Sleep and Cancer
The Chimeric Antigen Receptor T Cell Target Claudin 6 Is a Marker for Early Organ-Specific Epithelial Progenitors and Is Expressed in Some Pediatric Solid Tumor Entities
Prognostic Value of Very Early Interim FDG PET/CT After Single Cycle of Chemotherapy for 10-Year Survival in Diffuse Large B-Cell Lymphoma

Journal Description

Cancers

Cancers is a peer-reviewed, open access journal of oncology, published semimonthly online by MDPI. The Irish Association for Cancer Research (IACR), Spanish Association for Cancer Research (ASEICA), Biomedical Research Centre (CIBM), British Neuro-Oncology Society (BNOS) and Spanish Group for Cancer Immuno-Biotherapy (GÉTICA) are affiliated with Cancers and their members receive a discount on the article processing charges.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
Journal Rank: JCR - Q1 (Oncology) / CiteScore - Q1 (Oncology)
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17.4 days after submission; acceptance to publication is undertaken in 2.5 days (median values for papers published in this journal in the second half of 2024).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Sections: published in 18 topical sections.
Companion journals for Cancers include: Radiation and Onco.

Impact Factor: 4.5 (2023); 5-Year Impact Factor: 4.9 (2023)

Imprint Information Journal Flyer Open Access ISSN: 2072-6694

Latest Articles

17 pages, 1054 KiB

Open AccessArticle

Immune Modulation During Treatment with Enzalutamide Alone or with Radium-223 in Patients with Castration Resistant Prostate Cancer

by Peter D. Zang, Diane M. Da Silva, Zhang-Xu Liu, Shivani Kandukuri, Denice Tsao-Wei, Anishka D’Souza, W. Martin Kast, Sumanta K. Pal, Cheryl Kefauver, Maribel Juanqueira, Lixin Yang, David I. Quinn and Tanya B. Dorff

Cancers 2025, 17(10), 1730; https://doi.org/10.3390/cancers17101730 - 21 May 2025

Abstract

Introduction: Prostate cancer has been generally resistant to immunotherapy approaches. Radiation can be immunostimulatory, but the extent to which standard prostate cancer treatments induce immune activation has not been well described. The bone-targeted radiopharmaceutical Radium223 (Ra223) has been proposed to enrich immune function, but clinical studies have not fully delineated whether this is true, or by what mechanisms. Enzalutamide has been shown to increase PD-L1 expression on dendritic cells, which could impact immune activation, though the extent to which this is associated with other evidence of immune activation remains uncertain, and combination strategies remain of interest. We performed a randomized phase II trial to evaluate whether Radium223 (Ra223) added to enzalutamide would induce greater immune activation and clinical responses compared to enzalutamide alone in men with metastatic castration-resistant prostate cancer (mCRPC). Methods: Eligible patients were randomized 2:1 to Arm A (enzalutamide 160 mg PO daily + Ra223 55 kBq/kg IV q4 weeks × 6 doses) or Arm B (enzalutamide 160 mg PO daily). Blood was collected at treatment start and during treatment to measure soluble immune checkpoint biomarkers (BTLA, TIM3, HVEM, GITR, LAG3, PD-1, CTLA-4, PD-L1, PD-L2, ICOS). Immunophenotyping by mass cytometry time of flight (CyTOF) was performed to measure peripheral blood mononuclear cell populations before and after treatment. CyTOF was used to determine changes in circulating immune cell population subsets before and after treatment. Biopsies were performed of an active bone metastatic lesion prior to study treatment and after at least 3 months. IHC was subsequently performed to examine changes in immune cell population subsets before and after treatment, and changes in pSTAT3 levels. Results: In total, 30 patients were enrolled, with median age 68. The median duration of follow up was 36 months. PSA responses, PFS, and OS were not significantly different between the two arms; however, the study was not powered for clinical endpoints. Peripheral blood and bone biopsy specimens were analyzed for immune correlatives. Soluble receptor concentrations showed significantly increased expression of PDL-2 in the combination arm, but this was not seen on CyTOF. Otherwise, there were no significant differences in markers of immune activation/exhaustion or immune cell population subsets in the combination arm and enzalutamide monotherapy arm. IHC also did not show a significant difference in immune cell population subsets in bone biopsy specimens before and after treatment in both arms. However, treatment with the combination arm did show significantly increased levels of pSTAT3 (p = 0.04), which was not seen in the enzalutamide monotherapy arm. Conclusions: Our study showed an overall lack of evidence for immune activation or cytokine induction with the combination, which does not make a strong case for combinatorial immunotherapy approaches. However, the combination did induce higher levels of pSTAT3, which has been implicated in radio-resistance. Therefore, the addition of a STAT3 inhibitor to the combination may be of interest to improve efficacy. Full article

