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Cancers
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Neoadjuvant- and Immuno-Therapy in Esophageal Cancer
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Neoadjuvant- and Immuno-Therapy in Esophageal Cancer

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

Deadline for manuscript submissions: closed (1 August 2021) | Viewed by 12147

Special Issue Editor

Dr. Dechen Lin

E-Mail Website
Guest Editor
Cedars-Sinai Medical Center, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA
Interests: : esophageal cancer; therapeutic resistance; cancer genomics; cancer immunology

Special Issue Information

Dear Colleagues,

Over 450,000 deaths annually worldwide are attributed to esophageal carcinoma. Esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) are the two predominant histological subtypes with distinct geographical and epidemiological characteristics, complicating the design of clinical trials and biomarker developments. Although ESCC accounts for about 90% of esophageal cancers worldwide, the incidence of EAC has strikingly increased more than eight-fold in developed countries over the last 4 decades. The prognosis for patients with esophageal cancer is poor: 5-year survival rate of EAC patients is approximately 17%, slightly higher than that of ESCC patients. In addition, surgical operations are always associated with significantly deceased life quality.

Neoadjuvant therapy has demonstrated its clinical benefit for locally advanced esophageal cancer. However, clinical results are still heterogeneous among randomized controlled trials, highlighting the need of further investigation. More recently, immune checkpoint blockade therapy (ICB) has shown encouraging efficacy in esophageal cancer patients. However, as with most solid tumors, only a minority of esophageal cancer patients benefit from ICB therapy. Clearly, further clinical and basic research studies are required to understand responsiveness or resistance to immunotherapies.

This Special Issue will highlight recent progress made in either neoadjuvant or immune-therapy in esophageal cancer, in both clinical and basic research fields.

Dr. Dechen Lin
Guest Editor

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 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 squamous cell carcinoma
  • esophageal adenocarcinoma
  • neoadjuvant therapy
  • immunotherapy
  • biomarker

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Published Papers (4 papers)

