Cancers

12 pages, 544 KB

Open AccessArticle

Initial Treatment and Outcomes of Complete Hydatidiform Mole in Women 40 Years or Older: A Multicenter Cohort Study

by Cecília Canêdo Freitas Desmarais, Izildinha Maestá, Sue Yazaki Sun, Jorge de Rezende-Filho, Roberto Antonio de Araújo Costa, Lawrence Hsu Lin, Mariza Branco-Silva, Neil S. Horowitz, Kevin M. Elias, Antonio Braga and Ross S. Berkowitz

Cancers 2025, 17(19), 3125; https://doi.org/10.3390/cancers17193125 (registering DOI) - 26 Sep 2025

Abstract

Objectives: To evaluate the potential associations of the type of complete hydatidiform mole (CHM) initial treatment (hysterectomy or uterine evacuation) with GTN development, need for chemotherapy, and treatment outcome in women aged ≥ 40 years. Methods: This multicentric retrospective cohort study [...] Read more.

Objectives: To evaluate the potential associations of the type of complete hydatidiform mole (CHM) initial treatment (hysterectomy or uterine evacuation) with GTN development, need for chemotherapy, and treatment outcome in women aged ≥ 40 years. Methods: This multicentric retrospective cohort study included women ≥ 40 years with CHM, initially treated between 1990 and 2018, at four different centers. Data collected included patient demographics and clinical characteristics. The outcome variables were post-CHM GTN development, need for chemotherapy for hCG normalization, surgical complications, and time to remission. Univariate and multivariate analyses were performed using chi-square, Mann–Whitney, Fisher’s exact tests, and Poisson regression. Results: 275 women with CHM aged ≥ 40 years were included in the analysis. Median patient age was significantly higher among hysterectomy patients (47 × 44 years, p = 0.01). Multivariate analysis showed that compared with uterine evacuation (244/275, 89%), hysterectomy (31/275, 11%) was associated with a 5.8-fold lower risk of GTN [RR = 0.17 95% CI = (0.04–0.71); p = 0.015] and an 11.3-fold lower risk of requiring chemotherapy [RR: 0.08 (0.01–0.64), p = 0.016]. Median time to hCG normalization did not statistically differ between treatments. No significant differences were observed between hysterectomy and uterine evacuation in terms of FIGO staging (p = 0.221) or prognostic risk score (p = 0.576). Resistance to first-line chemotherapy (17/72; 23.6%) and relapse (3/72; 4.1%) were observed only in patients undergoing initial uterine evacuation. Hysterectomy complications occurred in 45.1% (14) of the patients. Conclusions: CHM initial treatment with hysterectomy was associated with a lower risk for GTN occurrence and need for chemotherapy in women aged 40 years or older. However, shared decision-making about surgery should be tailored to each patient and their risk factors and preferences. Further, larger controlled studies are required to support our findings. Full article

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

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19 pages, 317 KB

Open AccessReview

Can Advances in Artificial Intelligence Strengthen the Role of Intraoperative Radiotherapy in the Treatment of Cancer?

by Marco Krengli, Marta Małgorzata Kruszyna-Mochalska, Francesco Pasqualetti and Julian Malicki

Cancers 2025, 17(19), 3124; https://doi.org/10.3390/cancers17193124 - 25 Sep 2025

Abstract

Intraoperative radiotherapy (IORT) is a radiation technique that allows for the delivery of a high radiation dose to the target while preserving the surrounding structures, which can be displaced during the surgical procedure. An important limitation of this technique is the lack of [...] Read more.

Intraoperative radiotherapy (IORT) is a radiation technique that allows for the delivery of a high radiation dose to the target while preserving the surrounding structures, which can be displaced during the surgical procedure. An important limitation of this technique is the lack of real-time image guidance, which is one of the main achievements of modern radiation therapy because it allows for treatment optimization. IORT can be delivered by low-energy X-rays or by accelerated electrons. The present review describes the most relevant clinical applications for IORT and discusses the potential advantages of using artificial intelligence (AI) to overcome some of the current limitations of IORT. In recent decades, IORT has proven to be an effective treatment in several cancer types. In breast cancer, IORT can be used to deliver a single dose of radiation (partial breast irradiation) or as a boost in high-risk patients. In locally advanced rectal cancer, a single dose to the tumor bed can improve local control and prevent pelvic relapse in primary and recurrent tumors. In sarcomas, IORT enables the delivery of high doses, achieving good functional outcomes with low toxicity in tumors located in the retroperitoneum and extremities. In pancreatic cancer, IORT shows promising results in borderline resectable and unresectable cases. Ongoing technological advances are addressing current challenges in imaging and radiation planning, paving the way for personalized, image-guided IORT. Recent innovations such as CT- and MRI-equipped hybrid operating theaters allow for real-time imaging, which could be used for AI-assisted segmentation and planning. Moreover, the implementation of AI in terms of machine learning, deep learning, and radiomics can improve the interpretation of imaging, predict treatment outcomes, and optimize workflow efficiency. Full article

(This article belongs to the Section Cancer Therapy)

23 pages, 3067 KB

Open AccessArticle

Investigating the Relationship Between Long Non-Coding RNAs and miR-200 Family Expression in Clear Cell Renal Cell Carcinoma

by Tanja Čugura, Nina Hauptman, Jera Jeruc and Emanuela Boštjančič

Cancers 2025, 17(19), 3123; https://doi.org/10.3390/cancers17193123 - 25 Sep 2025

Abstract

Objectives: MicroRNAs of the miR-200 family are recognized as key inhibitors of epithelial-to-mesenchymal transition (EMT). However, there is limited data on the potential regulation of miR-200 family expression by long non-coding RNAs (lncRNAs) in RCC. Methods: We conducted a comprehensive literature and database [...] Read more.

Objectives: MicroRNAs of the miR-200 family are recognized as key inhibitors of epithelial-to-mesenchymal transition (EMT). However, there is limited data on the potential regulation of miR-200 family expression by long non-coding RNAs (lncRNAs) in RCC. Methods: We conducted a comprehensive literature and database search to identify lncRNAs that had been already functionally validated as regulators of any member of the miR-200 family. We analyzed the expression levels of the miR-200 family and the identified lncRNAs by qPCR. The study included 42 samples of carcinoma and non-carcinoma tissue from 25 RCC patients. In addition, we used RNA sequencing data from The Cancer Genome Atlas (TCGA), encompassing 511 kidney RCC (KIRC) samples, to further analyze the expression of miRNAs and lncRNAs. Results: We identified 127 lncRNAs with confirmed regulatory functions, 31 of which were validated in our samples. The majority of lncRNAs, along with all members of the miR-200 family, showed consistent downregulation in carcinoma tissues compared to non-carcinoma tissues. We observed a significant correlation between the expression of at least one member of the miR-200 family and 17 lncRNAs. In particular, three lncRNAs (MALAT1, OIP5-AS1, and LINC00467) showed a correlation with the expression of all members of the miR-200 family. Our results were at least partially confirmed in KIRC samples from the TCGA dataset. Conclusions: Our results suggest that the expression of the miR-200 family in RCC might be at least partially influenced by lncRNAs. Based on our cohort of samples, MALAT1, OIP5-AS1, and LINC00467 appear to be potentially important contributors to RCC development. Full article

(This article belongs to the Special Issue State-of-the-Art Strategies for Non-Coding RNA Function Detection and Regulation in Cancer)

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10 pages, 860 KB

Open AccessPerspective

The Role of Robot-Assisted Radical Prostatectomy in the Management of Prostate Cancer and Future Perspectives

by Marco Rinaldi, Sebastiano Di Lena, Antonio Amodeo, Angelo Porreca and Alessandro Crestani

Cancers 2025, 17(19), 3122; https://doi.org/10.3390/cancers17193122 - 25 Sep 2025

Abstract

Robotic-assisted radical prostatectomy (RARP) has emerged as a leading surgical approach for localized prostate cancer in many centers worldwide. Leveraging minimally invasive techniques and advanced visualization, RARP has demonstrated benefits in perioperative and functional outcomes, and at least comparable, if not better, oncologic [...] Read more.

