Cancers

15 pages, 1161 KiB

Open AccessSystematic Review

Rectovaginal Extra-Gastrointestinal Stromal Tumors (EGISTs): A Systematic Review of the Literature and a Pooled Survival Analysis

by Eleni Papamattheou, Ioannis Katsaros, Stavros P. Papadakos, Evangelos Lianos and Elissaios Kontis

Cancers 2025, 17(8), 1382; https://doi.org/10.3390/cancers17081382 - 21 Apr 2025

Abstract

Background/Objectives: Extra-gastrointestinal stromal tumors (EGISTs) are rare mesenchymal tumors arising outside the gastrointestinal tract, making up <5% of all GISTs. Rectovaginal EGISTs are particularly uncommon, with limited available data. This study systematically reviews the clinicopathological features, management, and outcomes of rectovaginal EGISTs. [...] Read more.

Background/Objectives: Extra-gastrointestinal stromal tumors (EGISTs) are rare mesenchymal tumors arising outside the gastrointestinal tract, making up <5% of all GISTs. Rectovaginal EGISTs are particularly uncommon, with limited available data. This study systematically reviews the clinicopathological features, management, and outcomes of rectovaginal EGISTs. Methods: A systematic review of the English-language literature was conducted for studies on rectovaginal EGISTs (search date: 15 January 2025). Results: Thirty-one studies, including 40 female patients (mean age: 55.2 ± 15.4 years), met the inclusion criteria. Presenting symptoms included vaginal bleeding (24.3%), palpable mass (13.5%), constipation (10.8%), and abdominal pain (8.1%); however, the majority of patients (45.9%) were asymptomatic. Surgical excision was undertaken in 95% of patients, more often via local resection (61.1%). A high-grade mitotic index (>5/50 HPF) was noted in 63.2%. CD117, DOG-1, and vimentin was expressed in all cases, while CD34 was positive in 97.1%. Adjuvant therapy with tyrosine kinase inhibitors (TKIs) was administered in 57.5%, and neoadjuvant therapy was rare (8.6%). Recurrence occurred in 39.4% over a median follow-up of 40 ± 61.5 months, with a median disease-free survival (DFS) of 48 months. One death occurred 13 months postoperatively. Conclusions: Rectovaginal EGISTs are exceedingly rare and often asymptomatic, complicating preoperative diagnosis. Surgical resection remains the cornerstone of treatment, complemented by stage-specific neoadjuvant or adjuvant TKI therapy. The challenging location predisposes to recurrence, underscoring the need for further studies to optimize management and improve outcomes. Full article

(This article belongs to the Special Issue Gastrointestinal Cancer Surgery)

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24 pages, 4987 KiB

Open AccessReview

Aberrant Splicing as a Mechanism for Resistance to Cancer Therapies

by Duygu Duzgun and Sebastian Oltean

Cancers 2025, 17(8), 1381; https://doi.org/10.3390/cancers17081381 - 21 Apr 2025

Abstract

Cancer is biologically diverse, highly heterogeneous, and associated with molecular alterations, significantly contributing to mortality worldwide. Currently, cancer patients are subjected to single or combination treatments comprising chemotherapy, surgery, immunotherapy, radiation therapy, and targeted therapy. Chemotherapy remains the first line of treatment in [...] Read more.

Cancer is biologically diverse, highly heterogeneous, and associated with molecular alterations, significantly contributing to mortality worldwide. Currently, cancer patients are subjected to single or combination treatments comprising chemotherapy, surgery, immunotherapy, radiation therapy, and targeted therapy. Chemotherapy remains the first line of treatment in cancer but faces a major obstacle in the form of chemoresistance. This obstacle has resulted in relapses and poor patient survival due to decreased treatment efficacy. Aberrant pre-mRNA alternative splicing can significantly modulate gene expression and function involved in the resistance mechanisms, potentially shaping the intricate landscape of tumour chemoresistance. Thus, novel strategies targeting abnormal pre-mRNA alternative splicing and understanding the molecular mechanisms of chemotherapy resistance could aid in overcoming the chemotherapeutic challenges. This review first highlights drug targets, drug pumps, detoxification mechanisms, DNA damage response, and evasion of apoptosis and cell death as key molecular mechanisms involved in chemotherapy resistance. Furthermore, the review discusses the progress of research on the dysregulation of alternative splicing and molecular targets involved in chemotherapy resistance in major cancer types. Full article

(This article belongs to the Section Cancer Therapy)

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12 pages, 3303 KiB

Open AccessArticle

Exploring the Role of Practical and Emotional Death Preparation in Reducing Emotional Distress Among Family Caregivers of Terminally Ill Cancer Patients: A Multicenter Cross-Sectional Study

by Boram Kim, Jaemin Kim, Hong Yup Ahn, Sunyoung Park, In Cheol Hwang and So-Jung Park

Cancers 2025, 17(8), 1380; https://doi.org/10.3390/cancers17081380 - 21 Apr 2025

Abstract

Family caregivers (FCs) play a vital role in supporting terminally ill patients with cancer by providing emotional, physical, and practical care throughout the illness trajectory [...] Full article

(This article belongs to the Section Cancer Survivorship and Quality of Life)

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30 pages, 7745 KiB

Open AccessArticle

Single-Cell Profiling Reveals Global Immune Responses During the Progression of Murine Epidermal Neoplasms

by Xiying Fan, Tonya M. Brunetti, Kelsey Jackson and Dennis R. Roop

Cancers 2025, 17(8), 1379; https://doi.org/10.3390/cancers17081379 - 21 Apr 2025

Abstract

Background/Objectives: Immune cells determine the role of the tumor microenvironment during tumor progression, either suppressing tumor formation or promoting tumorigenesis. This study aimed to fully characterize immune cell responses during skin tumor progression. Methods: Using single-cell RNA sequencing, we analyzed the profile of [...] Read more.

Background/Objectives: Immune cells determine the role of the tumor microenvironment during tumor progression, either suppressing tumor formation or promoting tumorigenesis. This study aimed to fully characterize immune cell responses during skin tumor progression. Methods: Using single-cell RNA sequencing, we analyzed the profile of immune cells in the tumor microenvironment of control mouse skins and skin tumors at the single-cell level. Results: We identified 15 CD45⁺ immune cell clusters, which broadly represent the most functionally characterized immune cell types including macrophages, Langerhans cells (LC), conventional type 1 dendritic cells (cDC1), conventional type 2 dendritic cells (cDC2), migratory/mature dendritic cells (mDC), dendritic epidermal T cells (DETC), dermal γδ T cells (γδT), T cells, regulatory T cells (Tregs), natural killer cells (NK), type 2 innate lymphoid cells (ILC2), neutrophils (Neu), mast cells (Mast), and two proliferating populations (Prolif.1 and Prolif.2). Skin tumor progression reprogramed immune cells and led to a marked increase in the relative percentages of macrophages, cDC2, mDC, Tregs, and Neu. Macrophages, the largest cell cluster of immune cells in skin tumors. In addition, macrophages emerged as the predominant communication ‘hub’ in skin tumors, highlighting the importance of macrophages during skin tumor progression. In contrast, other immune cell clusters decreased during skin tumor progression, including DETC, γδT, ILC2, and LC. In addition, skin tumor progression dramatically upregulated Jak2/Stat3 expression and the interferon response across various immune cell clusters. Further, skin tumor progression activated T cells and NK cells indicated by elevated expression of IFN-γ and Granzyme B in skin tumors. Meanwhile, a pronounced infiltration of M2-macrophages and Tregs in skin tumors created an immunosuppressive microenvironment, consistent with the elevated expression of the Stat3 pathway in skin tumors. Conclusions: Our study elucidates the immune cell landscape of epidermal neoplasms, offering a comprehensive understanding of the immune response during skin tumor progression and providing new insights into cancer immune evasion mechanisms. Full article

(This article belongs to the Special Issue The Tumor Microenvironment: Interplay Between Immune Cells)

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29 pages, 2914 KiB

Open AccessReview

Interplay Between the Cytoskeleton and DNA Damage Response in Cancer Progression

by Clarissa Esmeralda Halim, Shuo Deng, Karen Carmelina Crasta and Celestial T. Yap

Cancers 2025, 17(8), 1378; https://doi.org/10.3390/cancers17081378 - 21 Apr 2025

Abstract

DNA damage has emerged as a critical factor in fuelling the development and progression of cancer. DNA damage response (DDR) pathways lie at the crux of cell fate decisions following DNA damage induction, which can either trigger the repair of detrimental DNA lesions [...] Read more.