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Research

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15 pages, 861 KiB  
Article
Preoperative Radiochemotherapy in Esophageal Squamous Cell Cancer with 5-Fluorouracil/Cisplatin or Carboplatin/Paclitaxel: Treatment Practice over a 20-Year Period and Implications for the Individual Treatment Modalities
by Leif Hendrik Dröge, Philipp Johannes Karras, Manuel Guhlich, Markus Anton Schirmer, Michael Ghadimi, Stefan Rieken, Lena-Christin Conradi and Martin Leu
Cancers 2021, 13(8), 1834; https://doi.org/10.3390/cancers13081834 - 12 Apr 2021
Cited by 5 | Viewed by 2114
Abstract
We retrospectively studied outcomes in patients treated with preoperative radiochemotherapy and surgery for esophageal squamous cell cancer. We put special focus on the comparison of patients treated with 5-fluorouracil/cisplatin (‘Walsh’) or carboplatin/paclitaxel (‘CROSS’). We compared characteristics between patients treated according to ‘Walsh’ vs. [...] Read more.
We retrospectively studied outcomes in patients treated with preoperative radiochemotherapy and surgery for esophageal squamous cell cancer. We put special focus on the comparison of patients treated with 5-fluorouracil/cisplatin (‘Walsh’) or carboplatin/paclitaxel (‘CROSS’). We compared characteristics between patients treated according to ‘Walsh’ vs. ‘CROSS’. Cox regression was performed to test for an association of parameters with outcomes. Study eligibility was met by 90 patients. First, the higher age and more comorbidities of the ‘CROSS’ patients, along with a shorter intensive care/intermediate care stay, might reflect an improvement in supportive and surgical/perioperative procedures over the periods. Second, the ‘CROSS’ patients experienced more hematologic toxicity and were less likely to complete chemotherapy as per protocol. This indicates that efforts should be taken to guide patients through a toxic treatment regimen by supportive measures. Third, the negative prognostic impact of radiochemotherapy-related toxicities (i.e., dysphagia and hematologic toxicities) and the duration of the intensive care/intermediate care unit stay underlines that further optimization of treatment procedures remains an important goal. We found no differences in tumor downstaging and survival between treatment regimen. Toxicity profiles could be improved by tailoring the regimen to individual patients (e.g., careful use of the taxane-based regimen in elderly patients). Full article
(This article belongs to the Special Issue Neoadjuvant- and Immuno-Therapy in Esophageal Cancer)
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14 pages, 1849 KiB  
Article
Neoadjuvant Chemoradiotherapy Followed by Esophagectomy with Three-Field Lymph Node Dissection for Thoracic Esophageal Squamous Cell Carcinoma Patients with Clinical Stage III and with Supraclavicular Lymph Node Metastasis
by Yusuke Sato, Satoru Motoyama, Yuki Wada, Akiyuki Wakita, Yuta Kawakita, Yushi Nagaki, Kaori Terata, Kazuhiro Imai, Akira Anbai, Manabu Hashimoto and Yoshihiro Minamiya
Cancers 2021, 13(5), 983; https://doi.org/10.3390/cancers13050983 - 26 Feb 2021
Cited by 20 | Viewed by 3048
Abstract
Background: Neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy is now the standard treatment for patients with resectable advanced thoracic esophageal squamous cell carcinoma (ESCC) worldwide. However, the efficacy of NACRT followed by esophagectomy with three-field lymph node dissection for clinical Stage III patients and [...] Read more.
Background: Neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy is now the standard treatment for patients with resectable advanced thoracic esophageal squamous cell carcinoma (ESCC) worldwide. However, the efficacy of NACRT followed by esophagectomy with three-field lymph node dissection for clinical Stage III patients and for clinical Stage IVB patients with supraclavicular LN metastasis has not yet been determined. Methods: Between 2008 and 2018, 94 ESCC patients diagnosed as clinical Stage III and 18 patients diagnosed as clinical Stage IVB with supraclavicular LN metastasis as the only distant metastatic factor were treated with NACRT followed by esophagectomy with extended lymph node dissection at Akita University Hospital. Long-term survival and the patterns of recurrence in these 112 patients were analyzed. Results: The median follow-up period of censored cases was 60 months. The five-year OS and DSS rates among the clinical Stage III patients were 57.6% and 66.6%, respectively. The five-year OS and DSS rates among the clinical Stage IVB patients were 41.3% and 51.6%, respectively. The most frequent recurrence pattern was distant metastasis (69.2%) in the Stage III patients and LN metastasis (75.0%) in the Stage IVB patients. Conclusion: NACRT followed by esophagectomy with three-field LN dissection is feasible and offers the potential for long-term survival of clinical Stage III ESCC patients and even clinical Stage IVB patients with supraclavicular LN metastasis as the only distant metastatic factor. At least in patients with upper and middle thoracic ESCC, treating supraclavicular LNs as regional LNs seems to be appropriate. Full article
(This article belongs to the Special Issue Neoadjuvant- and Immuno-Therapy in Esophageal Cancer)
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Figure 1

