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Search Results (1,368)

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12 pages, 486 KiB  
Article
Efficacy and Safety of Dose-Dense Chemotherapy in Breast Cancer: Real Clinical Data and Literature Review
by Keiko Yanagihara, Masato Yoshida, Tamami Yamakawa, Sena Kato, Miki Tamura and Koji Nagata
Curr. Oncol. 2025, 32(8), 441; https://doi.org/10.3390/curroncol32080441 - 6 Aug 2025
Abstract
Dose-dense chemotherapy shortens the interval between chemotherapy cycles and has shown improved outcomes in high-risk breast cancer patients. We retrospectively evaluated the efficacy and safety of dose-dense chemotherapy in 80 breast cancer patients treated at our hospital from 2020 to 2024. The regimen [...] Read more.
Dose-dense chemotherapy shortens the interval between chemotherapy cycles and has shown improved outcomes in high-risk breast cancer patients. We retrospectively evaluated the efficacy and safety of dose-dense chemotherapy in 80 breast cancer patients treated at our hospital from 2020 to 2024. The regimen included epirubicin and cyclophosphamide followed by paclitaxel or docetaxel, with pegfilgrastim support. The overall treatment completion rate was 82.5%. Of the 80 patients, 55 underwent neoadjuvant chemotherapy, and the pathological complete response rate was significantly higher in triple-negative breast cancer (59.1%) compared to that in luminal-type cancer (9.1%). Common adverse events included anemia, liver dysfunction, myalgia, and peripheral neuropathy. Febrile neutropenia occurred in 8.8% of patients, with some cases linked to pegfilgrastim body pod use, particularly in individuals with low subcutaneous fat. Notably, two patients developed pneumocystis pneumonia, potentially associated with steroid administration. Despite these toxicities, most were manageable and resolved after treatment. Our findings support the efficacy of dose-dense chemotherapy, particularly in triple-negative breast cancer, while highlighting the importance of individualized supportive care and vigilance regarding hematologic and infectious complications. Full article
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23 pages, 406 KiB  
Systematic Review
Advances in Bidirectional Therapy for Peritoneal Metastases: A Systematic Review of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Combined with Systemic Chemotherapy
by Manuela Robella, Marco Vitturini, Andrea Di Giorgio, Matteo Aulicino, Martin Hubner, Emanuele Koumantakis, Felice Borghi, Paolo Catania, Armando Cinquegrana and Paola Berchialla
Cancers 2025, 17(15), 2580; https://doi.org/10.3390/cancers17152580 - 6 Aug 2025
Abstract
Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic [...] Read more.
Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic review aimed to analyze the study design, characteristics, and timing of the treatments administered—including the type of systemic chemotherapy, intraperitoneal agents used in PIPAC, and interval between administrations—as well as the clinical outcomes, safety profile, and overall methodological quality of the available literature on bidirectional treatment for peritoneal metastases. Methods: A systematic literature search was conducted across the PubMed, Embase, and Cochrane Library databases up to April 2025. Studies were included if they reported clinical outcomes of patients undergoing bidirectional treatment. Data extraction focused on survival, response assessment (PRGS, PCI), adverse events, systemic and intraperitoneal regimens, treatment interval, and study methodology. Results: A total of 22 studies involving 1015 patients (742 treated with bidirectional therapy) were included. Median overall survival ranged from 2.8 to 19.6 months, with the most favorable outcomes observed in gastric and colorectal cancer cohorts. PRGS improvement after multiple PIPAC cycles was reported in >80% of evaluable cases. High-grade adverse events (CTCAE ≥ 3) occurred in up to 17% of patients in most studies, with only one study reporting treatment-related mortality. However, methodological quality was generally moderate, with considerable heterogeneity in treatment protocols, response criteria, systemic regimens, and toxicity attribution. Conclusions: Bidirectional therapy with PIPAC and systemic chemotherapy appears to be a feasible and potentially effective strategy for selected patients with peritoneal metastases. Despite encouraging outcomes, definitive conclusions are limited by the retrospective nature and heterogeneity of available studies. Prospective standardized trials are needed to confirm efficacy, clarify patient selection, and optimize treatment protocols. Full article
(This article belongs to the Section Cancer Therapy)
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18 pages, 3834 KiB  
Article
Therapeutic Potential of BMX-001 for Preventing Chemotherapy-Induced Peripheral Neuropathic Pain
by Tianshu Pan, Olawale A. Alimi, Bo Liu, Mena A. Krishnan, Mitchell Kuss, Wei Shi, Jairam Krishnamurthy, Jianghu James Dong, Rebecca E. Oberley-Deegan and Bin Duan
Pharmaceuticals 2025, 18(8), 1159; https://doi.org/10.3390/ph18081159 - 5 Aug 2025
Abstract
Background/Objectives: Chemotherapy-induced neuropathic pain (CINP) represents a critical challenge in oncology, emerging as a common and debilitating side effect of widely used chemotherapeutic agents, such as paclitaxel (PTX). Current therapeutic interventions and preventive strategies for CINP are largely insufficient, as they fail [...] Read more.
