Cancers

22 pages, 7806 KiB

Open AccessArticle

Patient-Derived Gastric Cancer Assembloid Model Integrating Matched Tumor Organoids and Stromal Cell Subpopulations

by Irit Shapira-Netanelov, Olga Furman, Dikla Rogachevsky, Galia Luboshits, Yael Maizels, Dmitry Rodin, Igor Koman and Gabriela A. Rozic

Cancers 2025, 17(14), 2287; https://doi.org/10.3390/cancers17142287 (registering DOI) - 9 Jul 2025

Abstract

Background/Purpose: Conventional three-dimensional in vitro tumor models often fail to fully capture the complexity of the tumor microenvironment, particularly the diverse populations of cancer-associated fibroblasts that contribute to poor prognosis and treatment resistance. The purpose of this study is to develop a [...] Read more.

Background/Purpose: Conventional three-dimensional in vitro tumor models often fail to fully capture the complexity of the tumor microenvironment, particularly the diverse populations of cancer-associated fibroblasts that contribute to poor prognosis and treatment resistance. The purpose of this study is to develop a patient-specific gastric cancer assembloid model that integrates tumor epithelial cells with matched stromal cell subtypes, each derived using tailored growth media to enhance cancer preclinical research and advance personalized therapeutic strategies. Methods: Tumor tissue was dissociated, and cells expanded in media for organoids, mesenchymal stem cells, fibroblasts, or endothelial cells. The resulting tumor-derived subpopulations were co-cultured in an optimized assembloid medium supporting each cell type’s growth. Biomarker expression was assessed by immunofluorescence staining, and transcriptomic profiles were analyzed by RNA sequencing. Drug responsiveness was evaluated using cell viability assays following treatment with various therapeutic agents. Results: The optimized co-culture conditions yielded assembloids that closely mimicked the cellular heterogeneity of primary tumors, confirmed by the expression of epithelial and stromal markers. Compared to monocultures, the assembloids showed higher expression of inflammatory cytokines, extracellular matrix remodeling factors, and tumor progression-related genes across different organoids and stromal ratios. Drug screening revealed patient- and drug-specific variability. While some drugs were effective in both organoid and assembloid models, others lost efficacy in the assembloids, highlighting the critical role of stromal components in modulating drug responses. Conclusions: This assembloid system offers a robust platform to study tumor–stroma interactions, identify resistance mechanisms, and accelerate drug discovery and personalized therapeutic strategies for gastric cancer. Full article

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

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12 pages, 774 KiB

Open AccessArticle

Preliminary Experience with Electronic Brachytherapy in the Treatment of Locally Advanced Cervical Carcinoma

by Desislava Hitova-Topkarova, Virginia Payakova, Angel Yordanov, Desislava Kostova-Lefterova, Mirela Ivanova, Ilko Iliev, Marin Valkov, Nikolay Mutkurov, Stoyan Kostov and Elitsa Encheva

Cancers 2025, 17(14), 2286; https://doi.org/10.3390/cancers17142286 (registering DOI) - 9 Jul 2025

Abstract

Background/Objectives: Image-guided adaptive brachytherapy is a standard modality in the treatment of locally advanced cervical cancer. However, the availability of isotope-based brachytherapy is limited in countries with lower resources. The objective of this study is to report the first institutional dosimetric and [...] Read more.

Background/Objectives: Image-guided adaptive brachytherapy is a standard modality in the treatment of locally advanced cervical cancer. However, the availability of isotope-based brachytherapy is limited in countries with lower resources. The objective of this study is to report the first institutional dosimetric and clinical data on intracavitary electronic brachytherapy. Methods: A total of 25 patients with histologically proven cervical cancer stage IB-IVA were treated with concurrent chemoradiotherapy and electronic brachytherapy. The patients were followed up for a median of 12 months (range 6–24). Toxicity was evaluated by the radiation oncologist and gynecologist on each visit and scored by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: All patients completed the treatment successfully with a median overall treatment time (OTT) of 52 days (range 39–89). The desired target coverage was achieved in all patients, and the dose limits for the organs at risk were achieved in 88% of the patients. No Grade 3 toxicities occurred. A total of 84% of the patients achieved local control in the cervix, and a complete response was noted in 72% of the patients. Conclusions: Electronic brachytherapy provides the option to deliver a high dose of radiation to the uterine cervix without leading to severe toxicity. Further improvements to the treatment protocol could provide better locoregional and systemic control of the disease. Studies with larger cohorts and longer follow-up are necessary. Full article

(This article belongs to the Special Issue New Insights into Cancer Radiotherapy)

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18 pages, 1760 KiB

Open AccessArticle

Integrating ⁶⁸Ga-PSMA-11 PET/CT with Clinical Risk Factors for Enhanced Prostate Cancer Progression Prediction

by Joanna M. Wybranska, Lorenz Pieper, Christian Wybranski, Philipp Genseke, Jan Wuestemann, Julian Varghese, Michael C. Kreissl and Jakub Mitura

Cancers 2025, 17(14), 2285; https://doi.org/10.3390/cancers17142285 (registering DOI) - 9 Jul 2025

Abstract

Background/Objectives: This study evaluates whether combining ⁶⁸Ga-PSMA-11-PET/CT derived imaging biomarkers with clinical risk factors improves the prediction of early biochemical recurrence (eBCR) or clinical progress in patients with high-risk prostate cancer (PCa) after primary treatment, using machine learning (ML) models. Methods: We [...] Read more.

