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Cancers
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Research Progress in Esophageal Squamous Cell Carcinoma
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Research Progress in Esophageal Squamous Cell Carcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 August 2023) | Viewed by 9365

Special Issue Editors

Dr. Abraham J. Wu

E-Mail Website
Guest Editor
Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Interests: radiotherapy; non-operative strategies for ESCC; RT for oligometastatic disease; proton therapy
Dr. Geoffrey Y. Ku

E-Mail Website
Guest Editor
Memorial Sloan-Kettering Cancer Center, New York, MY, USA
Interests: systemic therapy; perioperative therapy; immunotherapy; next-generation sequencing; biomarker development

Special Issue Information

Dear Colleagues,

Esophageal squamous cell carcinoma (ESCC) is a globally important malignancy for which improvements in diagnosis, prognostication, and both local and systemic therapy are greatly needed. The biology and optimal treatment for ESCC is increasingly recognized to be distinct from adenocarcinoma, the other major subtype of esophageal cancer. This Special Issue aims to summarize the current state of the art in treating ESCC and to disseminate new research findings pertaining to ESCC. We welcome both original research articles and reviews. Areas of focus may include (but are not limited to) the following:

  • State-of-the art radiotherapy for ESCC (e.g., protons);
  • Management of oligometastatic ESCC;
  • Surgical vs. non-surgical treatment for ESCC;
  • NGS and biomarker development in ESCC;
  • Peri-operative strategies for ESCC (e.g. chemo vs. chemoradiation);
  • Immunotherapy and targeted agents for ESCC;
  • Optimal systemic chemotherapy regimens for ESCC.

We look forward to receiving your contributions.

Dr. Abraham J. Wu
Dr. Geoffrey Y. Ku
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • esophageal cancer
  • squamous cell carcinoma
  • radiotherapy
  • chemotherapy
  • immunotherapy
  • biomarkers
  • chemoradiotherapy
  • surgery

Published Papers (6 papers)

