1. A pilot surveillance study in TP53 mutation carriers utilizing whole body MRI Mandy Ballinger PhD Peter MacCallum Cancer Centre Melbourne, Australia

2. Cancer risk  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

3. Current guidelines  LFS spectrum of cancers sarcomas, leukemias, brain tumours, breast cancers, adrenocorticol tumours & others  Surveillance recommendations focus on breast and CRC risk

4. Previous studies

5. Collaborations  SIGNIFY Ros Eeles UK  Li Fraumeni Exploration (LiFE) Consortium Mai et al. Cancer Genet 2012 205(10):479-87 Institut Gustav Roussy France LIFSCREEN Sick Kids Canada TORONTO PROTOCOL AC Camargo Cancer Centre Brazil Dana Farber Cancer Institute USA National Cancer Institute USA

6. Surveillance protocol  Primary objective Estimate the prevalence and incidence of investigable lesions by WBMRI  Eligibility criteria TP53 mutation carrier or 50% risk Aged 18-70 yrs ECOG 0 or 1 No active cancer diagnosis

7. Schedule

8. Demographics

9. WBMRI WBMRI ~ 2 hrs 2 independent reads Discussion Comparison with previous scans Further investigations or not Further investigations or not 13 scans completed 10 yr1, 3 yr2 4 patients requiring further investigations

10. WBMRI follow up Patient 4 Lumbar region L2-L5 105 x 63 x 39mm mass T2 hyperintense nodule WDLPS

11. 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)

12. Psychological impact

13. 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

14. Acknowledgements SMOC participants The Johanna Sewell Memorial Fund SMOC investigators Gillian Mitchell (Principal Investigator) Sue Shanley David Thomas Nick Ferris Kate Moodie Clair Shadbolt Marion Harris Mary-Anne Young Janet Hiller Kate McBride SIGNIFY Ros Eeles Emma Killick LiFE Consortium Data Management Eveline Niedermayr Jo McKinley Lara Petelin kConFab team