A pilot surveillance study in TP53 mutation carriers

utilizing whole body MRI

Mandy Ballinger PhD

Peter MacCallum Cancer CentreMelbourne, Australia

Cancer r isk Lifetime cancer risk in TP53 families ascertained on family history

>90% females & 60% males by age 50 - Li Fraumeni Syndrome

International Sarcoma Kindred Study (ISKS) 1/30 sarcoma cases carry a germ line TP53 variant

Penetrance in families ascertained by genotype is not known

Increasing genomic capacity detecting more TP53 carriers creating a pressing clinical need

Current guidel ines

LFS spectrum of cancerssarcomas, leukemias, brain tumours, breast cancers,adrenocorticol tumours & others

Surveillance recommendations focus on breast and CRC risk

Previous studies

Col laborati ons

SIGNIFY Ros Eeles UK

Li Fraumeni Exploration (LiFE) ConsortiumMai et al.

Cancer Genet 2012 205(10):479-87

Institut Gustav Roussy France LIFSCREEN Sick Kids Canada TORONTO PROTOCOL AC Camargo Cancer Centre BrazilDana Farber Cancer Institute USANational Cancer Institute USA

Survei l lance protocol

Primary objective Estimate the prevalence and incidence of

investigable lesions by WBMRI

Eligibility criteriaTP53 mutation carrier or 50% riskAged 18-70 yrsECOG 0 or 1No active cancer diagnosis

Schedule

Demographics

WBMRIWBMRI ~ 2 hrs

2 independent reads

Discussion

Comparison with previous scans

Further investigations or not

13 scans completed 10 yr1, 3 yr2

4 patients requiring further investigations

WBMRI fo l low up

Patient 4Lumbar region L2-L5105 x 63 x 39mm massT2 hyperintense noduleWDLPS

Other screening 15 clinical reviews & physical exams (11 yr1 & 4 yr2)

8 referrals: 5 skin reviews (2 lesions excised, 1 BCC)

1 urology (PSA)

2 radiology (2 US of surgical scars)

2 colonoscopies 2 gastroscopies 15 full blood evaluations 4 breast MRI 5 clinical breast exams 1 US liver lesion (seen on breast MRI)

4 FOBT (2 results pending)

Psychologica l impact

Summary

12 participants, 13 WBMRI

WBMRI F/UP 7 further investigations in 4 individuals 2 malignancies detected

No adverse psychological impact

Findings so far support continuation to allow longer term evaluation

AcknowledgementsSMOC participants

The Johanna Sewell Memorial Fund

SMOC investigatorsGillian Mitchell (Principal Investigator)Sue ShanleyDavid ThomasNick FerrisKate MoodieClair ShadboltMarion HarrisMary-Anne YoungJanet HillerKate McBride

SIGNIFYRos EelesEmma Killick

LiFE Consortium

Data ManagementEveline Niedermayr

Jo McKinleyLara PetelinkConFab team