(This article belongs to the Collection Oncology: State-of-the-Art Research in the USA)

15 pages, 934 KiB

Open AccessArticle

The Association Between Skeletal Muscle Mass and Surgical Site Infection and Prognosis in Patients Undergoing Free Flap Reconstructive Surgery for Oral Squamous Cell Carcinoma: A Single-Center, Retrospective Study

by Atsuro Noguchi, Kenji Yamagata, Satoshi Fukuzawa, Kaoru Sasaki, Shohei Takaoka, Fumihiko Uchida, Naomi Ishibashi-Kanno, Mitsuru Sekido and Hiroki Bukawa

Cancers 2025, 17(10), 1729; https://doi.org/10.3390/cancers17101729 - 21 May 2025

Abstract

Background/Objectives: Local and systemic factors, including nutritional status, influence the prognosis of oral squamous cell carcinoma (OSCC). Skeletal muscle mass (SMM) loss is a poor prognostic factor in older patients and those with cancer. Herein, we examined the SMM index (SMI), rates of surgical site infection (SSI), and prognosis of 92 patients (59 males and 33 females) who underwent resection and free flap reconstructive surgery (FFRS) between 2013 and 2021. Methods: Preoperative computed tomography was performed to measure SMM at L3. The median SMI was 45.94 and 38.03 cm²/m² in males and females, respectively. Patients were classified into low and high SMI groups based on median SMI, and overall survival (OS) was analyzed. Results: Overall, 47 (51.1%) and 45 (48.9%) patients had low and high SMIs, respectively. SSI occurred in 11 (12.0%) patients; wound dehiscence and delayed wound healing were observed in 22 (23.9%). SSI rates were not significantly different between the low and high SMI groups. Conversely, OS was significantly associated with age, pathological N (pN), extranodal extension (ENE), and SMI (high, 81.1%; low, 60.2%). Univariate analyses revealed significant associations between OS and age (≥65 vs. <65 years), SMI (low vs. high), pN (present vs. none), ENE (present vs. none), and albumin (<4.0 vs. ≥4.0 mg/dL). Cox multivariate analysis included SMI (low vs. high; hazard ratio [HR]: 2.339, 95% confidence interval [CI]: 1.008‒5.429; p = 0.015) and ENE (present vs. none; HR: 7.727, 95% CI: 3.083‒19.368; p < 0.001). Conclusions: SMI and ENE were identified as independent predictive factors of OS in patients with OSCC undergoing FFRS. Full article

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

16 pages, 818 KiB

Open AccessArticle

Charity-Provided Community-Based PSA Testing for Assessment of Prostate Cancer Risk in the UK: Clinical Implications and Future Opportunities

by Artitaya Lophatananon, Graham Fulford, Jon Young, Susan Hart, Matthew Brine and Kenneth R. Muir

Cancers 2025, 17(10), 1728; https://doi.org/10.3390/cancers17101728 - 21 May 2025