DNA damage has emerged as a critical factor in fuelling the development and progression of cancer. DNA damage response (DDR) pathways lie at the crux of cell fate decisions following DNA damage induction, which can either trigger the repair of detrimental DNA lesions to protect cancer cells or induce the cell death machinery to eliminate damaged cells. Cytoskeletal dynamics have a critical role to play and influence the proper function of DDR pathways. Microfilaments, intermediate filaments, microtubules, and their associated proteins are well involved in the DDR. For instance, they are not only implicated in the recruitment of specific DDR molecules to the sites of DNA damage but also in the regulation of the mobility of the damaged DNA to repair sites in the periphery of the nucleus. The exquisite roles that these cytoskeletal proteins play in different DDR pathways, such as non-homologous end joining (NHEJ), homologous recombination (HR), base excision repair (BER), and nucleotide excision repair (NER), in cancer cells are extensively discussed in this review. Many cancer treatments are reliant upon inducing DNA damage in cancer cells to eliminate them; thus, it is important to shed light on factors that could affect their efficacy. Although the cytoskeleton is intricately involved in the DDR process, this has often been overlooked in cancer research and has not been exploited in developing DDR-targeting cancer therapy. Understanding the interplay between the cytoskeleton and the DDR in cancer will then provide insights into improving the development of cancer therapies that can leverage the synergistic action of DDR inhibitors and cytoskeleton-targeting agents. Full article

(This article belongs to the Section Molecular Cancer Biology)

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17 pages, 601 KiB

Open AccessReview

The Role of Visfatin in Gastric and Esophageal Cancer: From Biomarker to Therapeutic Target

by Adam Mylonakis, Alexandros Kozadinos, Maximos Frountzas, Emmanouil I. Kapetanakis, Irene Lidoriki, Markos Despotidis, Eva Karanikki, Tania Triantafyllou, Dimitrios Theodorou, Konstantinos G. Toutouzas and Dimitrios Schizas

Cancers 2025, 17(8), 1377; https://doi.org/10.3390/cancers17081377 - 21 Apr 2025

Abstract

Background: Gastric and esophageal cancers are among the most lethal malignancies worldwide, necessitating improved biomarkers and therapeutic targets to improve patient outcomes. Visfatin, also known as nicotinamide phosphoribosyltransferase (NAMPT), is a metabolic enzyme and adipokine with emerging significance in cancer progression. It has [...] Read more.

Background: Gastric and esophageal cancers are among the most lethal malignancies worldwide, necessitating improved biomarkers and therapeutic targets to improve patient outcomes. Visfatin, also known as nicotinamide phosphoribosyltransferase (NAMPT), is a metabolic enzyme and adipokine with emerging significance in cancer progression. It has been implicated in tumor cell proliferation, angiogenesis, immune modulation, and chemotherapy resistance, yet its clinical relevance in upper gastrointestinal (GI) cancers remains unclear. This review aims to explore visfatin’s biochemical properties, its role in the pathogenesis of upper GI cancers, and its implications for potential therapeutic interventions. Methods: A comprehensive review of the literature was conducted to evaluate the role of visfatin in gastric and esophageal cancer. We analyzed studies investigating visfatin expression in tumor tissues, blood, and adipose tissue, its prognostic significance, and its potential as a therapeutic target. Preclinical and clinical studies evaluating visfatin inhibitors were also reviewed. Results: Visfatin promotes tumor progression through the activation of key oncogenic pathways leading to increased angiogenesis, epithelial–mesenchymal transition (EMT), and immune suppression. Elevated visfatin levels are associated with advanced tumor stage, reduced response to chemotherapy, and poor prognosis in both gastric and esophageal cancers. Therapeutic agents targeting visfatin, such as the inhibitor FK866, have shown promising results in reducing tumor proliferation by >50%, improving chemoresistance, and restoring antitumor immunity in preclinical studies. However, clinical translation remains limited due to toxicity concerns and the need for more targeted therapies. Conclusions: Visfatin is a promising biomarker and potential therapeutic target in gastric and esophageal cancer. However, its precise role and mechanisms require further investigation. The standardization of measurement techniques and large-scale clinical studies is needed to validate its prognostic and predictive value. Future research should focus on optimizing visfatin-targeted therapies, particularly in the context of obesity-associated malignancies and chemoresistant tumors. Full article

(This article belongs to the Special Issue Advances in the Treatment of Upper Gastrointestinal Cancer)

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21 pages, 2798 KiB

Open AccessArticle

High-Speed Videoendoscopy and Stiffness Mapping for AI-Assisted Glottic Lesion Differentiation

by Magdalena M. Pietrzak, Justyna Kałuża-Olszewska, Ewa Niebudek-Bogusz, Artur Klepaczko and Wioletta Pietruszewska

Cancers 2025, 17(8), 1376; https://doi.org/10.3390/cancers17081376 - 21 Apr 2025

Abstract

Objectives: This study evaluates the potential of high-speed videoendoscopy (HSV) in differentiating between benign and malignant glottic lesions, offering a non-invasive diagnostic tool for clinicians. Moreover, a new parameter derived from high-speed videoendoscopy (HSV) had been proposed and implemented in the analysis [...] Read more.

Objectives: This study evaluates the potential of high-speed videoendoscopy (HSV) in differentiating between benign and malignant glottic lesions, offering a non-invasive diagnostic tool for clinicians. Moreover, a new parameter derived from high-speed videoendoscopy (HSV) had been proposed and implemented in the analysis for an objective assessment of the vocal fold stiffness. Methods: High-speed videoendoscopy (HSV) was conducted on 102 participants, including 21 normophonic individuals, 39 patients with benign vocal fold lesions, and 42 with glottic cancer. Laryngotopographic parameter describing the stiffness of vocal fold (SAI) and kymographic parameters describing amplitude, symmetry, and glottal dynamics were quantified. Statistical differences between groups were assessed using receiver operating characteristic (ROC) analysis and lesion classification was performed using a machine learning model. Results: Univariate receiver operating characteristic (ROC) analysis revealed that SAI (AUC = 0.91, 95% CI: 0.839–0.962) and weighted amplitude asymmetry (AUC = 0.92, 95% CI: 0.85–0.974) were highly effective in distinguishing between normophonic and organic lesions (p < 0.01). Further multivariate analysis using machine learning models demonstrated improved accuracy, with the SVM classifier achieving an AUC of 0.93 for detecting organic lesions and 0.83 for distinguishing benign from malignant lesions. Conclusions: The study demonstrates the potential value of parameter describing the pliability of infiltrated vocal fold (SAI) as a non-invasive tool to support histopathological evaluation in laryngeal lesions, with machine learning models enhancing diagnostic performance. Full article

(This article belongs to the Special Issue Application of Biostatistics in Cancer Research)

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31 pages, 2278 KiB

Open AccessReview

Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH): A Promising Molecular Marker and Therapeutic Target for Hepatocellular Carcinoma

by Eva Davis, Ali Gawi Ermi and Devanand Sarkar

Cancers 2025, 17(8), 1375; https://doi.org/10.3390/cancers17081375 - 21 Apr 2025

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. The 5-year survival rate has been estimated to be less than 20% while its incidence rates have more than tripled since the 1980s. Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) has been demonstrated to [...] Read more.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. The 5-year survival rate has been estimated to be less than 20% while its incidence rates have more than tripled since the 1980s. Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) has been demonstrated to have an influential role in HCC progression and the development of an aggressive phenotype. AEG-1 has been shown to be upregulated in many cancers, including HCC. Studies have shown that it plays a crucial role in the proliferation, invasion and metastasis, and evasion of apoptosis in HCC. Its relationship with proteins and pathways, such as MYC, SND1, PI3K/AKT, and other signaling pathways demonstrates its pertinent role in oncogenic development and relevance as a biomarker and therapeutic target. Recent studies have shown that AEG-1 is present in tumor tissues, and the anti-AEG-1 antibody is detected in the blood of cancer patients, demonstrating its viability as a diagnostic/prognostic marker. This review paper shines light on recent findings regarding the molecular implications of AEG-1, with emphasis on its role of regulating metabolic dysfunction-associated steatohepatitis (MASH), a key predisposing factor for HCC, new treatment strategies targeting AEG-1, and challenges associated with analyzing this intriguing molecule. Full article

(This article belongs to the Special Issue Molecular Markers and Targeted Therapy for Hepatobiliary Tumors)

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19 pages, 9960 KiB

Open AccessArticle

Histology-Specific Treatment Strategies and Survival Prediction in Lung Cancer Patients with Spinal Metastases: A Nationwide Analysis

by Abdul Karim Ghaith, Xinlan Yang, Taha Khalilullah, Xihang Wang, Melanie Alfonzo Horowitz, Jawad Khalifeh, A. Karim Ahmed, Tej Azad, Joshua Weinberg, Abdel-Hameed Al-Mistarehi, Chase Foster, Meghana Bhimreddy, Arjun K. Menta, Kristin J. Redmond, Nicholas Theodore and Daniel Lubelski

Cancers 2025, 17(8), 1374; https://doi.org/10.3390/cancers17081374 - 21 Apr 2025

Abstract

Background/Objectives: Spinal metastases are a common and severe complication of lung cancer, particularly in small cell lung cancer (SCLC), and are associated with poor survival. Despite advancements in treatment, optimal management strategies remain unclear, with significant differences between non-small cell lung cancer (NSCLC) [...] Read more.