Background/Objectives: This study evaluates whether combining ⁶⁸Ga-PSMA-11-PET/CT derived imaging biomarkers with clinical risk factors improves the prediction of early biochemical recurrence (eBCR) or clinical progress in patients with high-risk prostate cancer (PCa) after primary treatment, using machine learning (ML) models. Methods: We analyzed data from 93 high-risk PCa patients who underwent ⁶⁸Ga-PSMA-11 PET/CT and received primary treatment at a single center. Two predictive models were developed: a logistic regression (LR) model and an ML derived probabilistic graphical model (PGM) based on a naïve Bayes framework. Both models were compared against each other and against the CAPRA risk score. The models’ input variables were selected based on statistical analysis and domain expertise including a literature review and expert input. A decision tree was derived from the PGM to translate its probabilistic reasoning into a transparent classifier. Results: The five key input variables were as follows: binarized CAPRA score, maximal intraprostatic PSMA uptake intensity (SUVmax), presence of bone metastases, nodal involvement at common iliac bifurcation, and seminal vesicle infiltration. The PGM achieved superior predictive performance with a balanced accuracy of 0.73, sensitivity of 0.60, and specificity of 0.86, substantially outperforming both the LR (balanced accuracy: 0.50, sensitivity: 0.00, specificity: 1.00) and CAPRA (balanced accuracy: 0.59, sensitivity: 0.20, specificity: 0.99). The decision tree provided an explainable classifier with CAPRA as a primary branch node, followed by SUVmax and specific PET-detected tumor sites. Conclusions: Integrating ⁶⁸Ga-PSMA-11 imaging biomarkers with clinical parameters, such as CAPRA, significantly improves models to predict progression in patients with high-risk PCa undergoing primary treatment. The PGM offers superior balanced accuracy and enables risk stratification that may guide personalized treatment decisions. Full article

(This article belongs to the Special Issue Bridging the Gap: Integrating AI into Clinical Practice for Oncological PET/CT Imaging)

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28 pages, 2579 KiB

Open AccessReview

Telomere Maintenance and DNA Repair: A Bidirectional Relationship in Cancer Biology and Therapy

by Nina Rembiałkowska, Mikołaj Sędzik, Monika Kisielewska, Wiktoria Łuniewska, Kamil Sebastianka, Klaudia Molik, Katarzyna Skinderowicz, Jacek Kuźnicki, Joanna Tunikowska and Julita Kulbacka

Cancers 2025, 17(14), 2284; https://doi.org/10.3390/cancers17142284 (registering DOI) - 9 Jul 2025

Abstract

Telomeres are repetitive DNA sequences at the ends of chromosomes that protect against genomic instability and prevent unwanted DNA damage responses. In most somatic cells, telomeres progressively shorten with each division, limiting cellular lifespan. However, cancer cells bypass this limitation by activating telomerase [...] Read more.

Telomeres are repetitive DNA sequences at the ends of chromosomes that protect against genomic instability and prevent unwanted DNA damage responses. In most somatic cells, telomeres progressively shorten with each division, limiting cellular lifespan. However, cancer cells bypass this limitation by activating telomerase or the alternative lengthening of telomeres, enabling unchecked proliferation and tumor progression. This review examines the molecular mechanisms underlying telomere maintenance and their intricate relationship with DNA repair pathways. We discuss how telomere-associated proteins regulate genomic stability and explore therapeutic strategies targeting telomerase and alternative lengthening of telomeres. Challenges such as resistance mechanisms and off-target effects are also considered, highlighting the need for precision approaches in telomere-based cancer therapies. Full article

(This article belongs to the Section Molecular Cancer Biology)

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12 pages, 789 KiB

Open AccessArticle

Feasibility of Adjuvant Radiotherapy or Chemoradiation for Elderly Patients with Squamous Cell Carcinoma of the Head and Neck, and Its Correlation with Different Comorbidity Scores: A Retrospective Cohort Study

by Christoph Suess, Matthias Hipp, Tobias Ettl, Julian Kuenzel, Julia Maurer, Anna Ratzisberger, Fabian Baier, Felix Steger, Oliver Koelbl and Matthias Hautmann

Cancers 2025, 17(14), 2283; https://doi.org/10.3390/cancers17142283 (registering DOI) - 9 Jul 2025

Abstract

Background: With aging populations, the incidence of squamous cell carcinoma of the head and neck (SCCHN) among elderly patients is increasing. Although adjuvant radiotherapy or chemoradiation is a well-established component of multimodal treatment, elderly patients remain underrepresented in clinical trials. This study [...] Read more.

Background: With aging populations, the incidence of squamous cell carcinoma of the head and neck (SCCHN) among elderly patients is increasing. Although adjuvant radiotherapy or chemoradiation is a well-established component of multimodal treatment, elderly patients remain underrepresented in clinical trials. This study evaluates the feasibility of adjuvant radiotherapy and chemoradiation in patients over 70 years with SCCHN and explores the correlation between treatment feasibility and various comorbidity scores. Methods: We retrospectively analyzed patients over 70 years of age who received adjuvant radiotherapy or chemoradiation at the University Hospital Regensburg between 2004 and 2018. A total of 71 patients, with a median age of 75 years, were included. The majority were classified as UICC stage IVa. Median follow-up was 27 months. Results: Sixty-two patients completed treatment without interruption, and sixty-five received at least 95% of the prescribed radiation dose. The median total dose was 64 Gy. Acute toxicity of grade III or IV (CTC) occurred in 37 patients. Local tumor control rates were 99% at 12 months, 88% at 24 months, and 76% at 5 years. Overall survival rates were 87% at 12 months, 67% at 24 months, and 41% at 60 months, with a median overall survival of 51 months. The Elixhauser Comorbidity Score showed significant predictive value for treatment feasibility (p = 0.006). Conclusions: Adjuvant radiotherapy and chemoradiation are feasible and effective treatment options for elderly patients with SCCHN. The favorable local and locoregional control rates reported here suggest, in line with other recent reports in the literature, that age alone should not be a justification for treatment de-intensification. Full article

(This article belongs to the Special Issue Radiotherapy for Head and Neck Squamous Cell Carcinoma (2nd Edition))

