The Impact of Signet Ring Cell Differentiation on Outcome in Patients with Esophageal and Gastroesophageal Junction Adenocarcinoma

Sander J M Van Hootegem,Iain G Thomson,Bas P L Wijnhoven,David C Gotley,B Mark Smithers,Andrew P Barbour,Janine M Thomas,Sjoerd M Lagarde,Jan J B Van Lanschot,Sandra Brosda,Michael Gartside

doi:10.1245/s10434-019-07322-x

Abstract

BackgroundLittle is known about the association between signet ring cell (SRC) differentiation and response to neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal and junctional adenocarcinoma (EAC). We aimed to assess if SRC differentiation is associated with survival and response to nCT or nCRT in patients with EAC.MethodsPatients who underwent nCT and nCRT followed by surgery for EAC from 2000 until 2016 were identified from two institutional prospectively maintained databases. The pretreatment biopsy report or surgical resection specimen was used to differentiate patients into an SRC or non-SRC group.ResultsOverall, 129 (19%) of 689 patients included had SRCs (nCT: n = 64; nCRT: n = 65). The SRC group had a more advanced ypT stage (p = 0.003), a higher number of positive lymph nodes in the resection specimen {median (interquartile range [IQR]) 2 [0–5] vs. 1 [0–3]; p = 0.002} and a higher rate of R1/R2 resections (19.4% vs. 12%; p = 0.026). SRC differentiation was not an independent prognostic factor for overall survival (OS) or disease-free survival (DFS). Following nCT, the SRC group had significantly shorter DFS (median [IQR] 12 [5–50] vs. 23 [8–164]; p = 0.013), but not OS, compared with the non-SRC group. In contrast, no differences according to SRC status for OS or DFS were found in patients who underwent nCRT.ConclusionsSRC differentiation was not independently associated with worse OS in patients with EAC who underwent neoadjuvant therapy and surgery. However, nCRT was associated with greater tumor downstaging and better DFS.

Highlights

Little is known about the association between signet ring cell (SRC) differentiation and response to neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy in patients with esophageal and junctional adenocarcinoma (EAC)
Of the remaining 689 study patients, 129 patients had tumors that showed SRC histology, and 560 patients had no evidence of SRC
No statistically significant differences in clinical characteristics were found between the SRC and non-SRC groups (Table 1); pathological T stage [p = 0.003], number of positive lymph nodes in the resection specimen and proportion of R1/R2 resections (19.4% vs. 12.0%; p = 0.026) were higher in the SRC group (Table 2)

Summary

Introduction

Little is known about the association between signet ring cell (SRC) differentiation and response to neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal and junctional adenocarcinoma (EAC). We aimed to assess if SRC differentiation is associated with survival and response to nCT or nCRT in patients with EAC. Patients who underwent nCT and nCRT followed by surgery for EAC from 2000 until 2016 were identified from two institutional prospectively maintained databases. The pretreatment biopsy report or surgical resection specimen was used to differentiate patients into an SRC or non-SRC group.

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