Background/Objectives: Spinal metastases are a common and severe complication of lung cancer, particularly in small cell lung cancer (SCLC), and are associated with poor survival. Despite advancements in treatment, optimal management strategies remain unclear, with significant differences between non-small cell lung cancer (NSCLC) and SCLC. This study evaluates treatment patterns, survival outcomes, and prognostic factors in lung cancer patients with spinal metastases, integrating deep learning survival prediction models. Methods: This retrospective cohort study analyzed the National Cancer Database (NCDB) to identify NSCLC and SCLC patients diagnosed with spinal metastases. Demographics and treatment modalities were analyzed and adjusted for age, sex, and comorbidities. Kaplan–Meier analysis and Cox proportional hazards models assessed overall survival (OS). Five advanced survival prediction models estimated 1-year and 10-year mortality, with feature importance determined via permutation analysis. Results: Among 428,919 lung cancer patients, 5.1% developed spinal metastases, with a significantly higher incidence in SCLC (13.6%) than in NSCLC (5.1%). SCLC patients had poorer OS. Radiation therapy alone was the predominant treatment, and stereotactic body radiation therapy (SBRT) predicted better short- and long-term survival compared to other radiation techniques. High-dose radiation (71–150 Gy BED) improved OS in NSCLC, while reirradiation benefited NSCLC but had a limited impact in SCLC. SurvTrace demonstrated the highest predictive accuracy for 1-year and 10-year mortality, identifying age, radiation dose, reirradiation, and race as key prognostic factors. Conclusions: The management of spinal metastases requires a histology-specific approach. Radiation remains the primary treatment, with SBRT predicting better short- and long-term survival. High-dose radiation and reirradiation should be considered for NSCLC, while the benefits are limited in SCLC. These findings support histology-specific treatment strategies to improve survival of patients with metastatic lung cancer to the spine. Full article

(This article belongs to the Special Issue Advances in the Surgical Treatment of Spinal Tumors)

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10 pages, 1943 KiB

Open AccessArticle

Prognostic Value of Systemic Inflammatory Markers in Malignant Tumors of Minor Salivary Glands: A Retrospective Analysis of a Single Center

by Maria Giulia Cristofaro, Francesco Ferragina, Samuel Staglianò, Antonella Arrotta, Marianna D’Amico and Ida Barca

Cancers 2025, 17(8), 1373; https://doi.org/10.3390/cancers17081373 - 21 Apr 2025

Abstract

Background: Malignant tumors of minor salivary glands (MGSTs) are rare and exhibit significant heterogeneity in terms of etiology, histology and prognosis. Methods: This retrospective analysis of 48 resected MGSTs employed Receiver Operating Characteristic (ROC) curves and logistic regression models to evaluate the association [...] Read more.

Background: Malignant tumors of minor salivary glands (MGSTs) are rare and exhibit significant heterogeneity in terms of etiology, histology and prognosis. Methods: This retrospective analysis of 48 resected MGSTs employed Receiver Operating Characteristic (ROC) curves and logistic regression models to evaluate the association between the systemic inflammatory response index (SIRI), the systemic immuno-inflammation index (SII), the neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR) with overall survival (OS). Although these biomarkers showed some correlation with OS, none were statistically significant when considered individually. Results: Significant correlation was observed between the SIRI, SII, and NLR with overall survival (OS). Among these, SIRI was the most reliable predictor, with an area under the curve (AUC) of 0.713, 80% sensitivity, and 70% specificity. Conclusions: While these inflammatory biomarkers correlate with the prognosis and risk stratification of MGSTs, there is currently no clinical utility in decision making due to the lack of standardization and their limited application in clinical practice. Full article

(This article belongs to the Special Issue Novel Therapeutic Strategies in Salivary Gland Tumor)

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12 pages, 2926 KiB

Open AccessSystematic Review

Adrenalectomy Performed with the Da Vinci Single-Port Robotic System: A Systematic Review and Pooled Analysis

by Giuseppe Reitano, Arianna Tumminello, Carlo Prevato, Anna Cacco, Greta Gaggiato, Giorgia Baù, Lorenzo Sabato, Elisa Tonet, Anna Gambarotto, Valerio Fusca, Kevin Martina, Silvia Visentin, Giovanni Betto, Giacomo Novara, Fabrizio Dal Moro and Fabio Zattoni

Cancers 2025, 17(8), 1372; https://doi.org/10.3390/cancers17081372 - 20 Apr 2025

Abstract

Introduction: The Da Vinci Single-Port (DV-SP) system emerged in 2018 but there is limited evidence on its use and perioperative outcomes for robot-assisted adrenalectomy (RAA). Methods: A systematic search was performed through PubMed, Scopus, Ovid, and WoS in December 2024. A PICO framework [...] Read more.

Introduction: The Da Vinci Single-Port (DV-SP) system emerged in 2018 but there is limited evidence on its use and perioperative outcomes for robot-assisted adrenalectomy (RAA). Methods: A systematic search was performed through PubMed, Scopus, Ovid, and WoS in December 2024. A PICO framework was used. Population: adult patients with adrenal masses; Intervention: DV-SP RAA; Outcomes: feasibility, reproducibility and safety of DV-SP RAA. A total of five retrospective studies involving 342 patients were included. The quantitative analysis was conducted using a random-effect model or a fixed-effect model as appropriate. A risk of bias assessment for non-randomized comparative studies and case series was performed. Results: The pooled mean operative time was 92.5 min (95% confidence interval [CI] 71.2, 113.9, p I² = 0%, four studies), and the mean estimated blood loss (EBL) was 26.5 mL (95%CI −8.1, 61.2, I² = 98.2%, three studies). Most of the procedures were completed with a single incision, though some required additional port placement, with a proportion of 9% (95%CI 0, 29, I² = 71.7%, five studies). Perioperative complications were rare (0%, 95% CI 0, 4, I² = 0%, five studies). Two studies comparing DV-SP and DV multi-port (MP) found no significant differences in complications. One study compared DV-SP RAA to DV Si or Xi single-access procedures. DV-SP showed improved operative techniques and better cosmetic outcomes. Limitations of this study are small sample size and potential selection bias due to smaller masses in the DV-SP RAA group. Conclusions: DV-SP RAA is a promising approach, offering reduced operative time, low EBL, and excellent cosmetic results. This study shows that DV-SP RAA seems reproducible, feasible, and safe. Limitation of the included studies are small sample size and selection bias, which limits the generalizability of the results. Randomized comparative studies between DV-SP and MP RAA are needed to further validate these findings. Full article

(This article belongs to the Special Issue Urologic Cancer: Endoscopic, Laparoscopic, and Robot-Assisted Surgery Management)

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18 pages, 1451 KiB

Open AccessArticle

The Mesothelioma Systemic Inflammation Score Is Independently Associated with Overall Survival and Predicts Benefit of Multimodality Treatment in Pleural Mesothelioma

by Berta Mosleh, Katharina Sinn, Anna Cho, Anton Reiner, Ariane Steindl, Christian Lang, Sabine Zöchbauer-Müller, Karin Dieckmann, Joachim Widder, Helmut Prosch, Balazs Dome, Karin Schelch, Clemens Aigner, Thomas Klikovits, Michal Benej, Stefan Watzka, Martin Filipits, Servet Bölükbas, Pavla Sarova, Daniela Gompelmann, Michael Grusch and Mir Alireza Hoda Show full author list Hide full author list

Cancers 2025, 17(8), 1371; https://doi.org/10.3390/cancers17081371 - 20 Apr 2025

Abstract

Background/Objectives: Malignant pleural mesothelioma (MPM) remains challenging to treat, with a poor prognosis. As controversy about clinical management continues, predictive biomarkers for patient selection to indicate the benefit of treatment modalities are urgently needed. Methods: In a retrospective analysis of 195 patients between [...] Read more.

Background/Objectives: Malignant pleural mesothelioma (MPM) remains challenging to treat, with a poor prognosis. As controversy about clinical management continues, predictive biomarkers for patient selection to indicate the benefit of treatment modalities are urgently needed. Methods: In a retrospective analysis of 195 patients between 1994 and 2020 at the Department of Thoracic Surgery, Medical University of Vienna, Austria, the Mesothelioma Systemic Inflammation Score (MSIS)—consisting of pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), and fibrinogen—was tested for its prognostic and predictive significance. The prognostic impact of MSIS was subsequently validated in an independent cohort of 80 patients treated at the Department of Thoracic Surgery, Karl Landsteiner Institute for Clinical and Translational Thoracic Surgery Research, Clinic Floridsdorf, Vienna, Austria. Results: Median overall survival (OS) was 14 months for the entire cohort (95% CI: 11.4–16.6). Patients undergoing multimodality treatment including macroscopic complete resection had a longer OS (22.3 months, 95% CI: 18.6–26.0; p < 0.001). In multivariable analysis, MSIS (p < 0.001), disease stage (p = 0.001), and the type of treatment (p = 0.004) were confirmed as independent predictors for OS. Higher MSIS was associated with shorter OS (p < 0.001). Significant survival benefit of multimodality regimens including surgery was limited to patients with low MSIS. Among patients with low (≤ 2) MSIS, multimodality therapy was associated with significantly prolonged OS when compared with chemo- and/or radiotherapy alone (25.8 months [95% CI: 16.4–35.3] vs. 14.4 months [95% CI: 10.4–18.4], p < 0.001). In contrast, among patients with elevated MSIS, no survival benefit was achieved by surgery over conservative treatment (11.8 months [95% CI: 8.3–15.3] vs. 8.2 months [95% CI: 5.2–11.3], p = 0.233). The ability of MSIS to predict survival was equivalent between the baseline and the independent validation cohort (p < 0.001). Conclusions: The Mesothelioma Systemic Inflammation Score was found to be an independent prognostic score in pleural mesothelioma, predicting benefit from macroscopic complete resection as part of multimodality treatment in distinct patients. Full article

(This article belongs to the Section Cancer Therapy)

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12 pages, 2404 KiB

Open AccessArticle

The Clinical Relevance of Distinguishing Between Simple and Complex Adnexal Cystic Structures by Ultrasound in Peri- and Postmenopause

by Balazs Erdodi, Gergo Jozsef Szollosi, Zoltan Toth, Zoard Tibor Krasznai and Attila Jakab

Cancers 2025, 17(8), 1370; https://doi.org/10.3390/cancers17081370 - 20 Apr 2025

Abstract

Background/Objectives: We aimed to determine the reliability of simple ultrasound (US) markers and CA-125 measurements in diagnosing peri- and postmenopausal ovarian masses. Methods: The study was conducted in a retrospective setting. The preoperative imaging properties of peri- (PEM) and postmenopausal (POM) [...] Read more.

