The relevance and implications of signet-ring cell adenocarcinoma of the oesophagus

Bleaney, Christopher W.; Barrow, Mickhaiel; Hayes, Stephen; Ang, Yeng

doi:10.1136/jclinpath-2017-204863

Cited by 19 publications

(17 citation statements)

References 21 publications

(20 reference statements)

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“…Esophageal SRCC predicts a poor response to preoperative chemoradiation, with no survival benefit from neoadjuvant treatment even if downstaging occurs [ 36 ]. This finding was further supported on systematic review [ 37 ]. SRCCs though with microsatellite instability-high (MSI-H tumors), are predominately in the right colon, and show good response to immune checkpoint therapy [ 38 ].…”

Section: Discussionsupporting

confidence: 68%

Epidemiology of Signet Ring Cell Adenocarcinomas

Benesch

Mathieson

2020

Cancers

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Signet ring cell adenocarcinomas (SRCCs) are a rare histological subtype of adenocarcinomas with a poor prognosis, typically due to advanced disease at diagnosis. A signet ring cell, mimicking its moniker, contains abundant intracytoplasmic mucin that pushes the nucleus to the periphery. In these cancers, this cell feature comprises more than 50% of the tumor. Despite predilection for the gastrointestinal tract, and in particular the stomach, primary SRCCs are also described in other sites, typically in case reports. This literature, however, lacks a standardized overview of the SRCC disease entity. Using a retrospective cohort approach, we summarize the clinicodemographic and mortality outcomes of SRCCs in thirteen primary sites, comprising 95% of all SRCCs in the Surveillance, Epidemiology, and End Results Program (SEER), a population-level cancer database covering nearly one-third of the United States population. SRCCs general trends compared to matching nonvariant adenocarcinomas are earlier age of onset, with initial presentation favoring higher rates of regional or distant disease presentation and poor tumor differentiation. After multivariable analysis, SRCCs typically have worse overall survivals, but substantial variances exist depending on tumor location. Identifying SRCCs at earlier disease stages is likely the single most important intervention to improving outcomes for these patients.

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Section: Discussionsupporting

confidence: 68%

Epidemiology of Signet Ring Cell Adenocarcinomas

Benesch

Mathieson

2020

Cancers

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“…Other studies have shown that tumors with SRC differentiation possess unique clinical features, but still little is known about the optimal treatment strategy for these tumors 10. Median survival of SRC patients was inferior to non-SRC patients.…”

Section: Discussionmentioning

confidence: 98%

“…Due to the local infiltrating character of SRC, chemoradiotherapy could potentially have a positive effect in these patients as adjunctive locoregional treatment prior to surgery 4. In their study, Bleaney et al10 concluded that patients with adenocarcinomas with SRC differentiation have a different response to neoadjuvant therapy than non-SRC adenocarcinomas, but the exact impact of SRC differentiation on neoadjuvant treatment and prognosis in esophageal adenocarcinomas remains unclear. Therefore, the aim of this study was to investigate the association of SRC differentiation with response to neoadjuvant treatment and survival in patients with EACs.…”

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confidence: 99%

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

et al. 2019

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Background 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. Methods 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. Results Overall, 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. Conclusions SRC 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. Electronic supplementary material The online version of this article (10.1245/s10434-019-07322-x) contains supplementary material, which is available to authorized users.

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“…The presence of an SRC component, seen in 16% of EACs was also associated with a lower likelihood of pCR. The proportion of EAC with SRC differentiation ranges from 1 to 26% in studies and is thought to be associated with poor prognosis [27]. Even a small SRC component was associated with a lower likelihood of pCR and radical resection [28,29].…”

Section: Discussionmentioning

confidence: 99%

Impact of pathological tumor response after CROSS neoadjuvant chemoradiotherapy followed by surgery on long-term outcome of esophageal cancer: a population-based study

et al. 2021

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Background: With increasing interest in organ-preserving strategies for potentially curable esophageal cancer, real-world data is needed to understand the impact of pathological tumor response after neoadjuvant chemoradiotherapy (CRT) on patient outcome. The objective of this study is to assess the association between pathological tumor response following CROSS neoadjuvant CRT and long-term overall survival (OS) in a nationwide cohort. Material and methods: All patients diagnosed in the Netherlands with potentially curable esophageal cancer between 2009 and 2017, and treated with neoadjuvant CRT followed by esophagectomy were included. Through record linkage with the nationwide Dutch Pathology Registry (PALGA), pathological data were obtained. The primary outcome was pathological tumor response based on ypTNM, classified into pathological complete response (ypT0N0) and incomplete responders (ypT0Nþ, ypTþN0, and ypTþNþ). Multivariable logistic and Cox regression models were used to identify predictors of pathological complete response (pCR) and survival. Results: A total of 4946 patients were included. Overall, 24% achieved pCR, with 19% in adenocarcinoma and 42% in squamous cell carcinoma. Patients with pCR had a better estimated 5-year OS compared to incomplete responders (62% vs. 38%, p< .001). Of the patients with incomplete response, ypTþNþ patients (32% of total population) had the lowest estimated 5-year OS rate, followed by ypT0Nþ and ypTþ N0 (22%, 47%, and 49%, respectively, p< .001). Adenocarcinoma, well to moderate differentiation, cT3-4, cNþ, signet ring cell differentiation and lymph node yield (15) were associated with lower likelihood of pCR. Conclusion:In this population-based study, pathological tumor response based on the ypTNM-stage was associated with different prognostic subgroups. A quarter of patients achieved ypT0N0 with favorable long-term survival, while one-third had an ypTþNþ response with very poor survival. The association between pathological tumor response and long-term survival could help in more accurate assessments of individual prognosis and treatment decisions.

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The relevance and implications of signet-ring cell adenocarcinoma of the oesophagus

Cited by 19 publications

References 21 publications

Epidemiology of Signet Ring Cell Adenocarcinomas

Epidemiology of Signet Ring Cell Adenocarcinomas

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

Impact of pathological tumor response after CROSS neoadjuvant chemoradiotherapy followed by surgery on long-term outcome of esophageal cancer: a population-based study

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