Robotic-assisted radical prostatectomy (RARP) has emerged as a leading surgical approach for localized prostate cancer in many centers worldwide. Leveraging minimally invasive techniques and advanced visualization, RARP has demonstrated benefits in perioperative and functional outcomes, and at least comparable, if not better, oncologic control relative to open radical prostatectomy (ORP) and laparoscopic radical prostatectomy (LRP). This review summarizes the current evidence on the efficacy, safety, and functional outcomes associated with RARP and discusses its role in contemporary prostate cancer management. Full article

(This article belongs to the Special Issue Robot-Assisted Radical Prostatectomy for Prostate Cancer)

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20 pages, 1036 KB

Open AccessReview

Radiomics-Driven Tumor Prognosis Prediction Across Imaging Modalities: Advances in Sampling, Feature Selection, and Multi-Omics Integration

by Mohan Huang, Helen K. W. Law and Shing Yau Tam

Cancers 2025, 17(19), 3121; https://doi.org/10.3390/cancers17193121 - 25 Sep 2025

Abstract

Radiomics has shown remarkable potential in predicting cancer prognosis by noninvasive and quantitative analysis of tumors through medical imaging. This review summarizes recent advances in the use of radiomics across various cancer types and imaging modalities, including computed tomography (CT), magnetic resonance imaging [...] Read more.

Radiomics has shown remarkable potential in predicting cancer prognosis by noninvasive and quantitative analysis of tumors through medical imaging. This review summarizes recent advances in the use of radiomics across various cancer types and imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, positron emission tomography (PET), and interventional radiology. Innovative sampling methods, including deep learning-based segmentation, multiregional analysis, and adaptive region of interest (ROI) methods, have contributed to improved model performance. The review examines various feature selection approaches, including least absolute shrinkage and selection operator (LASSO), minimum redundancy maximum relevance (mRMR), and ensemble methods, highlighting their roles in enhancing model robustness. The integration of radiomics with multi-omics data has further boosted predictive accuracy and enriched biological interpretability. Despite these advancements, challenges remain in terms of reproducibility, workflow standardization, clinical validation and acceptance. Future research should prioritize multicenter collaborations, methodological coordination, and clinical translation to fully unlock the prognostic potential of radiomics in oncology. Full article

(This article belongs to the Special Issue Radiomics and Imaging in Cancer Analysis)

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16 pages, 911 KB

Open AccessSystematic Review

The Role of Perioperative Interleukin-6 Serum Levels on Liver Dysfunction and Infectious Complications After Hepatectomy—A Systematic Review

by Alexander Kofler, Marlene Trattner, Vivien Mairinger, Iveta Urban, Kjetil Søreide, Stefan Stättner and Florian Primavesi

Cancers 2025, 17(19), 3120; https://doi.org/10.3390/cancers17193120 - 25 Sep 2025

Abstract

Background: Interleukin-6 (IL-6) is used as a marker for infection and inflammation. After liver surgery, IL-6 is also crucial for hepatic regeneration. The value of IL-6 serum-levels to differentiate infection from imminent post-hepatectomy liver failure (PHLF) remains unclear. This review focuses on IL-6 [...] Read more.

Background: Interleukin-6 (IL-6) is used as a marker for infection and inflammation. After liver surgery, IL-6 is also crucial for hepatic regeneration. The value of IL-6 serum-levels to differentiate infection from imminent post-hepatectomy liver failure (PHLF) remains unclear. This review focuses on IL-6 and complications after liver resections, specifically PHLF and infections. Methods: A systematic review was performed in the PubMed, Embase, and Cochrane libraries from January 2000 to June 2025 according to PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). All English language human data publications were assessed. Results: Overall, 12 studies (n = 589 patients) evaluating perioperative serum IL-6 levels were included. Six publications reported PHLF rates, and two specifically addressed IL-6, PHLF, and infection. Several patient and surgical parameters influence IL-6 dynamics. Despite five randomized trials being published, the overall study quality was low, with a high risk of bias. In particular, IL-6 on the first postoperative day was associated with PHLF and infections, but multivariable analyses of confounding factors are lacking. A meta-analysis of studies with a specific cut-off calculation was precluded by heterogeneous cohorts and endpoints. Conclusions: IL-6 levels may have early diagnostic value regarding imminent infectious complications or PHLF early after liver resection, but the evidence is exploratory and limited by methodological weaknesses. At present, IL-6 as a single marker does not seem to show sufficient clinical discriminatory potential to differentiate between infection and impaired hepatic regeneration. Future studies should address confounding factors, ideal timepoints of assessment, different methods of serum IL-6 assays, specific cut-offs, and multi-marker combinations. Full article

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

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14 pages, 1360 KB

Open AccessArticle

Multicenter Prospective Comparative Study of Patient Radiation Doses in Localization Techniques for Small Lung Lesions

by Tomoki Nishida, Yuichi Saito, Takeshi Takata, Shizuka Morita, Ryo Takeyama, Shinya Kohmaru, Tomohiro Watanabe, Nobuo Yamaguchi, Hikaru Takahashi, Yasuyuki Kanamoto, Hiroaki Morooka, Takayuki Ibi, Yoshikane Yamauchi, Ryuta Fukai, Nobumasa Takahashi, Tetsu Kanauchi, Ikuo Kobayashi, Masafumi Kawamura and Yukinori Sakao

Cancers 2025, 17(19), 3119; https://doi.org/10.3390/cancers17193119 - 25 Sep 2025

Abstract

Background/Objectives: Although surgeries employing cone-beam computed tomography (CBCT) for small lung lesions have been reported, the association between CBCT scan frequency and patient radiation exposure remains unclear. This study aimed to investigate patient radiation doses from CBCT during thoracic surgeries, and the patient [...] Read more.

Background/Objectives: Although surgeries employing cone-beam computed tomography (CBCT) for small lung lesions have been reported, the association between CBCT scan frequency and patient radiation exposure remains unclear. This study aimed to investigate patient radiation doses from CBCT during thoracic surgeries, and the patient radiation doses were compared with those from other preoperative marking methods. Methods: This multicenter prospective study included 81 patients who underwent surgery for small lung lesions requiring marking between January 2021 and June 2024 at three institutions. CBCT-guided surgeries involved the use of metal clips in a hybrid operating room with 1–4 scans, depending on the lesion. For other preoperative marking methods, hook-wire or virtual-assisted lung mapping (VAL-MAP) was used. Patient radiation doses were measured using wearable dosimeters at five anterior thorax sites, and the total dose was compared across methods. Results: The study included 81 patients: CBCT (n = 61), VAL-MAP (n = 10), and hook-wire (n = 10). CBCT cases were distributed as follows: single scan (n = 10), double scans (n = 34), triple scans (n = 15), and quadruple scans (n = 2). The radiation doses were 86.9 ± 61.7 mGy for hook-wire, 39.8 ± 27.5 mGy for VAL-MAP, and 11.0 ± 6.5 mGy for single-scan CBCT, 17.3 ± 7.8 mGy for double scans, 23.1 ± 14.0 mGy for triple scans, and 22.7 ± 0.1 mGy for quadruple scans. Although radiation exposure increased with more CBCT scans, performing up to triple scans resulted in significantly lower exposure compared to other methods. Conclusions: Intraoperative CBCT is a feasible and safe technique for identifying small lung lesions, providing lower radiation exposure compared to other preoperative localization methods. Full article

(This article belongs to the Special Issue Clinical Research on Thoracic Cancer)

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21 pages, 4875 KB

Open AccessSystematic Review

Reporting Matters: Severe Adverse Events in Soft Tissue Sarcoma Therapy—A 30-Year Systematic Review of Placebo- and Non-Systemic-Controlled Randomized Trials

by Rahel Aeschbacher, Bruno Fuchs, Gabriela Studer and Philip Heesen

Cancers 2025, 17(19), 3118; https://doi.org/10.3390/cancers17193118 - 25 Sep 2025

Abstract

Background: Systemic therapy for soft tissue sarcoma (STS) provides modest survival benefit but carries clinically relevant toxicity. Published trials report adverse events (AEs) of varying quality and extension. Poor toxicity reporting hampers balanced risk–benefit appraisal. Methods: A PRISMA-2020 systematic review was registered in [...] Read more.