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Research

16 pages, 6342 KiB  
Article
Molecular Characterization of Esophageal Squamous Cell Carcinoma Using Quantitative Proteomics
by Kiran K. Mangalaparthi, Krishna Patel, Aafaque Ahmad Khan, Bipin Nair, Rekha V. Kumar, Thottethodi Subrahmanya Keshav Prasad, David Sidransky, Aditi Chatterjee, Akhilesh Pandey and Harsha Gowda
Cancers 2023, 15(13), 3302; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15133302 - 23 Jun 2023
Viewed by 2212
Abstract
Esophageal squamous cell carcinoma (ESCC) is a heterogeneous cancer associated with a poor prognosis in advanced stages. In India, it is the sixth most common cause of cancer-related mortality. In this study, we employed high-resolution mass spectrometry-based quantitative proteomics to characterize the differential [...] Read more.
Esophageal squamous cell carcinoma (ESCC) is a heterogeneous cancer associated with a poor prognosis in advanced stages. In India, it is the sixth most common cause of cancer-related mortality. In this study, we employed high-resolution mass spectrometry-based quantitative proteomics to characterize the differential protein expression pattern associated with ESCC. We identified several differentially expressed proteins including PDPN, TOP2A, POSTN and MMP2 that were overexpressed in ESCC. In addition, we identified downregulation of esophagus tissue-enriched proteins such as SLURP1, PADI1, CSTA, small proline-rich proteins such as SPRR3, SPRR2A, SPRR1A, KRT4, and KRT13, involved in squamous cell differentiation. We identified several overexpressed proteins mapped to the 3q24-29 chromosomal region, aligning with CNV alterations in this region reported in several published studies. Among these, we identified overexpression of SOX2, TP63, IGF2BP2 and RNF13 that are encoded by genes in the 3q26 region. Functional enrichment analysis revealed proteins involved in cell cycle pathways, DNA replication, spliceosome, and DNA repair pathways. We identified the overexpression of multiple proteins that play a major role in alleviating ER stress, including SYVN1 and SEL1L. The SYVN1/SEL1L complex is an essential part of the ER quality control machinery clearing misfolded proteins from the ER. SYVN1 is an E3 ubiquitin ligase that ubiquitinates ER-resident proteins. Interestingly, there are also other non-canonical substrates of SYVN1 which are known to play a crucial role in tumor progression. Thus, SYVN1 could be a potential therapeutic target in ESCC. Full article
(This article belongs to the Special Issue Research Progress in Esophageal Squamous Cell Carcinoma)
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12 pages, 980 KiB  
Article
Socioeconomic Deprivation Is Not Associated with Outcomes after Esophagectomy at a German High-Volume Center
by Marius Kemper, Jana Zagorski, Jonas Wagner, Julia-Kristin Graß, Jakob R. Izbicki, Nathaniel Melling, Stefan Wolter and Matthias Reeh
Cancers 2023, 15(10), 2827; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15102827 - 18 May 2023
Viewed by 820
Abstract
In Germany, socioeconomically deprived citizens more often develop esophageal carcinoma, since typical risk factors follow the social gradient. Therefore, we hypothesized that socioeconomic deprivation might also be associated with advanced tumor stages and comorbidities at the time of surgery. As a consequence, socioeconomic [...] Read more.
In Germany, socioeconomically deprived citizens more often develop esophageal carcinoma, since typical risk factors follow the social gradient. Therefore, we hypothesized that socioeconomic deprivation might also be associated with advanced tumor stages and comorbidities at the time of surgery. As a consequence, socioeconomic deprivation may be related to postoperative complications and reduced overall survival. Therefore, 310 patients who had undergone esophagectomy for cancer in curative intent between 2012 and 2020 at the University Medical Center Hamburg-Eppendorf (UKE) were included in this study. Socioeconomic status (SES) was estimated using the purchasing power of patients’ postal codes as a surrogate parameter. No association was found between SES and tumor stage or comorbidities at the time of surgery. Moreover, SES was neither associated with postoperative complications nor overall survival. In conclusion, socioeconomic inequalities of patients treated at a high-volume center do not affect treatment outcomes. Full article
(This article belongs to the Special Issue Research Progress in Esophageal Squamous Cell Carcinoma)
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16 pages, 1213 KiB  
Article
Impact of Perineural Invasion and Preexisting Type 2 Diabetes on Patients with Esophageal Squamous Cell Carcinoma Receiving Neoadjuvant Chemoradiotherapy
by Nai-Wen Su, Lai-Man Mok, Mei-Lin Chan, Hung-Chang Liu, Wei-Chin Chang, Chun-Ho Yun, Tze-Yu Shieh, Ming-Che Wu, Huan-Chau Lin, Wen-Chien Huang and Yu-Jen Chen
