Poster Presentation 35th Lorne Cancer Conference 2023

Characterizing the tumour microenvironment in multiple primary cancers (#206)

Imalki Kariyawasam 1 2 , Kristy L Shield-Artin 1 2 , Justin Bedo 1 2 , Ling Min Amelia Ang 1 , Holly Barker 1 2 , Jocelyn Penington 1 , Rachael Taylor 1 , Ratana Lim 1 , Amandine Carmagnac 1 , Gayanie Ratnayake 3 , Suzan Sam 1 , Cassandra Vandenberg 1 2 , Matthew Wakefield 1 2 3 , Magdalena Plebanski 4 , Tony Papenfuss 1 2 , Clare Scott 1 2 3
  1. WEHI, Parkville, VIC, Australia
  2. University of Melbourne, Parkville, Vic, Australia
  3. Royal Women's Hospital, Parkville, VIC, Australia
  4. RMIT, Bundoora, VIC, Australia

The survival rate of cancer patients is improving globally, resulting in an increased likelihood of the development of a second or third primary cancer(1). Interestingly, individuals who develop three or more unrelated cancers in their lifetime (3+ cancers), have a life expectancy similar to the normal population, suggesting an ability to restrict tumour growth and metastasis(2). Some individuals respond well to therapy for many years and even decades, often only eventually succumbing to one of their cancers later in life.  Therefore, investigating the cancers from these patients might reveal host factors contributing to relative longevity, despite the presence of cancer.

The WEHI-Stafford Fox Rare Cancer Program (SFRCP) has 72 individuals enrolled who have had multiple primary cancer diagnoses, including 32 individuals with 3+cancers. In our SFRCP cohort, the current median age for people with 3+ and 2 primary cancer is 73 and 61 years respectively, which is consistent with a previous study(2). Archival tumour tissue, from these individuals along with control individuals who either responded well to therapy over a long time (super responders) or whose cancer progressed rapidly, from SFRCP were used for this study.

Germline and tumour DNA were sequenced by whole exome sequencing (WES) to identify pathogenic variants. Of 25 cases in the cohort with 3+ cancers who have had germline sequencing, eight (32%) harbored pathogenic variants and another three (12%) had variants of unknown significance (VUS), confirming the expected finding that genetic predisposition contributes to the development of multiple primary cancers.

The relationship of the tumour micro-environment on tumour response is being studied using OPALTM 7-colour multiplexed immunofluorescence images of 50 tumours from 34 patients, including 24 cancer types and 16 which were considered rare. OPAL analysis allows broad profiling of the presence and relative location of immune cells in a tumour. Investigating what is special about these individuals with multiple primary cancers has the potential to uncover new mechanisms that could be used to improve cancer treatments

  1. 1. Vogt A, Schmid S, Heinimann K, Frick H, Herrmann C, Cerny T, et al. Multiple primary tumours: challenges and approaches, a review. ESMO Open. 2017;2(2):e000172.
  2. 2. Amer MH. Multiple neoplasms, single primaries, and patient survival. Cancer Manag Res. 2014;6:119-34.