E-Poster Presentation 34th Lorne Cancer Conference 2022

Developing and Surviving Multiple Primary Cancers (#325)

Kristy Shield-Artin 1 2 , Justin Bedo 1 2 , Amelia Ang 1 2 , Holly Barker 1 2 , Gayanie Ratnayake 3 , Damien Kee 1 3 4 , Warren Zhou 1 , Orla McNally 3 , Jocelyn Penington 1 , Matthew J Wakefield 1 2 3 , Roger L Milne 2 5 6 , Melissa C Southey 2 5 6 , Susan J Ramus 7 , Tony Papenfuss 1 2 4 , Magdalena Plebanski 8 , Clare Scott 1 2 3 4
  1. WEHI, Parkville, VIC, Australia
  2. University of Melbourne, Parkville, Vic, Australia
  3. Royal Women's Hospital, Parkville, VIC, Australia
  4. Peter MacCallum Cancer Institute, Parkville, VIC, Australia
  5. Monash University, Melbourne, VIC, Australia
  6. Cancer Council Victoria, Melbourne, Australia
  7. University of New South Wales, Sydney, NSW, Australia
  8. RMIT, Bundoora, VIC, Australia

Developing two primary cancers is not uncommon and presents an ongoing clinical problem. However, surprisingly, individuals who have been diagnosed with three or more primary cancers (3+ primary) in their lifetime appear to live to an age that is similar to age-matched controls (Amer et al. 2014). How these individuals are able to survive, and often thrive, despite multiple cancer diagnoses is not currently known.

In order to study the genetics and biology of developing and surviving multiple primary cancers, a comprehensive cohort of patient samples is needed. The WEHI Stafford Fox Rare Cancer Program (WEHI-SFRCP) collates a comprehensive repository of clinical information and patient samples. To date, WEHI-SFRCP has accrued 59 patients with multiple cancers, including 26 patients who have been diagnosed with 3+ primary cancers. Collectively, these 26 patients with 3+ primary cancers have been diagnosed with 95 independent cancers representing more than 30 different cancer types. Importantly, data from WEHI-SFRCP patients who develop 3+ primary cancers in their life-time have a 3x reduced risk of dying compared to patients diagnosed with only two cancers in their lifetime. This parallels the earlier Amer et al.study and currently equates to living around a decade longer with an average age of 69.8 yrs (3+ primary) compared with 59.8yrs (2 cancers only).

To elucidate why these individuals to survive so well, we have designed a comprehensive analysis program that uses whole exome sequencing (WES), multiplex imaging, transcriptomics and biomarker studies. Each tumour is reviewed by an anatomical pathologist and annotated, then assigned a response score based on the clinical response and general patient history. Tumours are then grouped by response score for analysis. To date, WES for 30 tumours (of 44 available) from 20 patients and OPAL multiplex imaging of 32 tumours from 14 patients has been completed. In our cohort, where all participants have had a rare cancer diagnosis, there is notable genetic predisposition to developing 3+ Primary cancers, with a known germline predisposition mutation identified in 9 of 20 (45%) patients so far. More work is required to uncover the mechanism of survival. We will discuss initial results from the tumour sequencing and multiplex imaging.