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19 pages, 347 KiB

Open AccessArticle

A Formative Evaluation of Interventions to Enhance Clinical Trial Diversity Guided by the Socioecological Model

by Melany Garcia, Carley Geiss, Rebecca Blackwell, Melinda L. Maconi, Rossybelle P. Amorrortu, Elliott Tapia-Kwan, Kea Turner, Lindsay Fuzzell, Yayi Zhao, Steven A. Eschrich, Dana E. Rollison and Susan T. Vadaparampil

Cancers 2025, 17(14), 2282; https://doi.org/10.3390/cancers17142282 (registering DOI) - 9 Jul 2025

Abstract

Background/objectives: Racial and ethnic minority patients are underrepresented in cancer clinical trials (CCTs) and multilevel strategies are required to increase participation. This study describes barriers and facilitators to minority CCT participation alongside feedback on a multilevel intervention (MLI) designed to reduce participation barriers, [...] Read more.

Background/objectives: Racial and ethnic minority patients are underrepresented in cancer clinical trials (CCTs) and multilevel strategies are required to increase participation. This study describes barriers and facilitators to minority CCT participation alongside feedback on a multilevel intervention (MLI) designed to reduce participation barriers, as posited by the socioecological model (SEM). Methods: Interviews with Moffitt Cancer Center (MCC) physicians, community physicians, patients with cancer, community residents, and clinical research coordinators (CRCs) were conducted from June 2023–February 2024. Verbal responses were analyzed using thematic analysis and categorized into SEM levels. Mean helpfulness scores rating interventions (from 1 (not helpful) to 5 (very helpful)) were summarized. Results: Approximately 50 interviews were completed. Thematic findings confirmed CCT referral and enrollment barriers across all SEM levels. At the c community level, MCC patients and community residents felt that community health educators can improve patient experiences and suggested they connect patients to social/financial resources, assist with patient registration, and provide CCT education. While physicians and CRCs reacted positively to all institutional-level tools, the highest scored tool simultaneously addressed CCT referral and enrollment at the institution (e.g., trial identification/referrals) and interpersonal level (communication platform for community and MCC physicians) (mean = 4.27). At the intrapersonal level, patients were enthusiastic about a digital CCT decision aid (mean = 4.53) and suggested its integration into MCC’s patient portal. Conclusions: Results underscore the value of conducting formative research to tailor interventions to target population needs. Our approach can be leveraged by future researchers seeking to evaluate MLIs addressing additional CCT challenges or broader health topics. Full article

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

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20 pages, 293 KiB

Open AccessArticle

Perceived Barriers, Facilitators, and Needs Related to Promoting Physical Activity in Cancer Care: Qualitative Insights from Oncology Care Providers

by Gaurav Kumar, Priyanka Chaudhary, Apar Kishor Ganti, Jungyoon Kim, Lynette M. Smith and Dejun Su

Cancers 2025, 17(14), 2281; https://doi.org/10.3390/cancers17142281 (registering DOI) - 9 Jul 2025

Abstract

Background: Physical activity (PA) is associated with lower mortality and cancer recurrence risks. Although evidence shows health benefits for cancer patients before, during, and immediately after treatment, PA recommendations are not regularly included in the standard care. Objective: The study aimed to identify [...] Read more.

Background: Physical activity (PA) is associated with lower mortality and cancer recurrence risks. Although evidence shows health benefits for cancer patients before, during, and immediately after treatment, PA recommendations are not regularly included in the standard care. Objective: The study aimed to identify perceived knowledge, barriers, and facilitators of oncology providers’ PA promotion for cancer patients using the 5A (Assess, Advise, Agree, Assist, and Arrange) framework. Methods: A qualitative research design with a phenomenological approach was adopted. A purposive sample of 16 oncology care providers in Nebraska participated in semi-structured interviews via Zoom/phone. Interviews were audio-recorded, transcribed, and imported into MAXQDA 2024 for thematic analysis. Results: Analysis of the qualitative data identified five themes: (i) Broad and inclusive conceptualizations of PA among oncology care providers suggested that they were able to define PA; (ii) Current Practices in PA Counseling included advising on PA and assessment; (iii) Barriers to PA counseling included lack of guideline awareness, insufficient training, low prioritization, uncertainty about responsibility, time constraints, limited resources, lack of referral systems, patient health conditions, and environmental factors; (iv) Facilitators were identified as acknowledged health benefits for cancer survivors, awareness of PA recommendations, access to community resources, and support from interdisciplinary teams; and (v) Expressed desire among oncology care providers for training on incorporating PA into oncology care. Conclusions: Oncology providers recognized PA’s health benefits for cancer survivors but did not promote it due to inadequate knowledge of guidelines and lack of resources. These barriers require improved PA counselling education to help providers incorporate PA into clinical care. Full article

(This article belongs to the Special Issue Disparities in Cancer Prevention, Screening, Diagnosis and Management)

15 pages, 1003 KiB

Open AccessReview

Patient-Reported Outcome Measurement and Reporting for Patients with Soft Tissue Tumors: A Scoping Literature Review

by Alessandro Mazzocca, Flavia Paternostro, Serena Garofalo, Marianna Silletta, Davide Romandini, Sarah Orlando, Laura Risi Ambrogioni, Pierangelo Gorgone, Giuseppe Tonini and Bruno Vincenzi

Cancers 2025, 17(14), 2280; https://doi.org/10.3390/cancers17142280 (registering DOI) - 9 Jul 2025

Abstract

(1) Background: Quality of life (QoL) assessment is a crucial aspect for patients diagnosed with cancer. Over the years, different tools have been developed to measure QoL, both generic and pathology specific, but the inclusion of quality of life among other indicators of [...] Read more.