Abstract

Background: Prostate cancer is the most common malignancy among UK men, yet the lack of a national screening program creates disparities in early detection. PSA testing during primary care is inconsistent, limiting timely diagnosis. The Graham Fulford Charitable Trust (GFCT) and its associated support groups offer community-based PSA testing to help bridge this gap. Objectives: This study evaluates GFCT’s historical testing records and a participant survey (2021–2024) to assess their community-based PSA testing program, which is widely used and offers shared decision support. Additionally, we examine the GFCT’s alignment with emerging initiatives such as the UK TRANSFORM trial and other PSA screening developments across Europe and the USA. Methods: The GFCT systematically collects PSA testing data, conducting over 50,000 tests annually. The study assesses the performance of their traffic light scoring system and a previously defined combination algorithm, “Riskman”, which incorporates PSA, PSAft%, and age to classify individuals into risk categories. Multivariable logistic regression was used to evaluate and compare the predictive performance of each approach. Results: Based on the self-reported data in the survey, the GFCT’s traffic light system—using age-specific PSA thresholds to assign green, amber, or red risk—showed good predictive ability. Men in the red group had over 15-fold increased odds of clinically significant cancer (Grade Group ≥ 3) compared to those in the green group. While the Riskman score achieved a higher AUC (0.84 vs. 0.76), both tools were effective in identifying high-risk individuals. Conclusions: This study highlights the GFCT’s role in improving access to PSA screening and integrating practical risk stratification. Its alignment with evolving screening initiatives demonstrates the value of community-based, data-driven approaches for earlier detection of aggressive prostate cancer. Full article

(This article belongs to the Special Issue Cancer Causes and Control)

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21 pages, 553 KiB

Open AccessArticle

Radiological, Pathological, and Surgical Outcomes with Neoadjuvant Cemiplimab for Stage II–IV Cutaneous Squamous Cell Carcinoma in the Deep Sequencing in Cutaneous Squamous Cell Carcinomas (DISCERN) Trial

by Annette M. Lim, Benjamin Baker, Peter Lion, Christopher M. Angel, Jennifer Simmons, Bryce Jackson, Matthew Magarey, Angela Webb, Kevin Nguyen, Jo Hudson, Kwang Yang Chin, Anthony Cardin, Rajeev Ravi, Edwin Morrison, Tam Quinn, Ian Hunt and Danny Rischin

Cancers 2025, 17(10), 1727; https://doi.org/10.3390/cancers17101727 - 21 May 2025

Abstract

Background: A previous published Phase 2 trial using 2–4 doses of neoadjuvant cemiplimab in stage II–IV resectable cutaneous squamous cell carcinoma (CSCC) demonstrated that a complete pathological (pCR) rate of 51% and major pathological response (mPR) rate of 13% could be achieved with durable disease control. Methods: In this open-label, single-institution phase II trial (NCT05878288), patients with stage II–IV resectable CSCC received up to four doses of neoadjuvant cemiplimab prior to surgery. The primary endpoint of the study was to perform comprehensive molecular profiling. The focus of this report are the secondary clinical endpoints of pCR rate, mPR (defined as <10% viable tumour) rate, overall response rate (ORR) using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, immune-modified RECIST (imRECIST) and Immune PET Response Criteria in Solid Tumours (iPERCIST), disease-free survival (DFS), overall survival (OS), safety, and to describe changes in planned surgery. Results: Eleven patients were enrolled, with all proceeding with surgery. An ORR and pCR rate of 73% (8/11; 95% CI 0.39–0.93) was achieved, whilst 3/11 patients progressed on treatment. On pre-operative imaging, all 8/11 pCR patients demonstrated a partial response (RECIST 1.1), whilst 6/8 achieved a complete metabolic response and 2/8 a partial metabolic response (iPERCIST). Median follow-up was 10.2 (IQR 6.7–16.4) months. DFS was 91% (95% CI 0.57–1) and OS was 100% (95% CI 0.68–1), with one non-responder patient who developed recurrent locoregional and distant metastatic disease. There were no unexpected safety signals. Pathological features of response to neoadjuvant immunotherapy most commonly were granulomatous inflammation with keratin, fibrosis and inflammation. No cases with a dense inflammatory infiltrate were observed. Neoadjuvant immunotherapy did not impact the intra-operative planning and execution of surgery, but in the eight pCR cases, it reduced the extent of required surgery, whilst in the three non-responder cases, surgery was more extensive than originally planned. Conclusions: The DISCERN trial confirms that an excellent complete response rate can be achieved with four doses of neoadjuvant immunotherapy in stage II–IV CSCC. Proposed refinements to the pathological assessment of response and metabolic response criteria in CSCC for the neoadjuvant context are provided. Full article

