Match!

Identification of Prognostic Phenotypes of Esophageal Adenocarcinoma in 2 Independent Cohorts

Published on Dec 1, 2018in Gastroenterology19.233
· DOI :10.1053/j.gastro.2018.08.036
Tarek Sawas6
Estimated H-index: 6
(Mayo Clinic),
Sarah Killcoyne9
Estimated H-index: 9
(Medical Research Council)
+ 90 AuthorsRichard Turkington9
Estimated H-index: 9
Abstract
Background & Aims Most patients with esophageal adenocarcinoma (EAC) present with de novo tumors. Although this could be due to inadequate screening strategies, the precise reason for this observation is not clear. We compared survival of patients with prevalent EAC with and without synchronous Barrett esophagus (BE) with intestinal metaplasia (IM) at the time of EAC diagnosis. Methods Clinical data were studied using Cox proportional hazards regression to evaluate the effect of synchronous BE-IM on EAC survival independent of age, sex, TNM stage, and tumor location. We analyzed data from a cohort of patients with EAC from the Mayo Clinic (n=411; 203 with BE and IM) and a multicenter cohort from the United Kingdom (n=1417; 638 with BE and IM). Results In the Mayo cohort, BE with IM had a reduced risk of death compared to patients without BE and IM (hazard ratio [HR] 0.44; 95% CI, 0.34–0.57; P Conclusion Two types of EAC can be characterized based on the presence or absence of BE. These findings could increase our understanding the etiology of EAC, and be used in management and prognosis of patients.
  • References (29)
  • Citations (6)
References29
Newest
#1Gianmarco Contino (Medical Research Council)H-Index: 5
#2Thomas L. Vaughan (UW: University of Washington)H-Index: 54
Last. Rebecca C. Fitzgerald (Medical Research Council)H-Index: 20
view all 4 authors...
We have recently gained unprecedented insight into genetic factors that determine risk for Barrett's esophagus (BE) and progression to esophageal adenocarcinoma (EA). Next-generation sequencing technologies have allowed us to identify somatic mutations that initiate BE and track genetic changes during development of tumors and invasive cancer. These technologies led to identification of mechanisms of tumorigenesis that challenge the current multistep model of progression to EA. Newer, cost-effec...
17 CitationsSource
#1Gregory Tiesi (UM: University of Miami)H-Index: 2
#2Wungki Park (UM: University of Miami)H-Index: 7
Last. Dido Franceschi (UM: University of Miami)H-Index: 34
view all 8 authors...
Abstract Background Neoadjuvant treatment is standard for locally advanced esophageal cancer. However, whether the addition of radiation to neoadjuvant regimen improves survival remains unclear. The aim of this study was to compare survival in locally advanced esophageal cancer treated with neoadjuvant chemotherapy versus chemoradiation. Materials and methods A prospectively maintained database of esophagectomies (1999-2012) was analyzed. We identified 297 patients with locally advanced esophage...
7 CitationsSource
#1Thomas W. Rice (Cleveland Clinic)H-Index: 68
#2Donna M. Gress (American Joint Committee on Cancer)H-Index: 7
Last. Eugene H. Blackstone (Cleveland Clinic)H-Index: 119
view all 6 authors...
Answer questions and earn CME/CNE New to the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for epithelial cancers of the esophagus and esophagogastric junction are separate, temporally related cancer classifications: 1) before treatment decision (clinical); 2) after esophagectomy alone (pathologic); and 3) after preresection therapy followed by esophagectomy (postneoadjuvant pathologic). The addition of clinical and postneoadjuvant pathologic stage groupin...
29 CitationsSource
#1Judith Offman (QMUL: Queen Mary University of London)H-Index: 11
#2Rebecca C. Fitzgerald (University of Cambridge)H-Index: 36
4 CitationsSource
#1Dag Holmberg (Karolinska University Hospital)H-Index: 2
#2Eivind Ness-Jensen (Karolinska University Hospital)H-Index: 9
Last. Jesper Lagergren ('KCL': King's College London)H-Index: 56
view all 5 authors...
Abstract Introduction Recent studies have indicated a lower incidence rate of oesophageal adenocarcinoma (OAC) in individuals with Barrett's oesophagus (BO) than most earlier studies. Our objective was to assess the risk of OAC in a Swedish unselected cohort of individuals with BO. Methods This population-based cohort study included all Swedish residents diagnosed with BO in 2006–2013, identified through the Swedish Patient Registry. The cohort members were followed from the date of first BO dia...
5 CitationsSource
#1Maria SecrierH-Index: 9
#2Xiaodun LiH-Index: 6
Last. Rebecca C. FitzgeraldH-Index: 36
view all 26 authors...
Nat. Genet.; 10.1038/ng.3659; corrected online 19 September 2016 In the version of this article initially published online, the mutation signature illustrations for S1 and S2 in Figure 3a were switched. Additionally, in the Online Methods, the text originally stated that structural variants were called using BWA-MEM, when it should have stated that these were called using BWA.
2 CitationsSource
#1Maria SecrierH-Index: 9
#2Xiaodun LiH-Index: 6
Last. Rebecca C. FitzgeraldH-Index: 20
view all 26 authors...
Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RT...
118 CitationsSource
#1Kavel Visrodia (Mayo Clinic)H-Index: 9
#2S. Singh (UCSD: University of California, San Diego)H-Index: 5
Last. David A. Katzka (Mayo Clinic)H-Index: 41
view all 7 authors...