(1) Background: Quality of life (QoL) assessment is a crucial aspect for patients diagnosed with cancer. Over the years, different tools have been developed to measure QoL, both generic and pathology specific, but the inclusion of quality of life among other indicators of efficacy in randomized controlled trials (RCTs) remains a controversial issue. In this review, we aim to review the frequency and modality of QoL assessment in RCTs, enrolling patients diagnosed with mesenchymal tumors. (2) Methods: An electronic literature search of bone and soft tissue sarcoma and GIST-related RCTs published between January 2000 and December 2023 was performed by two independent reviewers using PubMed. English-language phase II and III clinical trials enrolling at least more than 15 patients were included, regardless of the disease stage. Studies involving patients under the age of 18 years or for which the full text was not available were excluded. For each study, data regarding the journal and year of publication, the study design, the primary objective, and the evaluation of quality of life as an endpoint with any type of patient-reported outcomes used were extracted. (3) Results: Among the 742 publications screened, 171 resulted eligible. QoL assessment was listed among the endpoints in 35 trials and QoL results were reported in 29 primary publications. In these trials, 16 included patients with soft tissue sarcomas, 8 Kaposi sarcomas, 6 GIST, and 3 desmoid tumors. Among all the trials included, 10.4% on an adjuvant/neoadjuvant setting and 24.4% on a metastatic setting included QoL as an endpoint. The proportion of trials, including QoL, was variable over time, as follows: 16.9% of trials in 2000–2014 vs. 23.4% in 2015–2023. In 35 trials, including QoL endpoints, 27 had a superiority design and 25 reported a positive result. In the majority of trials (80%), the tools for QoL assessment were generic and those mostly used were the EORTC QLQ-C30, the EQ-5D questionnaire, and the modified Brief Pain Inventory–Short Form. (4) Conclusions: Quality of life has not been assessed or published in many phase II and III trials, despite an improvement over time. QoL evaluation in RCTs should be considered even more carefully in patients with rare tumors, where the low number of patients who can be enrolled makes it difficult to draw statistically significant conclusions on the effectiveness of treatments. Full article

(This article belongs to the Special Issue Clinical and Surgical Outcomes in the Management of Extremity Soft Tissue Sarcomas)

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23 pages, 524 KiB

Open AccessReview

A Narrative Review of the Role of Non-Viral Circulating Tumor DNA Profiling in Predicting the Treatment Response and Recurrence in Head and Neck Squamous Cell Carcinoma

by Ugur Gezer, Rasim Meral, Emre Özgür, Ebru. E. Yörüker, Abel Bronkhorst and Stefan Holdenrieder

Cancers 2025, 17(14), 2279; https://doi.org/10.3390/cancers17142279 (registering DOI) - 9 Jul 2025

Abstract

Head and neck squamous cell carcinomas (HNSCCs) that develop from the mucosal epithelium in the oral cavity, pharynx, and larynx are a heterogeneous group of malignant tumors. A lack of appropriate screening and diagnostic methods leads to late diagnoses, with the majority of [...] Read more.

Head and neck squamous cell carcinomas (HNSCCs) that develop from the mucosal epithelium in the oral cavity, pharynx, and larynx are a heterogeneous group of malignant tumors. A lack of appropriate screening and diagnostic methods leads to late diagnoses, with the majority of patients having locally advanced disease, which is associated with a high risk of local recurrence and a poor prognosis and is usually treated with combination therapies. Biomarkers for predicting the therapy response and risk of recurrence in HNSCC patients are urgently needed. Liquid biopsy, e.g., the profiling of circulating biomarkers in bodily fluids, is a promising approach with increasing utility in the early detection and diagnosis of cancer, monitoring cancer progression, patient stratification and treatment selection, detecting minimal residual disease (MRD), and predicting recurrence across different cancer types, including HNSCC. Among liquid biomarkers, circulating tumor DNA (ctDNA), which is based on detecting tumor-specific mutations, insertions/deletions, copy number alterations, and methylation, is the most promising transformative tool in cancer management and personalized cancer treatment. In this review, we provide an update of recent data on the role of non-viral ctDNA in the management of HNSCC patients. Accumulating data suggests the enormous potential of ctDNA profiling by serial sampling during and after definitive therapy in detecting MRD and predicting recurrence in HNSSC patients treated with a single treatment modality (surgery or radiotherapy) or with combination therapies, including immune-checkpoint-inhibitor-based immunotherapy. By incorporating the latest immunotherapy trials and organizing the data by the treatment modality, this review offers a novel perspective not found in previous surveys. Full article

(This article belongs to the Special Issue Cell-Free DNA as Prognostic and Predictive Biomarker in Solid Cancers (2nd Edition))

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29 pages, 1127 KiB

Open AccessReview

Ozone Treatment in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Review of Rationale and Research Directions

by Bernardino Clavo, Angeles Cánovas-Molina, Mario Federico, Gregorio Martínez-Sánchez, Gretel Benítez, Saray Galván, Yolanda Ramallo-Fariña, Himar Fabelo, Sara Cazorla-Rivero, Elba Lago-Moreno, Carla Antonilli, Juan A. Díaz-Garrido, Ignacio J. Jorge, Gustavo Marrero-Callico, Delvys Rodríguez-Abreu and Francisco Rodríguez-Esparragón

Cancers 2025, 17(14), 2278; https://doi.org/10.3390/cancers17142278 (registering DOI) - 8 Jul 2025