Background/Objectives: We aimed to determine the reliability of simple ultrasound (US) markers and CA-125 measurements in diagnosing peri- and postmenopausal ovarian masses. Methods: The study was conducted in a retrospective setting. The preoperative imaging properties of peri- (PEM) and postmenopausal (POM) ovarian cysts were examined. Based on ultrasound findings, lesions were categorized as either (1) simple cysts, defined as unilocular, anechoic structures without solid components, or (2) complex cysts, characterized by any deviation from this morphology. Imaging characteristics, mass size, and demographic data were matched with histology and CA125 levels. Results: In total, 379 cystic structures (PEM: N = 195, average age: 45.6 years; range: 40–54 years, POM: N = 184, average age 61.2 years; range: 41–88 years) were analyzed. In the PEM group, there were 75 simple (Ø < 5 cm N = 32, Ø ≥ 5 cm N = 43) and 122 complex cysts (Ø < 5 cm N = 29, Ø ≥ 5 cm, N = 93), while in the POM group, 49 simple (Ø < 5 cm N = 9, Ø ≥ 5 cm N = 40) and 135 complex cysts (Ø < 5 cm N = 15, Ø ≥ 5 cm N = 120) were found. In the PEM group, malignancy was detected in complex cysts larger than 5 cm (N = 16, 17.58%). In the POM group, malignancy was present in 40 cases, and 3 of them proved to be smaller than 5 cm. The majority of cysts were functional (54.36%) in the PEM group. In the POM group, serous cysts were the most frequent (38.04%), followed by malignant (21.74%) and mucinous cysts (13.04%). CA125 was elevated in 66 of 217 cases (30.41%); only 23 were malignant (NPV: 0.95, PPV: 0.35). Conclusions: Functional cysts are frequently found among perimenopausal ovarian cysts, with malignancy occurring exclusively in complex cysts exceeding 5 cm in diameter. However, complex cysts of any size carry a significant risk of malignancy in menopause, thus, surgery is recommended. Simple cysts can be followed by serial scans in both groups. CA-125 does not give added value to the detection of malignancy in perimenopausal patients. However, in postmenopausal complex morphology cysts larger than 5 cm, it may give added value to the suspicion of malignancy. Full article

(This article belongs to the Special Issue Gynecologic Cancer: From Diagnosis to Treatment)

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15 pages, 1728 KiB

Open AccessArticle

Risk Factors for Neurological Deficits Following Brain Tumor Resection in the Supplementary Motor Area (SMA): A 66-Case Double-Center Study

by Lucio De Maria, Karl Schaller, Daniel Kiss-Bodolay, Giuseppe Barbagallo and Jibril Osman Farah

Cancers 2025, 17(8), 1369; https://doi.org/10.3390/cancers17081369 - 19 Apr 2025

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Abstract

Background: Resection or damage of the supplementary motor area (SMA) is associated with the development of a transient negative motor response defined as SMA syndrome. The risk of neurological deficits after resection in the SMA has been reported to vary widely from 23% [...] Read more.

Background: Resection or damage of the supplementary motor area (SMA) is associated with the development of a transient negative motor response defined as SMA syndrome. The risk of neurological deficits after resection in the SMA has been reported to vary widely from 23% to 100%. Various influencing factors can be involved. However, since tumors in the SMA are relatively infrequent, most of the evidence for surgical treatment of these lesions is based on small, retrospective, single-center case series. Furthermore, previous studies focused only on a few variables, and our knowledge regarding the outcome of these patients is still limited. Objective: To better define the risk of neurological deficits after brain tumor resection in the SMA. Methods: We retrospectively reviewed 66 surgeries that involved the SMA for gliomas and metastasis in 53 patients from two separate centers. Out of those, 13 cases were recurrence of the disease. We carefully evaluated various clinical factors, preoperative neuroimaging, intraoperative neurophysiology monitoring, and anatomical factors. By using Fisher’s exact probability test, we examined the relationship between these factors and the occurrence of postoperative neurological deficits. Statistical significance was considered at a p-value of less than 0.05. Results: In 28 cases, patients experienced neurological deficits after surgery. Among those cases, 26 experienced partial SMA syndrome, one experienced complete SMA syndrome, and one experienced a permanent neurological deficit. The research found that the patient’s past medical history (p = 0.005), lack of intraoperative language mapping (p = 0.044), and extent of resection (p = 0.040) significantly influenced the occurrence of language deficits. Additionally, the proximity between the corticospinal tract and the tumor (p = 0.005) and fMRI activation of the SMA in response to motor tasks (p = 0.044) were found to correlate with the development of motor deficits. However, there was no correlation found between the lack of intraoperative monitoring of motor-evoked potentials (MEPs) and the development of motor deficits (p > 0.05). Conclusions: Certain pre-existing medical conditions may increase the risk of postoperative language deficits. Intraoperative language mapping can help prevent these deficits. The extent of resection, along with the anatomical characteristics of the resection cavity, correlates with postoperative outcomes. Tractography and fMRI can assist in predicting the risk of motor deficits. Although intraoperative MEP monitoring can help prevent permanent motor deficits, it does not appear to prevent the transient deficits characteristic of SMA syndrome. Further intraoperative studies are needed to refine mapping and monitoring strategies for tumors involving the SMA and pre-SMA. Full article

(This article belongs to the Section Methods and Technologies Development)

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23 pages, 1915 KiB

Open AccessReview

A Systematic Review and Meta-Analysis on Opioid Management of Dyspnea in Cancer Patients

by Elena Chitoran, Vlad Rotaru, Giuseppe Gullo, Daniela Viorica Mosoiu and Laurentiu Simion

Cancers 2025, 17(8), 1368; https://doi.org/10.3390/cancers17081368 - 19 Apr 2025

Viewed by 54

Abstract

Background/Objectives: Dyspnea accompanies end-of-life in many cancer patients, with around 50% experiencing moderate/severe dyspnea, and is an independent factor for poor prognosis and declining quality of life. Managing dyspnea becomes a key component of palliative treatment and end-of-life support for cancer patients. [...] Read more.

Background/Objectives: Dyspnea accompanies end-of-life in many cancer patients, with around 50% experiencing moderate/severe dyspnea, and is an independent factor for poor prognosis and declining quality of life. Managing dyspnea becomes a key component of palliative treatment and end-of-life support for cancer patients. Opioids seem to be the obvious choice in cancer patients as they also address the pain component (often important in such patients). Evidence-based conclusions on the effectiveness/safety of opioids in dyspnea management are scarce, and the results are still controversial. We aim to address this knowledge gap. Methods: In order to achieve the objective of this paper, we conducted a comprehensive search of international databases (PubMed, Medline, Embase, and Cochrane Library) for randomized controlled trials on the use of opioids to treat refractory dyspnea in adult cancer patients, and we performed a pooled meta-analysis of the results. Results: The effect of opioids on the relief of dyspnea was significant (SMD −0.44, 95% CI [−0.75,−0.12], p = 0.007). The significance of the opioid effect is maintained only for morphine administration (SMD −078, 95% CI [−1.45,−0.10], p = 0.02) and only for exertional dyspnea (SMD −1.00, 95% CI [−1.98, −0.03], p = 0.04). No correlation was noted between fentanyl/hydromorphone and dyspnea relief or opioids administered for dyspnea at rest. The subcutaneous route seems to be significantly correlated with dyspnea relief (SMD −0.73, 95% CI [−1.27, −0.19], p = 0.008), while the other administration modalities lack such an effect. No significant correlation was present between the usage of morphine/fentanyl and increased odds of severe adverse effects (OR 1.48, 95% CI [0.57,3.86], p = 0.42); however, fentanyl seems to be associated with increased somnolence. Although we aimed to evaluate how opioids impact the quality of life of cancer patients with dyspnea, we were unable to obtain such results due to the absolute lack of the literature available discussing QoL. Conclusions: Although we managed to provide some insights into the efficiency and safety of opioids usage for dyspnea management in cancer patients, the evidence based on the available literature is low grade. There is a marked need to address this knowledge gap with future high-quality studies with large sample sizes and standardized protocols. Full article

(This article belongs to the Special Issue Integrating Palliative Care in Oncology)

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11 pages, 660 KiB

Open AccessArticle

Comparison of Tumor Diameter and Tumor Volume in Terms of Aggressive Tumor Behavior and Prognosis in Papillary Thyroid Cancer

by Sevgül Fakı, Abbas Ali Tam, Nurcan İnce, Pervin Demir, Didem Özdemir, Ayşegül Aksoy Altınboğa, Oya Topaloğlu, Reyhan Ersoy and Bekir Çakır

Cancers 2025, 17(8), 1367; https://doi.org/10.3390/cancers17081367 - 19 Apr 2025

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Abstract

Background: Tumor diameter may not reflect tumor burden accurately in all cancers. In this study, we aimed to investigate the relationship between tumor volume (TV) and aggressive features and prognosis in papillary thyroid cancer (PTC). Methods: Patients diagnosed with single foci PTC were [...] Read more.