Background/Objectives: Chemotherapy-induced neuropathic pain (CINP) represents a critical challenge in oncology, emerging as a common and debilitating side effect of widely used chemotherapeutic agents, such as paclitaxel (PTX). Current therapeutic interventions and preventive strategies for CINP are largely insufficient, as they fail to address the underlying peripheral nerve damage, highlighting an urgent need for the development of new drugs. This study aimed to investigate the dual-function effects on normal cell protection and tumor suppression of BMX-001, a redox-active manganese metalloporphyrin that has demonstrated antioxidant and anti-inflammatory properties, which offers potential in protecting central nervous system tissues and treating CINP. Methods: This study assessed BMX-001’s different roles in protecting normal cells while acting as a pro-oxidant and pro-inflammatory molecule in cancer cells in vitro. We also evaluated its neuroprotective effect in preclinical PTX-induced CINP models in vivo. Results: Our results showed significant reductions in mechanical and cold allodynia, decreased pro-inflammatory cytokine levels, and restored antioxidant capacity in peripheral nerves and dorsal root ganglia (DRGs) following BMX-001 treatment. Conclusions: Overall, our study highlights the therapeutic potential of BMX-001 to mitigate CINP and enhance anticancer efficiency. Its dual-selective mechanism supports the future clinical investigation of BMX-001 as a novel adjunct to chemotherapeutic regimens. Full article
(This article belongs to the Section Pharmaceutical Technology)
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17 pages, 1474 KiB  
Review
Treatment Strategies for First-Line PD-L1-Unselected Advanced NSCLC: A Comparative Review of Immunotherapy-Based Regimens by PD-L1 Expression and Clinical Indication
by Blerina Resuli, Diego Kauffmann-Guerrero, Maria Nieves Arredondo Lasso, Jürgen Behr and Amanda Tufman
Diagnostics 2025, 15(15), 1937; https://doi.org/10.3390/diagnostics15151937 - 31 Jul 2025
Viewed by 406
Abstract
Background: Lung cancer remains the leading cause of cancer-related mortality worldwide. Advances in screening, diagnosis, and management have transformed clinical practice, particularly with the integration of immunotherapy and target therapies. Methods: A systematic literature search was carried out for the period between October [...] Read more.
Background: Lung cancer remains the leading cause of cancer-related mortality worldwide. Advances in screening, diagnosis, and management have transformed clinical practice, particularly with the integration of immunotherapy and target therapies. Methods: A systematic literature search was carried out for the period between October 2016 to September 2024. Phase II and III randomized trials evaluating ICI monotherapy, ICI–chemotherapy combinations, and dual ICI regimens in patients with advanced NSCLC were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (AEs). Results: PD-1-targeted therapies demonstrated superior OS compared to PD-L1-based regimens, with cemiplimab monotherapyranking highest for OS benefit (posterior probability: 90%), followed by sintilimab plus platinum-based chemotherapy (PBC) and pemetrexed—PBC. PFS atezolizumab plus bevacizumab and PBC, and camrelizumab plus PBC were the most effective regimens. ICI–chemotherapy combinations achieved higher ORRs but were associated with greater toxicity. The most favorable safety profiles were observed with cemiplimab, nivolumab, and avelumab monotherapy, while atezolizumab plus PBC and sugemalimab plus PBC carried the highest toxicity burdens. Conclusions: In PD-L1-unselected advanced NSCLC, PD-1 blockade—particularly cemiplimab monotherapy—and rationally designed ICI–chemotherapy combinations represent the most efficacious treatment strategies. Balancing efficacy with safety remains critical, especially in the absence of predictive biomarkers. These findings support a patient-tailored approach to immunotherapy and highlight the need for further biomarker-driven and real-world investigations to optimize treatment selection. Full article
(This article belongs to the Special Issue Lung Cancer: Screening, Diagnosis and Management: 2nd Edition)
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37 pages, 1856 KiB  
Review
Current and Future Directions in Immunotherapy for Gastrointestinal Malignancies
by Catherine R. Lewis, Yazan Samhouri, Christopher Sherry, Neda Dadgar, Moses S. Raj and Patrick L. Wagner
Int. J. Transl. Med. 2025, 5(3), 33; https://doi.org/10.3390/ijtm5030033 - 31 Jul 2025
Viewed by 474
Abstract
Gastrointestinal (GI) malignancies are diverse and particularly challenging in terms of current immunotherapy but hold great opportunity for impact given that they constitute the highest cancer incidence and mortality rates worldwide. Traditional treatment options for solid GI malignancies include surgical intervention, chemotherapy, radiation, [...] Read more.
