Aim

Neoadjuvant chemoradiotherapy is given with hopes to facilitate radical surgery and decrease the risk of recurrence by downstaging the tumour, partially or ideally completely. Partial response classifications are biased and have a low interobserver agreement, which leads to conflicting results on the relevance of tumour regression grading (TRG) systems1,2. TRG and tumour downstaging are well-known response indicators and have even been proposed as surrogate outcome measures of neoadjuvant therapies3. For this to become feasible and reliable, TRG systems need to be improved. Understanding the biological processes happening will shed light on possible future treatment strategies. In previous studies in oesophageal4 (OC) and rectal cancer (RC), two main patterns of response were observed among partial responders to therapy. These patterns were predictors of survival, although their biological reason is unknown. In this study, we aim to characterize a cohort of 190 patients with AC (NOS) of the rectum who have undergone neoadjuvant chemoradiotherapy. For this, we will explore the relationship between these two patterns of response and other clinicopathological features. Further, we will optimize a hyperplex immunofluorescence panel with tumour, immune, fibroblast, EMT, and other markers to understand the spatial proteomic landscape of these tumours. Results will follow.