There will be two study arms:

1. patients with suspected or diagnosed localized gastroesophageal adenocarcinoma (GEA) and
2. patients diagnosed with de novo metastatic gastroesophageal adenocarcinoma. Fresh tumour, adjacent normal tissue materials, and blood samples will be acquired and utilized to generate molecular data. Stool or rectal swab samples will also be acquired for microbiome analysis. Physiologic, quality of life, epidemiologic, frailty, and other clinical data will be systematically collected as standard of care to serve as clinical correlates for the molecular data.

Arm 1 Primary Objectives

1. Feasibility to produce a potential molecular signature in a clinically meaningful time point in patients with locally advanced GEA
2. Study the molecular characteristics of GEA in patients with localized and resectable disease and identify predictive signatures of response to induction therapy and the development of novel treatment regimens
3. To validate previously identified mutational signatures that defined subgroups of GEA

Arm 2 Primary Objectives

1. Feasibility to produce a potential molecular signature in a clinically meaningful time point for patients with advanced GEA on 1st line chemotherapy
2. Use of genotypes and genomic analyses to define therapies, and develop predictive and prognostic models
3. Assess the feasibility of prospectively identifying distinct genomic characteristics which associate with response to systemic therapy and survival

STUDY ENDPOINTS:

1. Feasibility of obtaining timely sequencing data (8-12 weeks) to guide treatment for patients progressing on 1st line treatment
2. Feasibility of using ctDNA, metabolome, immune profiling and other emerging technologies to guide treatment
3. Establish a program of personalized care for GEA patients in terms of pre-treatment assessment (Physiological and Frailty Risk Assessment, QOLQ, 4. Sarcopenia and Adiposity measurements) and treatment based on clinical-genomic correlations
4. Establishment of repository of biospecimens (tumour, blood and microbiome)
5. Establishment of robust preclinical models of GEA: PDO and PDX models
6. Assess the feasibility of using PDO models to identify drug sensitivity to guide treatment decisions