Gastrointestinal (GI) malignancies are diverse and particularly challenging in terms of current immunotherapy but hold great opportunity for impact given that they constitute the highest cancer incidence and mortality rates worldwide. Traditional treatment options for solid GI malignancies include surgical intervention, chemotherapy, radiation, or a combination of these treatments. Emerging modalities within immunotherapy are anticipated to extend the results with conventional therapy by stimulating the patient’s own intrinsic potential for tumor-specific immunologic rejection. Combination regimens of chemotherapy and tumor-infiltrating lymphocyte (TIL) therapy in advanced colorectal cancer and pancreatic cancer, autologous monocyte therapy in advanced gastric cancer, and CAR-T therapy trained against GI-selective tumor antigens such as carcinoembryonic antigen are currently being studied. Clinical trials are underway to study the combination of various chemotherapeutic agents along with immunotherapy in the management of cholangiocarcinoma, hepatocellular carcinoma, and esophageal cancer. Alternative therapies are needed based on the tumor immune microenvironment, which can lead to a personalized approach to treatment. In this review, we discuss the current status of various modalities of immunotherapy in common GI malignancies, along with their mechanisms of immune activation and cancer suppression. We will also discuss the use of immunotherapy in less common solid GI malignancies and touch on recent advancements and clinical trials. Full article
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18 pages, 836 KiB  
Article
CAPOX vs. FOLFOX for Colorectal Cancer—Real World Outcomes in Ontario, Canada
by Deepro Chowdhury, Gregory R. Pond and John R. Goffin
Curr. Oncol. 2025, 32(8), 435; https://doi.org/10.3390/curroncol32080435 - 31 Jul 2025
Viewed by 193
Abstract
CAPOX and FOLFOX are widely used chemotherapy regimens for colorectal cancer (CRC). The superiority of one regimen over the other in a real-world setting (RWE) could have significant clinical implications given their common use, but such RWE is limited. This study analyzed provincial [...] Read more.
CAPOX and FOLFOX are widely used chemotherapy regimens for colorectal cancer (CRC). The superiority of one regimen over the other in a real-world setting (RWE) could have significant clinical implications given their common use, but such RWE is limited. This study analyzed provincial database records of 13,461 Canadian patients treated from 2005 to 2017. The primary outcomes were rates of Emergency Department visits and/or hospitalizations (ED/H) and overall survival (OS). CAPOX was used less frequently (8.4%) than FOLFOX (91.6%), often in older patients (p < 0.003 for Stage I–III; p < 0.001 for Stage IV). CAPOX recipients had shorter treatment durations (median 15 vs. 20 weeks, p = 0.002) and higher unadjusted ED/H rates (60.8% vs. 50.9%, p < 0.001), though this difference was nonsignificant on multivariate analysis (MVA) (HR 1.05 (0.92, 1.20), p = 0.466). Patients receiving CAPOX had worse OS than those on FOLFOX, (5-year OS 70.1% vs. 77.2% (p < 0.001) non-metastatic; 16.6% vs. 33.2% (p < 0.001) metastatic). MVA confirmed inferior OS with CAPOX (HR 1.42, p < 0.001). Other predictors of shorter OS included older age, male sex, comorbidities, rural residence, and lower income. This administrative data is at risk of bias but highlights the need for careful patient selection and informed treatment decision making. Full article
(This article belongs to the Section Gastrointestinal Oncology)
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12 pages, 294 KiB  
Review
Targeting Advanced Pancreatic Ductal Adenocarcinoma: A Practical Overview
by Chiara Citterio, Stefano Vecchia, Patrizia Mordenti, Elisa Anselmi, Margherita Ratti, Massimo Guasconi and Elena Orlandi
Gastroenterol. Insights 2025, 16(3), 26; https://doi.org/10.3390/gastroent16030026 - 30 Jul 2025
Viewed by 275
Abstract
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors, with a five-year overall survival rate below 10%. While the introduction of multi-agent chemotherapy regimens has improved outcomes marginally, most patients with advanced disease continue to have limited therapeutic options. Molecular [...] Read more.