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

23 pages, 2262 KiB

Open AccessReview

The Role of Nanoparticles in Therapy of Real-World Patients with Pancreatic Cancer: A Scoping Review

by Ioannis Konstantinidis, Sophia Tsokkou, Dimitrios Katsikeros, Paraskevi Chatzikomnitsa, Menelaos Papakonstantinou, Eftychia Liampou, Evdokia Toutziari, Dimitrios Giakoustidis, Petros Bageas, Vasileios Papadopoulos, Alexandros Giakoustidis and Theodora Papamitsou

Cancers 2025, 17(10), 1726; https://doi.org/10.3390/cancers17101726 - 21 May 2025

Abstract

Pancreatic cancer (PC) is one of the most aggressive and fatal malignancies worldwide, posing a significant global health challenge due to its high mortality rates, late-stage diagnosis, and limited therapeutic efficacy [...] Full article

(This article belongs to the Special Issue Management of Pancreatic Cancer)

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18 pages, 1784 KiB

Open AccessArticle

JC Polyomavirus in Prostate Cancer—Friend or Foe?

by Jacek Kiś, Dominika Sikora, Mirosław J. Jarosz and Małgorzata Polz-Dacewicz

Cancers 2025, 17(10), 1725; https://doi.org/10.3390/cancers17101725 - 21 May 2025

Abstract

Background/Objectives: Recently, many researchers have evaluated various viruses, including polyomaviruses (JCV, BKV) and EBV, as potential factors playing a role in the development and/or progression of prostate cancer (PCa), one of the most common cancers in men. Therefore, we aimed to assess the frequency of the JCPyV DNA in tissue collected from PCa patients. Methods: We detected the presence of viral DNA (PCR) in 49.6% of clinical samples, including 71.9% with single EBV infection and 28.1% with EBV/JCV co-infection. We did not detect BKV or a single JCV infection. Therefore, we compared patients with EBV mono-infection with EBV/JCV co-infected patients in the context of risk group, Gleason score, and TNM classification. Results: Our results showed differences in clinicopathological features between single EBV infection and EBV/JCV co-infection. In the group of patients with single EBV infection, most patients were classified as medium/high risk, while in the group with EBV/JCV co-infection, most patients were classified as low risk. Conclusions: Among patients with single EBV infection, a more advanced stage of cancer was observed than in EBV/JCV co-infection. Moreover, the level of anti-EBVCA and anti-EBNA antibodies as well as EBV load was higher in the case of single infection compared to EBV/JCV co-infection. Higher antibody levels were detected in more advanced tumor stages in single EBV infection. Does JCV only “reside” in prostate cells or is it a co-factor in EBV infection? In light of these studies, there is a need to clarify the role of JCV virus in the development and/or progression of prostate cancer. Full article

(This article belongs to the Special Issue Prostate Cancer Epidemiology and Genetics: 2nd Edition)

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19 pages, 1233 KiB

Open AccessArticle

From Intensification to Optimization: Balancing Efficacy, Safety, and Costs in High-Risk Localized Soft Tissue Sarcomas

by Bruno Fuchs, Georg Schelling, Christoph Glanzmann, Gabriela Studer and on behalf of the Swiss Sarcoma Network

Cancers 2025, 17(10), 1724; https://doi.org/10.3390/cancers17101724 - 21 May 2025

