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Developments in the Management of Gastrointestinal Malignancies (2nd Edition)

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

Deadline for manuscript submissions: 31 May 2026 | Viewed by 19191

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Dr. Zachary J. Brown

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Division of Surgical Oncology, NYU Langone Health, NYU Grossman Long Island School of Medicine, New York, NY, USA
Interests: hepatocellular carcinoma; gastrointestinal malignancies; cancer metastasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of the Special Issue “Developments in the Management of Gastrointestinal Malignancies”, available at https://www.mdpi.com/journal/cancers/special_issues/671LU3Q1C7.

Gastrointestinal (GI) malignancies are a major cause of morbidity and mortality worldwide. Treatment of these malignancies often consists of multimodal therapy with a combination of chemotherapy, radiation, and surgery. In addition, immune-based therapies are being utilized at increased rates in patients with GI malignancies.

In this Special Issue, we focus on advances in the multimodal treatment of patients with GI malignancies, including patients with localized and metastatic disease. Comments are encouraged on the role of biomarkers and molecular profiling techniques to help guide therapeutic decisions as well as emerging novel therapies.

We look forward to receiving your contributions.

Dr. Zachary J. Brown
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 250 words) can be sent to the Editorial Office for assessment.

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

gastrointestinal malignancies
multimodal therapy
chemotherapy
radiotherapy
immunotherapy
localized and metastatic

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Published Papers (9 papers)

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Research

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12 pages, 1900 KB

Open AccessArticle

Impact of Sarcopenia on Prognosis, Treatment Toxicity and Surgical Complications in Locally Advanced Gastric Cancer

by David da Silva Dias, Paulo Luz, Ana Fortuna, Ana Águas, Mafalda Machado, Beatriz Gosálbez, Rosa Farate, Rita Clemente Pinho, Ana Carmo Valente, José Leão Mendes, Marta Maria Seladas, Carolina Trabulo and Paula Ravasco

Cancers 2026, 18(9), 1430; https://doi.org/10.3390/cancers18091430 - 30 Apr 2026

Viewed by 294

Abstract

Background: Weight loss and skeletal muscle wasting are frequent in cancer and may influence treatment tolerance and outcomes. Computed tomography (CT) based body composition analysis at the third lumbar vertebra (L3) is an accurate method to quantify skeletal muscle in routine oncology care. Methods: We performed a multicenter retrospective cohort study including 202 adults with locally advanced (stage IB–III) gastric cancer treated in four Portuguese hospitals (January 2020–December 2022). Skeletal muscle area (SMA) was assessed on baseline CT at the L3 vertebral level, using Data Analysis Facilitation Suite (DAFS) software v3.11.2, and skeletal muscle index (SMI) was subsequently calculated. Patients with low muscle quantity were classified as sarcopenic (below sex-specific SMI mean). We evaluated associations with relapse-free survival (RFS), overall survival (OS), FLOT chemotherapy dose-limiting toxicities (DLTs), and postoperative complications after gastrectomy. Results: Mean age was 69 years, 65% had ECOG PS 0, 53% received FLOT chemotherapy protocol. Mean SMI was 49.6 cm²/m² in males and 40.9 cm²/m² in females and correlated positively, though moderately, with BMI (p < 0.01; r = 0.424). Sarcopenia was not significantly associated with RFS (p = 0.186) or OS (p = 0.168) at 30-month follow-up. Although numerical differences were observed (64% vs. 56% of patients did not relapse and 74% vs. 63% were alive, for non-sarcopenic vs. sarcopenic patients). Sarcopenia was associated with a higher risk of DLTs (p = 0.021; OR 2.56, 95% CI 1.15–5.73) and postoperative complications (p = 0.024; OR 2.16, 95% CI 1.11–4.21). Conclusions: Sarcopenia significantly increases the risk of chemotherapy toxicity and postoperative complications in locally advanced gastric cancer. However, its effect on OS and RFS was not statistically significant at 30-month follow-up. Standardization of CT-based sarcopenia cut-offs remains a major barrier to clinical implementation. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies (2nd Edition))