Abstract

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. CIPN can lead to a dose reduction and/or the interruption of chemotherapy, limiting its effectiveness, while chronic CIPN decreases patients’ quality of life. Improvements in cancer treatment and patients’ survival have [...] Read more.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. CIPN can lead to a dose reduction and/or the interruption of chemotherapy, limiting its effectiveness, while chronic CIPN decreases patients’ quality of life. Improvements in cancer treatment and patients’ survival have increased the number of patients living with CIPN. The only evidence-based treatment for CIPN-related pain, duloxetine, provides only modest clinical benefit, and there is no effective clinical management option for numbness and tingling. Several experimental studies and clinical reports suggest that adjuvant ozone treatment may be beneficial in managing CIPN. Methods: This narrative review aims to provide an overview of current knowledge regarding CIPN and ozone therapy. Specifically, it summarizes experimental studies (18) and clinical reports (27) published between 1995 and 2025 that offer preliminary evidence supporting the potential role of ozone treatment in managing CIPN, highlighting the need for ongoing randomized clinical trials to establish its efficacy. Additionally, this review highlights existing gaps in the literature and proposes directions for future research. Results: The hypothesized mechanisms of action and experimental findings suggest that ozone therapy may be a valuable intervention for CIPN, a concept supported by preliminary clinical observations. Conclusions: Clinically relevant approaches for established CIPN are currently unavailable. While preliminary data suggest a potential role of ozone therapy, clinical evidence remains limited. Further high-quality randomized controlled trials are needed to confirm its efficacy and safety in this context; several trials are currently ongoing. Full article

(This article belongs to the Special Issue Quality of Life and Side Effects Management in Cancer Treatment (3rd Edition))

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14 pages, 1143 KiB

Open AccessArticle

The Incidence, Mortality, and Survival Trends of Pancreatic Cancer in Kazakhstan: Data from the National Electronic Registry of Oncological Patients (2014–2023)

by Aigerim Biniyazova, Ruslan Akhmedullin, Ayana Ablayeva, Altynay Beyembetova, Diyora Abdukhakimova, Abzal Zhumabekov, Temirgali Aimyshev, Gulnur Zhakhina, Temirlan Seyil, Yuliya Semenova and Abduzhappar Gaipov

Cancers 2025, 17(14), 2277; https://doi.org/10.3390/cancers17142277 - 8 Jul 2025

Abstract

Background: Pancreatic cancer (PC) has an extremely poor prognosis and is growing worldwide. In Kazakhstan, it is among the five leading causes of cancer death. However, local epidemiological studies of PC are scarce. A retrospective population-based study was conducted to investigate the PC [...] Read more.

Background: Pancreatic cancer (PC) has an extremely poor prognosis and is growing worldwide. In Kazakhstan, it is among the five leading causes of cancer death. However, local epidemiological studies of PC are scarce. A retrospective population-based study was conducted to investigate the PC incidence, mortality, and survival in Kazakhstan, using data from the Electronic Registry of Oncological Patients for the period 2014–2023. Methods: Incidence, prevalence, and crude mortality rates were calculated per 100,000 population. The all-cause mortality rate per 1000 person-years (PY) was obtained based on socio-demographic and medical characteristics and for different regions. Survival analysis was performed using the Kaplan–Meier method and Cox regression models. Results: A total of 11,934 cases were analyzed. The annual incidence rate significantly increased from 5.9 to 6.9 per 100,000. The mortality rate per 100,000 also increased from 4 to 6. The highest incidence was observed in the 60–74 age group (49.2%), with an equal sex distribution. The mortality rate was the highest in patients aged 75 and older. Northern and central regions had the highest incidence rates as of 2023. Atyrau, West Kazakhstan, Pavlodar, and Abay had the highest mortality rates per 1000 PY. The five-year survival rate was 10.9%. An older age, a male sex, advanced cancer stages, and a Russian ethnicity significantly increased the risk of death. Conclusions: PC represents a significant healthcare problem in Kazakhstan, with late diagnosis and poor survival being the main challenges. This study highlights the need to improve the timely detection of PC and address the identified disparities. Full article

(This article belongs to the Special Issue Clinical Epidemiology and Risk Prediction for Gastrointestinal Cancers)

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20 pages, 444 KiB

Open AccessSystematic Review

Characteristics and Treatment of Primary Hepatic Perivascular Epithelioid Cell Tumor (PEComa) in Adults: A Systematic Review

by Konstantinos Papantoniou, Ioanna Aggeletopoulou, Maria Kalafateli and Christos Triantos

Cancers 2025, 17(14), 2276; https://doi.org/10.3390/cancers17142276 (registering DOI) - 8 Jul 2025

Abstract

Background: Perivascular epithelioid cell tumors (PEComas) are a rare group of mesenchymal neoplasms with distinctive histological and immunohistochemical features. This systematic review aims to characterize the clinical presentation, diagnostic approach, treatment, and outcomes of adult patients with hepatic PEComa. Methods: We performed a [...] Read more.

Background: Perivascular epithelioid cell tumors (PEComas) are a rare group of mesenchymal neoplasms with distinctive histological and immunohistochemical features. This systematic review aims to characterize the clinical presentation, diagnostic approach, treatment, and outcomes of adult patients with hepatic PEComa. Methods: We performed a systematic literature search for English-language articles regarding hepatic PEComas using the terms (perivascular epithelioid cell tumor) OR (PEComa) AND (liver) OR (hepatic), up to 25 May 2025. Results: A total of 145 studies encompassing 281 patients were included in the analysis. Most studies originated from Asia. The mean age at diagnosis was 46 years (IQR: 35.25–53.75) with a female predominance. The underlying comorbidities were uncommon among the reported cases, and more than half were asymptomatic at presentation. The tumor presented as a single liver lesion in almost 9 out of 10 patients. Surgical excision was the primary treatment, and diagnosis in 74% of patients was made with positive immunohistochemistry for markers such as HMB-45 and smooth muscle actin. A malignant phenotype was reported in 30 cases. The median follow-up duration was 24 months (IQR: 12–48); recurrence occurred in 17 patients, and disease-related mortality occurred in 8 patients. Conclusions: Primary hepatic PEComa is a rare liver tumor with mostly benign clinical behavior and non-specific presentation. Future studies are needed to support clinician decisions regarding this entity and improve patient care. Full article