Background: Tumor diameter may not reflect tumor burden accurately in all cancers. In this study, we aimed to investigate the relationship between tumor volume (TV) and aggressive features and prognosis in papillary thyroid cancer (PTC). Methods: Patients diagnosed with single foci PTC were recruited for the study. The largest tumor diameter was considered as the primary tumor diameter. TV was calculated using the formula for an ellipsoid shape, considering the three pathologically specified dimensions. Primary tumor diameter and TV were compared in terms of aggressive tumor characteristics and prognosis. Results: The data of 118 patients were analyzed. There was no significant relationship between primary tumor diameter and lymph node metastasis (LNM), extrathyroidal extension (ETE), and vascular invasion (p > 0.05 for each). In patients with tumor diameter >2 cm, TV was negatively associated with LNM (p = 0.015). One-unit increase in TV was associated with 1.629 times greater likelihood of absence of LNM (95% CI: 1.099–2.415). When the TV was ≤5.26 cm³, the sensitivity and specificity for the presence of LNM were 88.9% and 75.8%, respectively. Again in this group, the sensitivity for the occurrence of ETE was 100.0% and specificity was 45.7% when the TV was ≤9.49 cm³. There was no significant difference in the five-year disease-free survival between tumor diameter and TV. Conclusions: In contrary to studies with other cancer types in the literature, there was a significant but negative relationship between TV and LNM. Further large-scale studies are needed to determine whether TV can be used as a prognostic factor in PTC. Full article

(This article belongs to the Section Cancer Metastasis)

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15 pages, 1181 KiB

Open AccessArticle

Comprehensive Clinical Characterization and Long-Term Follow-Up of the Institut Català d’Oncologia Breast Cancer Observational Cohort Study

by Helena Pla, Bartomeu Fullana, Anna Esteve, Roser Fort-Culillas, Angelica Ferrando-Díez, Adela Fernández-Ortega, Anna Pous, Agostina Stradella, Rafael Villanueva-Vázquez, Beatriz Cirauqui, Catalina Falo, Evelyn Martínez-Pérez, Guadalupe Molina, Sonia del Barco, Arantxa Eraso, Mireia Margelí, Gemma Viñas, Miguel Gil-Gil, Lourdes Petriz and Sonia Pernas

Cancers 2025, 17(8), 1366; https://doi.org/10.3390/cancers17081366 - 19 Apr 2025

Viewed by 111

Abstract

Background/Objectives: Few large cohorts with relatively uniform treatment approaches and long-term follow-up are available for assessing clinical outcomes for breast cancer (BC) patients. The Institut Català d’Oncologia (ICO) Breast Cancer Cohort was designed to well characterize treatment patterns and overall survival outcomes [...] Read more.

Background/Objectives: Few large cohorts with relatively uniform treatment approaches and long-term follow-up are available for assessing clinical outcomes for breast cancer (BC) patients. The Institut Català d’Oncologia (ICO) Breast Cancer Cohort was designed to well characterize treatment patterns and overall survival outcomes at 5 and 10 years, with a particular focus on patients < 40 and ≥70 years old, age groups often underrepresented in clinical trials. Methods: In this retrospective, observational study, we included all pathologically confirmed invasive BC patients diagnosed and treated between 2010 and 2014 at ICO, a Spanish reference cancer center, with a follow-up until November 2023. We collected comprehensive real-world data on clinicopathologic characteristics and treatment modalities. Overall survival (OS) was estimated using the Kaplan–Meier technique and was reported stratified by prognostic factors for the age groups of ≤40, 41–69 and ≥70. The Multivariate Cox model was used to estimate the risk of death for subgroups of age, adjusting for subtype, stage and grade. Results: Overall, 3451 patients with stage I to IV BC were diagnosed and treated, with a mean age of 58 years (range 19–98); 371 (10.8%) were diagnosed ≤40 years, and 756 (21.9%) were ≥70 years. With a mean follow-up of 9.9 years (SD = 3.5), the 5- and 10-year OS were 89% (95% CI: 86–92%) and 85% (95% CI: 81–88%) for patients ≤ 40, respectively; for those aged 41–69 years, 91% (95% CI: 90–92%) and 85% (95% CI: 83–86%), respectively; and 70% (95% CI: 66–73%) and 50% (95% CI: 47–54%) for those ≥70 years, respectively. The 5- and 10-year relative survival (RS) were 92% and 88% for patients < 70 years, respectively, and 82% and 77% for those ≥70 years, respectively. The Multivariate Cox model identified a HR of 4.90 (95% CI: 3.44–6.97, p < 0.001) for patients ≥ 70 years compared to those between 41 and 69 years. Conclusions: The ICO Breast Cancer Cohort, as far as we know, the largest in Spain with long-term follow-up, underscores the critical role of age and subtype in determining overall survival outcomes in patients with breast cancer. Full article

(This article belongs to the Section Clinical Research of Cancer)

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16 pages, 266 KiB

Open AccessArticle

Thyroid Nodules with Nuclear Atypia of Undetermined Significance (AUS-Nuclear) Hold a Two-Times-Higher Risk of Malignancy than AUS-Other Nodules Regardless of EU-TIRADS Class of the Nodule or Borderline Tumor Interpretation

by Dorota Słowińska-Klencka, Bożena Popowicz, Joanna Duda-Szymańska and Mariusz Klencki

Cancers 2025, 17(8), 1365; https://doi.org/10.3390/cancers17081365 - 19 Apr 2025

Viewed by 117

Abstract

Background/Objectives: The 2023 revision of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) simplified the subcategorization of category III into two groups: “AUS-nuclear” and “AUS-other”. The aim of this study was to investigate the risk of malignancy (ROM) of individual BSRTC categories with [...] Read more.

Background/Objectives: The 2023 revision of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) simplified the subcategorization of category III into two groups: “AUS-nuclear” and “AUS-other”. The aim of this study was to investigate the risk of malignancy (ROM) of individual BSRTC categories with a particular emphasis on the “AUS-nuclear” and “AUS-other” subcategories and to check whether the low-risk follicular-cell-derived thyroid neoplasm (LRTN) interpretation or EU-TIRADS class of the nodule modify ROM. Methods: The analysis covered the FNA results of 18,225 nodules in 12,470 patients. The rate of malignancy (the upper limit of ROM) was established on the basis of the assessment of 1660 nodules treated surgically in 978 patients. Results: In the broadest variant, with all LRTNs regarded as malignant, the ROM for subsequent categories was as follows: I: 0.4–3.5%, II: 0.1–1.3%, III: 3.8–17.7%, IV: 23.3–27.8%, V: 79.6–90.1%, and VI: 86.3–100.0%. In AUS-nuclear nodules, the ROM was 10.5–28.9%, while in AUS-other nodules, it was 2.2–12.2%. The exclusion of NIFTP or all LRTNs from cancers mainly affected the ROM of AUS-nuclear nodules: 9.4–25.9% or 8.6–23.7%, respectively. EU-TIRADS 5 class increases the ROM in AUS-nuclear nodules to 78.3%, OR: 15.7 and in AUS-other to 40.7%, OR: 6.6. Conclusions: The 2023 BSRTC is a welcome step towards simplification of the way nodules are classified within category III. The AUS-nuclear subcategory is associated with a two-times-higher incidence of malignancy than the AUS-other regardless of LRTN interpretation and EU-TIRADS class of the nodule. The EU-TIRADS 5 class of the nodule is helpful in the identification of category III nodules with a high risk of malignancy. Full article

(This article belongs to the Section Cancer Causes, Screening and Diagnosis)

16 pages, 5989 KiB

Open AccessArticle

Lack of Evidence Supporting a Significant Benefit of Pre-Transplant Consolidation Therapy in AML CR2 Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

by Meng Lv, Ting Huang, Xiao-Dong Mo, Yu-Qian Sun, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Xiao-Jun Huang and Yu Wang

Cancers 2025, 17(8), 1364; https://doi.org/10.3390/cancers17081364 - 19 Apr 2025

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Abstract

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established curative treatment option for acute myeloid leukemia (AML) in second complete remission (CR2). However, whether the addition of consolidation chemotherapy after achieving CR2 can improve transplant outcomes remains controversial. Methods: In [...] Read more.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established curative treatment option for acute myeloid leukemia (AML) in second complete remission (CR2). However, whether the addition of consolidation chemotherapy after achieving CR2 can improve transplant outcomes remains controversial. Methods: In this single-center retrospective study, we analyzed consecutive AML patients who underwent their first HSCT in CR2 at our institution between January 2015 and December 2019. Results: For the consolidation (n = 72) and no consolidation groups (n = 63), the 5-year cumulative incidence of relapse (CIR) was (17.6% vs. 19.9%; p = 0.54), the 5-year non-relapse mortality rate (NRM) was (9.7% vs. 17.5%; p = 0.20), the 5-year leukemia-free survival (LFS) was (72.7% vs. 62.7%; p = 0.15), and the 5-year overall survival (OS) was (81.9% vs. 68.3%; p = 0.08). Additional consolidation therapy to achieve negative measurable residual disease (MRD) did not result in significantly improved outcomes compared to immediate HSCT in MRD positive status, with similar LFS (76.9% vs. 67.0%, p = 0.2) and OS (88.3% vs. 75.0%, p = 0.14). Multivariable analysis indicated that consolidation chemotherapy did not significantly affect CIR, NRM, LFS, or OS. Conclusions: Our findings suggest no significant differences in clinical outcomes between the groups, indicating that AML patients in CR2 might proceed to HSCT without delay. Full article

(This article belongs to the Special Issue Current Use of Hematopoietic Cell Transplantation in Hematologic Malignancies)

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13 pages, 1544 KiB

Open AccessArticle

Inflammation and Thyroid Cancer: Deciphering the Role of Blood Immune Indexes

by Salvatore Sorrenti, Gregorio Scerrino, Eleonora Lori, Fabrizio Vassallo, Stefania Saverino, Calogera Amato, Giuseppina Melfa, Pierina Richiusa, Sergio Mazzola, Antonella Lopes, Giuseppina Orlando and Giuseppa Graceffa

Cancers 2025, 17(8), 1363; https://doi.org/10.3390/cancers17081363 - 19 Apr 2025

Viewed by 76

Abstract

Background: Inflammation within tumor microenvironments has been correlated to numerous malignancies. This study aims to explore its significance in thyroid cancer (TC). Methods: Retrospective analysis of 157 thyroid carcinomas and 40 benign cases involved initial univariate analysis. The value of neutrophils/value of lymphocytes [...] Read more.