Abstract

Background/Objectives: The SU2C-SARC032 randomized controlled trial (RCT) tested pembrolizumab combined with preoperative normofractionated radiotherapy as an intensified treatment for high-risk stage III resectable soft tissue sarcoma (STS), demonstrating a moderate improvement in disease-free survival (DFS) compared to preoperative radiotherapy alone, but accompanied by significantly increased toxicity, prolonged treatment durations, elevated resource source, and limited real-world applicability. To address the gap between highly controlled trial outcomes and routine clinical practice, this comparative analysis evaluated a streamlined ultra-hypofractionated preoperative radiotherapy (uhpRT) protocol using real-world data (RWD) as a potentially more balanced approach. Methods: Prospectively collected observational RWD from 54 consecutive patients with Stage III (T2 N0 M0) high-risk resectable STS treated at a single institution with uhpRT (25 Gy in 5 fractions in one week, no systemic therapy, median interval of 14 days to surgery) were analyzed. Survival endpoints (overall survival [OS], DFS, local disease-free survival [LDFS], distant disease-free survival [DDFS]), toxicity, and treatment duration were compared qualitatively with published outcomes from the SU2C-SARC032 trial’s intensified pembrolizumab arm and control arm. Results: At 2 years, the optimized uhpRT protocol achieved OS (90%), DFS (66%), and DDFS (70%) comparable to the intensified pembrolizumab arm (OS: 88%, DFS: 67%, DDFS (67%)) and clearly exceeded outcomes of the control arm (OS/DFS/DDFS: 85%/52%/52%). Importantly, the uhpRT protocol markedly reduced treatment-related toxicities (0% Grade 3/4 events vs. 56% in the intensified trial arm) and total treatment duration (<1 month vs. 3–11 months). Conclusions: These findings challenge the necessity of broad treatment intensification for high-risk localized STS, strongly supporting the concept of therapeutic optimization. Given substantial real-world variability in treatment practices and feasibility highlighted by recent research, our findings advocate for treatment strategies that prioritize realistic applicability, patient safety, and value-based care principles over pure intensification. Full article

(This article belongs to the Section Cancer Therapy)

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27 pages, 5360 KiB

Open AccessReview

Positron Emission Tomography Radiotracers for Identification of Site of Recurrence in Prostate Cancer After Primary Treatment Failure

by Ryan Bitar, Pablo Zurita, Lucia Martiniova, Amado J. Zurita and Gregory C. Ravizzini

Cancers 2025, 17(10), 1723; https://doi.org/10.3390/cancers17101723 - 21 May 2025

Abstract

Despite substantial improvement in the definitive management of primary prostate cancer, a significant number of patients experience biochemical recurrence—a clinical state in which serum prostate-specific antigen (PSA) levels rise prior to the development of physical signs or symptoms. The early detection and localization of biochemical recurrence may confer eligibility for salvage therapy; therefore, imaging techniques that provide accurate disease visualization are imperative. In this review, we discuss various imaging methods for localizing disease in the context of biochemical recurrence in prostate cancer. Particularly, we describe available or investigational positron emission tomography (PET) radiotracers, such as ¹⁸F-FDG, ¹⁸F-NaF, choline (both ¹⁸F and ¹¹C), the ¹⁸F-labeled amino acid derivative fluciclovine, prostate-specific membrane antigen (PSMA) radioligands, and the short peptide compound bombesin. Generally, PET radiotracers such as ¹⁸F-FDG, ¹⁸F-NaF, and ¹⁸F/¹¹C choline have fallen out of favor because of their inferior sensitivity and/or specificity in relation to more recently developed radiotracers. ¹⁸F-fluciclovine has addressed these shortcomings by exploiting the upregulation of amino acid transporters in tumors; however, PSMA-targeting agents have significantly advanced the management of biochemical recurrence of prostate cancer through their high sensitivity and specificity, enabling the identification of candidates for radionuclide therapy. Investigational agents, such as bombesin-based radiotracers, may address the shortcomings of treating prostate cancer with little to no PSMA expression. Full article

