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Novel Therapeutic Approaches for Gastroesophageal Cancer
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Novel Therapeutic Approaches for Gastroesophageal Cancer

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

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 9528

Special Issue Editors

Dr. Massimiliano Salati

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Guest Editor
University-Hospital of Modena, Modena Cancer Center, Modena, Italy
Interests: gastrointestinal cancer; cancer biology; translational research, immunotherapy, precision medicine, biomarker discovery, clinical trials
Dr. Andrea Spallanzani

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Guest Editor
Medical Oncology Unit, Azienda Ospedaliero Universitaria di Modena, 41125 Modena, Italy
Interests: gastrointestinal cancer; cancer biology; clinical trials

Special Issue Information

Dear Colleagues,

Gastroesophageal cancers remain a public health problem worldwide with over 1 million new cases and a fatality-to-case ratio of 70%. In recent years, a better knowledge of disease biology and advances in the multimodal management has produce a significant survival benefit in gastroesophageal cancers. Indeeed, the availability of a more accurate staging, less-invasive surgical techniques and more effective perioperative chemotherapy has improved the curability by 10% in the resectable setting. Moreover, incremental yet steadily survival advantages have been recorded in the unresectable advanced disease as a result of the growing array of evidence-based options including targeted agents and immunotherapy in second and later lines and the improved patients’ selection through molecular characterization. In parallel, emerging precision-medicine tools such as liquid biopsy and patients-derived organoids provide a reliable platform for drug screening, studying resistance mechanisms and identifying novel therapeutic targets and ultimately personalize treatment strategies.

The aim of this Special Issue is to provide readers with most updated research findings on novel approaches in the multidisciplinary management of gastroesophageal cancer, including research papers, narrative reviews, systematic reviews and meta-analysis. 

Dr. Massimiliano Salati
Dr. Andrea Spallanzani
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. 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
  • gastric cancer
  • immunotherapy
  • surgery
  • loco-regional therapies
  • targeted therapies
  • precision medicine
  • personalized strategies
  • clinical trials
  • translational research.

Published Papers (5 papers)

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Editorial

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2 pages, 169 KiB  
Editorial
New Horizons for Personalised Treatment in Gastroesophageal Cancer
by Massimiliano Salati and Andrea Spallanzani
J. Clin. Med. 2022, 11(2), 311; https://doi.org/10.3390/jcm11020311 - 9 Jan 2022
Cited by 3 | Viewed by 1253
Abstract
Gastric and gastroesophageal junction adenocarcinoma (GEA) is still responsible for a huge health burden worldwide, being the second most common cause of cancer-related death globally [...] Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Gastroesophageal Cancer)