Background: Inflammation within tumor microenvironments has been correlated to numerous malignancies. This study aims to explore its significance in thyroid cancer (TC). Methods: Retrospective analysis of 157 thyroid carcinomas and 40 benign cases involved initial univariate analysis. The value of neutrophils/value of lymphocytes (NLR), value of platelets/value of lymphocytes (PLR), value of lymphocytes/value of monocytes (LMR), and value of platelets × value of neutrophils/value of lymphocytes (SII) indexes were related to TC characteristics and number and location of involved lymph nodes using χ² or Fischer’s exact tests for categorical variables and Student’s t-tests for continuous ones. A 1:1 propensity score matching balanced malignant and benign TC groups based on age, sex, and tumor size was used. Post-matching, a multivariate logistic model integrated sex, age, Central lymph node metastases (CLNM), and SII index. Statistically significant immune index values underwent ROC curve analysis for determining cut-offs. Among the 157 malignant TC, median test and density plots were performed. Results: The SII index emerged as a predictor of malignancy in both univariate and multivariate analyses (p-value = 0.0202). The ROC curve indicated a cut-off SII value of 465.71, (specificity = 58% [95% CI: 0.43–0.73]; sensitivity = 80% [95% CI: 0.68–0.93]). Median SII index values for tumor sizes of 1 and >1 were 522.8 and 654.8, respectively (p-value = 0.016). When central lymph nodes metastases(CLNMs) was considered (CLNM = 0 vs. CLNM > 0), median SII values were 530.7 and 1121.7, respectively (p-value = 0.011). Conclusions: The SII index appears to be a valuable tool in the presence of TC, showing correlations with malignancy, tumor size, and CLNMs. Full article

(This article belongs to the Special Issue Thyroid Cancer: Diagnosis, Prognosis and Treatment (2nd Edition))

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64 pages, 1570 KiB

Open AccessReview

The Impact of Implementing Indicators of Quality of Oncological Care on Improving Patient Outcomes: A Cross-Sectional Review of Experiences from Countries Using Indicators in the Quality Assessment Process

by Karolina Piekarska, Piotr Bednarski, Barbara Politynska, Anna M. Wojtukiewicz, Maciej Krzakowski and Marek Z. Wojtukiewicz

Cancers 2025, 17(8), 1362; https://doi.org/10.3390/cancers17081362 - 18 Apr 2025

Viewed by 102

Abstract

The implementation of QIs in the pursuit of improving patient outcomes in oncological care has become a primary goal for many countries. The purpose of this cross-sectional review is to present the experiences of several countries that have implemented different strategies in using [...] Read more.

The implementation of QIs in the pursuit of improving patient outcomes in oncological care has become a primary goal for many countries. The purpose of this cross-sectional review is to present the experiences of several countries that have implemented different strategies in using QIs to assess the quality of cancer care. Countries such as the United States, the United Kingdom, Canada, the Netherlands, Australia, and Israel have been pioneers in integrating QIs into their healthcare systems, which has led to significant improvements in the delivery of care. These indicators help assess adherence to clinical guidelines, timeliness of treatment, safety of practices, and overall patient survival. Data from these countries show that the use of QIs correlates with improved five-year survival rates, earlier diagnosis, better adherence to evidence-based treatment protocols, and increased patient satisfaction. For example, in the Netherlands and Germany, the introduction of quality cancer care programs has led to improved surgical outcomes and overall survival for patients with colorectal cancer. The United Kingdom and Denmark have reported improvements in waiting times for diagnosis and treatment, and in Israel, screening rates for breast and colorectal cancer increased after the introduction of QIs for monitoring these conditions. The current review highlights the fact that countries with robust reporting systems and national cancer registries with high levels of data completeness, such as Denmark, Sweden, and Norway, were able to effectively monitor outcomes and adjust clinical practices accordingly. The findings suggest that implementing QIs in cancer care not only improves clinical outcomes but also promotes accountability and stimulates improved healthcare, ensuring better long-term patient care. This study highlights the value of adopting QIs as a global standard for assessing cancer care. Full article

(This article belongs to the Section Cancer Survivorship and Quality of Life)

17 pages, 4190 KiB

Open AccessArticle

Identification of Molecular Subtypes of Clear-Cell Renal Cell Carcinoma in Patient-Derived Xenografts Using Multi-Omics

by Zhengyuan Qiu, Dalin Zhang, Fernando Jose Garcia-Marques, Abel Bermudez, Hongjuan Zhao, Donna M. Peehl, Sharon J. Pitteri and James D. Brooks

Cancers 2025, 17(8), 1361; https://doi.org/10.3390/cancers17081361 - 18 Apr 2025

Viewed by 131

Abstract

Background/Objectives: Clear-cell renal cell carcinoma (ccRCC) is a heterogenous disease that can be classified into multiple molecular subtypes with differential prognosis and sensitivities to treatments based on their genomic, transcriptomic, proteomic, and metabolic profiles. Patient-derived xenografts (PDXs) are high-fidelity cancer models because [...] Read more.

Background/Objectives: Clear-cell renal cell carcinoma (ccRCC) is a heterogenous disease that can be classified into multiple molecular subtypes with differential prognosis and sensitivities to treatments based on their genomic, transcriptomic, proteomic, and metabolic profiles. Patient-derived xenografts (PDXs) are high-fidelity cancer models because they maintain similar genotypes and immunohistologic phenotypes to the parental tumors and respond to standard-of-care therapies as expected. However, whether the molecular subtypes identified in ccRCC patient samples are preserved in PDX models is not clear. Our objective is to compare the transcriptional and proteomic profiles of our PDX models to those of ccRCC patients and identify both similarities and distinctions between molecular profiles of PDX subtypes and corresponding ccRCC patient subtypes, so that proper PDX subtypes can be used when investigating the corresponding ccRCC patient subtypes. Methods: To match PDXs to the human ccRCC molecular subtypes, we compared the transcriptomic and proteomic profiles of five ccRCC PDX models established in our lab to those of the human ccRCC molecular subtypes reported by our group, as well as other groups, using hierarchical analysis, Principal Component Analysis (PCA), and Permutation Correlation Analysis. The enrichment of key molecular pathways in PDXs and ccRCC subtypes was determined using Gene Set Enrichment Analysis. Results: We found that each PDX resembles one of the molecular subtypes closely at both transcript and protein levels. In addition, PDXs representing different molecular subtypes show unique metabolic characteristics. Moreover, molecular subtypes of PDXs correlated with ccRCC patient subtypes in key pathway activities implicated in ccRCC progression and therapy resistance. Conclusions: Our results suggest that PDX subtypes should be used when investigating the molecular mechanism of cancer progression and therapy resistance for corresponding ccRCC patient subtypes. This “matching” strategy will greatly facilitate the clinical translation of positive findings into the optimal management of ccRCC patients. Full article

(This article belongs to the Special Issue Recent Advances in Management of Renal Cell Carcinoma)

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28 pages, 15072 KiB

Open AccessArticle

Unravelling Paclitaxel Resistance in Gastric Cancer: The Role of Small Extracellular Vesicles in Epithelial Mesenchymal Transition and Extracellular Matrix Remodelling

by Giorgia Panzetta, Annalisa Schirizzi, Francesco Balestra, Maria De Luca, Nicoletta Depalo, Federica Rizzi, Angela Dalia Ricci, Giampiero De Leonardis, Claudio Lotesoriere, Gianluigi Giannelli, Rosalba D’Alessandro and Maria Principia Scavo

Cancers 2025, 17(8), 1360; https://doi.org/10.3390/cancers17081360 - 18 Apr 2025

Viewed by 132

Abstract

Background: Gastric cancer (GC) is a highly aggressive disease often complicated by resistance to chemotherapy agents like paclitaxel (PTX), which targets microtubules to induce apoptosis. Resistance arises through complex molecular mechanisms, including the overexpression of pro-angiogenic factors (VEGFA, ANG-2), activation of survival pathways [...] Read more.