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors, with a five-year overall survival rate below 10%. While the introduction of multi-agent chemotherapy regimens has improved outcomes marginally, most patients with advanced disease continue to have limited therapeutic options. Molecular profiling has uncovered actionable genomic alterations in select subgroups of PDAC, yet the clinical impact of targeted therapies remains modest. This review aims to provide a clinically oriented synthesis of emerging molecular targets in PDAC, their therapeutic relevance, and practical considerations for biomarker testing, including current FDA and EMA indications. Methods: A narrative review was conducted using data from PubMed, Embase, Scopus, and international guidelines (NCCN, ESMO, ASCO). The selection focused on evidence published between 2020 and 2025, highlighting molecularly defined PDAC subsets and the current status of targeted therapies. Results: Actionable genomic alterations in PDAC include KRAS G12C mutations, BRCA1/2 and PALB2-associated homologous recombination deficiency, MSI-H/dMMR status, and rare gene fusions involving NTRK, RET, and NRG1. While only a minority of patients are eligible for targeted treatments, early-phase trials and real-world data have shown promising results in these subgroups. Testing molecular profiling is increasingly standard in advanced PDAC. Conclusions: Despite the rarity of targetable mutations, systematic molecular profiling is critical in advanced PDAC to guide off-label therapy or clinical trial enrollment. A practical framework for identifying and acting on molecular targets is essential to bridge the gap between precision oncology and clinical management. Full article
(This article belongs to the Special Issue Advances in the Management of Gastrointestinal and Liver Diseases)
16 pages, 1238 KiB  
Article
Mortality Risk of Colistin vs. Non-Colistin Use in Cancer Patients with Multidrug-Resistant Gram-Negative Bacterial Infections: Stratified by Resistance Profile and Concomitant Medications
by Soo Hyeon Lee, Yongwon Choi, Chang-Young Choi, Yeo Jin Choi and Sooyoung Shin
Medicina 2025, 61(8), 1361; https://doi.org/10.3390/medicina61081361 - 28 Jul 2025
Viewed by 350
Abstract
Background and Objectives: Cancer patients are particularly susceptible to infections caused by multidrug-resistant Gram-negative bacteria (MDR GNB) due to chemotherapy- or radiation therapy-induced immunosuppression. Colistin is often prescribed as a last-resort agent for MDR GNB infection, but its clinical benefit in oncology patients [...] Read more.
Background and Objectives: Cancer patients are particularly susceptible to infections caused by multidrug-resistant Gram-negative bacteria (MDR GNB) due to chemotherapy- or radiation therapy-induced immunosuppression. Colistin is often prescribed as a last-resort agent for MDR GNB infection, but its clinical benefit in oncology patients remains unclear. This study aims to evaluate the mortality risk associated with colistin versus non-colistin regimens in cancer patient with MDR GNB infections, stratified by resistance profiles, infection sites, and concomitant medication use. Materials and Methods: A retrospective cohort study was conducted in adult cancer patients with MDR GNB infections that are resistant to at least three antibiotic classes and identified from at least two anatomical sites at a tertiary care hospital in Korea. Propensity score-matched in a 1:3 ratio either to the colistin group or non-colistin group and multivariate Cox hazard regression analyses were used to evaluate mortality in cancer patients with MDR GNB infections, primarily Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Results: A total of 85 patients (29 patients in the colistin and 56 patients in the non-colistin group) were included in the analysis. Overall, colistin use did not show a statistically significant mortality benefit compared to non-colistin regimens (hazard ratio (HR) 0.93, 95% CI 0.47–1.87). However, the subgroup analysis revealed that colistin had a potential association with significantly lower mortality in pneumonia patients with aminoglycoside-resistant infections (HR 0.04, 95% CI 0.002–0.69). Concomitant use of antipsychotics and benzodiazepines in selected resistance profiles also correlated with improved outcomes. In contrast, a potential association was found between concomitant macrolide use and increased mortality in patients with fluoroquinolone- or penicillin-resistant profiles. Conclusions: Colistin may offer survival benefits in selected high-risk cancer patients with MDR GNB pneumonia. Treatment outcomes are influenced by resistance profiles, infection sites, and concomitant medications, indicating the significant importance of individualized antimicrobial therapy and antimicrobial stewardship in oncology patients. Full article
(This article belongs to the Section Pharmacology)
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21 pages, 861 KiB  
Review
Bispecific Antibodies and Antibody–Drug Conjugates in Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma, Focusing on Diffuse Large B-Cell Lymphoma
by Santino Caserta, Chiara Campo, Gabriella Cancemi, Santo Neri, Fabio Stagno, Donato Mannina and Alessandro Allegra
Cancers 2025, 17(15), 2479; https://doi.org/10.3390/cancers17152479 - 26 Jul 2025
Viewed by 575
Abstract
Relapsed/refractory diffuse large B-cell lymphoma and other non-Hodgkin lymphomas represent significant clinical challenges, particularly in patients who have exhausted standard immunochemotherapy and cellular therapies. Bispecific antibodies and antibody–drug conjugates have emerged as promising treatments, offering targeted and more effective treatment options compared to [...] Read more.