Research

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11 pages, 1694 KiB  
Article
Development and Multicenter Validation of a Novel Immune-Inflammation-Based Nomogram to Predict Survival in Western Resectable Gastric and Gastroesophageal Junction Adenocarcinoma (GEA): The NOMOGAST
by Massimiliano Salati, Nicola De Ruvo, Mariano Cesare Giglio, Lorena Sorrentino, Giuseppe Esposito, Sara Fenocchi, Giovanni Cucciarrè, Francesco Serra, Elena Giulia Rossi, Giovanni Vittimberga, Giorgia Radi, Leonardo Solaini, Paolo Morgagni, Giulia Grizzi, Margherita Ratti, Fabio Gelsomino, Andrea Spallanzani, Michele Ghidini, Giorgio Ercolani, Massimo Dominici and Roberta Gelminiadd Show full author list remove Hide full author list
J. Clin. Med. 2022, 11(18), 5439; https://doi.org/10.3390/jcm11185439 - 16 Sep 2022
Viewed by 1370
Abstract
Background. More than 50% of operable GEA relapse after curative-intent resection. We aimed at externally validating a nomogram to enable a more accurate estimate of individualized risk in resected GEA. Methods. Medical records of a training cohort (TC) and a validation [...] Read more.
Background. More than 50% of operable GEA relapse after curative-intent resection. We aimed at externally validating a nomogram to enable a more accurate estimate of individualized risk in resected GEA. Methods. Medical records of a training cohort (TC) and a validation cohort (VC) of patients undergoing radical surgery for c/uT2-T4 and/or node-positive GEA were retrieved, and potentially interesting variables were collected. Cox proportional hazards in univariate and multivariate regressions were used to assess the effects of the prognostic factors on OS. A graphical nomogram was constructed using R software’s package Regression Modeling Strategies (ver. 5.0-1). The performance of the prognostic model was evaluated and validated. Results. The TC and VC consisted of 185 and 151 patients. ECOG:PS > 0 (p < 0.001), angioinvasion (p < 0.001), log (Neutrophil/Lymphocyte ratio) (p < 0.001), and nodal status (p = 0.016) were independent prognostic values in the TC. They were used for the construction of a nomogram estimating 3- and 5-year OS. The discriminatory ability of the model was evaluated with the c-Harrell index. A 3-tier scoring system was developed through a linear predictor grouped by 25 and 75 percentiles, strengthening the model’s good discrimination (p < 0.001). A calibration plot demonstrated a concordance between the predicted and actual survival in the TC and VC. A decision curve analysis was plotted that depicted the nomogram’s clinical utility. Conclusions. We externally validated a prognostic nomogram to predict OS in a joint independent cohort of resectable GEA; the NOMOGAST could represent a valuable tool in assisting decision-making. This tool incorporates readily available and inexpensive patient and disease characteristics as well as immune-inflammatory determinants. It is accurate, generalizable, and clinically effectivex. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Gastroesophageal Cancer)
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11 pages, 1020 KiB  
Article
Reduction of Cancer-Induced Thrombocytosis as a Biomarker of Improved Outcomes in Advanced Gastric Cancer
by Kamil Konopka, Paulina Frączek, Maciej Lubaś, Agnieszka Micek, Łukasz Kwinta, Joanna Streb, Paweł Potocki and Piotr J. Wysocki
J. Clin. Med. 2022, 11(5), 1213; https://doi.org/10.3390/jcm11051213 - 24 Feb 2022
Cited by 1 | Viewed by 1781
Abstract
Background: Interplay between non-specific inflammatory reaction and tumor microenvironment in gastric cancer (GC) can be measured indirectly by assessing fluctuations in concentration of platelets. Cytotoxic chemotherapy affects these morphotic elements directly by inducing myelosuppression. It was hypothesized that chemotherapy not only directly affects [...] Read more.
Background: Interplay between non-specific inflammatory reaction and tumor microenvironment in gastric cancer (GC) can be measured indirectly by assessing fluctuations in concentration of platelets. Cytotoxic chemotherapy affects these morphotic elements directly by inducing myelosuppression. It was hypothesized that chemotherapy not only directly affects malignant cells, but also through immunomodulation related to myelosuppression. Methods: Metastatic GC patients (N: 155) treated with chemotherapy +/− trastuzumab were enrolled in this retrospective study. Platelet pretreatment concentration (PLT-count) and the deepest level of platelet reduction, as well as other inflammatory and general confounders were collected in the first 12 weeks of treatment (PLT-red). Martingale residuals were used to visualize the relationship between PLT-count, PLT-red, and overall survival (OS). Multiple multivariate Cox regression models were built to assess the impact of platelet reduction on OS and progression-free survival (PFS). Results: Reduction of PLT (PLT-red) to 60% of baseline concentration was associated with improved survival rates (HR = 0.60, p = 0.026 for OS and HR 0.56, p = 0.015 for PFS). Cross-classification into four groups based on PLT-count (high vs low) and PLT-red (high vs low) showed significantly worse survival rates in both high PLT-count (HR = 3.60, p = 0.007 for OS and HR = 2.97, p = 0.024 for PFS) and low PLT-count (HR = 1.75, p = 0.035 for OS and HR = 1.80, p = 0.028 for PFS) patients with insufficient platelets reduction. Conclusion: Thrombocytosis reduction represents a novel, clinically important, prognostic factor for OS and PFS in patients with stage IV GC. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Gastroesophageal Cancer)
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Review

