Oesophageal adenocarcinoma (OAC) is an aggressive cancer with a five-year survival of 15%, and incidence is predicted to double in Ireland within the next 20 years. Current neo-adjuvant chemotherapy or chemoradiotherapy (neo-CRT) treatment strategies only benefit a minority (20-30% of patients) and there are currently no methods available to differentiate between responders and non-responders. Therefore, the majority of OAC patients given neo-CRT therapy will experience unnecessary side-effects and delays in time to surgery.
The goal of this study is to determine whether various tumour-scoring methods can predict patient clinical outcomes in OAC, such as response to neo-CRT treatment. The Immunoscore method involves measurement of immune markers (CD3, CD8, and CD45RO) in tumours and has shown superior predictive value to current UICC/TNM staging systems in colorectal cancer. We intend to assess the prognostic value of the traditional Immunoscore in OAC, and also in combination with expression of another immune marker, HLA-DR, which we have previously shown to have significant prognostic potential.
Other tumour characteristics such as tumour budding, poorly differentiated clusters, percentage tumour stroma and lymphovascular invasion and density, which have shown promise as prognostic markers in other cancer types, will also be assessed in the novel context of OAC, for their ability to predict patient outcomes. Digital pathology methodology will be employed to standardise our measurements and minimise variability. Circulating markers of inflammation will also be measured in matched OAC patient serum, and levels will be correlated with tumour microenvironment scores.
We aim to develop standardised methods of reliably measuring tumour and immune characteristics of potential prognostic value in OAC, which may be adopted for routine use in hospitals. As well as its timely clinical relevance, this project will yield plentiful data on the role of the immune system in cancer, and the factors required for successful tumour eradication.
