Towards biomarker-driven therapies for gastroesophageal cancer A changing landscape

Resectable gastroesophageal cancer has a poor outcome with a five-year survival rate of approximately 20%. Different treatment strategies based on chemotherapy or chemoradiotherapy are utilized across the globe. These therapies are given without stratification for patient or tumor characteristics. In this thesis we first conducted multiple literature reviews with (network) meta-analyses to systematically compare survival for different treatment strategies, prognostic or predictive factors and adverse events. In the second part we describe the results of two clinical trials and related translational biomarker research. In a phase II trial we combined atezolizumab with neoadjuvant chemoradiotherapy for resectable esophageal adenocarcinoma. Several biomarkers were identified from this trial in tissue (IFN-γ, PD-L1) and in blood (cell‐free DNA, peripheral blood mononuclear cells). We also investigated the additional value of combining imaging-derived radiomic features with patient characteristics and cell‐free DNA data for prognostic purposes. Finally, our findings from a randomized clinical trial investigating a gut microbiota intervention and a cohort of esophageal cancer microbiota samples contribute to the growing body of evidence regarding the therapy modulating role of the gastrointestinal microbiome. Concluding, this thesis will boost the further development of biomarker-based treatment stratification for gastroesophageal cancer.