Changes in Age, Stage Distribution, and Survival of Patients with Esophageal Adenocarcinoma over Three Decades in the United States

Cen, Putao; Banki, Farzaneh; Liu, Cheng; Khalil, Kamal; Du, Xianglin L.; Fallon, Margaret A.; Amato, Robert J.; Kaiser, Larry R.

doi:10.1245/s10434-011-2141-1

Cited by 38 publications

(36 citation statements)

References 28 publications

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“…Increase in incidence of adenocarcinoma is primarily responsible for the rise in esophageal cancer in western world [2]. Majority of patients with esophageal adenocarcinoma present with loco-regional (stage II-III) disease.…”

Section: Introductionmentioning

confidence: 99%

Antitumor effects of cyclin dependent kinase 9 inhibition in esophageal adenocarcinoma

et al. 2017

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Role of cyclin dependent kinase 9(CDK9) as a potential target in esophageal adenocarcinoma (EAC) is unknown. We investigated CDK9 protein expression in EAC and Barrett's esophagus and role of CDK9 in oncogenic processes of EAC in vitro and in murine xenografts. The CDK9 expression was significantly higher in EAC as compared to Barrett's esophagus in patient samples. Stable shCDK9 in SKGT4 reduced proliferation by 37% at day 4, increased apoptosis at 48 hours and induced G1 cell cycle arrest at 48 hours (58.4% vs. 45.8%) compared to controls SKGT4 cells. SKGT4-shCDK9 cell-derived tumors were significantly smaller than control SKGT4-derived tumors in xenografts (72.89mm3 vs. 270mm3). Pharmaceutical inhibition of CDK9 by Flavopiridol (0.1μm for 48 hours) and CAN508 (20 and 40μm for 72 hours) induced significant reduction in proliferation and 2-fold increase in apoptosis in SKGT4, FLO1 and OE33 cells. In xenograft models, CAN508 (60 mg/kg/dayx10 days) and Flavopiridol (4mg/kg/dayx10 days) caused 50.8% and 63.1% reduction in xenograft tumors as compared to control on post-treatment day 21. Reduction of MCL-1 and phosphorylated RNA polymerase II was observed with transient shCDK9 in SKGT4 cells but not with stable shCDK9. CAN508 (20 and 40 μm) and Flavopiridol (0.1, 0.2 and 0.3 μm) for 4 hours showed reduction in MCL-1 mRNA (84% and 96%) and protein. Mcl-1 overexpression conferred resistance to Flavopiridol (0.2 μm or 0.4 μm for 48 hours) and CAN 508 (20 or 40μm for 72 hours). Chromatin immunoprecipitation demonstrated significant reduction of binding of transcriptional factor HIF-1α to MCL-1 promoter in FLO-1 cells by CDK9 inhibitors.

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Section: Introductionmentioning

confidence: 99%

Antitumor effects of cyclin dependent kinase 9 inhibition in esophageal adenocarcinoma

et al. 2017

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“…During the past 20 years, the incidence of squamous-cell carcinomas has decreased in the United States, while the rate of adenocarcinoma has increased [3]. Smoking and obesity may account for some of these changes[1].…”

Section: Introductionmentioning

confidence: 99%

The clinicopathological features and prognosis of signet ring cell carcinoma of the esophagus: A 10-year retrospective study in China

et al. 2017

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ObjectivesThe aim of this study was to analyze the clinicopathological features and prognosis of esophageal signet ring cell (SRC) carcinoma in China.MethodsPatients with poorly differentiated adenocarcinoma were identified in two hospitals from January 2006 to June 2016. The patients were divided into three groups according to component of SRCs: SRC≥50% group, SRC < 50% group and non-SRC poorly differentiated adenocarcinoma group.ResultsFifty-seven patients had carcinoma (SRC≥50%), and 79 patients had tumors containing <50% SRCs, and 535 patients was in non-SRC poorly differentiated adenocarcinoma group. There were no significant differences among the three groups in clinicopathological characteristics. Patients in SRC≥50% group had a lower overall survival rate (at 3-year 37.6%versus71.1%; at 5-year 0% versus 43.3%; p<0.001) compared with the control group. Even survival outcome of patients in SRC < 50%was inferior to that of in control group (at 3-year 53.0%versus71.1%; at 5-year 25.9% versus 43.3%; p<0.001). Female sex, large tumor size and increasing TNM stage were independent prognostic factors for SRC ≥50% esophageal carcinoma patients.ConclusionsThe incidence of esophageal SRC carcinoma is relatively rare and the worst outcome is observed in the SRC≥ 50% group. It is necessary to explore new therapeutic modalities to achieve further improvements in the clinical outcome of these patients.

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“…4 Some randomized trials suggest that preoperative chemotherapy has a survival benefit in resectable AC of the stomach, EGJ, or lower esophagus; however, esophageal AC only accounted for 10%-15% of the cases. 10,59 A metaanalysis on preoperative chemotherapy trials in esophageal cancers, including nine randomized comparisons of neoadjuvant chemotherapy vs surgery alone (n=1,981), provided the strongest evidence for a survival benefit of neoadjuvant chemotherapy over surgery alone in patients with esophageal carcinoma with an hazard ratio (HR) of 0.87 (95% confidence interval [CI], 0.79-0.96; P=0.005). 40 Similarly, a Cochrane review including 14 randomized trials of AC of the stomach, EGJ, and lower esophagus also demonstrated that preoperative chemotherapy was associated with a significantly longer OS.…”

Section: Neoadjuvant Chemotherapy and Surgery Vs Surgery Alonementioning

confidence: 99%

“…Over the past 3 decades, surgical advances and improvement in radiation techniques have greatly improved the disease outcomes. [9][10][11] This article focuses on integrating these approaches and tailoring the treatment strategy for individual patients, compares the effectiveness of the various treatment approaches in the definitive or neoadjuvant…”

Section: Introductionmentioning

confidence: 99%

Esophageal cancer: comparative effectiveness of treatment options

Cai¹,

Lin²

2016

CER

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Esophageal cancer is a lethal disease. Multimodal therapy has improved the survival and local control for locally advanced esophageal cancer compared to surgery alone. Neoadjuvant chemoradiotherapy (CRT) plus surgery is the accepted standard of care for operable esophageal cancer. Pathologic complete response is very common, ranging from 18% to 43%, and it is an independent favorable prognostic factor for survival. Salvage surgery after definitive CRT may be safe and feasible for patients with esophageal cancer who achieve pathologic complete response after neoadjuvant CRT. For inoperable cases, definitive CRT is an alternative treatment modality. Intensity-modulated radiation therapy may reduce treatment-related toxicities due to its better dose homogeneity and conformity compared to three-dimensional conformal radiotherapy. Proton therapy can further improve target conformity and normal tissue sparing when compared to photon therapy (three-dimensional conformal radiotherapy and intensitymodulated radiation therapy) and, therefore, likely to further improve the treatment outcomes of patients. This article compares the effectiveness of the various treatment approaches in the definitive or neoadjuvant setting and reviews the evidence on the benefit of utilizing advanced radiation techniques for the curative management of esophageal cancer.

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Changes in Age, Stage Distribution, and Survival of Patients with Esophageal Adenocarcinoma over Three Decades in the United States

Cited by 38 publications

References 28 publications

Antitumor effects of cyclin dependent kinase 9 inhibition in esophageal adenocarcinoma

Antitumor effects of cyclin dependent kinase 9 inhibition in esophageal adenocarcinoma

The clinicopathological features and prognosis of signet ring cell carcinoma of the esophagus: A 10-year retrospective study in China

Esophageal cancer: comparative effectiveness of treatment options

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