Relapsed/refractory diffuse large B-cell lymphoma and other non-Hodgkin lymphomas represent significant clinical challenges, particularly in patients who have exhausted standard immunochemotherapy and cellular therapies. Bispecific antibodies and antibody–drug conjugates have emerged as promising treatments, offering targeted and more effective treatment options compared to current standards. Bispecific antibodies, including epcoritamab and glofitamab, third-line therapies for diffuse large B-cell lymphoma, are recombinant immunoglobulins engineered to recognize two distinct antigens or epitopes simultaneously. This capability enhances therapeutic precision by bridging immune effector cells and tumor cells and modulating multiple signaling pathways involved in the pathogenesis of non-Hodgkin lymphoma. In the context of new therapies, antibody–drug conjugates, such as loncastuximab tesirine, are therapies composed of monoclonal antibodies linked to cytotoxic agents, in which the antibody selectively binds to tumor-associated antigens, delivering the cytotoxic payload directly to cancer cells while minimizing off-target effects. They combine the specificity of antibodies with the potency of chemotherapy, offering enhanced efficacy and safety in hematological malignancies. Ongoing clinical trials are investigating other molecules like odronextamab and the use of bispecific antibodies in combination regimens and earlier lines of therapy. The aim of this review is to explore actual therapies in relapsed/refractory diffuse large B-cell lymphoma, focusing on bispecific antibodies and antibody–drug conjugates. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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17 pages, 440 KiB  
Review
Diagnosis and Management of Upper Tract Urothelial Carcinoma: A Review
by Domenique Escobar, Christopher Wang, Noah Suboc, Anishka D’Souza and Varsha Tulpule
Cancers 2025, 17(15), 2467; https://doi.org/10.3390/cancers17152467 - 25 Jul 2025
Viewed by 474
Abstract
Background/Objectives: Upper tract urothelial carcinoma (UTUC) is a rare and biologically distinct subset of urothelial malignancies, comprising approximately 5–10% of urothelial cancers. UTUC presents unique diagnostic and therapeutic challenges, with both a higher likelihood of invasive disease at presentation and a less favorable [...] Read more.
Background/Objectives: Upper tract urothelial carcinoma (UTUC) is a rare and biologically distinct subset of urothelial malignancies, comprising approximately 5–10% of urothelial cancers. UTUC presents unique diagnostic and therapeutic challenges, with both a higher likelihood of invasive disease at presentation and a less favorable prognosis compared to urothelial carcinoma of the bladder. Current treatment strategies for UTUC are largely derived from bladder cancer studies, underscoring the need for UTUC-directed research. This review provides a comprehensive overview of UTUC, encompassing diagnostic approaches, systemic and intraluminal therapies, surgical management, and future directions. Methods: A narrative review was conducted synthesizing evidence from guideline-based recommendations, retrospective and prospective clinical studies, and ongoing trials focused on UTUC. Results: Neoadjuvant cisplatin-based chemotherapy is increasingly preferred in UTUC due to the risk of postoperative renal impairment that may preclude adjuvant cisplatin use. Surgical management includes kidney-sparing approaches and radical nephroureterectomy (RNU), with selection guided by tumor risk and patient comorbidities. While endoscopic management (EM) preserves renal function, it carries a higher recurrence and surveillance burden; RNU remains standard for high-risk cases. Systemic therapy for advanced and metastatic UTUC mirrors that of bladder urothelial carcinoma. Enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy over chemotherapy in the EV-302 trial, with improved response rate, progression-free survival, and overall survival across subgroups, including UTUC. For patients ineligible for EV, the CheckMate-901 study supported first-line chemoimmunotherapy with gemcitabine, cisplatin, and nivolumab. Further systemic therapy strategies include maintenance avelumab post-chemotherapy (JAVELIN Bladder 100), targeted therapies such as erdafitinib (THOR trial), and trastuzumab deruxtecan (DESTINY-PanTumor02) in FGFR2/3-altered and HER2-positive disease, respectively. Conclusions: Historically, the therapeutic landscape of UTUC has been extrapolated from bladder cancer; however, ongoing research specific to UTUC is deriving more precise regimens involving the use of immune checkpoint inhibitors, antibody–drug conjugates, and biomarker-driven therapies. Full article
(This article belongs to the Special Issue Upper Tract Urothelial Carcinoma: Current Knowledge and Perspectives)
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14 pages, 1112 KiB  
Article
Neo-Adjuvant Chemotherapy in Gastric Adenocarcinoma: Impact on Surgical and Oncological Outcomes in a Western Referral Center
by Claudio Fiorillo, Beatrice Biffoni, Ludovica Di Cesare, Fausto Rosa, Sergio Alfieri, Lodovica Langellotti, Roberta Menghi, Vincenzo Tondolo and Giuseppe Quero
Cancers 2025, 17(15), 2465; https://doi.org/10.3390/cancers17152465 - 25 Jul 2025
Viewed by 245
Abstract
Background/Objectives: Neo-adjuvant chemotherapy (NACT) is increasingly utilized in Western countries for the treatment of gastric cancer (GC). While its oncologic benefits are well established, its impact on surgical safety and long-term outcomes remain a matter of debate. This study evaluates the real-world [...] Read more.
