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Development of prognostic screening tools to predict patient response to neoadjuvant chemoradiotherapy treatment for oesophageal adenocarcinoma

Oesophageal adenocarcinoma (OAC) is an aggressive malignancy with poor prognosis, and incidence has increased 5-fold in the last 30 years. Multi-modal neoadjuvant chemoradiotherapy (neo-CT) regimens are increasingly adopted with surgery as the standard of care. However, 70-80% of patients do not respond to neo-CT and may suffer unnecessary side effects and delay to surgery. There is currently no way to predict which patients will respond to neo-CT treatment.
We aim to develop methods for identifying OAC patients likely to benefit from neo-CT treatment by histological analysis of tumour tissue at the time of diagnosis. We have previously demonstrated a strong correlation between expression of the major histocompatibility complex class II molecule HLA-DR and patient survival. We hypothesise that HLA-DR may also be used to predict patient responses to neo-CT treatment. We are also interested in characterising cells expressing HLA-DR in tumours, in order to gain a better understanding of immune responses in OAC. As well as analysing specific markers, we will also explore the use of prognostic tumour scoring strategies to predict patient responses to neo-CT treatment. Such scoring strategies grade the level of immune response evident in the tumour microenvironment and have been shown to be useful in predicting patient outcomes in colorectal cancer. To date no such application of this technology has been tested in OAC.
The proposed project will be carried out in the Dept of Surgery at St James’s hospital, a well-established research environment and a National Centre for Oesophageal and Gastric Cancer. Work will be carried out using specimens from an ongoing clinical trial testing the efficacy of two different neo-CT regimens (CROSS and MAGIC). By clarifying the prognostic abilities of analysing immune responses evident in OAC tumours, this work will aid patient stratification, avoiding unnecessary treatment and ultimately improve current treatment strategies.