Background: Systemic therapy for soft tissue sarcoma (STS) provides modest survival benefit but carries clinically relevant toxicity. Published trials report adverse events (AEs) of varying quality and extension. Poor toxicity reporting hampers balanced risk–benefit appraisal. Methods: A PRISMA-2020 systematic review was registered in PROSPERO CRD420251087366. PubMed, CENTRAL, and Google Scholar were searched from 16 December 2024 to 16 April 2025 for randomized controlled trials (RCTs) evaluating chemotherapy, kinase inhibitors, or immune checkpoint inhibitors in STS. AE terms were harmonized to CTCAE v5.0; event rates were normalized to patients evaluable for safety. Pooled proportions used DerSimonian–Laird random-effects models; between-group comparisons employed unpaired t-tests. Risk of bias (RoB 2) was assessed with the Cochrane RoB 2 tool. Results: Ten RCTs (1079 treated, 979 control patients; 1994–2024) met the inclusion criteria, although two lacked sufficient presentation of toxicity data and seven failed to report parallel control-arm AEs. Pooled normalized incidences for treated patients were as follows: grade ≥ 3 hematological AEs, 17% (95% CI 14–20); severe gastrointestinal AEs, 9% (8–11); and grade 4 AEs, ≤6%. Anthracycline-based and kinase-inhibitor regimens displayed comparable composite grade ≥ 3 burdens (58% vs. 84%, p = 0.64). Between-study heterogeneity was considerable for gastrointestinal and hematological events (I² > 60%), driven by differing AE scales and denominators. Late-effect toxicities (cardiac, hepatic, neurological, and nephrological) were rarely reported, occurring in <1% of the patients. Across the three RCTs with control-arm data, experimental therapy increased common grade 3 AEs by 4–12 percentage points (p = 0.001). RoB 2 flagged serious concerns in 4/10 trials. Conclusions: Severe AEs in STS systemic therapy are moderately frequent; while the toxicity spectrum differs across drug classes (e.g., hematological for anthracyclines vs. neuropathic or fatigue-related for agents such as eribulin), the aggregate burden of severe AEs has not been lower for newer agents. Confidence in these estimates is limited by incomplete and non-standardized AE reporting. Future sarcoma trials must adopt CTCAE v5.0, specify explicit safety denominators, and publish full AE matrices to enable high-certainty risk–benefit assessment. Full article

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

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2 pages, 162 KB

Open AccessCorrection

Correction: Restaino et al. Management of Patients with Vulvar Cancers: A Systematic Comparison of International Guidelines (NCCN–ASCO–ESGO–BGCS–IGCS–FIGO–French Guidelines–RCOG). Cancers 2025, 17, 186

by Stefano Restaino, Giulia Pellecchia, Martina Arcieri, Giorgio Bogani, Cristina Taliento, Pantaleo Greco, Lorenza Driul, Vito Chiantera, Rosa Pasqualina De Vincenzo, Giorgia Garganese, Francesco Sopracordevole, Violante Di Donato, Andrea Ciavattini, Paolo Scollo, Giovanni Scambia, Giuseppe Vizzielli and Gynecologic Oncology Group

Cancers 2025, 17(19), 3117; https://doi.org/10.3390/cancers17193117 - 25 Sep 2025

Abstract

There was an error in the original publication [...] Full article

20 pages, 2340 KB

Open AccessReview

Hybrid Angio-CT with DICI-CT in Interventional Oncology and Beyond: A Narrative Review

by Michael Moche, Arjen Bogaards, Andreas Horst Mahnken, Philipp Paprottka, Jonathan Nadjiri, Maciej Pech, Thierry de Baere and Bruno Calazans Odisio

Cancers 2025, 17(19), 3116; https://doi.org/10.3390/cancers17193116 - 25 Sep 2025

Abstract

Background/Objectives: Hybrid Angio-CT suites have emerged in response to the growing demands for innovation and procedural complexity in minimally invasive therapies. It is hypothesized that enhanced image guidance capabilities enabled by multimodality imaging can improve procedural safety, accuracy, and efficacy. However, due to [...] Read more.

Background/Objectives: Hybrid Angio-CT suites have emerged in response to the growing demands for innovation and procedural complexity in minimally invasive therapies. It is hypothesized that enhanced image guidance capabilities enabled by multimodality imaging can improve procedural safety, accuracy, and efficacy. However, due to the current lack of sufficient data to support a systematic review, the objective of this article is to present a comprehensive synthesis of the existing literature through a narrative review. Methods: This narrative review is based on purposefully identified research reports, their critical evaluation, and synthesis by a group of experienced users. The analysis covers three key areas: (1) current state of available technologies and functionalities, (2) novel perspectives through ‘Direct Intravascular Contrast media Injection CT’ (DICI-CT), and (3) the role of Angio-CT in established and emerging image-guided procedures. Results: The review presents typical configurations and room layouts for Angio-CT systems and discusses further technological improvement potential. Selected literature is complemented by expert experience to report on the current state of the art and demonstrate its use and efficiency. Based on our expert experience, it is demonstrated how DICI-CT can be used to reduce contrast dose and improve lesion visualization, targeting, and endpoint determination. Furthermore, in this review the advantages, including survival benefit (i.e., in trans-arterial chemoembolization and in blunt trauma) and cost-effectiveness (i.e., in emergency care), are reviewed with reference to oncologic and non-oncologic applications in both elective and emergency medicine. Conclusions: Hybrid Angio-CT suites can provide significant additional imaging information with the potential to improve image-guided procedures. This perspective is increasingly supported by retrospective data in interventional oncology and beyond. Provided that further technological advancements are achieved and prospective clinical data substantiates the anticipated clinical and economical benefits, hybrid Angio-CT suites are anticipated to play a key role in the multimodality interventional suite of the future. Full article

(This article belongs to the Special Issue Novel Approaches and Advances in Interventional Oncology)

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21 pages, 1245 KB

Open AccessReview

Improving Advanced Communication Skills Towards the Family System: A Scoping Review of Family Meeting Training in Oncology and Other Healthcare Settings

by Sara Alquati, Loredana Buonaccorso, Nuria Maria Asensio Sierra, Francesca Sassi, Francesco Venturelli, Maria Chiara Bassi, Stefano David Scialpi and Silvia Tanzi

Cancers 2025, 17(19), 3115; https://doi.org/10.3390/cancers17193115 - 24 Sep 2025

Abstract

Background/Objectives: Family meetings (FMs) are clinical encounters in a structured space between the patient, family members, and care teams. Healthcare professionals (HPs) often lack formal training in conducting FMs. The scoping review aims to provide an overview of the available research evidence on [...] Read more.

Background/Objectives: Family meetings (FMs) are clinical encounters in a structured space between the patient, family members, and care teams. Healthcare professionals (HPs) often lack formal training in conducting FMs. The scoping review aims to provide an overview of the available research evidence on FMs’ education for HPs. Methods: We searched MEDLINE, Embase, CINAHL, PsycINFO, and Scopus. The PCC (Population-Concept-Context) framework was used to define inclusion criteria: educational intervention on FMs aimed at HPs in all settings of care and students of medicine and nursing sciences treating adult patients with oncological and non-oncological diseases. Results: The search retrieved 1017 articles, of which 26 were eligible. The training had as its primary aims the development of communication skills and curriculum development/evaluation. For the most part, palliative care physicians served as trainers, while medical students and residents represented a major part of trainees, underscoring a focus on early-career learners. FM training is mainly provided in the American countries and intensive care settings. Role-play or simulation was the most common teaching method. Pre- and post-interventional designs were the most common, with few studies incorporating longitudinal follow-up to assess skill retention. Quantitative and qualitative methodologies were used to evaluate interventions. Conclusions: The training topics are related to advanced communication, but there is a lack of an interprofessional perspective and long-term assessment of the skills learned. It is necessary to consider different family types as subjects of communication. Full article

(This article belongs to the Special Issue Impact of Social Determinants on Cancer Care)

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15 pages, 746 KB

Open AccessSystematic Review

Colorectal Cancer Risk Following Cholecystectomy: An Updated Systematic Review

by Pierre-Henri Nelis, Stefano Grotto, Kenza Azra Ibis, Nashaira Nahar, Azzadinne Belhaj, Myriam Benhadda, Aude Vanlander and Nouredin Messaoudi

Cancers 2025, 17(19), 3114; https://doi.org/10.3390/cancers17193114 - 24 Sep 2025

Abstract

Background/Objectives: Cholecystectomy (CE) is among the most commonly performed surgical procedures worldwide. While it effectively treats gallstone disease, concerns have been raised about a potential long-term association with colorectal cancer (CRC), given overlapping risk factors and post-surgical physiological changes. Previous studies have reported [...] Read more.