Background/Objectives: Neo-adjuvant chemotherapy (NACT) is increasingly utilized in Western countries for the treatment of gastric cancer (GC). While its oncologic benefits are well established, its impact on surgical safety and long-term outcomes remain a matter of debate. This study evaluates the real-world effect of NACT on perioperative and oncologic outcomes in a high-volume Western center. Methods: Data from 254 patients who underwent gastrectomy with D2 lymphadenectomy for GC between March 2016 and January 2024 were prospectively collected and retrospectively analyzed. Patients were categorized into an upfront surgery group (n = 144, 56.7%) and a NACT group (n = 110, 43.3%). The primary outcome was to compare the two study groups in terms of perioperative outcomes, as well as overall (OS) and disease-free survival (DFS). Multivariate analyses were conducted to identify factors associated with perioperative complications and long-term survival. Results: Patients in the NACT group were younger (median age 65 vs. 72 years; p = 0.001) and had fewer comorbidities. NACT was associated with a higher incidence of proximal tumors (54–49.1% vs. 37–25.7%; p = 0.001), diffuse-type tumors (27–45.8% vs. 39–31.7%; p = 0.03), and lymph-node metastases (82–74.1% vs. 84–58%; p = 0.007). No significant differences were observed in median hospital stay (9 (7–16) and 10 (8–22) days for the upfront and NACT groups, respectively; p = 0.26), post-operative mortality (11–7.6% and 5–4.5% for the upfront and NACT groups, respectively; p = 0.32), and major complications (30–20.8% and 23–20.9% for the upfront and NACT groups, respectively; p = 0.99). Among patients receiving NACT, the FLOT regimen was associated with a lower rate of complications (12–16.2% vs. 11–30.5% in the non-FLOT cohort; p = 0.05) and reoperations (4–5.4% vs. 8–22.2% in the non-FLOT group; p = 0.008). Tumor location was identified as an independent predictor of perioperative complications (OR 4.7, 95% C.I.: 1.56–14.18; p = 0.006), while non-FLOT regimens were independently associated with higher reoperation rates (OR 0.22, 95% C.I.: 0.06–0.86; p = 0.003). Five-year OS was comparable between the two groups (44.6% in the NACT group vs. 47.7% in the upfront surgery group; p = 0.96). N+ status (OR 2.5, 95% C.I. 1.42–4.40; p = 0.001) and R+ margins (OR 1.89, 95% C.I. 0.98–3.65; p = 0.006) were negative independent prognostic factors for DFS. Conclusions: Although several selection biases limit the generalizability of our findings, our results suggest that NACT prior to gastrectomy for GC does not increase postoperative morbidity and mortality in appropriately selected patients. However, its use in elderly and polymorbid patients should be carefully considered to determine the safest and most effective therapeutic approach, particularly in selecting the appropriate chemotherapy regimen, to minimize the risk of postoperative complications requiring surgical reintervention. Full article
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9 pages, 275 KiB  
Article
The Effect of Different Intraperitoneal Hyperthermic Chemotherapy (HIPEC) Regimens on Serum Electrolyte Levels: A Comparison of Oxaliplatin and Mitomycin C
by Vural Argın, Mehmet Ömer Özduman, Ahmet Orhan Sunar, Mürşit Dinçer, Aziz Serkan Senger, Selçuk Gülmez, Orhan Uzun, Mustafa Duman and Erdal Polat
Medicina 2025, 61(8), 1345; https://doi.org/10.3390/medicina61081345 - 25 Jul 2025
Viewed by 218
Abstract
Background and Objectives: This study aimed to compare the effects of HIPEC procedures using oxaliplatin and mitomycin C on serum electrolyte, glucose, and lactate levels, with a specific focus on the carrier solutions employed. Materials and Methods: A retrospective analysis was [...] Read more.
