary
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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.

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

Conditions
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Li-Fraumeni Syndrome

Intervention / Treatment
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* Other: Whole body MRI
* Other: Psychological questionnaires


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| TP53 mutation carriers<br>Carriers of TP53 mutation not known to be low penetrance | Other: Whole body MRI<br>* Individuals will undergo whole body and brain MRI<br>Other: Psychological questionnaires<br>* All recruits will complete questionnaires at 6 time points to assess psychological impact<br>|
| Population controls<br>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<br>* Individuals will undergo whole body and brain MRI<br>Other: Psychological questionnaires<br>* All recruits will complete questionnaires at 6 time points to assess psychological impact<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Li-Fraumeni Syndrome, Whole Body Magnetic Resonance Imaging, TP53, Psychological Impact