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14 pages, 517 KB

Open AccessArticle

Balancing Surgical Innovation with Indications: A Multicenter Retrospective Comparison of Reduced-Port Distal Gastrectomy Using da Vinci SP Versus Multi-Port Robotic Platforms from the KLASS-13 Cohort

by Jae Hun Chung, Hyoung-Il Kim, Sang-Hoon Ahn, Han Hong Lee, Yun-Suhk Suh, Yoo Min Kim, Young Suk Park, Sung Hyun Park and Chang Min Lee

Cancers 2026, 18(5), 823; https://doi.org/10.3390/cancers18050823 - 4 Mar 2026

Viewed by 692

Abstract

Background: The da Vinci single-port reduced-port robotic distal gastrectomy (spRRDG) approach shows promise in enhancing surgical recovery while maintaining oncologic safety, but robust multicenter comparative data across diverse robotic platforms are lacking. We aimed to compare clinical outcomes between spRRDG and conventional RRDG (cRRDG) using Korean Laparoendoscopic Gastrointestinal Surgery Study-13 data. Methods: Clinicopathologic variables and perioperative outcomes concerning 820 patients who underwent curative RRDG with D1+ or D2 lymph node dissection (LND) (da Vinci spRRDG, n = 86; cRRDG, n = 734) were analyzed. We compared continuous variables using Student’s t- or Wilcoxon rank-sum tests, as appropriate, and categorical variables using χ² or Fisher’s exact tests. Subgroup analyses were performed according to the extent of LND (D1+ vs. D2). Statistical significance was defined as p < 0.05. Results: spRRDG involved a longer operative time than cRRDG (227.06 ± 6.19 vs. 183.58 ± 2.18 min, p < 0.0001) and fewer retrieved LNs (rLNs) (36.38 ± 1.53 vs. 46.52 ± 0.66, p < 0.0001), but showed superior enhanced recovery after surgery (ERAS)-related outcomes, including shorter hospital stay (4.06 ± 0.23 vs. 5.95 ± 0.13 days), and earlier gas passage (postoperative day [POD] 2.24 ± 0.10 vs. 3.08 ± 0.04) and soft diet initiation (POD 1.59 ± 0.14 vs. 2.89 ± 0.07; all p < 0.0001). In subgroup analyses, the number of rLNs was lower in D1+ spRRDG (34.09 ± 1.58 vs. 44.36 ± 0.72, p < 0.0001), but remained above the oncologic threshold (≥16 LNs). In D2 dissections, no significant difference was observed (45.71 ± 3.69 vs. 53.30 ± 1.39, p = 0.1030). Faster postoperative recovery in spRRDG persisted after adjustment. Conclusion: spRRDG exhibited lower rLNs than cRRDG but remained within an oncologically acceptable range. Comparable complication rates and significantly improved ERAS outcomes suggest spRRDG is safe and feasible; however, its clinical application should remain limited to early gastric cancer until robust evidence from prospective studies emerges. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies (2nd Edition))

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11 pages, 261 KB

Open AccessArticle

Impact of Frailty on the Outcomes of Patients with Pancreatic Cancer Undergoing Neoadjuvant Therapy

by Nicholas R. Williams, Thomas Leuschner, Amanda K. Walsh, Kayla Gault, Amber Ingram, Alex B. Blair, Susan Tsai, Timothy M. Pawlik, Mary E. Dillhoff and Jordan M. Cloyd

Cancers 2025, 17(24), 4030; https://doi.org/10.3390/cancers17244030 - 18 Dec 2025