Background and Objectives: This study aimed to compare the effects of HIPEC procedures using oxaliplatin and mitomycin C on serum electrolyte, glucose, and lactate levels, with a specific focus on the carrier solutions employed. Materials and Methods: A retrospective analysis was performed on 82 patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases. Patients were assigned to one of two groups based on the chemotherapeutic agent used: oxaliplatin (n = 63) or mitomycin C (MMC, n = 19). The oxaliplatin group was further subdivided based on the carrier solution used: 5% dextrose (D5W, n = 29) or peritoneal dialysate (n = 34). The assignment of regimens was based on institutional protocols and surgeon preference. Pre- and post-HIPEC serum levels of sodium, potassium, bicarbonate, glucose, and lactate were compared. Results: Significant biochemical changes were observed across groups, depending on both the chemotherapeutic agent and carrier solution. In the MMC group (peritoneal dialysate), only lactate increased significantly post-HIPEC (p = 0.001). In the oxaliplatin–peritoneal dialysate group, significant changes were observed in bicarbonate (p = 0.009), glucose (p = 0.001), and lactate (p < 0.001), whereas sodium and potassium remained stable. The oxaliplatin–D5W group showed significant changes in all parameters: sodium (p = 0.001), potassium (p = 0.001), bicarbonate (p = 0.001), glucose (p < 0.001), and lactate (2.4 → 7.6 mmol/L, p < 0.001). Between-group comparisons revealed significant differences in sodium, potassium, glucose, and lactate changes (p < 0.05), but not in bicarbonate (p = 0.099). Demographic and clinical characteristics—including age, sex, primary disease, ICU stay, and 90-day mortality were similar across groups. Conclusions: The use of dextrose-containing solutions with oxaliplatin was associated with marked metabolic disturbances, including clinically meaningful hyponatremia, hypokalemia, and hyperglycemia in the early postoperative period. These findings suggest that the choice of carrier solution is as important as the chemotherapeutic agent in terms of perioperative safety. Closer postoperative electrolyte monitoring is recommended when using dextrose-based regimens. The retrospective design and sample size imbalance between groups are acknowledged limitations. Nonetheless, this study offers clinically relevant insights and lays the groundwork for future prospective research. Full article
(This article belongs to the Special Issue Advances in Colorectal Surgery and Oncology)
20 pages, 12367 KiB  
Article
Chemosensitizer Effects of Cisplatin- and 5-Fluorouracil-Treated Hepatocellular Carcinomas by Lidocaine
by Teng-Wei Chen, Hsiu-Lung Fan, Shu-Ting Liu and Shih-Ming Huang
Int. J. Mol. Sci. 2025, 26(15), 7137; https://doi.org/10.3390/ijms26157137 - 24 Jul 2025
Viewed by 269
Abstract
Approximately 90% of liver cancer cases are classified as hepatocellular carcinomas (HCCs), with chemotherapy and immunotherapy being the most recommended treatment options. While conventional chemotherapy specifically targets rapidly dividing cancer cells, it can also impact on healthy cells that are proliferating quickly. This [...] Read more.
Approximately 90% of liver cancer cases are classified as hepatocellular carcinomas (HCCs), with chemotherapy and immunotherapy being the most recommended treatment options. While conventional chemotherapy specifically targets rapidly dividing cancer cells, it can also impact on healthy cells that are proliferating quickly. This collateral damage to healthy cells, along with the potential for cancer cells to develop resistance, presents significant challenges for conventional chemotherapy in liver cancer patients. Hepatic artery infusion of chemotherapy (HAIC) generally leads to reduced toxicity and fewer side effects. The process of catheter insertion is usually performed under local anesthesia, with lidocaine being the preferred choice to combine with various chemotherapeutics in HCC treatment. In our study, we explored the effects of repurposing lidocaine in combination with cisplatin or 5-fluorouracil (5-FU) on two HCC cell lines, HepG2 and Hep3B. Our cytotoxicity analysis revealed that lidocaine functions as a chemosensitizer for cisplatin and 5-FU in both HepG2 and Hep3B cells. Specifically, we observed an increase in the subG1 population and a reduction in cytosolic reactive oxygen species in cisplatin- or 5-FU-treated HepG2 and Hep3B cells. Interestingly, lidocaine selectively decreased the reduced/oxidized glutathione ratio in cisplatin- or 5-FU-treated HepG2 cells but not in Hep3B cells. Furthermore, lidocaine induced endoplasmic reticulum stress, apoptosis, mitochondrial membrane depolarization, lipid peroxidation, and autophagy while suppressing cellular proliferation HepG2 and Hep3B cells. In conclusion, our study demonstrates the synergistic potential of combining lidocaine with cisplatin or 5-FU for the treatment of HCC, indicating that lidocaine may serve as an effective chemosensitizer. These findings highlight a new clinical advantage of using repurposing lidocaine as a chemosensitizer in the current HAIC procedure, suggesting that this combination warrants further exploration through rigorous clinical trials. In the future, we can better optimize therapeutic regimens, potentially leading to improved patient outcomes in HCCs. Full article
(This article belongs to the Special Issue Current Research on Cancer Biology and Therapeutics: Third Edition)
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14 pages, 662 KiB  
Article
Weekly Cisplatin and 5-Fluorouracil in Neoadjuvant Chemoradiotherapy for Esophageal Cancer: A Pandemic-Era Evaluation
by Yi-Ting Hwang, Cheng-Yen Chuang and Chien-Chih Chen
Medicina 2025, 61(8), 1326; https://doi.org/10.3390/medicina61081326 - 23 Jul 2025
Viewed by 190
Abstract
Background and Objectives: The COVID-19 pandemic disrupted cancer care, prompting adaptations to reduce patient exposure while preserving treatment efficacy. This retrospective observational study compared a weekly cisplatin and 5-fluorouracil (5-FU) regimen to the standard monthly regimen for neoadjuvant chemoradiotherapy in patients with [...] Read more.