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

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24 pages, 595 KiB

Open AccessArticle

Sex Disparities and Female Reproductive and Hormonal Factors Associated with Risk of Pancreatic Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

by Verena A. Katzke, Srimanti Dutta, Anna Rasokat, Livia Archibugi, Gabriele Capurso, Giulia Peduzzi, Manuel Gentiluomo, Federico Canzian, Anne Kirstine Eriksen, Anne Tjønneland, Christina C. Dahm, Therese Truong, Marianne Canonico, Nasser Laouali, Matthias B. Schulze, Rosario Tumino, Giovanna Masala, Claudia Agnoli, Lucia Dansero, Salvatore Panico, Marta Crous-Bou, Esther Molina-Montes, Ane Dorronsoro, María-Dolores Chirlaque, Marcela Guevara, Salma Tunå Butt, Malin Sund, Sofia Christakoudi, Elom K. Aglago, Elisabete Weiderpass, Marc Gunter, Daniele Campa and Rudolf Kaaks Show full author list Hide full author list

Cancers 2025, 17(14), 2275; https://doi.org/10.3390/cancers17142275 - 8 Jul 2025

Abstract

Background/Objectives: Worldwide, men experience a higher incidence of pancreatic cancer (PC) than women. Methods: To increase understanding of the underlying reasons for this sex-related difference, we analysed general and sex-related risk factors for PC in the European Prospective Investigation into Cancer [...] Read more.

Background/Objectives: Worldwide, men experience a higher incidence of pancreatic cancer (PC) than women. Methods: To increase understanding of the underlying reasons for this sex-related difference, we analysed general and sex-related risk factors for PC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (women/men No. = 293,682/136,728; 717/577 PC-cases). Results: Cox proportional hazards models showed a 1.31-fold higher risk of developing PC for men compared to women (HR, 95% CI 1.15–1.49) after adjustment for age, smoking history, BMI, diabetes, and alcohol consumption. Associations of PC with established risk factors did not differ between men and women, with the exception of a greater risk of PC among women with greater attained body height, meat consumption and cigarettes smoked (1.12 (1.05–1.19) per 5 cm, 1.18 (1.02–1.36) per 100 g/d, 1.42 (1.27–1.59) per 10/d; respectively). Among child-bearing women, long cumulative duration of breastfeeding was inversely associated with risk of PC (HR 0.74, 95% CI 0.61–0.89) for >5.7 months of breastfeeding (median) relative to ≤5.7 months and among HRT users, cumulative duration of HRT use was inversely associated with PC risk (HR 0.71, 95% CI 0.53–0.95, >2.4 versus ≤2.4 years). Further reproductive and hormonal factors, such as age at menarche, number of full-term pregnancies, age at menopause, or use of oral contraceptives, were not significantly associated with PC risk. Conclusions: Pooled analyses of large cohort studies are needed to confirm these results, and detailed data on the type and intensity of HRT are required to better evaluate its effect. Full article

(This article belongs to the Section Cancer Epidemiology and Prevention)

10 pages, 450 KiB

Open AccessArticle

The Role of Multidisciplinary Ocular and Periocular Cancers Meetings in Uveal Melanoma Management: A 2-Year Analysis

by Gustavo Savino, Monica Maria Pagliara, Maria Grazia Sammarco, Carmela Grazia Caputo, Maria Antonietta Blasi, Roberta Mattei, Sofia Marcelli, Luca Tagliaferri, Bruno Fionda, Giovanni Schinzari, Ernesto Rossi, Luca Zagaria, Tommaso Tartaglione, Luca Ausili Cefaro, Mattia Todaro, Alessandro Moro and Federico Giannuzzi

Cancers 2025, 17(14), 2274; https://doi.org/10.3390/cancers17142274 - 8 Jul 2025

Abstract

Purpose: The objective of this study was to evaluate the implementation of a Multidisciplinary Tumor Board (MDTB) strategy in the treatment of patients with uveal melanoma. Methods: A retrospective analysis was conducted on the implementation of MDTB meetings over a 24-month [...] Read more.

Purpose: The objective of this study was to evaluate the implementation of a Multidisciplinary Tumor Board (MDTB) strategy in the treatment of patients with uveal melanoma. Methods: A retrospective analysis was conducted on the implementation of MDTB meetings over a 24-month period. During this time, 72 intraocular tumors were discussed, including 59 confirmed cases of uveal melanoma. The MDTB involved a core group of specialists (e.g., ophthalmologists, oncologists, and radiologists), with other experts included when clinically appropriate. To assess patient satisfaction with the MDTB approach, a structured questionnaire was administered, including items on clarity of communication, perceived quality of care, and overall satisfaction, which were ranked on a 5-point scale. Results: A total of 319 patients with ocular, periocular, or orbital tumors were discussed during the study period, of which, 72 had intraocular tumors. A total of 13 (18%) were diagnosed to have choroidal metastases, whereas 59 (82%) had uveal melanomas. The average time between patient care and MDTB discussion was 15.9 days (IQR: 7.5–16.5). The mean time between the case discussion and the implementation of recommendations (diagnostic, therapeutic, or referral decisions) was 14.8 days (IQR: 6.0–23.75). Overall, 4 (7%) patients were classified as Stage I, 16 (27%) as Stage IIa, 18 (31%) as Stage IIb, 7 (12%) as Stage IIIa, 2 (3%) as Stage IIIb, and 12 (20%) as Stage IV. Regarding the satisfaction questionnaire, all patients (100%) agreed to have the clinical case discussed at the TB even though this could result in a delay in diagnostic/therapeutic implementation. However, only 60% of patients perceived they had been directly involved in the decision-making process. Conclusions: In selected cases of uveal melanoma and other types of cancer, MDTBs should be recognized as a gold standard in cancer care, allowing for comprehensive decision-making that draws on a wide range of highly specialized expertise. Full article

(This article belongs to the Section Cancer Therapy)

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18 pages, 1544 KiB

Open AccessArticle

Translational Insights into Interferon Alpha’s Effects on Immunomolecular Dynamics in Philadelphia-Negative Myeloproliferative Neoplasms

by Regina García-Delgado, Elena Luque-Lupiáñez, David Mora-Infante, Rodolfo Matías Ortíz-Flores, Borja Cidoncha-Morcillo, Julio Torres-González, Andrés Fontalba-Navas and Alejandro Escamilla-Sánchez

Cancers 2025, 17(14), 2273; https://doi.org/10.3390/cancers17142273 - 8 Jul 2025

Abstract

Background/Objectives: Interferon alpha (IFNα) remains a cornerstone in the management of Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPNs), yet its immunomolecular impact over time is not fully elucidated. The aim of the study was to explore how IFNα therapy dynamically reshapes immune and gene profiles [...] Read more.