Background/Objectives: Cholecystectomy (CE) is among the most commonly performed surgical procedures worldwide. While it effectively treats gallstone disease, concerns have been raised about a potential long-term association with colorectal cancer (CRC), given overlapping risk factors and post-surgical physiological changes. Previous studies have reported inconsistent findings. This updated systematic review aimed to reassess the association between CE and CRC risk by incorporating the most recent evidence. Methods: In accordance with PRISMA 2020 guidelines, a systematic literature search was conducted in PubMed, Embase, Medline, Web of Science, and the Cochrane Library for studies published after May 2022. Eligible studies were observational cohort studies reporting relative risk estimates for CRC following CE. Data were extracted manually, and study quality was assessed using the NewcastleOttawa Scale (NOS). Only high-quality studies were included to update the systematic review. Publication bias was assessed using funnel plots and Egger’s test. Results: Out of 156 identified records, three new high-quality cohort studies met the inclusion criteria and were added to the 18 studies from the previous review, resulting in a total of 21 studies. The findings were heterogeneous: while no consistent association with overall CRC risk was observed, several studies reported an elevated risk of proximal (right-sided) colon cancer following CE. Egger’s test indicated no significant publication bias (p = 0.50). Conclusions: This updated systematic review suggests a potential association between CE and an increased risk of proximal colon cancer; however, the evidence remains inconclusive. Further prospective studies with robust confounder control and detailed tumor location-specific analyses are warranted to clarify causality and guide future screening strategies. Full article

(This article belongs to the Section Cancer Therapy)

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19 pages, 976 KB

Open AccessArticle

Population-Based Survival of Childhood and Adolescent Cancers (0–19 Years) in Madrid: Analysis by Sex, Age, Tumour Type, and Stage

by Raquel López-González, David Parra-Blázquez, Daniel Moñino, Candela Pino-Rosón, Clotilde Sevilla-Hernández, Marina Pollán and Nuria Aragonés

Cancers 2025, 17(19), 3113; https://doi.org/10.3390/cancers17193113 - 24 Sep 2025

Abstract

Background/Objectives: In Europe, over 80% of children diagnosed with cancer survive at least 5 years. To improve cancer monitoring, the Paediatric Population-Based Cancer Registry (PCRM) was established in the Community of Madrid. This study aimed to describe population-based 1-, 3- and 5-year [...] Read more.

Background/Objectives: In Europe, over 80% of children diagnosed with cancer survive at least 5 years. To improve cancer monitoring, the Paediatric Population-Based Cancer Registry (PCRM) was established in the Community of Madrid. This study aimed to describe population-based 1-, 3- and 5-year survival for children and adolescents diagnosed with cancer, by sex, age, tumour type and stage at diagnosis. Methods: Data were extracted from the PCRM, which reviews all cases identified through integrated primary care, hospital discharge, and mortality data, using electronic medical records. Patients aged 0–19 diagnosed with primary malignant cancer between 2015 and 2018 were included, with follow-up for vital status through October 2024. Stage was classified using the 2014 Toronto Childhood Cancer Staging Guidelines (tier 2). Kaplan–Meier methods were used to estimate survival, and log-rank tests assessed group differences. Cox regression was used to quantify the effect of localized vs. advanced disease. Results: The analysis included 862 patients. Most frequent cancers were leukaemia (24.1%), lymphomas (22.2%) and central nervous system (CNS) tumours (12.6%). Stage was assigned to 88.4% tumours. Overall survival was 93.6% in 1 year and 85.9% in 5 years. Five-year survival was 83.7% for leukaemia, 97.4% for lymphomas, 66.1% for CNS tumours; 85.8% in boys vs. 85.9% in girls (p = 0.908); 85.2% in children aged 0–14 years vs. 87.8% in adolescents aged 15–19 years (p = 0.314); and 69.9% for advanced vs. 89.7% for early-stage (p < 0.001), with a 3.3-fold higher mortality risk. Conclusions: This population-based study offers promising survival estimates reaching 86% globally at 5 years while revealing differences by cancer type and stage. It also highlights the Toronto Guidelines as a valuable tool for standardizing cancer registry methods and providing useful epidemiological indicators. Full article

(This article belongs to the Special Issue Recent Advances in Epidemiology of Childhood Cancer)

13 pages, 1763 KB

Open AccessArticle

Dermal Mitoses Correlate with Surgical Burden in Lentigo Maligna Melanoma: PRAME for Margin Assessment

by Thomas Leibing, Clara Ziemann, Cyrill Géraud, Jochen Utikal and Sebastian A. Wohlfeil

Cancers 2025, 17(19), 3112; https://doi.org/10.3390/cancers17193112 - 24 Sep 2025

Abstract

Background/Introduction: Margin assessment in Lentigo maligna (LM) and Lentigo maligna melanoma (LMM) is challenging. Many of these lesions require extensive surgical procedures for R0 resections with unclear histological and clinical features predicting lateral spread. Recently, PRAME was described as a useful antibody to [...] Read more.

Background/Introduction: Margin assessment in Lentigo maligna (LM) and Lentigo maligna melanoma (LMM) is challenging. Many of these lesions require extensive surgical procedures for R0 resections with unclear histological and clinical features predicting lateral spread. Recently, PRAME was described as a useful antibody to determine margins in these entities. However, several questions, like acceptable PRAME⁺ cell number and density in resection margins and optimal safety margins, especially in head and neck areas, remain. Methods: We analyzed cases of LMIS and LMM since the introduction of PRAME and before the introduction of PRAME, with more than 171 cases in total. We re-stained security margins with PRAME. Results: We identified a correlation between reported dermal mitoses in LMM and the number of surgical procedures. In many LMM cases before the widespread use of PRAME from our archives, we detected a high density of PRAME⁺ cells in melanoma security margins previously labeled tumor-free. No local recurrence could be identified in these cases, with the caveat of limited follow-up and small case numbers. Conclusions: Our findings raise important questions regarding margin assessment with PRAME and the reporting of residual cells in margins. Full article

(This article belongs to the Special Issue The Latest Advancements in Cutaneous Melanoma)

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43 pages, 1601 KB

Open AccessReview

EZH2 Dysregulation and Its Oncogenic Role in Human Cancers

by Shiv Verma, Nikita Goyal, Suhani Goyal, Parminder Kaur and Sanjay Gupta

Cancers 2025, 17(19), 3111; https://doi.org/10.3390/cancers17193111 - 24 Sep 2025

Abstract

Enhancer of Zeste Homolog 2 (EZH2) is a key epigenetic regulator known for its role in global gene silencing and is involved in a variety of cellular processes, including cell survival, proliferation, invasion, and self-renewal. As a core component of the Polycomb Repressive [...] Read more.

Enhancer of Zeste Homolog 2 (EZH2) is a key epigenetic regulator known for its role in global gene silencing and is involved in a variety of cellular processes, including cell survival, proliferation, invasion, and self-renewal. As a core component of the Polycomb Repressive Complex 2 (PRC2), EZH2 catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3), leading to chromatin compaction and transcriptional repression. Dysregulated EZH2 expression is observed in a wide range of solid tumors and hematological malignancies and is frequently associated with increased metastatic potential and poor clinical outcomes. While EZH2 primarily mediates gene silencing through its canonical PRC2-dependent activity, it also exerts oncogenic effects via non-canonical mechanisms. In its non-canonical role, EZH2 acts independently of PRC2, interacting with other signaling molecules as a transcriptional activator or co-activator, thereby promoting the activation of oncogenic pathways. Through both canonical and non-canonical mechanisms, EZH2 significantly contributes to tumor initiation and its subsequent progression. Given its critical role in oncogenesis and cancer progression, EZH2 is under investigation as a potential biomarker for cancer diagnosis and prognosis. This review provides a comprehensive overview of EZH2’s function and oncogenic roles across human cancers. Enhanced insight into EZH2’s complex regulatory network may facilitate the development of more effective strategies to manage EZH2-driven malignancies. Full article

(This article belongs to the Special Issue Cancer Epigenetic Biomarkers: 2nd Edition)

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14 pages, 458 KB

Open AccessArticle

Contemporary Trends and Predictors of pT0 in Radical Cystectomy Specimens Among Non-Muscle and Muscle-Invasive Bladder Cancer Patients: A Propensity Score-Matched Analysis from a Single Tertiary Centre in the United Kingdom

by Francesco Del Giudice, Valerio Santarelli, Katarina Spurna, Syed Ghazi Ali Kirmani, Noor Huda Bhatti, Yasmin Abu-Ghanem, Elsie Mensah, Benjamin Challacombe, Samuel J. Davies, Mohammad Hegazy, Youssef Ibrahim, Mohammed Gad, Amir Khan, Roberta Corvino, Felice Crocetto, Jan Łaszkiewicz, Bernardo Rocco, Benjamin I. Chung, Ramesh Thuraraja, Muhammad Shamin Khan and Rajesh Nair Show full author list Hide full author list

Cancers 2025, 17(19), 3110; https://doi.org/10.3390/cancers17193110 - 24 Sep 2025

Abstract

Introduction: Absence of residual cancer in radical cystectomy (RC) specimens is a well-known positive prognostic factor for non-muscle and muscle-invasive bladder cancer (NMIBC and MIBC) in patients with or without neoadjuvant chemotherapy (NAC). Understanding the clinical and pathological features associated with a [...] Read more.