Cancers 2023, 15(4), 1122; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15041122 - 09 Feb 2023
Viewed by 1525
Abstract
Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the cornerstone treatment strategy in locally advanced esophageal squamous cell carcinoma (ESCC). Despite this high- intensity multimodality therapy, most patients still experience recurrences and metastases, especially those who do not achieve a pathological complete response (pCR) [...] Read more.
Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the cornerstone treatment strategy in locally advanced esophageal squamous cell carcinoma (ESCC). Despite this high- intensity multimodality therapy, most patients still experience recurrences and metastases, especially those who do not achieve a pathological complete response (pCR) after neoCRT. Here, we focused on identifying poor prognostic factors. In this retrospective cohort study; we enrolled 140 patients who completed neoCRT plus surgery treatment sequence with no interval metastasis. Overall, 45 of 140 patients (32.1%) achieved a pCR. The overall survival, disease-free survival (DFS), and metastasis-free survival was significantly better in patients with a pCR than in patients with a non-pCR. In the non-pCR subgroup, the presence of perineural invasion (PNI) and preexisting type 2 diabetes (T2DM) were two factors adversely affecting DFS. After adjusting for other factors, multivariate analysis showed that the hazard ratio (HR) was 2.354 (95% confidence interval [CI] 1.240–4.467, p = 0.009) for the presence of PNI and 2.368 (95% CI 1.351–4.150, p = 0.003) for preexisting T2DM. Patients with a combination of both factors had the worst survival. In conclusion, PNI and preexisting T2DM may adversely affect the prognosis of patients with ESCC receiving neoadjuvant chemoradiotherapy. Full article
(This article belongs to the Special Issue Research Progress in Esophageal Squamous Cell Carcinoma)
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14 pages, 2088 KiB  
Article
Nomogram-Based Survival Predictions and Treatment Recommendations for Locally Advanced Esophageal Squamous Cell Carcinoma Treated with Upfront Surgery
by Jie Zhu, Yongtao Han, Wenjie Ni, Xiao Chang, Lei Wu, Yi Wang, Li Jiang, Yan Tan, Zefen Xiao, Qifeng Wang and Lin Peng
Cancers 2022, 14(22), 5567; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14225567 - 13 Nov 2022
Cited by 3 | Viewed by 1259
Abstract
Background and purpose: The aim of this study is to develop a prognostic nomogram, quantify survival benefit, and guide risk-dependent adjuvant therapy for locally advanced esophageal squamous cell carcinoma (LA-ESCC) after esophagectomy. Materials and methods: This was a single-center, retrospective study of consecutive [...] Read more.
Background and purpose: The aim of this study is to develop a prognostic nomogram, quantify survival benefit, and guide risk-dependent adjuvant therapy for locally advanced esophageal squamous cell carcinoma (LA-ESCC) after esophagectomy. Materials and methods: This was a single-center, retrospective study of consecutive LA-ESCCs treated by curative-intent esophagectomy with internal validation and independent external validation in a randomized controlled trial. After factor selection by the least absolute shrinkage and selection operator regression, a nomogram was developed to estimate 5-year overall survival (OS) based on the Cox proportional hazards model. The area under the curve (AUC) and calibration plot were used to determine its discriminative and predictive capacities, respectively. Survival improvement from adjuvant therapy was quantified and plotted corresponding to nomogram score. Results: A total of 1077, 718, and 118 patients were included for model development, internal validation, and external validation, respectively. The nomogram identified eight significant prognostic factors: gender, pathological T and N stages, differentiation, surgical margin, lymphovascular invasion, number of lymph node resection, and adjuvant therapy. The nomogram showed superior discriminative capacity than TNM stage (AUC: 0.76 vs. 0.72, p < 0.01), with significant survival differences among different risk stratifications. The calibration plot illustrated a good agreement between nomogram-predicated and actual 5-year OS. Consistent results were concluded after external validation. At least 10% 5-year OS improvement from adjuvant chemoradiotherapy and chemotherapy was expected in almost all patients (nomogram score 110 to 260) and patients mainly with high-intermediate risk (nomogram score 159 to 207), respectively. Conclusions: The clinicopathological nomogram predicting 5-year OS for LA-ESCC after esophagectomy was developed with high accuracy. The proposed nomogram showed better performance than TNM stage and provided risk-dependent and individualized adjuvant treatment recommendations. Full article
(This article belongs to the Special Issue Research Progress in Esophageal Squamous Cell Carcinoma)