Background and Objectives: The COVID-19 pandemic disrupted cancer care, prompting adaptations to reduce patient exposure while preserving treatment efficacy. This retrospective observational study compared a weekly cisplatin and 5-fluorouracil (5-FU) regimen to the standard monthly regimen for neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. Materials and Methods: This single-center retrospective study included 91 patients, divided into two cohorts: weekly chemotherapy (n = 30) and standard chemotherapy (n = 61). Treatment assignment was based on hospital policy changes during the pandemic, with weekly outpatient chemotherapy implemented after November 2022 to conserve inpatient resources. All patients received radiotherapy at 50 Gy in 25 fractions. The weekly regimen consisted of cisplatin 20 mg/m2 and 5-FU 800 mg/m2, administered over 1–2 h weekly, while the standard regimen administered the same doses over four consecutive days on weeks 1 and 5. Primary endpoints were pathologic complete response (pCR), progression-free survival (PFS), and overall survival (OS). Results: The response rates were similar between groups (weekly: 86.7% vs. standard: 90.2%; p = 0.724). The weekly regimen group showed a higher pCR (40.0% vs. 26.2%; p = 0.181) and significantly lower recurrence (26.7% vs. 52.5%; p = 0.020). Mortality was also reduced in the weekly group (6.7% vs. 34.4%; p = 0.004), though the follow-up duration was shorter (10.6 vs. 22.8 months; p < 0.001). Conclusions: In this retrospective observational study, weekly cisplatin and 5-FU demonstrated comparable efficacy to the standard regimen, with potential advantages in reducing recurrence and mortality. This modified approach may be a viable alternative for maintaining oncologic outcomes while minimizing the burden on healthcare systems during pandemic conditions, although prospective validation is needed. Full article
(This article belongs to the Section Oncology)
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19 pages, 357 KiB  
Review
Advances in the Management of Pancreatic Cancer: Current Strategies and Emerging Therapies
by Supriya Peshin, Ehab Takrori, Naga Anvesh Kodali, Faizan Bashir and Sakshi Singal
Int. J. Mol. Sci. 2025, 26(15), 7055; https://doi.org/10.3390/ijms26157055 - 22 Jul 2025
Viewed by 790
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a formidable malignancy with rising incidence and dismal long-term survival, largely due to late-stage presentation and intrinsic resistance to therapy. Recent advances in the multidisciplinary management of PDAC have reshaped treatment paradigms across disease stages. For localized disease, [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) remains a formidable malignancy with rising incidence and dismal long-term survival, largely due to late-stage presentation and intrinsic resistance to therapy. Recent advances in the multidisciplinary management of PDAC have reshaped treatment paradigms across disease stages. For localized disease, innovations in surgical techniques and the adoption of neoadjuvant strategies have improved resection rates and survival outcomes. In metastatic settings, multiagent chemotherapy regimens and precision therapies targeting BRCA mutations and rare gene fusions are expanding treatment options. Immunotherapeutic modalities, including checkpoint inhibitors, adoptive cell therapies, and mRNA vaccines, show emerging promise despite PDAC’s traditionally immunosuppressive microenvironment. This review synthesizes the current evidence on established therapies and critically evaluates novel and investigational approaches poised to redefine the therapeutic landscape of pancreatic cancer. Full article
(This article belongs to the Special Issue Recent Advances in Gastrointestinal Cancer, 2nd Edition)
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