Introduction: Absence of residual cancer in radical cystectomy (RC) specimens is a well-known positive prognostic factor for non-muscle and muscle-invasive bladder cancer (NMIBC and MIBC) in patients with or without neoadjuvant chemotherapy (NAC). Understanding the clinical and pathological features associated with a final pT0 status can provide valuable prognostic insights, serve as a surrogate marker for survival outcomes, and help identify candidates suitable for bladder-sparing strategies. Methods: Temporal trends and clinical/demographic characteristics across clinically high-/very-high-risk NMIBC or MIBC RC patients from 2009 to 2024 were explored. Subsequently, RC pT0 patients were propensity score-matched (PSM, 1:1 ratio) with the >pT0 population based on age-adjusted CCI and preoperative clinical stage (cTis-T1 vs. cT2). Multivariable regression modelling was applied to explore predictors of pT0 status stratified according to clinical NMIBC or MIBC status. Results: A total of 655 RCs performed with curative intent were included (43% for MIBC, 57% for NMIBC). Of these, 117 were pT0 at final pathological assessment (68 NMIBC and 49 MIBC). Subsequently, 228 PSM patients (114 pT0 vs. 114 >pT0) were extracted from the original cohort and stratified according to preoperative clinical stage (MIBC vs. NMIBC). In multivariable analysis, male gender was associated with an increased likelihood of pT0 status in the NMIBC cohort (adjusted odds ratio [aOR] 2.89, 95% CI 1.13–7.90). Conversely, BCG failure and concomitant CIS independently reduced the chances of achieving pT0 status (aOR: 0.40, 95% CI 0.19–0.99; aOR: 0.16, 95% CI 0.03–0.97). For MIBC patients, as expected, NAC more than doubled the chances of achieving pT0 status (aOR: 2.20, 95% CI 1.01–6.82). On the other hand, the concomitant presence of CIS reduced the likelihood of pT0 achievement (aOR 0.22, 95% CI, 0.06–0.80). In both cohorts, the presence of variant histology (VH) demonstrated a negative association with pT0 achievement; however, the estimated effect did not reach statistical significance (p = 0.09 and p = 0.08). Conclusions: Our findings suggest potentially raising the threshold for RC consideration in high-risk or very-high-risk NMIBC patients with a favourable risk profile. MIBC patients without additional risk factors (CIS and VH) are more likely to achieve a tumour-free status, particularly when adequately receiving NAC. Full article

(This article belongs to the Special Issue Diagnosis and Therapy in Urothelial Cancer)

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14 pages, 280 KB

Open AccessReview

Patient Education and Communication in Palliative Radiotherapy: A Narrative Review

by Erika Galietta, Costanza M. Donati, Filippo Mammini, Arina A. Zamfir, Alberto Bazzocchi, Rebecca Sassi, Renée Hovenier, Clemens Bos, Milly Buwenge, Silvia Cammelli, Helena M. Verkooijen and Alessio G. Morganti

Cancers 2025, 17(19), 3109; https://doi.org/10.3390/cancers17193109 - 24 Sep 2025

Abstract

Palliative radiotherapy (PRT) is central to symptom control in advanced cancer, yet referrals are often late, and patients and clinicians frequently hold misconceptions about intent, benefits, and logistics. Patient education may address these gaps, but the PRT-specific evidence base has not been consolidated. [...] Read more.

Palliative radiotherapy (PRT) is central to symptom control in advanced cancer, yet referrals are often late, and patients and clinicians frequently hold misconceptions about intent, benefits, and logistics. Patient education may address these gaps, but the PRT-specific evidence base has not been consolidated. We conducted a narrative review following SANRA guidance. We searched PubMed, Scopus, and the Cochrane Library for English-language studies from 1 January 2000 to 18 July 2025. Eligible articles evaluated structured patient-education interventions or characterized education or communication content, information needs, or decision processes among adults referred to or receiving PRT. Two reviewers independently screened and extracted data. Owing to heterogeneity of designs and endpoints, we performed a narrative synthesis without meta-analysis. Six studies met criteria: two randomized controlled trials, two prospective pre–post studies, one qualitative interview study, and one observational communication study, conducted in the Netherlands, the United States, Canada, and Hong Kong. Education at referral or consultation improved knowledge, reduced decisional uncertainty, and increased readiness to proceed with PRT. Education integrated with treatment improved symptom outcomes, including higher rates of pain control at 12 weeks and faster time to pain control when a nurse-led pain-education program accompanied PRT for painful bone metastases, and improvements in dyspnea, fatigue, anxiety, and function in advanced lung cancer. Observational and qualitative work showed low patient question-asking and persistent curative expectations; overall quality of life generally did not change. Although the evidence is limited and heterogeneous, targeted, standardized education appears to improve decision quality and selected symptoms in PRT pathways. Pragmatic multi-site trials and implementation studies are needed to define content, timing, personnel, and delivery models that are scalable in routine care. Full article

(This article belongs to the Special Issue Palliative Radiotherapy of Cancer)

18 pages, 5099 KB

Open AccessSystematic Review

Dynamics in Quality of Life of Breast Cancer Patients Following Surgery: Systematic Review and Meta-Analysis

by Iryna Makhnevych, Mussab Ibrahim Mohamed Fadl Elseed, Ibrahim Mohamed Ahmed Musa, Jood Jasem Shaddad Alblooshi, Darya Smetanina, Faisal Tahsin and Yauhen Statsenko

Cancers 2025, 17(19), 3108; https://doi.org/10.3390/cancers17193108 - 24 Sep 2025

Abstract

Background and Objectives: Surgical treatment is central to breast cancer management; however, its long-term impact on QoL varies substantially among patients. This study sought to model the dynamic trajectories of postoperative QoL following breast-conserving surgery (BCS), mastectomy with immediate reconstruction (Mx+IR), and mastectomy [...] Read more.

Background and Objectives: Surgical treatment is central to breast cancer management; however, its long-term impact on QoL varies substantially among patients. This study sought to model the dynamic trajectories of postoperative QoL following breast-conserving surgery (BCS), mastectomy with immediate reconstruction (Mx+IR), and mastectomy alone (MA). It also examined how these trajectories varied across different age groups and over time. Materials and Methods: The review and meta-analysis identified 150 peer-reviewed studies reporting QoL outcomes using validated instruments (EORTC QLQ-C30 or BREAST-Q). A total of 123 observations from 45 studies were included for analysis of global QoL. We standardized QoL scores to a 0–100 scale and harmonized postoperative assessments across six time intervals, extending to more than 73 months. Multilevel random-effects models evaluated linear, quadratic, and logarithmic functions. Subgroup analyses and meta-regressions assessed the moderating effects of surgical type and age. Results: BCS showed the steepest QoL gains, followed by Mx+IR, while MA had the lowest scores and slowest recovery. Compared to BCS, MA showed significantly poorer and delayed recovery, and Mx+IR showed a smaller, borderline decrease. All groups displayed modest long-term QoL plateauing. Conclusions: Global QoL after breast cancer surgery follows distinct, time-dependent patterns shaped by surgical approach and age. These findings emphasize the importance of discussing patients’ quality-of-life expectations with them so that survivorship care can be personalized to their needs. Full article

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

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13 pages, 567 KB

Open AccessReview

The FSIP Family: Roles in Health and Cancer

by Zhan Zhang, Yunfan Liu, Chao Liu, Lujia Qin, Mone Zaidi and Caigang Liu

Cancers 2025, 17(19), 3107; https://doi.org/10.3390/cancers17193107 - 24 Sep 2025

Abstract

Fibrous sheath interacting proteins 1 and 2 (FSIP1 and FSIP2) are evolutionarily conserved testis-specific antigens, exclusively expressed in germ cells of adult human tissues, where they play essential roles in spermatogenesis and testicular development. Aberrant re-expression of FSIP1 and FSIP2, however, has been [...] Read more.