Cited by 1 | Viewed by 889

Abstract

Background: Neoadjuvant therapy (NT) is increasingly utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). Toxicities during NT are common, often leading to the inability to undergo surgical resection, yet risk factors for attrition are poorly understood. Therefore, we sought to evaluate the impact of baseline frailty on outcomes of patients with PDAC undergoing NT. Methods: All patients with potentially resectable (PR) or borderline resectable (BR) PDAC who initiated neoadjuvant chemotherapy and/or chemoradiation between 2019 and 2025 at a single institution were assessed retrospectively in an intention-to-treat fashion. The association between frailty as defined by the modified 11-item frailty index (mFI-11) and receipt of surgical resection as well as other secondary endpoints was assessed. Comprehensive functional frailty assessments were prospectively obtained in a subset of patients. Results: Among 252 eligible patients, the median age was 67 years, 56.7% were male, 90.9% were White, 49.6% had PR disease, and 5.2% were frail according to mFI-11. After a median 3.6 months of NT, 62.7% underwent surgical resection. Frail individuals had worse performance status and increased comorbidities compared with non-frail patients. On multivariable analysis, male sex, BR anatomic staging, initial use of Gemcitabine + nab-paclitaxel, and frailty (OR 0.09; 95%CI 0.02–0.44) were associated with reduced odds of undergoing resection. Along with increased baseline CA 19-9 levels, frailty was independently associated with worse overall survival (HR 3.00; 95%CI 1.46–6.20). Among 39 patients who underwent formal functional frailty assessment, only abnormal posture was associated with lower odds of surgical resection following NT (OR, 0.22; 95% CI, 0.05–0.92), and no aspects of functional frailty were associated with overall survival. Conclusions: Among patients with localized PDAC initiating NT, frailty as assessed by mFI-11 was associated with reduced odds of undergoing surgical resection and worse overall survival. Future research should focus on efforts to improve functional status during NT. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies (2nd Edition))

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Review

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23 pages, 1037 KB

Open AccessReview

Therapeutic Cancer Vaccines in Gastrointestinal Malignancies: Advances, Challenges, and Emerging Strategies

by Kyle Taing, Keeyon Dabirian and Aditya Shreenivas

Cancers 2026, 18(9), 1420; https://doi.org/10.3390/cancers18091420 - 29 Apr 2026

Viewed by 558

Abstract

Gastrointestinal (GI) malignancies—which comprise esophageal, gastric, colorectal, hepatobiliary, and pancreatic cancers—remain a leading global cause of oncologic morbidity and mortality. The prognosis for many patients (especially those diagnosed with advanced-stage disease) remains poor despite conventional therapies—namely, surgery, chemotherapy, and radiation. Immunotherapy, however, has emerged as a new strategy in oncology, and, in particular, the advent of cancer vaccines now provides an investigational approach to improving clinical outcomes in patients with GI malignancies. This review aims to provide a comprehensive overview of multiple vaccine-based strategies developed to better target GI cancers, spanning from early preclinical studies to the most recently completed clinical trials. We first introduce the main vaccine therapy classes and the immunologic rationale underlying each. We then summarize key findings from past and ongoing trials using a cancer-type-based approach, primarily focusing on vaccine safety and immunogenicity, and commenting on limitations in overall efficacy. Finally, we identify the challenges of applying mostly early-phase trials to clinical practice as well as future directions for integrating these vaccine-based approaches into personalized treatments for GI cancer patients. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies (2nd Edition))

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18 pages, 658 KB

Open AccessReview

Focused Ultrasound in Pancreatic Ductal Adenocarcinoma: Mechanisms, Preclinical Evidence, and Emerging Clinical Applications