SummaryBackground The proportion of oesophageal adenocarcinoma that is detected concurrently with initial Barrett's oesophagus diagnosis is not well studied. Aim To compare the proportion of prevalent adenocarcinoma vs. incident adenocarcinoma found during surveillance of Barrett's. Methods We performed a systematic search of MEDLINE, EMBASE and Web of Science (from their inception to 31 May 2015) for cohort studies in adults with Barrett's (nondysplastic Barrett's ± Barrett's with low-grade dys...
9 CitationsSource
#1Basile Njei (Yale University)H-Index: 16
#2Thomas R. McCarty (Yale University)H-Index: 11
Last. John W. Birk (UConn: University of Connecticut)H-Index: 10
view all 3 authors...
The rise in incidence of esophageal cancer (EC) in the USA over the last four decades has been well documented; however, data on trends in long-term survival and impact on modern therapies associated with survival are lacking.The Surveillance, Epidemiology, and End Results database was queried to identify patients with confirmed EC. Cox proportional hazard regression was used to determine independent mortality factors.Of 93 167 patients diagnosed with EC between 1973 and 2009, 49% had a histolog...
47 CitationsSource
#1Reema Mallick (UMN: University of Minnesota)H-Index: 4
#2Santosh K. Patnaik (Roswell Park Cancer Institute)H-Index: 14
Last. Ajay BansalH-Index: 36
view all 4 authors...
Background Esophageal epithelial microRNAs may be used to diagnose Barrett’s esophagus (BE) and possibly monitor its progression to esophageal adenocarcinoma (EAC).
24 CitationsSource
Cited By6
Newest
#1David A. Katzka (Mayo Clinic)H-Index: 41
#2John E. Pandolfino (NU: Northwestern University)H-Index: 55
Last. Peter J. Kahrilas (NU: Northwestern University)H-Index: 95
view all 3 authors...
Abstract Gastroesophageal reflux disease (GERD) is now one of the most common diagnoses made in a gastroenterology practice. From a conventional pathophysiological perspective GERD is conceptualized as incompetence of the antireflux barrier at the esophagogastric junction; the more severe that incompetence, the worse the disease. However, it is increasingly clear that many presentations of GERD represent distinct phenotypes with unique predisposing cofactors and pathophysiology outside of this p...
Source
#1Sriganesh Jammula (University of Cambridge)H-Index: 3
#2Annalise Katz-Summercorn (University of Cambridge)H-Index: 2
Last. A. Blasko (University of Cambridge)
view all 18 authors...
Abstract Background & Aims Esophageal adenocarcinomas (EAC) are heterogeneous and often preceded by Barrett’s esophagus (BE). Many genomic changes have been associated with development of BE and EAC, but little is known about epigenetic alterations. We performed epigenetic analyses of BE and EAC tissues and combined these data with transcriptome and genomic data to identify mechanisms that control gene expression and genome integrity. Methods In a retrospective cohort study, we collected tissue ...
Source
#1David A. Katzka (Mayo Clinic)H-Index: 41
#2Rebecca C. Fitzgerald (Medical Research Council)H-Index: 36
Source
#1Ankur K. Nagaraja (Harvard University)H-Index: 12
#2Osamu Kikuchi (Harvard University)H-Index: 23
Last. Adam J. Bass (Broad Institute)H-Index: 37
view all 3 authors...
Gastroesophageal adenocarcinomas (GEA) are devastating diseases with stark global presence. Over the past 10 years, there have been minimal improvements in treatment approach despite numerous clinical trials. Here, we review recent progress toward understanding the molecular features of these cancers and the diagnostic and therapeutic challenges posed by their intrinsic genomic instability and heterogeneity. We highlight the potential of genomic heterogeneity to influence clinical trial outcomes...
Source
#1Tarek Sawas (Mayo Clinic)H-Index: 6
#2Nabila Azad (Mayo Clinic)
Last. David A. Katzka (Mayo Clinic)H-Index: 41
view all 7 authors...
Abstract Background & Aims The incidence of esophageal adenocarcinoma (EAC) has increased over the last decades. It is unclear if this increase is the result of a new cancer phenotype or an increase in risk factors for EAC. We aimed to compare risk factors, the proportions of intestinal and non-intestinal phenotypes of EAC, and survival times patients during the 2009–2012 time period vs the 1996–1997 time periods Methods We performed a retrospective single center cohort study of 829 patients wit...
Source
#1Dag Holmberg (Karolinska University Hospital)H-Index: 2
#2Eivind Ness-Jensen (NTNU: Norwegian University of Science and Technology)H-Index: 9
Last. Jesper Lagergren ('KCL': King's College London)H-Index: 56
view all 4 authors...
Source
#1Tarek Sawas (Mayo Clinic)H-Index: 6
Last. David A. Katzka (Mayo Clinic)H-Index: 41
view all 5 authors...
Background & Aims Obesity is increasing in younger populations. Barrett’s esophagus is associated with central obesity, so we investigated the occurrence of esophageal adenocarcinoma (EAC) in younger patients and compared them with older patients to determine differences in features at presentation and survival times. Methods We performed a single-center, retrospective study of 682 patients with a diagnosis of EAC treated from 2009 through 2012. We used a Cox proportional hazards model to compar...
Source
#1Jianwen Que (Columbia University)H-Index: 10
#2Katherine S. Garman (Duke University)H-Index: 16
Last. Stuart J. Spechler (Scott & White Hospital)H-Index: 64
view all 4 authors...
In patients with Barrett’s esophagus (BE), metaplastic columnar mucosa containing epithelial cells with gastric and intestinal features replaces esophageal squamous mucosa damaged by gastroesophageal reflux disease. This condition is estimated to affect 5.6% of adults in the United States, and is a major risk factor for esophageal adenocarcinoma. Despite the prevalence and importance of BE, its pathogenesis is incompletely understood and there are disagreements over the cells of origin. We revie...
Source
Source
Source