Fibrous sheath interacting proteins 1 and 2 (FSIP1 and FSIP2) are evolutionarily conserved testis-specific antigens, exclusively expressed in germ cells of adult human tissues, where they play essential roles in spermatogenesis and testicular development. Aberrant re-expression of FSIP1 and FSIP2, however, has been frequently reported in multiple malignancies, driving oncogenic processes including uncontrolled proliferation, invasion, migration, and metastasis, and correlating with unfavorable clinical outcomes. Their restricted expression in normal tissues, together with their consistent association with poor prognosis across cancer types, highlights their potential as diagnostic biomarkers, therapeutic targets, and prognostic indicators. This review summarizes the structural features and biological functions of the FSIP family, emphasizes recent advances in elucidating their regulatory roles in tumor-associated signaling pathways, and outlines the major challenges and future perspectives in this emerging field. Full article

(This article belongs to the Section Molecular Cancer Biology)

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32 pages, 1494 KB

Open AccessReview

Exploring the Tumor Microenvironment in Osteosarcoma: Driver of Resistance and Progression

by Aidan A. Schmidt, Advay Prasad, Alex R. Huisman, Mark R. Wakefield and Yujiang Fang

Cancers 2025, 17(19), 3106; https://doi.org/10.3390/cancers17193106 - 24 Sep 2025

Abstract

Osteosarcoma (OS) is the most common bone-based cancer in both the US and the world in children, teenagers, and young adults. It is an aggressive form of sarcoma which forms mainly in the long bones of the legs and arms, often metastasizing prior [...] Read more.

Osteosarcoma (OS) is the most common bone-based cancer in both the US and the world in children, teenagers, and young adults. It is an aggressive form of sarcoma which forms mainly in the long bones of the legs and arms, often metastasizing prior to diagnosis. Every year across the globe, there are approximately 28,000 new cases, yet this sarcoma remains difficult to manage with standard treatments, partly due to its solid and immune resistant tumor microenvironment (TME). The quantity of research conducted on OS because of these difficulties has greatly increased over the past decade, meaning a comprehensive review of new findings on the TME may prove beneficial. This article aims to give a broad overview of the components of the TME of osteosarcoma, discuss its resistances and detrimental effects, and illustrate current and future immune therapy treatments which effectively target the microenvironment. Additionally, it will seek to highlight any knowledge gaps in the current literature and propose further studies to improve clinical outcomes. These studies could be beneficial in increasing drug and treatment efficacy for OS. Full article

(This article belongs to the Special Issue Feature Papers in Section "Tumor Microenvironment")

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29 pages, 719 KB

Open AccessReview

Decision-Making Biomarkers Guiding Therapeutic Strategies in Hepatocellular Carcinoma: From Prediction to Personalized Care

by Dongming Liu and Norihiro Imai

Cancers 2025, 17(19), 3105; https://doi.org/10.3390/cancers17193105 - 24 Sep 2025

Abstract

Hepatocellular carcinoma (HCC) management has evolved remarkably with the advent of diverse therapeutic options, particularly systemic and surgical treatments. Combination immunotherapy has redefined the treatment paradigm for advanced HCC and contributed to improved patient outcomes. However, this brings forth challenges such as immune-related [...] Read more.

Hepatocellular carcinoma (HCC) management has evolved remarkably with the advent of diverse therapeutic options, particularly systemic and surgical treatments. Combination immunotherapy has redefined the treatment paradigm for advanced HCC and contributed to improved patient outcomes. However, this brings forth challenges such as immune-related adverse events that complicate decision-making. Surgical strategies have expanded with the emergence of conversion therapy and borderline resectability, offering curative potential for a broader patient population. However, robust evidence of their long-term efficacy is lacking. Therefore, decision-making biomarkers have gained prominence across treatment modalities. This review explores the current landscape of predictive, prognostic, and treatment-response biomarkers in HCC, from molecular and immune signatures to radiological and biochemical markers, highlighting their role in optimizing therapeutic strategies. By integrating recent advances in basic and translational research with clinical practice, we aim to outline a biomarker-driven framework for individualized care in HCC. Full article

(This article belongs to the Special Issue Decision-Making Biomarkers in the Treatment of Hepatocellular Carcinoma)

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18 pages, 1346 KB

Open AccessReview

Understanding and Exacerbating the Biological Response of Uveal Melanoma to Proton Beam Therapy

by Laura Hawkins, Helen Kalirai, Karen Aughton, Rumana N. Hussain, Sarah E. Coupland and Jason L. Parsons

Cancers 2025, 17(19), 3104; https://doi.org/10.3390/cancers17193104 - 24 Sep 2025

Abstract

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, associated with a high tendency for metastasis to the liver. Proton beam therapy (PBT) is the preferred external radiotherapy treatment for primary UM of certain sizes and locations in the eye, [...] Read more.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, associated with a high tendency for metastasis to the liver. Proton beam therapy (PBT) is the preferred external radiotherapy treatment for primary UM of certain sizes and locations in the eye, due to its efficacy and good local tumour control, as well as its precision to spare surrounding ocular structures. PBT is an effective alternative to surgical enucleation and other non-precision-targeted radiotherapies. Despite this, the radiobiology of UM in response to PBT is still not fully understood. This enhanced knowledge would help to further optimise UM treatment and improve patient outcomes through reducing radiation dosage to ocular structures, treating larger tumours that would otherwise require enucleation, or even offering a treatment strategy for the otherwise fatal liver metastases. In this review, we explore current knowledge of the treatment of UM with PBT, evaluating the biological responses to the therapy. Molecular factors, such as tumour size, oxygen tension levels, DNA damage proficiency, and autophagy, are known to influence the cellular response to radiotherapy, and these will be discussed. Furthermore, we examine innovative strategies to enhance radiotherapy outcomes, such as combination therapies with DNA damage repair and autophagy modulators, as well as advancements in PBT planning and delivery. By integrating current research and emerging technologies, we aim to provide opportunities to improve the therapeutic effectiveness of PBT in UM management. Full article

(This article belongs to the Special Issue Advances in Uveal Melanoma)

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12 pages, 904 KB

Open AccessArticle

Decline of PD-L1 Immunoreactivity with Storage Duration in Formalin-Fixed Paraffin-Embedded Breast Cancer Specimens: Implications for Diagnostic Accuracy and Immunotherapy Eligibility in Triple-Negative Breast Cancer

by Keiko Yanagihara, Koji Nagata, Tamami Yamakawa, Sena Kato, Miki Tamura and Masato Yoshida

Cancers 2025, 17(19), 3103; https://doi.org/10.3390/cancers17193103 - 23 Sep 2025

Abstract

Backgrounds: Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is a critical predictive biomarker for immune checkpoint inhibitor (ICI) therapy in triple-negative breast cancer (TNBC). However, prolonged storage of formalin-fixed paraffin-embedded (FFPE) tissue may reduce antigenicity, potentially leading to false-negative results. False-negative results may [...] Read more.

Backgrounds: Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is a critical predictive biomarker for immune checkpoint inhibitor (ICI) therapy in triple-negative breast cancer (TNBC). However, prolonged storage of formalin-fixed paraffin-embedded (FFPE) tissue may reduce antigenicity, potentially leading to false-negative results. False-negative results may lead to the inappropriate selection of ICI therapy. We investigated the effect of FFPE storage duration on PD-L1 immunoreactivity. Methods: We retrospectively analyzed 63 TNBC cases with PD-L1 testing using the 22C3 pharmDx assay at diagnosis and repeated IHC on the same FFPE blocks after varying storage durations (<1, 1–2, 2–3, ≥3 years). PD-L1 positivity was defined as Combined Positive Score (CPS) ≥ 10. Associations with clinicopathologic features, pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC), and survival were evaluated. Results: At diagnosis, 41 patients (65.1%) were PD-L1–positive. In the PD-L1–positive group, decreased staining was observed in 0%, 11%, 13%, and 50% of cases for <1, 1–2, 2–3, and ≥3 years of storage, respectively (p = 0.015). PD-L1 positivity correlated with higher Ki67 and nuclear grade. pCR was achieved in 33% of PD-L1–positive vs. 0% of PD-L1–negative NAC patients (p = 0.0527). Survival analysis showed a non-significant trend toward shorter recurrence-free and overall survival in PD-L1–positive patients. Conclusions: Prolonged FFPE storage, particularly beyond three years, significantly reduces PD-L1 immunoreactivity. Testing on recent specimens is recommended to avoid false-negative results that may impact ICI eligibility. Full article

(This article belongs to the Special Issue Breast Cancer Biomarkers and Clinical Translation: 2nd Edition)

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10 pages, 511 KB

Open AccessArticle

Efficacy and Toxicity Profile of Carboplatin/Gemcitabine Chemotherapy in Locally Advanced or Metastatic Biliary Tract Cancer: A Single UK Centre Experience

by Bahaaeldin Baraka, Dwiti Jatin Ponda, Jennifer Hanna, Dhanny Gomez, Guruprasad Aithal and Arvind Arora

Cancers 2025, 17(19), 3102; https://doi.org/10.3390/cancers17193102 - 23 Sep 2025

Abstract

Background/Objectives: Biliary tract cancers (BTCs) refer to an invasive group of malignancies consisting of gallbladder cancer, ampullary cancer, and cholangiocarcinoma (CCA). BTCs are often diagnosed at advanced stages, leading to poor prognoses. While cisplatin-based chemotherapy remains the standard first-line treatment, carboplatin/gemcitabine serves as [...] Read more.