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9 pages, 587 KiB  
Review
Anti-Claudin Treatments in Gastroesophageal Adenocarcinoma: Mainstream and Upcoming Strategies
by Giulia Grizzi, Kostantinos Venetis, Nerina Denaro, Maria Bonomi, Andrea Celotti, Antonia Pagkali, Jens Claus Hahne, Gianluca Tomasello, Fausto Petrelli, Nicola Fusco and Michele Ghidini
J. Clin. Med. 2023, 12(8), 2973; https://doi.org/10.3390/jcm12082973 - 19 Apr 2023
Cited by 6 | Viewed by 2631
Abstract
Claudins (CLDNs) are a multigene family of proteins and the principal components of tight junctions (TJs), which normally mediate cell–cell adhesion and selectively allow the paracellular flux of ions and small molecules between cells. Downregulation of claudin proteins increases the paracellular permeability of [...] Read more.
Claudins (CLDNs) are a multigene family of proteins and the principal components of tight junctions (TJs), which normally mediate cell–cell adhesion and selectively allow the paracellular flux of ions and small molecules between cells. Downregulation of claudin proteins increases the paracellular permeability of nutrients and growth stimuli to malignant cells, which aids the epithelial transition. Claudin 18.2 (CLDN18.2) was identified as a promising target for the treatment of advanced gastroesophageal adenocarcinoma (GEAC), with high levels found in almost 30% of metastatic cases. CLDN18.2 aberrations, enriched in the genomically stable subgroup of GEAC and the diffuse histological subtype, are ideal candidates for monoclonal antibodies and CAR-T cells. Zolbetuximab, a highly specific anti-CLDN18.2 monoclonal antibody, demonstrated efficacy in phase II studies and, more recently, in the phase III SPOTLIGHT trial, with improvements in both PFS and OS with respect to standard chemotherapy. Anti-CLDN18.2 chimeric antigen receptor (CAR)-T cells showed a safety profile with a prevalence of hematologic toxicity in early phase clinical trials. The aim of this review is to present new findings in the treatment of CLDN18.2-positive GEAC, with a particular focus on the monoclonal antibody zolbetuximab and on the use of engineered anti-CLDN18.2 CAR-T cells. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Gastroesophageal Cancer)
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26 pages, 18237 KiB  
Review
Laparoscopic versus Open Surgery for Gastric Cancer in Western Countries: A Systematic Review and Meta-Analysis of Short- and Long-Term Outcomes
by Giovanni Maria Garbarino, Giovanni Guglielmo Laracca, Alessio Lucarini, Gianmarco Piccolino, Paolo Mercantini, Alessandro Costa, Giuseppe Tonini, Giulia Canali, Edoardo Maria Muttillo and Gianluca Costa
J. Clin. Med. 2022, 11(13), 3590; https://doi.org/10.3390/jcm11133590 - 22 Jun 2022
Cited by 11 | Viewed by 1807
Abstract
Background. The advantages of a laparoscopic approach for the treatment of gastric cancer have already been demonstrated in Eastern Countries. This review and meta-analysis aims to merge all the western studies comparing laparoscopic (LG) versus open gastrectomies (OG) to provide pooled results and [...] Read more.
Background. The advantages of a laparoscopic approach for the treatment of gastric cancer have already been demonstrated in Eastern Countries. This review and meta-analysis aims to merge all the western studies comparing laparoscopic (LG) versus open gastrectomies (OG) to provide pooled results and higher levels of evidence. Methods. A systematic literature search was performed in MEDLINE(PubMed), Embase, WebOfScience and Scopus for studies comparing laparoscopic versus open gastrectomy in western centers from 1980 to 2021. Results. After screening 355 articles, 34 articles with a total of 24,098 patients undergoing LG (5445) or OG (18,653) in western centers were included. Compared to open gastrectomy, laparoscopic gastrectomy has a significantly longer operation time (WMD = 47.46 min; 95% CI = 31.83–63.09; p < 0.001), lower blood loss (WMD = −129.32 mL; 95% CI = −188.11 to −70.53; p < 0.0001), lower analgesic requirement (WMD = −1.824 days; 95% CI = −2.314 to −1.334; p < 0.0001), faster time to first oral intake (WMD = −1.501 days; 95% CI = −2.571 to −0.431; p = 0.0060), shorter hospital stay (WMD = −2.335; 95% CI = −3.061 to −1.609; p < 0.0001), lower mortality (logOR = −0.261; 95% the −0.446 to −0.076; p = 0.0056) and a better 3-year overall survival (logHR 0.245; 95% CI = 0.016–0.474; p = 0.0360). A slight significant difference in favor of laparoscopic gastrectomy was noted for the incidence of postoperative complications (logOR = −0.202; 95% CI = −0.403 to −0.000 the = 0.0499). No statistical difference was noted based on the number of harvested lymph nodes, the rate of major postoperative complication and 5-year overall survival. Conclusions. In Western centers, laparoscopic gastrectomy has better short-term and equivalent long-term outcomes compared with the open approach, but more high-quality studies on long-term outcomes are required. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Gastroesophageal Cancer)
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