(This article belongs to the Special Issue Advancements in the Diagnosis and Surgical Treatment of Prostate Cancer)

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11 pages, 316 KiB

Open AccessPerspective

Optimising Cancer Medicine in Clinical Practices: Are Neoadjuvant and Adjuvant Immunotherapies Affordable for Cancer Patients in Low- and Middle-Income Countries?

by Rashidul Alam Mahumud

Cancers 2025, 17(10), 1722; https://doi.org/10.3390/cancers17101722 - 21 May 2025

Abstract

Cancer immunotherapy, encompassing neoadjuvant and adjuvant interventions, has transformed treatment paradigms in multiple malignancies by leveraging the host immune system to combat tumour cells. While immunotherapies have demonstrated remarkable efficacy, particularly immune checkpoint inhibitors, high treatment costs undermine their accessibility and affordability in low- and middle-income countries (LMICs). This paper provides a prospective overview of the clinical benefits of neoadjuvant and adjuvant immunotherapies, examines the barriers to implementing these treatments in LMICs, and suggests potential strategies to improve equitable access. Such interventions necessitate a combined effort from healthcare providers, policymakers, and stakeholders to ensure their sustainable integration into global cancer care. Full article

(This article belongs to the Special Issue Perioperative and Neoadjuvant Immunotherapy in Non-Small Cell Lung Cancer)

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14 pages, 1477 KiB

Open AccessArticle

Global Burden of Rare Cancers: Insights from GLOBOCAN 2022 Estimates

by Mohammed Elmadani, Simon Klara, Mohammed Mustafa, Evans Kasmai Kiptulon and Mate Orsolya

Cancers 2025, 17(10), 1721; https://doi.org/10.3390/cancers17101721 - 21 May 2025

Abstract

Background: Rare cancers, defined as those with an incidence rate of fewer than 6 cases per 100,000 individuals, contribute to a substantial portion of the global cancer burden. Despite their impact, they receive less attention than more common malignancies, leading to challenges in early detection, treatment strategies, and research funding. This study aims to assess the global incidence and mortality patterns of rare cancers in 2022 to better understand their contribution to the overall cancer burden and regional disparities. Methods: We conducted a comprehensive analysis using 2022 GLOBOCAN estimates to assess the global incidence and mortality of rare cancers. The study included 24 major rare cancers, such as bladder cancer, leukemia, non-Hodgkin lymphoma, esophageal cancer, and pancreatic cancer. Age-standardized rates (ASRs) were calculated to compare cancer burden across continents, and absolute case and death counts were reported. Results: In 2022, rare cancers accounted for 26.7% of all new cancer cases (5,347,784 cases) and 30% of all cancer-related deaths (2,959,369 deaths) worldwide. Bladder cancer was the most common rare cancer, with an incidence rate of 5.58 per 100,000, followed by non-Hodgkin lymphoma (5.57) and leukemia (5.26). Mortality rates were highest for pancreatic, esophageal, and brain cancers, reflecting their aggressive nature and limited treatment options. Significant regional disparities were observed, with Europe and North America reporting the highest incidence rates for bladder cancer and leukemia, while Asia bore the largest absolute burden of rare cancers. Conclusions: Rare cancers represent a considerable share of the global cancer burden, with notable geographic variations in incidence and mortality. These findings underscore the need for improved early detection, expanded treatment access, and targeted research efforts to address disparities and improve outcomes for patients with rare cancers worldwide. Full article

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

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14 pages, 694 KiB

Open AccessArticle

The Italian Score for Organ Allocation: A Ten-Year Monocentric Retrospective Analysis in Liver Transplantation for Hepatocellular Carcinoma

by Enrico Prosperi, Matteo Cescon, Quirino Lai, Chiara Bonatti, Edoardo Prosperi, Francesca Rizzo, Lorenzo Maroni, Andrea Laurenzi, Matteo Serenari, Maria Cristina Morelli and Matteo Ravaioli