Background: Gastric cancer (GC) is a highly aggressive disease often complicated by resistance to chemotherapy agents like paclitaxel (PTX), which targets microtubules to induce apoptosis. Resistance arises through complex molecular mechanisms, including the overexpression of pro-angiogenic factors (VEGFA, ANG-2), activation of survival pathways (PDGFRβ, PPARγ), and epithelial-mesenchymal transition (EMT) driven by proteins such as VIM, E-CAD, N-CAD, and FLOT-1. The extracellular matrix (ECM), regulated by COL1A1 and influenced by PPARγ, acts as a physical barrier to drug penetration. Small extracellular vesicles (sEVs) have emerged as critical mediators of intercellular communication and may influence these resistance pathways. Methods: This study investigated the role of sEVs isolated from metastatic GC patients treated with Ramucirumab and PTX. Patients were stratified by progression-free survival (PFS) into rapidly progressing (RP) and controlled disease (CD) groups. sEVs from these patients were applied to HCEC-1CT and HEPA-RG cell lines. Cell viability assays, gene and protein expression analyses, and bioinformatic studies were conducted to assess the impact of sEVs on resistance-related markers. Results: Results showed that sEVs from CD patients reduced the expression of markers associated with drug resistance, while sEVs from RP patients increased these markers, promoting angiogenesis, EMT, and ECM remodeling. These changes correlated with enhanced cell survival and resistance phenotypes. Bioinformatic analyses confirmed that sEVs modulate inflammation, ECM dynamics, and EMT pathways. Conclusions: In conclusion, sEVs from metastatic GC patients significantly influence chemoresistance and tumor progression. Targeting sEV-mediated signaling may offer novel therapeutic strategies to overcome resistance and improve treatment outcomes in gastric cancer. Full article

(This article belongs to the Special Issue Extracellular Matrix Proteins in Cancer)

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11 pages, 1340 KiB

Open AccessArticle

The Effect of Staging Intervals on Progression-Free Survival in Registration Studies of Oncologic Drugs: A Meta-Analysis

by Jonas A. Zuellig, Roman Adam, Filomena Udry, Ariadna Tibau, Bostjan Šeruga, Alberto Ocaña, Eitan Amir and Arnoud J. Templeton

Cancers 2025, 17(8), 1359; https://doi.org/10.3390/cancers17081359 - 18 Apr 2025

Viewed by 72

Abstract

Background/Objectives: To study whether shorter restaging intervals are associated with lower hazard ratios (HRs) for progression-free survival (PFS), as suggested in breast cancer. Methods: Studies supporting the registration of oncologic drugs in Switzerland from 2010 to 2022 were analyzed. HRs and 95% confidence [...] Read more.

Background/Objectives: To study whether shorter restaging intervals are associated with lower hazard ratios (HRs) for progression-free survival (PFS), as suggested in breast cancer. Methods: Studies supporting the registration of oncologic drugs in Switzerland from 2010 to 2022 were analyzed. HRs and 95% confidence intervals (CIs) for PFS were pooled in a meta-analysis using the generic inverse-variance method and a random-effects model in RevMan v5.4. The HRs were stratified by restaging intervals (<median vs. ≥median), both overall and within prespecified subgroups. Results: A total of 112 studies comprising 69,579 patients were included. The median restaging interval was 8 weeks, with a range of 4 to 18 weeks. Longer restaging intervals (≥8 weeks) were associated with lower HRs compared to shorter intervals (<8 weeks), with pooled HRs of 0.48 (95% CI: 0.44–0.52) and 0.58 (95% CI: 0.53–0.63), respectively. The difference between the groups was statistically significant (p = 0.005), with a substantial heterogeneity (Cochran’s Q p < 0.001; I² = 90%). Subgroup analyses based on treatment type, including immunotherapy, monoclonal antibodies, and tyrosine kinase inhibitors, did not show any statistically significant differences in HRs. Studies of melanoma with shorter staging intervals were associated with lower HRs (0.44 vs. 0.58, p = 0.02), whereas shorter interval studies of kidney cancer had higher HRs (0.67 vs. 0.44, p = 0.01). Sensitivity analyses with other cut-offs and a meta-regression yielded similar results. Conclusions: Studies leading to the authorization of drugs to treat incurable solid tumors applying restaging intervals ≥ 8 weeks were associated with lower HRs for PFS. The potential impact of restaging intervals on the results for PFS warrants further investigation. Full article

(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)

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19 pages, 6607 KiB

Open AccessArticle

Machine Learning Model Development for Malignant Prostate Lesion Prediction Using Texture Analysis Features from Ultrasound Shear-Wave Elastography

by Adel Jawli, Ghulam Nabi, Zhihong Huang, Abeer J. Alhusaini, Cheng Wei and Benjie Tang

Cancers 2025, 17(8), 1358; https://doi.org/10.3390/cancers17081358 - 18 Apr 2025

Viewed by 123

Abstract

Introduction: Artificial intelligence (AI) is increasingly utilized for texture analysis and the development of machine learning (ML) techniques to enhance diagnostic accuracy. ML algorithms are trained to differentiate between normal and malignant conditions based on provided data. Texture feature analysis, including first-order [...] Read more.

Introduction: Artificial intelligence (AI) is increasingly utilized for texture analysis and the development of machine learning (ML) techniques to enhance diagnostic accuracy. ML algorithms are trained to differentiate between normal and malignant conditions based on provided data. Texture feature analysis, including first-order and second-order features, is a critical step in ML development. This study aimed to evaluate quantitative texture features of normal and prostate cancer tissues identified through ultrasound B-mode and shear-wave elastography (SWE) imaging and to develop and assess ML models for predicting and classifying normal versus malignant prostate tissues. Methodology: First-order and second-order texture features were extracted from B-mode and SWE imaging, including four reconstructed regions of interest (ROIs) from SWE images for normal and malignant tissues. A total of 94 texture features were derived, including features for intensity, Gray-Level Co-Occurrence Matrix (GLCM), Gray-Level Dependence Length Matrix (GLDLM), Gray-Level Run Length Matrix (GLRLM), and Gray-Level Size Zone Matrix (GLSZM). Five ML models were developed and evaluated using 5-fold cross-validation to predict normal and malignant tissues. Results: Data from 62 patients were analyzed. All ROIs, except those derived from B-mode imaging, exhibited statistically significant differences in features between normal and malignant tissues. Among the developed models, Support Vector Machines (SVM), Random Forest (RF), and Naive Bayes (NB) demonstrated the highest performance across all ROIs. These models consistently achieved strong predictive accuracy for classifying normal versus malignant tissues. Gray Pure SWE and Gray Reconstructed images Provided the highest sensitivity and specificity in PCa prediction by 82%, 90%, and 98%, 96%, respectively. Conclusions: Texture analysis with machine learning on SWE-US and reconstructed images effectively differentiates malignant from benign prostate lesions, with features like contrast, entropy, and correlation playing a key role. Random Forest, SVM, and Naïve Bayes showed the highest classification performance, while grayscale reconstructions (GPSWE and GRRI) enhanced detection accuracy. Full article

(This article belongs to the Section Methods and Technologies Development)

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18 pages, 3884 KiB

Open AccessSystematic Review

The Impact of Beta Blockers on Survival in Cancer Patients: A Systematic Review and Meta-Analysis

by Alisha E. Sharma, Stephanie Chan, Adam S. Komorowski, Xingshan Cao, Yizhuo Gao, Kushal Kshatri, Kairavi Desai, Markus Kuksis, Michael Rosen, Anjali Sachdeva, Isabella Kojundzic, Saif Samari, Iacovos P. Michael, Husam Abdel-Qadir and Katarzyna J. Jerzak

Cancers 2025, 17(8), 1357; https://doi.org/10.3390/cancers17081357 - 18 Apr 2025

Viewed by 163

Abstract

Background/Objectives: Beta adrenergic signaling has been implicated in cancer progression, leading to interest in repurposing beta blockers (BBs) as adjunctive anti-cancer agents. However, clinical findings are inconsistent. This systematic review and meta-analysis evaluates the association between BB use and survival outcomes in cancer [...] Read more.

Background/Objectives: Beta adrenergic signaling has been implicated in cancer progression, leading to interest in repurposing beta blockers (BBs) as adjunctive anti-cancer agents. However, clinical findings are inconsistent. This systematic review and meta-analysis evaluates the association between BB use and survival outcomes in cancer patients. Methods: A systematic search of OVID Medline, EMBASE, and CENTRAL was conducted through 13 September 2023, for studies comparing survival outcomes in solid tumor patients using BBs versus non-users. Eligible studies reported hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS), or cancer-specific survival (CSS). Perioperative studies and those without BB-specific HRs were excluded. Data extraction and quality assessment were performed in duplicate using ROBINS-I. A random-effects model was used, with heterogeneity assessed by the I² statistic. Results: Seventy-nine studies (492,381 patients) met the inclusion criteria; 2.5% were prospective. The most frequently studied cancers were breast (n = 33), ovarian (n = 30), and colorectal (n = 28). BB use was associated with improved PFS (HR 0.78, 95% CI: 0.66–0.92, I² = 79.8%), with significance maintained after excluding high-bias studies (HR 0.74, 95% CI: 0.61–0.91, I² = 36.6%). No significant associations were observed for OS (HR 0.99, 95% CI: 0.94–1.04, I² = 84.9%) or CSS (HR 0.95, 95% CI: 0.91–1.00, I² = 77.4%). Conclusions: BB use may be associated with longer PFS in cancer patients, but findings are limited by study design and heterogeneity; high-quality prospective studies are needed. Full article

(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)

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24 pages, 682 KiB

Open AccessReview

Intraoperative Radiation Therapy (IORT) in Gynecologic Cancers: A Scoping Review

by Evrim Erdemoglu, Stuart A. Ostby, Sanjanaa Senthilkumar, Amanika Kumar, Sujay A. Vora, Longwen Chen, Sarah E. James and Kristina A. Butler

Cancers 2025, 17(8), 1356; https://doi.org/10.3390/cancers17081356 - 18 Apr 2025

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Abstract

Objective: We aimed to analyze the current literature for IORT in gynecological cancers and summarized clinical outcomes regarding patient selection. Methods: A systematic search was conducted utilizing PUBMED, Embase, and CINAHL to identify studies following PRISMA-ScR guidelines. A PICOS structure was utilized: population: [...] Read more.

