Esophageal Cancer — Pathogenesis and Therapeutic Strategies

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 3675

Special Issue Editors

Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Interests: esophageal cancer; gastric cancer; neuroendocrine tumor; biomarkers; molecular epidemiology
Department of Digestive Endoscopy, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
Interests: endoscopy; endoscopic submucosal dissection; radiofrequency ablation; anti-reflux mucosectomy; endoscopic sleeve gastroplasty; per-oral endoscopic myotomy; esophageal cancer; Barrett’s esophagus; achalasia; colon cancer; reflux disease
Special Issues, Collections and Topics in MDPI journals
Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
Interests: endoscopy; endoscopic ultrasound; esophageal cancer; molecular biology; translational study

Special Issue Information

Dear Colleagues,

Targeted therapies for esophageal cancer are important personalized treatments and may improve cancer outcomes. Previous studies and the genetic profiling of esophageal cancer have lead the treatment strategy from traditional chemoradiotherapy to immunotherapy. For poor responders to palliative chemotherapy, clinical trials on immune checkpoint inhibitors, targeting programmed death-1 (PD-1), PD-ligand 1 (PD-L1), or CTLA-4, have shown promising activity. Responders to immunotherapy may enjoy sustainable effects, but there is still no reliable biomarker to predict the response. Moreover, studies on esophageal carcinogenesis are ongoing, but the exact mechanisms behind it as well as the tumor microenvironment remain unclear.

In this Special Issue, we welcome original research and comprehensive review articles addressing the pathogenesis and potential targeted strategies of esophageal cancer to provide insights into clinical practice and future innovations. Researchers studying biomarkers, model systems, and preclinical or clinical trials using a targeted approach are invited to submit their work.

Dr. I-Chen Wu
Dr. Wen-Lun Wang
Dr. Wei-Lun Chang
Guest Editors

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Keywords

  • esophageal cancer
  • pathogenesis
  • next generation sequence
  • immunotherapy
  • immune check point inhibitors
  • targeting programmed death-1
  • biomarkers

Published Papers (2 papers)

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Research

13 pages, 1014 KiB  
Article
Adjuvant Chemoradiotherapy Associated with Improved Overall Survival in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy in Intensity-Modulated Radiotherapy Era
by Wing-Keen Yap, Ming-Chieh Shih, Yu-Chen Chang, Chia-Hsin Lin, Shih-Ming Huang, Tsung-You Tsai, Ching-Fu Chang, Chih-Chung Hsu, Chen-Kan Tseng, Miao-Fen Chen, Din-Li Tsan, Chi-Ting Liau, Ming-Mo Hou, Yin-Kai Chao, Chien-Hung Chiu and Tsung-Min Hung
Biomedicines 2022, 10(11), 2989; https://doi.org/10.3390/biomedicines10112989 - 21 Nov 2022
Cited by 1 | Viewed by 1505
Abstract
Background: The prognosis of patients with resected esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy is particularly poor in those who were staged as ypT3/T4 and/or ypN+. This study investigated whether adjuvant chemoradiotherapy was associated with improved clinical outcomes in these patients. Methods: we [...] Read more.
Background: The prognosis of patients with resected esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy is particularly poor in those who were staged as ypT3/T4 and/or ypN+. This study investigated whether adjuvant chemoradiotherapy was associated with improved clinical outcomes in these patients. Methods: we identified patients with esophageal squamous cell carcinoma who were staged as ypT3/T4 and/or ypN+ after being treated with neoadjuvant chemoradiotherapy followed by esophagectomy between the years 2013 and 2019. Patients were divided into two groups based on whether they received adjuvant chemoradiotherapy. The Kaplan-Meier method and Cox regression modeling were performed for survival analyses and multivariable analysis, respectively. Results: 76 eligible patients were included in the analyses. The median follow-up for the study cohort was 43.4 months. On Kaplan-Meier analyses of the overall population, adjuvant chemoradiotherapy was associated with significantly improved median overall survival (31.7 months vs. 16.3 months, p = 0.036). On Kaplan-Meier analyses of the 35 matched pairs generated by propensity score matching, adjuvant chemoradiotherapy was associated with significantly longer median overall survival (31.7 months vs. 14.3 months; p = 0.004) and median recurrence-free survival (18.9 months vs. 11.7 months; p = 0.020). In multivariable analysis, adjuvant chemoradiotherapy was independently associated with a 60% reduction in mortality (p = 0.003) and a 48% reduction in risk of recurrence (p = 0.035) after adjusting for putative confounders. In addition, microscopic positive resection margin and Mandard tumor regression grade 3–4 were independently associated with increased mortality and risk of recurrence. While a greater number of lymph nodes dissected was independently associated with significantly improved overall survival, the number of positive lymph nodes was independently associated with significantly worse overall survival and a trend (p = 0.058) towards worse recurrence-free survival. Conclusions: This study demonstrated that adjuvant CRT was independently associated with a significantly improved survival and lower risk of recurrence than observation in esophageal squamous cell carcinoma patients staged as ypT3 and/or ypN+ after receiving neoadjuvant chemoradiotherapy and radical surgery. The results of this study have implications for the design of future clinical trials and may improve treatment outcomes of patients in this setting who cannot afford or are without access to adjuvant nivolumab. Full article
(This article belongs to the Special Issue Esophageal Cancer — Pathogenesis and Therapeutic Strategies)
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12 pages, 971 KiB  
Article
Change in PD-L1 and CD8 Expression after Chemoradiotherapy for Esophageal Squamous Cell Carcinoma
by Wei-Chung Chen, Chun-Chieh Wu, Yi-Hsun Chen, Jui-Ying Lee, Yao-Kuang Wang, Nian-Siou Wu, Ming-Tsang Wu and I-Chen Wu
Biomedicines 2022, 10(8), 1888; https://doi.org/10.3390/biomedicines10081888 - 04 Aug 2022
Cited by 2 | Viewed by 1757
Abstract
Esophageal cancer has a dismal prognosis with a five-year survival rate below 20%. Recently, immunotherapy has become a new standard of care for this cancer; therefore, we aimed to examine the programmed death ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) [...] Read more.
Esophageal cancer has a dismal prognosis with a five-year survival rate below 20%. Recently, immunotherapy has become a new standard of care for this cancer; therefore, we aimed to examine the programmed death ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) tissues before and after concurrent chemoradiation therapy (CCRT). In total, 64 patients with pre-CCRT ESCC specimens were examined for PD-L1 expression, with twenty-three of them having a partial response (N = 23) or stable disease (N = 1) after CCRT while post-CCRT tissue specimens were collected. All of them were tested for PD-L1 and 15 of them also had CD8 expression in the paired ESCC samples. The prevalence of PD-L1 positivity was 54.7% and we found a trend of decreased PD-L1 expression and increased CD8 positive signal after CCRT. High pre-CCRT PD-L1 H-score in tumors was related to poor prognosis (adjusted hazard ratio = 2.81; p = 0.02), although CD8 signal was not associated with overall survival either in pre- or post-CCRT treatment. In conclusion, we found that PD-L1 expression tended to decrease in CCRT responders and our result supports PD-L1 expression in tumor as a predictor of ESCC prognosis. Full article
(This article belongs to the Special Issue Esophageal Cancer — Pathogenesis and Therapeutic Strategies)
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