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Gastroesophageal Cancer: Outcomes and Therapeutic Management
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Gastroesophageal Cancer: Outcomes and Therapeutic Management

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 1655

Special Issue Editor

Dr. Michael K. Gibson

E-Mail Website
Guest Editor
Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Interests: translational therapeutics; gastric cancer; molecular subtypes; head and neck cancers; circulating tumor DNA; presicion medicine

Special Issue Information

Dear Colleagues,

Gastroesophageal malignancies are a diverse group of cancers affecting the stomach, gastroesophageal junction, and esophagus, and they constitute a major cause of cancer-related fatalities globally. Current FDA-approved therapies include chemotherapy, immune checkpoint inhibitors (ipilimumab, pembrolizumab, and nivolumab), anti-VEGFR2 inhibitors (ramucirumab), and HER2-targeted drugs. However, managing advanced/metastatic disease remains challenging. In the case of distant metastatic disease, the 5-year overall survival (OS) rate is only around 5%. As the innovation of immunotherapy and HER2-targeted therapy have improved the outcomes of advanced/metastatic disease, they are currently being investigated for use in earlier localized disease.

An era of personalized therapies is emerging, with newer molecular targets being evaluated, such as claudin 18.2 (CLDN18.2), Dickkopf-1 protein (DKK1), tyrosine kinase inhibitors, and fibroblast growth factor receptor-2 (FGFR2). For instance, zolbetuximab, a monoclonal antibody targeting the tight junction protein CLDN-18.2, has shown promising results among patients with HER2-negative, CLDN-18-positive gastroesophageal cancer. While most of these biomarkers require tissue biopsy, blood-based assays are rapidly evolving, with circulation cell-free DNA (cfDNA) being used to detect genetic alterations. This newer, minimally invasive technology can aid in searching for molecular drug targets, monitoring treatment failure and the emergence of drug-resistant subclones, and capturing the genetic heterogeneity of tumor cells. In summary, these studies have paved the way for precision medicine’s utility in gastroesophageal cancer, providing hope for this challenging disease. As a result, we must continue to widen our knowledge of the precision treatment of gastroesophageal malignancies in clinical practice.

Dr. Michael K. Gibson
Guest Editor

Manuscript Submission Information

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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. Journal of Clinical Medicine 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 2600 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

  • gastroesophageal cancer
  • targeted therapy
  • circulating tumor DNA
  • precision medicine
  • immune checkpoint inhibitors
  • esophageal cancer
  • gastric cancer
  • biomarkers
  • molecular characterization

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Published Papers (2 papers)

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12 pages, 537 KiB  
Article
Induction Radiochemotherapy for Esophageal Cancer: Long-Term Outcomes from a Single-Center Study
by Bartłomiej Strzelec, Piotr Paweł Chmielewski and Renata Taboła
J. Clin. Med. 2025, 14(2), 394; https://doi.org/10.3390/jcm14020394 - 10 Jan 2025
Viewed by 814
Abstract
Background/Objectives: The management of esophageal cancer (EC) remains a significant clinical challenge, particularly in optimizing therapeutic strategies for different stages and subgroups. This study assessed the impact of preoperative radiochemotherapy (CRT) on clinical staging and identified subgroups for whom definitive CRT (dCRT) may [...] Read more.
Background/Objectives: The management of esophageal cancer (EC) remains a significant clinical challenge, particularly in optimizing therapeutic strategies for different stages and subgroups. This study assessed the impact of preoperative radiochemotherapy (CRT) on clinical staging and identified subgroups for whom definitive CRT (dCRT) may provide a favorable alternative to surgery. Methods: Sixty-one patients with esophageal adenocarcinoma or squamous cell carcinoma were enrolled. Pre-treatment staging included computed tomography, gastroscopy with biopsy, and comprehensive laboratory evaluations. Patients received preoperative CRT following the CROSS or dCRT protocols based on tumor stage. Surgical approaches included staged esophagectomy or single-stage Ivor Lewis procedures. Four patients declined surgery and were treated with dCRT. Postoperative outcomes were evaluated using pTNM classification. Follow-up included imaging and endoscopic surveillance. Statistical analyses assessed changes in staging and factors influencing treatment outcomes. Results: CRT significantly reduced T stage across the entire cohort (p = 0.0002), with complete pathological response (pT0N0M0) observed in 54.5% of patients following induction CRT (p = 0.0001). Male patients demonstrated a significant reduction in T stage (p = 0.0008), while a similar trend in females was not significant (p = 0.068). Among patients declining surgery, dCRT demonstrated acceptable oncologic control over a mean follow-up of 4 ± 0.79 years. Conclusions: Preoperative CRT effectively downstages EC and achieves high rates of response, especially in male patients. Therefore, dCRT may be a viable alternative in selected patients, emphasizing the need for individualized treatment strategies to optimize outcomes. These findings underscore the importance of refining multimodal approaches in EC care. Full article
(This article belongs to the Special Issue Gastroesophageal Cancer: Outcomes and Therapeutic Management)
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Review

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18 pages, 1930 KiB  
Review
Gastroesophageal Neuroendocrine Tumors: Outcomes and Management
by Christine Son, Joshua Kalapala, Jeff Leya, Michelle Marion Popadiuk, Mohammed K. Atieh, Daniel Havlichek III, Lawrence Feldman, Paul Roach and Promila Banerjee
J. Clin. Med. 2025, 14(7), 2148; https://doi.org/10.3390/jcm14072148 - 21 Mar 2025
Viewed by 449
Abstract
Background/Objectives: Neuroendocrine tumors (NETs) can arise in any organ and are most commonly found in the lungs and gastroenteropancreatic (GEP) system. GEP-NETs represent a small percentage of gastrointestinal cancers, and therefore, the standard treatment is not well-defined, especially for advanced disease. Our [...] Read more.
Background/Objectives: Neuroendocrine tumors (NETs) can arise in any organ and are most commonly found in the lungs and gastroenteropancreatic (GEP) system. GEP-NETs represent a small percentage of gastrointestinal cancers, and therefore, the standard treatment is not well-defined, especially for advanced disease. Our objective is to review GI NETs among veterans and analyze their therapeutic outcomes. Methods: A total of 61 GI NET cases were identified from our institution from 2019–2024. In total, twenty-seven review papers, ten population-based/multicenter/outcome studies, six case reports, and one case series were reviewed for the literature review. Results: The incidence of GI NETs at our institution was higher than the known epidemiology of GI NETs. Small intestine NETs were one of the most common sites of GEP-NETs at our institution, with only one of nineteen cases being grade 3 poorly differentiated neuroendocrine carcinoma. All cases of colonic and rectal NETs had good clinical outcomes consistent with findings from the literature. Most of the gastric NETs were type 1 and had benign courses of disease, except for one case with an intermediate grade and metastatic liver lesions. One case of esophageal neuroendocrine carcinoma (E-NEC) showed a complete response to chemotherapy despite a significant tumor burden on presentation and high-grade pathology, while another case of ENEC had recurrent disease despite systemic therapy. Conclusions: While the role of surgery or endoscopic resection is limited to localized tumors, combined treatment with chemoradiation can significantly improve patient outcomes, especially in high-grade, poorly differentiated tumors. Further studies are needed to establish systemic (i.e., chemotherapy and radiation) treatment strategies for poorly differentiated GI NETs. Full article
(This article belongs to the Special Issue Gastroesophageal Cancer: Outcomes and Therapeutic Management)
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