453. THE EFFECTIVITY OF NEOADJUVANT CHEMORADIOTHERAPY IN ESOPHAGEAL ADENOCARCINOMA WITH PRESENCE OF EXTRACELLULAR MUCINE, SIGNET-RING CELLS OR POORLY COHESIVE CELLS

Abstract

Abstract Five-year overall survival of patients with locally advanced esophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgery is 40%. Better understanding of histopathological factors that influence treatment response is necessary to identify patients with expected poor prognosis. Aim of the study was to assess whether pre- and post-treatment presence of excessive (≥1%) extracellular mucus accumulation, signet-ring cells (SRC) and/or poorly cohesive cells were associated with poor response to nCRT, independent of tumor differentiation grade. This was a retrospective cohort study. Patients included were diagnosed with an adenocarcinoma of the esophagus or GEJ, who underwent CROSS and were planned to undergo esophagectomy between 2001–2019 at two university hospitals. Percentages of the factors extracellular mucus, SRC and poorly cohesive cells were scored by experienced pathologists in pre-treatment biopsies and resection specimen slides relative to the primary tumor area. Multivariable logistic regression models and Cox proportional-hazards models were used to evaluate the histopathological factors in relation to tumor regression grade (TRG) 1–2 (<10% tumor) vs TRG 3–4 (>10% tumor), overall survival (OS) and disease-free survival (DFS). Some 325 patients were included (median age 65 years, 280/325 (86%) male). In pre-treatment biopsies, ≥1% extracellular mucus was present in 66/325 (20%); ≥1% SRC 43/325 (13%); ≥1% poorly cohesive cells 126/325 (39%). In patients undergoing esophagectomy, 150/284 (53%) had TRG 3–4. Median OS in all patients was 44 months (95%CI: 36–62). Factors in pre-treatment biopsies were not associated with outcomes independent of differentiation grade. Only patients with ≥1% SRC in the resection specimen had poorer OS (Fig 1): HR for death 1.71, 95%CI: 1.06–2.76, adjusted for age, sex, pre-treatment pathological tumor and nodal stage (pre-pT/pre-pN), ypN and tumor differentiation grade. Extracellular mucus accumulation, SRC and/or poorly cohesive cells in pre-treatment biopsies in patients with esophageal adenocarcinoma treated with nCRT are not associated with response to nCRT, OS or DFS. Their presence should not be a reason to refrain from CROSS nCRT. However, persistence of SRC in the resection specimen after nCRT is an indicator of poor prognosis.