Strikingly, and somewhat unexpectedly, people who develop three or more primary cancers have less aggressive malignancies, presenting at earlier stages, some with strong family histories. Importantly, it has been previously reported that individuals who develop three or more distinct cancers have a prolonged survival rate similar to the age-matched normal population (Amer et al 2014). This prolonged survival suggests an ability to restrict tumour growth/metastasis, with some individuals responding well to therapy for many years and even decades, often only eventually succumbing to one of their cancers later in life. Consistent with the previous study, our cohort of 26 individuals currently have a median age of 72 years, with 23 of 26 (88%) individuals still alive.
In order to examine the host response to cancer in these individuals, OPAL multiplex immunostaining of 42 tumours from 24 patients were selected. Fourteen cases (52%) were patients with ³ three primary cancers; as controls, two cases (7.4%) had two primary cancers and one non-malignant tumour; three cases (11%) were super-responders (diagnosed with only one cancer, but which responded well to treatment over more than 5 years), and five cases (30%) were rapid progressors (survived less than one year from diagnosis). Our aim was to compare features of the tumour microenvironment that could potentially be used as predictors of survival outcome. After evaluating tumour size and quality as being appropriate for multiplex immunostaining, each tumour sample was assigned to a response score based on the known clinical outcomes for each tumour and time during patient journey and survival.
Using the image analysis software, QuPath, and the spatial analysis R package, SPIAT, a spatial image analysis pipeline was established and used to explore the interactions between the tumour and the associated tumour microenvironment. Preliminary analysis of images from the first 12 tumours stained with one of two six-marker panels, indicated that specific tumour infiltrating lymphocytes may contribute to a patient’s survival. Additional analyses will be presented.