Background/Objectives: Interferon alpha (IFNα) remains a cornerstone in the management of Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPNs), yet its immunomolecular impact over time is not fully elucidated. The aim of the study was to explore how IFNα therapy dynamically reshapes immune and gene profiles in Ph-neg MPNs and assess their potential as treatment-related biomarkers. Methods: This single-center, prospective, observational study included a translational substudy conducted within a previously established clinical cohort of 44 IFNα-treated patients, selecting a representative subset of 18 individuals stratified by treatment duration. Cytokine profiling (ELISA) and gene expression (RT-qPCR) analysis were performed using plasma and peripheral blood mononuclear cells (PBMCs), respectively. Results: Patients with prolonged exposure showed reduced pro-inflammatory cytokines and downregulation of inflammatory-signalling STAT1/STAT3 expression. In contrast, those with intermediate exposure exhibited transient TH2/regulatory cytokine peaks and upregulation of immunomodulatory genes such as CXCL10, SOCS3, and TNFAIP3. Spearman correlations revealed functional associations between cytokine and gene expression patterns including notable links such as STAT1–IL-13 and MYB–IL-13. Conclusions: These results describe a sequential immune reprogramming driven by IFNα, supporting the development of dynamic immunomolecular biomarkers of response in Ph-neg MPNs. Full article

(This article belongs to the Section Cancer Immunology and Immunotherapy)

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11 pages, 643 KiB

Open AccessArticle

2D Intraoperative Ultrasound in Brain Metastasis Resection: A Matched Cohort Analysis from a Single-Center Experience

by Octavian Mihai Sirbu, Alin Chirtes, Mircea Radu Gorgan and Marian Mitrica

Cancers 2025, 17(14), 2272; https://doi.org/10.3390/cancers17142272 - 8 Jul 2025

Abstract

Background: Intraoperative ultrasound (IOUS) provides real-time imaging during brain tumor surgery but remains underused in brain metastasis resection. This study evaluates the effectiveness of 2D IOUS in improving the extent of resection compared to standard neuronavigation. Methods: We retrospectively analyzed 55 [...] Read more.

Background: Intraoperative ultrasound (IOUS) provides real-time imaging during brain tumor surgery but remains underused in brain metastasis resection. This study evaluates the effectiveness of 2D IOUS in improving the extent of resection compared to standard neuronavigation. Methods: We retrospectively analyzed 55 adult patients with brain metastases treated surgically at a single center. Patients were divided into two groups: IOUS-guided surgery (n = 20) and standard neuronavigation (n = 35). Gross total resection (GTR) was defined as the extent of resection > 96%, assessed volumetrically. Statistical analyses included chi-square tests, logistic regression, and ROC curve analysis. Results: GTR > 96% was achieved in 80% of IOUS-guided cases compared to 42.86% in the control group (p = 0.008). IOUS significantly increased the odds of achieving GTR (OR = 5.33, p = 0.011). Larger tumor volume reduced the likelihood of GTR (OR = 0.469, p = 0.025), but this effect was mitigated by IOUS use (interaction OR = 1.986, p = 0.044). The regression model showed excellent discrimination (AUC = 0.930, p < 0.001). Functional outcomes improved postoperatively in both groups. Conclusions: 2D IOUS significantly enhances the extent of resection in brain metastasis surgery, including that for larger tumors. Its accessibility, real-time feedback, and low cost support its wider adoption in neurosurgical practice, especially in settings with limited resources. Full article

(This article belongs to the Section Cancer Metastasis)

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17 pages, 1064 KiB

Open AccessArticle

Real-World Outcomes of Adjuvant Paclitaxel and Trastuzumab Therapy in Lymph Node-Negative, HER2-Positive Early-Stage Breast Cancer: A Multicenter Retrospective Data Analysis

by Buket Şahin Çelik, Pınar Peker, Ender Eren Özçelik, Ömer Faruk Kuzu, Erhan Gökmen, Gül Başaran and Türkkan Evrensel

Cancers 2025, 17(14), 2271; https://doi.org/10.3390/cancers17142271 - 8 Jul 2025

Abstract

Background: Approximately 15–20% of early-stage breast cancers overexpress HER2, which is associated with an increased risk of recurrence. Although adjuvant anti-HER2 therapies have significantly improved patient outcomes, the optimal treatment strategy remains uncertain, particularly for patients with small, lymph node-negative tumors, where [...] Read more.