19 pages, 4521 KiB  
Article
STAT3β Enhances Sensitivity to Concurrent Chemoradiotherapy by Inducing Cellular Necroptosis in Esophageal Squamous Cell Carcinoma
by Zhen-Yuan Zheng, Ping-Lian Yang, Wei Luo, Shuai-Xia Yu, Hong-Yao Xu, Ying Huang, Rong-Yao Li, Yang Chen, Xiu-E Xu, Lian-Di Liao, Shao-Hong Wang, He-Cheng Huang, En-Min Li and Li-Yan Xu
Cancers 2021, 13(4), 901; https://doi.org/10.3390/cancers13040901 - 21 Feb 2021
Cited by 20 | Viewed by 3132
Abstract
Concurrent chemoradiotherapy (CCRT), especially platinum plus radiotherapy, is considered to be one of the most promising treatment modalities for patients with advanced esophageal cancer. STAT3β regulates specific target genes and inhibits the process of tumorigenesis and development. It is also a good prognostic [...] Read more.
Concurrent chemoradiotherapy (CCRT), especially platinum plus radiotherapy, is considered to be one of the most promising treatment modalities for patients with advanced esophageal cancer. STAT3β regulates specific target genes and inhibits the process of tumorigenesis and development. It is also a good prognostic marker and a potential marker for response to adjuvant chemoradiotherapy (ACRT). We aimed to investigate the relationship between STAT3β and CCRT. We examined the expression of STAT3α and STAT3β in pretreatment tumor biopsies of 105 ESCC patients who received CCRT by immunohistochemistry. The data showed that ESCC patients who demonstrate both high STAT3α expression and high STAT3β expression in the cytoplasm have a significantly better survival rate, and STAT3β expression is an independent protective factor (HR = 0.424, p = 0.003). Meanwhile, ESCC patients with high STAT3β expression demonstrated a complete response to CCRT in 65 patients who received platinum plus radiation therapy (p = 0.014). In ESCC cells, high STAT3β expression significantly inhibits the ability of colony formation and cell proliferation, suggesting that STAT3β enhances sensitivity to CCRT (platinum plus radiation therapy). Mechanistically, through RNA-seq analysis, we found that the TNF signaling pathway and necrotic cell death pathway were significantly upregulated in highly expressed STAT3β cells after CCRT treatment. Overall, our study highlights that STAT3β could potentially be used to predict the response to platinum plus radiation therapy, which may provide an important insight into the treatment of ESCC. Full article
(This article belongs to the Special Issue Neoadjuvant- and Immuno-Therapy in Esophageal Cancer)
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Review

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19 pages, 358 KiB  
Review
Recent Progress in the Neoadjuvant Treatment Strategy for Locally Advanced Esophageal Cancer
by Sicong Hou, Ziyin Pan, Xin Hao, Qinglei Hang and Yanbing Ding
Cancers 2021, 13(20), 5162; https://doi.org/10.3390/cancers13205162 - 14 Oct 2021
Cited by 16 | Viewed by 3236
Abstract
Neoadjuvant therapies, primarily chemotherapy and chemoradiotherapy, are able to improve the overall survival (OS) in patients with locally advanced resectable esophageal cancer (EC) based on the results of several randomized clinical trials. The advantage of neoadjuvant therapy is chiefly attributed to the decreased [...] Read more.
Neoadjuvant therapies, primarily chemotherapy and chemoradiotherapy, are able to improve the overall survival (OS) in patients with locally advanced resectable esophageal cancer (EC) based on the results of several randomized clinical trials. The advantage of neoadjuvant therapy is chiefly attributed to the decreased risk of local–regional recurrence and distant metastasis. Thus, it has been recommended as standard treatment for patients with resectable EC. However, several fundamental problems remain. First, the combination of neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), and surgery for EC patients with different histological types remain controversial. Furthermore, to reduce the toxicity of preoperative chemotherapy and the risk of complications caused by preoperative radiation therapy, the treatment protocols of nCT and nCRT still need to be investigated and optimized by prospective trials. Moreover, for patients with complete clinical response following neoadjuvant therapy, it is worth ascertaining whether a “watch and wait” surveillance plus surgery-as-needed policy is more favorable, as well as, in addition to preoperative chemoradiotherapy, whether immunotherapy, especially when combined with the traditional neoadjuvant therapy regimens, brings new prospects for EC treatment. In this review, we summarize the recent insights into the research progress and existing problems of neoadjuvant therapy for locally advanced resectable EC. Full article
(This article belongs to the Special Issue Neoadjuvant- and Immuno-Therapy in Esophageal Cancer)
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