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10 pages, 3147 KiB  
Article
Overall Survival for Esophageal Squamous Cell Carcinoma with Multiple Primary Cancers after Curative Esophagectomy—A Retrospective Single-Institution Study
by Ping-Chung Tsai, Ying-Che Ting, Po-Kuei Hsu, Jung-Jyh Hung, Chien-Sheng Huang, Wen-Hu Hsu and Han-Shui Hsu
Cancers 2022, 14(21), 5263; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14215263 - 26 Oct 2022
Cited by 2 | Viewed by 1316
Abstract
Background: Advances in surgical techniques and treatment modalities have improved the outcomes of esophageal cancer, yet difficult decision making for physicians while encountering multiple primary cancers (MPCs) continues to exist. The aim of this study was to evaluate long-term survival for esophageal squamous [...] Read more.
Background: Advances in surgical techniques and treatment modalities have improved the outcomes of esophageal cancer, yet difficult decision making for physicians while encountering multiple primary cancers (MPCs) continues to exist. The aim of this study was to evaluate long-term survival for esophageal squamous cell carcinoma (SCC) associated with MPCs. Methods: Data from 544 patients with esophageal SCC who underwent surgery between 2005 and 2017 were reviewed to identify the presence of simultaneous or metachronous primary cancers. The prognostic factors for overall survival (OS) were analyzed. Results: Three hundred and ninety-seven patients after curative esophagectomy were included, with a median observation time of 44.2 months (range 2.6–178.6 months). Out of 52 patients (13.1%) with antecedent/synchronous cancers and 296 patients without MPCs (control group), 49 patients (12.3%) developed subsequent cancers after surgery. The most common site of other primary cancers was the head and neck (69/101; 68.3%), which showed no inferiority in OS. Sex and advanced clinical stage (III/IV) were independent risk factors (p = 0.031 and p < 0.001, respectively). Conclusion: Once curative esophagectomy can be achieved, surgery should be selected as a potential therapeutic approach if indicated, even with antecedent/synchronous MPCs. Subsequent primary cancers were often observed in esophageal SCC, and optimal surveillance planning was recommended. Full article
(This article belongs to the Special Issue Research Progress in Esophageal Squamous Cell Carcinoma)
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12 pages, 2538 KiB  
Article
Clinical Trends in Management of Locally Advanced ESCC: Real-World Evidence from a Large Single-Center Cohort Study
by Yeong Jeong Jeon, Junsang Yoo, Jong Ho Cho and Young Mog Shim
Cancers 2022, 14(19), 4953; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194953 - 10 Oct 2022
Viewed by 1456
Abstract
Neoadjuvant chemoradiation followed by surgery (NCRT+S) has been widely applied to patients with locally advanced esophageal squamous cell carcinoma (ESCC); however, treatment trends and their survival outcomes in a real-world clinical setting are poorly understood. This study aimed to analyze real-world evidence to [...] Read more.
Neoadjuvant chemoradiation followed by surgery (NCRT+S) has been widely applied to patients with locally advanced esophageal squamous cell carcinoma (ESCC); however, treatment trends and their survival outcomes in a real-world clinical setting are poorly understood. This study aimed to analyze real-world evidence to understand treatment patterns and outcomes for patients with ESCC. We analyzed the treatment pattern and 5-year overall survival (5yOS) by synthesizing the individuals’ general characteristics, cancer information, and treatment records extracted from the Clinical Data Warehouse from 1994 to 2018. Of a total of 2151 patients, most patients received upfront surgery and 5yOS was 36.8% (31.4–43.1%). From 2003 to 2012, the use of NCRT increased, and 5yOS was improved to 42.2% (38.8–45.7%). Notably, after 2013, the proportion of NCRT+S markedly increased up to >50% of patients: 5yOS was much improved to 56.3% (53.2–59.6%). With regard to treatment, patients with NCRT+S had the most favorable 5yOS of 58.1% (53–63.7%), although that for patients with upfront surgery was 48.6% (45.9–51.5%, p < 0.001). Moreover, patients who received adjuvant therapy after surgery had better OS than those with surgery alone (58.4% (52.7–64.7%) vs. 47.3% (44.1–50.7%), p < 0.001). This analysis of real-world data demonstrated a significantly improved survival outcome for locally advanced ESCC over time since NCRT prior to surgery had been routinely applied. We revealed that NCRT+S was the most effective treatment for locally advanced ESCC and that adjuvant chemotherapy may be an encouraging therapeutic option for patients with positive nodes after upfront surgery. Full article
(This article belongs to the Special Issue Research Progress in Esophageal Squamous Cell Carcinoma)
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