by Olivia Sears, Hongji Zhang, Natalie Blatz, Xiao Cui and Allan Tsung

Cancers 2026, 18(4), 574; https://doi.org/10.3390/cancers18040574 - 10 Feb 2026

Viewed by 859

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy due to late presentation, limited resectability, therapeutic resistance, and a dense desmoplastic immunosuppressive tumor microenvironment that impairs drug penetration and antitumor immunity. Focused ultrasound (FUS) is an emerging non-invasive, image-guided therapeutic platform capable of delivering spatially confined acoustic energy to induce tumor ablation, disrupt stromal barriers, and enhance delivery of drugs, nanoparticles, and nucleic acids. Depending on acoustic parameters, FUS can produce thermal effects resulting in coagulative necrosis or non-thermal mechanical effects, including cavitation, sonoporation, and histotripsy which remodel extracellular matrix architecture, increase vascular and cellular permeability, and facilitate tumor debulking. In addition, FUS-induced cell injury can promote immunogenic cell death and release tumor-associated antigens and danger signals, providing a rationale for combination strategies with chemotherapy, radiation, and immunotherapy. This review synthesizes the mechanistic foundations, preclinical modeling advances, and emerging clinical applications of FUS in PDAC, with emphasis on treatment integration, patient selection, real-time monitoring, and acoustic parameter optimization, while acknowledging current safety considerations and limited clinical toxicity data. Key limitations, translational challenges, and priority knowledge gaps are also discussed to define the role of FUS in multimodal PDAC care. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies (2nd Edition))

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15 pages, 1163 KB

Open AccessReview

The Role of MUC1 in Gastric Cancer Development

by Iwona Radziejewska

Cancers 2025, 17(20), 3331; https://doi.org/10.3390/cancers17203331 - 15 Oct 2025

Cited by 3 | Viewed by 1781

Abstract

Gastric cancer (GC) remains the most common malignancy and the main cause of cancer-related death worldwide. Due to its asymptomatic beginning, most gastric cancer cases are diagnosed in the advanced stages, which is connected with poor outcomes. Therefore, there is an urgent need for the development of early preventive and screening strategies for GC. A full understanding of GC pathogenesis, including examining key factors participating in cancer progress, is important. MUC1 is a glycoprotein that is highly overexpressed in most epithelial tumors, including gastric tumors. MUC1 presents a specifically altered glycosylation pattern, which is important for the creation of a cancerous environment. This mucin has been proposed as a biomarker for predicting GC outcomes. This review summarizes the involvement of MUC1 in GC progression. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies (2nd Edition))

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20 pages, 1138 KB

Open AccessReview

Integrating Circulating Tumor DNA into Clinical Management of Colorectal Cancer: Practical Implications and Therapeutic Challenges

by Nikhil Vojjala, Viktoriya Gibatova, Raj N. Shah, Sakshi Singal, Rishab Prabhu, Geetha Krishnamoorthy, Karen Riggins and Nagaishwarya Moka

Cancers 2025, 17(15), 2520; https://doi.org/10.3390/cancers17152520 - 30 Jul 2025

Cited by 4 | Viewed by 6814

Abstract

The American Cancer Society estimates that over 152,000 new cases of colorectal cancer (CRC) were diagnosed in 2024, with more than 105,000 cases affecting the colon and 46,000 involving the rectum. CRC remains the second leading cause of cancer-related deaths in the United States, with an estimated 53,010 deaths in 2024. In the era of precision medicine, which incorporates molecular and environmental information into clinical decision-making, identifying patients harboring a deficiency in Deoxyribonucleic acid (DNA) repair allowed for targeted immunotherapies and significantly reduced CRC-related mortality. A significant advancement in this domain is the application of liquid biopsy, which has emerged as a promising tool for prognostication, guiding therapy, and monitoring treatment response in CRC. This review aims to comprehensively explore the role of liquid biopsy in colorectal malignancies, describing its practical applications, prognostic significance, and potential to revolutionize CRC management in the future. At the end, we also aim to show a schematic representation of showing integration of Circulating Tumor (Ct) DNA in routine clinical management of CRC. The highlight of this article is the structured and evidence-based schematic framework and its integration into future practice. The schematic pathway is designed to optimize ctDNA utilization across various stages of colorectal cancer management. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies (2nd Edition))