Objective: We aimed to analyze the current literature for IORT in gynecological cancers and summarized clinical outcomes regarding patient selection. Methods: A systematic search was conducted utilizing PUBMED, Embase, and CINAHL to identify studies following PRISMA-ScR guidelines. A PICOS structure was utilized: population: patients with epithelial gynecological cancers; intervention: IORT; C: a comparator was not required, as we aimed to analyze patient selection; outcome: clinical outcomes and overall survival; and S: experimental and quasi-experimental analytical observational studies and descriptive observational studies, excluding case series published in English and limited to the last 10 years. Data extraction was conducted for patient selection, IORT, oncological outcomes, and morbidity. Results: A total of 707 results were identified, and 509 studies were uploaded to Covidence for screening after removing duplications. Of the 21 eligible studies, 9 were included in the final review. The total number of patients included was 348. The studies were retrospective single-institution studies, except for one. There was significant heterogeneity in their design and protocols. IORT was exclusively used for recurrent and advanced stage gynecological cancers adjunct to pelvic exenteration or laterally extended endopelvic resections with variable indications across institutions. The mean number of IORT patients per study was 2.8 per year. Survival rates were variable and dependent on the surgical margin. Endometrial cancer had a favorable outcome compared to vulvar and cervical cancers. Conclusions: Current clinical practice, as demonstrated by the research, is consistent with NCCN guidelines that endorse the application of IORT in instances of recurrent cervical, vaginal, and vulvar malignancies; however, there are no established recommendations for primary tumors. The analysis shows that there are gaps in our knowledge, mainly regarding the status of the margins, the criteria used to choose patients, and the outcomes that are specific to each histology. The standardization of protocols and prospectively powered studies are needed to refine patient selection criteria. Full article

(This article belongs to the Special Issue Paradigm Shifts in Gynaecological Oncology Surgery)

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32 pages, 1799 KiB

Open AccessReview

Understanding and Targeting Metabolic Vulnerabilities in Acute Myeloid Leukemia: An Updated Comprehensive Review

by Sridevi Addanki, Lana Kim and Alexandra Stevens

Cancers 2025, 17(8), 1355; https://doi.org/10.3390/cancers17081355 - 18 Apr 2025

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Abstract

Acute Myeloid Leukemia (AML) is characterized by aggressive proliferation and metabolic reprogramming that support its survival and resistance to therapy. This review explores the metabolic distinctions between AML cells and normal hematopoietic stem cells (HSCs), emphasizing the role of altered mitochondrial function, oxidative [...] Read more.

Acute Myeloid Leukemia (AML) is characterized by aggressive proliferation and metabolic reprogramming that support its survival and resistance to therapy. This review explores the metabolic distinctions between AML cells and normal hematopoietic stem cells (HSCs), emphasizing the role of altered mitochondrial function, oxidative phosphorylation (OXPHOS), and biosynthetic pathways in leukemic progression. AML cells exhibit distinct metabolic vulnerabilities, including increased mitochondrial biogenesis, reliance on glycolysis and amino acid metabolism, and unique signaling interactions that sustain leukemic stem cells (LSCs). These dependencies provide potential therapeutic targets, as metabolic inhibitors have demonstrated efficacy in disrupting AML cell survival while sparing normal hematopoietic cells. We examine current and emerging metabolic therapies, such as inhibitors targeting glycolysis, amino acid metabolism, and lipid biosynthesis, highlighting their potential in overcoming drug resistance. However, challenges remain in translating these strategies into clinical practice due to AML’s heterogeneity and adaptability. Further research into AML’s metabolic plasticity and precision medicine approaches is crucial for improving treatment outcomes. Understanding and exploiting AML’s metabolic vulnerabilities could pave the way for novel, more effective therapeutic strategies. Full article

(This article belongs to the Section Molecular Cancer Biology)

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22 pages, 1223 KiB

Open AccessArticle

Association Between B-Cell Marker Expression and RUNX1 Lesions in Acute Myeloid Leukemia, Beyond RUNX1::RUNX1T1 Fusion: Diagnostic Pitfalls with Mixed-Phenotype Acute Leukemia—B/Myeloid

by Giby V. George, Malgorzata Kajstura, Audrey N. Jajosky, Hong Fang, Fatima Zahra Jelloul, Andrew G. Evans, W. Richard Burack, John M. Bennett, L. Jeffrey Medeiros, Wei Wang and Siba El Hussein

Cancers 2025, 17(8), 1354; https://doi.org/10.3390/cancers17081354 - 18 Apr 2025

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Abstract

Acute myeloid leukemia (AML) with RUNX1::RUNX1T1 fusion is well known to often demonstrate aberrant upregulation of CD19 expression. We studied the clinicopathologic and genetic features of 16 cases of AML with various RUNX1 lesions, including mutations, copy number gains, and translocations [...] Read more.

Acute myeloid leukemia (AML) with RUNX1::RUNX1T1 fusion is well known to often demonstrate aberrant upregulation of CD19 expression. We studied the clinicopathologic and genetic features of 16 cases of AML with various RUNX1 lesions, including mutations, copy number gains, and translocations other than fusions with RUNX1T1. Most of these cases were classified as AML-myelodysplasia-related or AML-post-cytotoxic therapy based on the cytogenetic and molecular work-up. These neoplasms showed partial expression of one or more B-cell antigens by flow cytometry and/or immunohistochemistry, fulfilling the criteria for mixed-phenotype acute leukemia (MPAL)-B/myeloid (i.e., ≥20% blasts expressing B and myeloid lineage antigens) in most cases. These findings suggest that AML cases with RUNX1 lesions including mutations, copy number gains, and translocations other than RUNX1T1 fusion, also commonly express B-cell markers, imparting a “mixed-lineage-like” immunophenotype in cases of AML that otherwise fulfill the criteria for other defined subtypes. We present these cases as to caution regarding this potential diagnostic pitfall and favor a diagnosis of AML with RUNX1 lesion(s) in the setting of a case of AML with myeloid/B-cell antigen expression, a history of myelodysplasia or cytotoxic therapy, the demonstration of pDC differentiation by flow cytometry (generally associated with the presence of a RUNX1 mutation), and the presence of a RUNX1 lesion (mutation, copy number gain, and/or translocation exclusive of a rearrangement with RUNX1T1). Full article

(This article belongs to the Special Issue Advances in Pathology of Lymphoma and Leukemia)

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14 pages, 780 KiB

Open AccessArticle

Perceptions of Artificial Intelligence Among Gastroenterologists in Italy: A National Survey

by Marcello Maida, Sandro Sferrazza, Giulio Calabrese, Giovanni Marasco, Alessandro Vitello, Manuele Furnari, Ivo Boskoski, Emanuele Sinagra and Antonio Facciorusso

Cancers 2025, 17(8), 1353; https://doi.org/10.3390/cancers17081353 - 17 Apr 2025

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Abstract

Background: An extensive body of evidence regarding artificial intelligence (AI) in gastroenterology is currently available, but the transition of these technologies to the bedside is still in progress. This national survey aims to assess the perceptions of AI among gastroenterologists in Italy. [...] Read more.

Background: An extensive body of evidence regarding artificial intelligence (AI) in gastroenterology is currently available, but the transition of these technologies to the bedside is still in progress. This national survey aims to assess the perceptions of AI among gastroenterologists in Italy. Methods: A total of 320 Italian gastroenterologists and trainees in gastroenterology were invited to answer a web-based survey. A sub-group analysis between the two categories was performed. Results: Data from 150 respondents were analyzed. Of these, 67.3% were gastroenterologists and 32.7% trainees. Notably, 99.3% reported familiarity with AI in gastroenterology, with 49.3% currently using AI tools, indicating high levels of awareness and current use. Participants expressed low concerns regarding reliability on a 0-to-10-point scale (median = 4), legal and ethical issues (median = 5), and data protection (median 5), whereas regulatory concerns were moderate (median = 6), representing a key concern. Subgroup analysis revealed that male gastroenterologists had a higher understanding of AI (median = 7) compared to females (median 6, p = 0.036). Additionally, older gastroenterologists showed greater ease of use in AI endoscopy tools (median 8 vs. 7, p = 0.040) and raised more regulatory concerns (median 7 vs. 6, p = 0.036). Conclusions: The data from this survey show that Italian gastroenterologists have high-level awareness and a favorable perception of AI systems, with a good diffusion of AI tools across the national territory and reasonable concerns about regulatory issues, raising attention on international AI regulations. Full article

(This article belongs to the Special Issue Medical Imaging and Artificial Intelligence in Cancer)

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Cancers, Volume 17, Issue 8 (April-2 2025) – 129 articles

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