Background: Approximately 15–20% of early-stage breast cancers overexpress HER2, which is associated with an increased risk of recurrence. Although adjuvant anti-HER2 therapies have significantly improved patient outcomes, the optimal treatment strategy remains uncertain, particularly for patients with small, lymph node-negative tumors, where concerns about potential overtreatment and toxicity persist. The objective of this study was to evaluate overall survival (OS), recurrence-free survival (RFS), and treatment-related neuropathy in patients with early-stage HER2-positive breast cancer treated with adjuvant trastuzumab and paclitaxel. Methods: A total of 129 patients, aged 18 to 75 years, diagnosed with early-stage HER2-positive breast cancer, were retrospectively analyzed in this multicenter study. All patients had received adjuvant treatment with trastuzumab and paclitaxel (TH regimen) between November 2016 and July 2023. The study involved the collection of demographic information, pathological features, and treatment-related details. Overall survival (OS) was defined as the primary study endpoint, while recurrence-free survival (RFS), disease control rate (DCR), and treatment-related neuropathy were evaluated as secondary outcomes. Results: The median follow-up time was 70.9 months. The 2-year and 5-year OS rates were 95.3%, and the 5-year RFS rate was 96.8%. No statistically significant differences in OS or RFS were observed in relation to tumor size (T1 vs. T2), hormone receptor status, Ki-67 index, tumor grade, or the use of adjuvant endocrine or radiotherapy (all p > 0.05). Neuropathy developed in 53.5% of patients, mostly grade 1. Conclusions: Adjuvant TH therapy shows favorable long-term outcomes in early-stage HER2-positive breast cancer. Full article

(This article belongs to the Section Cancer Therapy)

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17 pages, 897 KiB

Open AccessArticle

Physical Activity and Sedentary Behavior Patterns Among Korean Cancer Survivors: A Cross-Sectional Analysis (2017–2021)

by Jiin Ryu and Jihee Min

Cancers 2025, 17(14), 2270; https://doi.org/10.3390/cancers17142270 - 8 Jul 2025

Abstract

Background/Objectives: This study examined differences in physical activity (PA) and sedentary behavior among Korean cancer survivors compared to cancer-free individuals from 2017 to 2021 and identified differences based on their cancer treatment status. Methods: We used data for 28,528 adults (1585 [...] Read more.

Background/Objectives: This study examined differences in physical activity (PA) and sedentary behavior among Korean cancer survivors compared to cancer-free individuals from 2017 to 2021 and identified differences based on their cancer treatment status. Methods: We used data for 28,528 adults (1585 cancer survivors and 26,943 cancer-free individuals) from the 2017–2021 Korea National Health and Nutrition Examination Survey. PA and sedentary behavior were assessed using the Korean version of the Global Physical Activity Questionnaire. We examined adherence to aerobic and resistance training guidelines, domain-specific activity, and sedentary time. We also analyzed the descriptive statistics and conducted chi-square tests, the Mann–Whitney U test, and the non-parametric Kruskal–Wallis test, stratified by demographic and clinical subgroups. Results: Compared with cancer-free individuals, cancer survivors showed significantly lower adherence to aerobic PA guidelines in 2017 (p < 0.01), 2018 (p < 0.05), and 2021 (p < 0.01). Transportation-related activity accounted for the highest share of the total PA (mean: 59.1%). Sedentary time increased among survivors from 8.1 h/day (2017) to 9.0 h/day (2021). In 2021, resistance training adherence was higher among survivors (24.7%) than among non-cancer individuals (22.9%). In the subgroup analyses, male sex, younger age, recent diagnosis, higher income, and living with a spouse were associated with higher adherence. Conclusions: The findings underscore a clear need to address both PA and sedentary behavior in cancer survivors, irrespective of treatment phase. Full article

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

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21 pages, 3581 KiB

Open AccessArticle

Association of Tumor-Infiltrating Lymphocytes and Inflammation Status with Survival Outcome in Patients with High-Grade Serous Ovarian Carcinoma

by Simona Miceska, Cvetka Grašič Kuhar, Snježana Frković Grazio, Erik Škof, Praveen Krishnamoorthy, Dineo Khabele and Veronika Kloboves Prevodnik

Cancers 2025, 17(14), 2269; https://doi.org/10.3390/cancers17142269 - 8 Jul 2025

Abstract

Background/Objectives: Tumor-infiltrating lymphocytes (TILs) and inflammation status are emerging prognostic markers in various cancers, but their significance in high-grade serous ovarian carcinoma (HGSC) remains unclear. Our objective was to evaluate different TIL subtypes and inflammation status in relation to progression-free survival (PFS) [...] Read more.

Background/Objectives: Tumor-infiltrating lymphocytes (TILs) and inflammation status are emerging prognostic markers in various cancers, but their significance in high-grade serous ovarian carcinoma (HGSC) remains unclear. Our objective was to evaluate different TIL subtypes and inflammation status in relation to progression-free survival (PFS) in primary HGSC. Methods: CD3⁺/CD4⁺/CD8⁺/PD-1+ stromal TILs (sTILs) and intraepithelial TILs (iTILs) were evaluated by manual assessment and digital image analysis (DIA), following TIL Working Group recommendations. Inflammation status was evaluated through the following scores: systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), CA125, and lactate dehydrogenase (LDH). Results: CD8⁺ TILs were the most prevalent subtype in both iTILs and sTILs. However, sTILs were significantly more abundant than iTILs (p < 0.001) among all subsets, except for PD-1+ cells. DIA results of TIL assessments were in agreement with manual assessments. High stromal CD3⁺ and CD8⁺ TILs, PIV, CA125, and LDH, were associated with improved PFS. Potential independent prognostic factors for PFS in manual assessment were PIV (HR = 0.32, CI 95% = 0.12–0.82) and CD8⁺ sTILs (HR = 0.30, CI 95% = 0.12–0.79), whereas in DIA assessment they were CD3⁺ sTILs (HR = 0.31, CI 95% = 0.15–0.67), PIV (HR = 0.35, 95% CI 0.13–0.96), and residual disease (HR = 0.21 95% CI 0.08–0.53). Conclusions: CD3⁺/CD8⁺ sTILs and PIV are promising prognostic indicators in HGSC; however, further research is needed to confirm their clinical utility. Full article

(This article belongs to the Special Issue Women’s Health and Gynaecological Cancers: From Nutrition and Environmental Factors to Novel Diagnostics and Therapies)

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