380. GROWTH CHARACTERISTICS OF ESOPHAGEAL PATIENT DERIVED ORGANOIDS REFLECT CLINICOPATHOLOGIC VARIABLES

Abstract Background Esophageal patient derived organoids (PDOs) are three-dimensional cell culture models derived from esophageal cancer tissue. We have previously shown that PDOs recapitulate the genetic and morphologic characteristics of the primary tumour, and that PDOs may predict patient responses to neoadjuvant regimens and potentially allow personalisation perioperative therapies. Nevertheless, up to 30% of tissue samples fail to establish organoids in vivo, although the reasons for this are unclear. This study interrogates the clinical characteristics of biopsies that establish or fail to establish PDOs. Methods Esophageal adenocarcinomas from locally advanced (LA) or metastatic (M) disease were biopsied at initial endoscopy, following surgical resection, or image-guided biopsy of metastatic disease (n=75 total). Following a standardised protocol, cells were dissociated and seeded for organoid culture. Organoids are considered ‘established’ after passage 4. Samples were discarded if there was obvious contamination (n=9) or if there were no obvious tumour cells (n=6). Clinicopathologic variables for successfully established or unsuccessfully established were compared for both LA and M disease. Statistical analysis was performed to interrogate characteristics associated with successfully establishing organoids. Results There were significant differences between successful and unsuccessful organoids. Organoids were more likely to be established from endoscopic biopsies (p=0.002). Samples pre-treated with neoadjuvant chemoradiation or chemotherapy were less likely to grow (p=0.02). Samples from poorly differentiated tumours were less likely to grow compared with well and moderately differentiated tumours (p=0.05). Tumour stage, lymphovascular invasion, perineural invasion, MSI status and HER-2 status were not associated with growth characteristics. Conclusion Growth characteristics of esophageal adenocarcinoma PDOs correlate with clinicopathologic characteristics. Samples from patients who have undergone chemotherapy or chemoradiation, and poorly differentiated tumours are less likely to establish in vitro models. Understanding the altered in vitro growth patterns is key to translating use of organoids into clinical practice.