Background/Objectives: Biliary tract cancers (BTCs) refer to an invasive group of malignancies consisting of gallbladder cancer, ampullary cancer, and cholangiocarcinoma (CCA). BTCs are often diagnosed at advanced stages, leading to poor prognoses. While cisplatin-based chemotherapy remains the standard first-line treatment, carboplatin/gemcitabine serves as an alternative, particularly for patients with contraindications to cisplatin. This retrospective study evaluates the real-world efficacy and safety of carboplatin/gemcitabine in patients with advanced BTC who were ineligible for cisplatin-based treatment at a single UK centre. Methods: Data from 66 patients treated between March 2018 and July 2023 were analysed for overall survival (OS), progression-free survival (PFS), and toxicities. Results: The median OS was 8.97 months (95% CI: 6.78–11.16), and the median PFS was 5.88 months (95% CI: 4.78–6.98). Tumour control rate was achieved in 70% of cases. Patients receiving fewer than four chemotherapy cycles or presenting with poor baseline markers exhibited significantly worse survival outcomes (p < 0.05). Haematological toxicities were common, including thrombocytopenia (63.7%), neutropenia (48.5%), and anaemia (50.0%). Conclusions: While carboplatin/gemcitabine is a viable treatment for advanced BTC, larger trials are necessary to confirm its efficacy. Full article

(This article belongs to the Section Cancer Therapy)

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30 pages, 851 KB

Open AccessArticle

Cancer Burden Attributable to Potentially Modifiable Risk Factors in Australia

by Tenaw Tiruye, Bereket Duko, Laychiluh Mekonnen, Paul Ward, Trang H. H. D. Nguyen, Stephanie Byrne, David Roder and Kerri Beckmann

Cancers 2025, 17(19), 3101; https://doi.org/10.3390/cancers17193101 - 23 Sep 2025

Abstract

Understanding the relative contribution of modifiable risk factors to cancer morbidity and mortality is crucial for designing effective cancer prevention and control strategies. Our study estimated cancer-related deaths and disability-adjusted life years (DALYs) lost attributable to potentially modifiable risk factors in Australia using [...] Read more.

Understanding the relative contribution of modifiable risk factors to cancer morbidity and mortality is crucial for designing effective cancer prevention and control strategies. Our study estimated cancer-related deaths and disability-adjusted life years (DALYs) lost attributable to potentially modifiable risk factors in Australia using data from the Global Burden of Diseases 2021 study. In 2021, an estimated 20,409 cancer deaths (37.5%) and 431,575 cancer DALYs lost (37.9%) in Australia were attributable to potentially modifiable risk factors. Males had higher modifiable risk attributed to cancer death and DALY rates than females. Behavioral risks accounted for 25.0% of cancer deaths and 26.5% of DALYs. Metabolic risks and environmental/occupational risks accounted for 9.4% and 9.3% of deaths, respectively. Smoking remained the leading attributable risk factor, accounting for 12.2% cancer deaths and 13.1% DALYs lost. Dietary risks accounted for 40.0% of colorectal cancer deaths and DALYs lost. Cervical, larynx, liver, lung, and colorectal cancers had a high proportion of deaths and DALYs lost attributed to modifiable risks. Liver and nasopharyngeal cancers had the highest burden attributed to alcohol use (39.1% and 39.0%, respectively), while 21.3% liver cancer deaths were attributed to drug use. Strengthening public health interventions, such as multi-disciplinary approaches to promote a healthy lifestyle, is required. Full article

(This article belongs to the Special Issue Emerging Trends in Global Cancer Epidemiology: 2nd Edition)

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41 pages, 520 KB

Open AccessReview

Childhood, Adolescent and Young Adult Poor-Prognosis Rhabdomyosarcoma

by Ajla T. Wasti, Gianni Bisogno, Raquel Hladun, Anne-Sophie Defachelles, Michela Casanova, Willemijn B. Breunis, Susanne A. Gatz, Reineke A. Schoot, Andrea Ferrari, Meriel Jenney, Rita Alaggio, Raquel Davila Fajardo, Sheila Terwisscha van Scheltinga, Janet Shipley, Michael Torsten Meister, Rick R. van Rijn, John Anderson, Monika Sparber-Sauer, Julia C. Chisholm and Johannes H. M. Merks

Cancers 2025, 17(19), 3100; https://doi.org/10.3390/cancers17193100 - 23 Sep 2025

Abstract

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and young people. Despite the advances in multimodality treatment over recent decades through successive prospective clinical trials, improved rates of survival for patients are mainly limited to those with localised RMS without [...] Read more.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and young people. Despite the advances in multimodality treatment over recent decades through successive prospective clinical trials, improved rates of survival for patients are mainly limited to those with localised RMS without adverse biologic features. Current clinicopathologic prognostic factors include PAX3(7)::FOXO1 fusion status, the site of primary disease, the pre-chemotherapy extent of disease (including microscopic vs. macroscopic residual disease, locoregional nodal involvement and metastatic status), tumour size and patient age. These factors are used to stratify patients into prognostic risk groups that guide treatment intensity and duration. Risk stratification algorithms are evolving, supported by advances in molecular biology and cancer genomics. In this review we focus on the poorest prognostic groups of paediatric-type RMS (i.e., Very High Risk or relapsed/progressive disease). These include patients whose tumours harbour poor biological characteristics such as PAX3(7)::FOXO1 fusion-positive tumours with locoregional nodal involvement and tumours harbouring other poor-risk genetic variants (particularly MYOD1 and TP53 variants); adolescent and young adult patients; newly diagnosed patients with metastatic RMS; and patients with relapsed and refractory disease. Here we aim to describe the clinical characteristics of these patients, outline current standard multimodality treatments in the context of sequential international clinical trials across the major cooperative groups and summarise emerging novel diagnostic and therapeutic approaches. Full article

(This article belongs to the Special Issue Improving Treatment for Rhabdomyosarcoma: A Collaborative Approach through the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG))

20 pages, 2130 KB

Open AccessArticle

Interaction Between Mesenchymal Stromal Cells and Tumor Cells Present in Cervical Cancer Influences Macrophage Polarization

by Eduardo Bautista-Sebastián, Víctor Adrián Cortés-Morales, Guadalupe Rosario Fajardo-Orduña, Alberto Monroy-García, Marta Elena Castro-Manrreza, Alberto Daniel Saucedo-Campos, Marcos Gutiérrez-de la Barrera, Héctor Mayani and Juan José Montesinos

Cancers 2025, 17(19), 3099; https://doi.org/10.3390/cancers17193099 - 23 Sep 2025

Abstract

Background/Objectives: Macrophages with the M2 phenotype are an immune population with great relevance for tumor development. We have previously demonstrated that mesenchymal stromal cells (MSCs) from cervical cancer (CeCa-MSCs) enhance the immunomodulatory activity of CeCa cells on T lymphocytes; however, the effect of [...] Read more.