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15 pages, 860 KB

Open AccessReview

Gut Microbiome Alterations in Colorectal Cancer: Mechanisms, Therapeutic Strategies, and Precision Oncology Perspectives

by Miriam Tudorache, Andreea-Ramona Treteanu, Gratiela Gradisteanu Pircalabioru, Irina-Oana Lixandru-Petre, Alexandra Bolocan and Octavian Andronic

Cancers 2025, 17(14), 2294; https://doi.org/10.3390/cancers17142294 - 10 Jul 2025

Cited by 6 | Viewed by 4818

Abstract

Colorectal cancer (CRC) is one of the most prevalent and lethal oncological diseases worldwide, with a concerning rise in incidence, particularly in developing countries. Recent advances in genetic sequencing have revealed that the gut microbiome plays a crucial role in CRC development. Mechanisms such as chronic inflammation, metabolic alterations, and oncogenic pathways have demonstrated that dysbiosis, a disruption of the gut microbiome, is linked to CRC. Associations have been found between tumor progression, treatment resistance, and pathogenic microbes such as Fusobacterium nucleatum and Escherichia coli. A promising approach for CRC prevention and treatment is microbiome manipulation through interventions such as probiotics, prebiotics, fecal microbiota transplantation, and selective antibiotics. This article explores how gut microbiome alterations influence CRC pathogenesis and examines microbiome modulation strategies currently used as adjuncts to traditional treatments. Advances in artificial intelligence, single-cell and spatial transcriptomics, and large-scale initiatives such as the ONCOBIOME Project are paving the way for the identification of microbiome-derived biomarkers for early CRC detection and personalized treatment. Despite promising progress, challenges such as interindividual variability, causal inference, and regulatory hurdles must be addressed. Future integration of microbiome analysis into multi-omics frameworks holds great potential to revolutionize precision oncology in CRC management. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies (2nd Edition))

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12 pages, 1060 KB

Open AccessReview

Role of B-Mode and Contrast-Enhanced Ultrasound in the Diagnostic Workflow of Gastro-Entero-Pancreatic Neuroendocrine Tumors (GEP-NETs)

by Linda Galasso, Maria Grazia Maratta, Valeria Sardaro, Giorgio Esposto, Irene Mignini, Raffaele Borriello, Antonio Gasbarrini, Maria Elena Ainora, Giovanni Schinzari and Maria Assunta Zocco

Cancers 2025, 17(11), 1879; https://doi.org/10.3390/cancers17111879 - 4 Jun 2025

Cited by 1 | Viewed by 1864

Abstract

Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) represent a rare and varied class of neoplasms, characterized by diverse clinical presentations and prognostic trajectories. Accurate and prompt diagnosis is vital to inform and optimize therapeutic decisions. Ultrasound, including standard B-mode imaging and advanced methods such as contrast-enhanced ultrasound (CEUS) and endoscopic ultrasound (EUS), serves as a key component in the diagnostic evaluation of these tumors. B-mode US and CEUS provide non-invasive, accessible methods for early detection and characterization. On B-mode imaging, GEP-NETs typically present as well-defined, hyperechoic, or iso-echoic lesions, while CEUS highlights their characteristic vascularity, marked by arterial-phase hyperenhancement and venous-phase washout. Compared to CT and MRI, ultrasound offers real-time, dynamic imaging without ionizing radiation or nephrotoxic contrast agents, making it particularly advantageous for patients requiring frequent monitoring or with contraindications to other imaging modalities. CT and MRI are widely regarded as the preferred methods for staging and surgical planning due to their detailed anatomical visualization. However, ultrasound, especially CEUS, provides a significant adjunctive role in both early detection and the follow-up on GEP-NETs. This analysis delves into the strengths, challenges, and innovations in ultrasound technology for diagnosing pancreatic NETs, focusing on its contribution to comprehensive imaging strategies and its impact on patient care decisions. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies (2nd Edition))

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