Background/Objectives: Macrophages with the M2 phenotype are an immune population with great relevance for tumor development. We have previously demonstrated that mesenchymal stromal cells (MSCs) from cervical cancer (CeCa-MSCs) enhance the immunomodulatory activity of CeCa cells on T lymphocytes; however, the effect of these cells on the ability of tumor cells to polarize macrophages had not been evaluated to date. Methods: To address this, we set out to analyze the effect of normal cervix (NCx) and CeCa-MSCs interacting with CeCa tumor cells (TCs) to polarize macrophages in a coculture system. Results: Our results show that macrophages from TC/NCx-MSC cocultures decreased CD163 expression. In turn, we observed that macrophages from TC/CeCa-MSC cocultures, in contrast to those in the presence of TCs/NCx-MSCs, increased the intracellular production of IDO, IL-4, and IL-10; decreased T lymphocyte proliferation; and increased the presence of soluble IL-10. Interestingly, coculture in the presence of TCs/NCx-MSCs decreased the capacity of macrophages to generate regulatory T lymphocyte populations, as well as their phagocytic capacity, and increased IL-6 secretion, unlike the coculture of macrophages in the presence of TCs/CeCa-MSCs. Our results show that TCs/CeCa-MSCs in cocultures, unlike TCs/NCx-MSCs, have a greater capacity to polarize macrophages to an M2 phenotype and that such macrophages have a greater immunosuppressive potential. Conclusions: This in vitro study suggests that intracellular communication between MSCs and tumor cells in CeCa may promote tumor growth through the polarization of macrophages with increased immunosuppressive activity. Full article

(This article belongs to the Special Issue Tumor Microenvironment of Gynecological Tumors)

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11 pages, 578 KB

Open AccessArticle

Sentinel Lymph Node Biopsy Versus Elective Neck Dissection in Carcinoma of the Tongue and Floor of the Mouth

by Carolin Naegeli-Pullankavumkal, Tamara Manser, Tarun Mehra, Niels Jan Rupp, Thomas Gander, Martin W. Huellner and Martin Lanzer

Cancers 2025, 17(19), 3098; https://doi.org/10.3390/cancers17193098 - 23 Sep 2025

Abstract

Background/Objectives: Lymph node metastases represent the most important prognostic factor for survival in patients with localized squamous cell carcinoma (SCC) of the oral cavity. In patients with carcinoma of the tongue or floor of the mouth, elective neck dissection (END) has been the [...] Read more.

Background/Objectives: Lymph node metastases represent the most important prognostic factor for survival in patients with localized squamous cell carcinoma (SCC) of the oral cavity. In patients with carcinoma of the tongue or floor of the mouth, elective neck dissection (END) has been the standard of care, but it has been replaced at many centers by sentinel lymph node biopsy (SLNB). This study’s purpose was to measure and compare recurrence rates between END and SLNB in patients with early SCC of the oral cavity. Methods: Patients were included in this retrospective monocenter cohort study, performed at the University Hospital of Zürich, if they underwent either END or SLNB for oral squamous cell carcinoma (OSCC) of the tongue or floor of the mouth between January 2008 and December 2018. Only patients with early-stage tumors and a clinically negative neck (T1 or T2; cN0) who had a follow-up period of at least 5 years were included. Patients with a T3 or T4 tumor or a clinically positive neck were excluded, as were those who previously underwent therapy for another head and neck carcinoma. The predictor variable was the surgical treatment used, with subjects divided into two groups: END and SLNB. The main outcome variable was the time to recurrent disease, defined as the time between the primary surgical treatment and the diagnosis of recurrence. The covariates were primary tumor location, pT status, pN status, histopathological grade and postoperative radiotherapy. We used descriptive analysis, univariate analysis and the logrank test, with a p-value < 0.05 considered statistically significant. We deliberately refrained from multivariate analysis due to insignificant statistical results in the univariate analysis. Results: In total, 82 patients (46 male, 36 female; median age at the time of surgery: 58.9 years) were included, with a median observation period of 4.3 years. The main primary tumor location was the floor of the mouth (62.2%). The SLNB cohort had smaller primary tumors in comparison to the END cohort (20% vs. 37% pT2, respectively). Furthermore, pN+ disease was more prevalent in the END group in comparison to the SLNB group (81.8% vs. 74.1% pN0, respectively). Recurrence-free survival was not significantly different between the two groups. Subgroup analysis demonstrated a higher risk of recurrent disease in pN+ groups undergoing SLNB compared to those undergoing END. Conclusions: We demonstrate that SLNB is a useful tool for assessing lymph nodes of the neck. In cases of pN+ necks after SLNB and subsequent neck dissection, patients need to be closely followed up with due to the risk of recurrent disease. Full article

(This article belongs to the Special Issue Oral Cancer: The Latest Advances in Clinical and Basic Research (Second Edition))

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16 pages, 839 KB

Open AccessArticle

Implementation of Robotic-Assisted Surgery for the Treatment of Patients with Endometrial Carcinoma

by Walid Shaalan, Kathrin Haßdenteufel, Fabiola Hoppe, Peter Sinn, Riku Togawa, Lara Meike Tretschock, Dina Batarseh, Helmi Ylitalo, Nourhan Hassan, Benedikt Schäfgen, Andre Hennigs, Katharina Smetanay, Andreas Schneeweiss, Lisa Katharina Nees, Fabian Riedel and Oliver Zivanovic

Cancers 2025, 17(19), 3097; https://doi.org/10.3390/cancers17193097 - 23 Sep 2025

Abstract

Objective: This retrospective cohort study compares surgical outcomes among patients with endometrial carcinoma (EC) after the implementation of a robotic-assisted (RA) surgical program at a tertiary care center. Methods: A total of 122 EC patients who underwent surgery between March 2022 and February [...] Read more.

Objective: This retrospective cohort study compares surgical outcomes among patients with endometrial carcinoma (EC) after the implementation of a robotic-assisted (RA) surgical program at a tertiary care center. Methods: A total of 122 EC patients who underwent surgery between March 2022 and February 2025 were included. Patients were divided into two cohorts based on the implementation of RA surgery: Group 1 (March 2022–August 2023) and Group 2 (September 2023–February 2025). Data collected included demographics, surgical approach, operative time, hospital stay, completion of staging procedures, and 30-day postoperative complications. Results: RA laparoscopy was used predominantly in Group 2, replacing conventional laparoscopy (CL). Laparotomy was significantly less frequent in group 2 (11.9% vs. 36.4%; p < 0.001). Among patients with FIGO stage I, all patients underwent minimally invasive surgery (MIS) in Cohort 2 (100% vs. 71.9%; p < 0.001). Median hospital stay was significantly shorter in Group 2 (3 days vs. 4 days; p < 0.001). A 30-day mortality occurred in one patient (n = 1) within the total study cohort (0.82%) and was attributed to pulmonary embolism on postoperative day 14 after RA laparoscopy. Rates of Grade ≥3 postoperative complications were similar (7.3% vs. 7.5%), as were wound complications (5.5% vs. 3%). The use of sentinel lymph node (SLN) mapping increased significantly in Group 2 (91% vs. 54.5%; p < 0.001). Completion staging procedures were significantly reduced in group 2 (9.1% vs. 0%; p = 0.017). Conclusions: The integration of RA laparoscopy significantly reduced laparotomy rates and hospital stays while increasing SLN mapping. These results support the continued adoption of RA laparoscopy to enhance MIS and improve patient outcomes. Full article

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

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13 pages, 295 KB

Open AccessSystematic Review

Breast Cancer in Men and Quality of Life: A Systematic Review

by Milena Giovanna Guarinoni and Paolo Carlo Motta

Cancers 2025, 17(19), 3096; https://doi.org/10.3390/cancers17193096 - 23 Sep 2025

Abstract

Background: Quality of Life is a multifaceted concept, and understanding it is essential for improving symptom management, patient care, and rehabilitation. The incidence of metastatic breast cancer in men appears to be rising, with data indicating an increase from 7.2% to 10.3% over [...] Read more.

Background: Quality of Life is a multifaceted concept, and understanding it is essential for improving symptom management, patient care, and rehabilitation. The incidence of metastatic breast cancer in men appears to be rising, with data indicating an increase from 7.2% to 10.3% over the past decade. Although male breast cancer remains rare, it is crucial for nurses to identify the most effective approaches to manage these patients and enhance the quality of care provided. This study aimed to conduct a systematic literature review to determine whether studies exist that assess quality of life in men with breast cancer. Methods: The databases Web of Science, PubMed, CINAHL, Embase, Cochrane, and Wiley were systematically searched by two independent reviewers, ensuring that the studies met the predefined inclusion criteria. Results: Out of 2410 references identified, 731 articles remained after removing duplicates. Following the screening process and exclusion of records not meeting the inclusion criteria, 6 studies were ultimately included in the review. Conclusions: The tools used to assess quality of life were heterogeneous, making it impossible to draw generalizable conclusions. Full article

(This article belongs to the Special Issue Latest Advancements in Health-Related Quality of Life Research in Cancer Survivorship (2nd Edition))

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Cancers, Volume 17, Issue 19 (October-1 2025) – 33 articles

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