Cancers 2025, 17(10), 1720; https://doi.org/10.3390/cancers17101720 - 21 May 2025

Abstract

Background: The Italian Score for Organ Allocation (ISO), a transplant benefit oriented allocation system, was introduced in Italy in 2016. The main objective of this study is to identify risk factors for Drop-Out in hepatocellular (HCC) patients enlisted for LT before (Pre-ISO Era) and after ISO (ISO Era) introduction, while the secondary objective is to evaluate the survival results. Methods: CIFs for liver transplantation and Drop-Out were estimated and compared between eras. Factors associated with Drop-Out were identified through multivariable competing risks regression. Survival results were compared using the log-rank test. Results: Between 2011 and 2020, 410 patients with HCC were listed for LT. We observed 103 vs. 217 LT and 49 vs. 41 Drop-Outs (p < 0.001) during the Pre-ISO and ISO Era, respectively. In the multivariable analysis, ISO ([sHR] 0.43; 95%CI 0.28–0.66, p < 0.001) and Alcoholic Cirrhosis ([sHR] 0.27, 95%CI 0.11–0.70; p = 0.007) were revealed to be protective factors for Drop-Out. One year after listing, the CI for Drop-Out decreased from 13.2% to 6.2% (p = 0.02). Despite no differences observed in post-LT survival, a significant difference in the intention-to-treat survival from enlisting was found (p = 0.0019). Conclusions: Among other factors, ISO results were protective for the Drop-Out risk in HCC patients awaiting LT, with a benefit in ITT-OS survival. Full article

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

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16 pages, 803 KiB

Open AccessReview

The Role of Microbiota in Upper Gastrointestinal Cancers

by Giovanni Marasco, Luigi Colecchia, Daniele Salvi, Angelo Bruni, Cecilia Capelli, Elton Dajti, Maria Raffaella Barbaro, Cesare Cremon, Vincenzo Stanghellini and Giovanni Barbara

Cancers 2025, 17(10), 1719; https://doi.org/10.3390/cancers17101719 - 21 May 2025

Abstract

The gut microbiota significantly impacts the development and progression of upper gastrointestinal (GI) cancers, including esophageal and gastric cancers. Microbial dysbiosis contributes to carcinogenesis through mechanisms such as inflammation, immune modulation, and direct DNA damage. Techniques for sampling oral, esophageal, and gastric microbiota vary, with standardization being essential for reliable results. Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) are associated with an enrichment of Gram-negative bacteria, promoting inflammation and cancer progression. Esophageal squamous cell carcinoma (ESCC) also shows distinct microbial patterns, with reduced diversity and increased harmful bacteria like Porphyromonas gingivalis and Fusobacterium nucleatum. In gastric cancer (GC), Helicobacter pylori (HP) and non-HP gastric microbiota play significant roles, with diverse microbial communities contributing to cancer development through nitrate reduction, immune modulation, and inflammation. Emerging evidence highlights the role of non-HP bacteria in promoting carcinogenesis, with specific taxa like Fusobacterium nucleatum and Lactobacillus influencing tumor growth and immune evasion. Further research is needed to elucidate the complex interactions between gut microbiota and upper GI cancers, paving the way for novel diagnostic and therapeutic approaches. Understanding these microbial dynamics offers potential for microbiota-based interventions, improving the early detection, prognosis, and treatment of upper GI cancers. This comprehensive review summarizes the available evidence on the role of microbiota in upper GI oncology and the need for continued exploration in this field. Full article

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

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10 pages, 1870 KiB

Open AccessArticle

Evaluation of Tumor Budding and Poorly Defined Clusters as Histological Biomarkers in Squamous Cell Carcinomas of the Vulva

by Gilbert Georg Klamminger, Annick Bitterlich, Bashar Haj Hamoud, Erich-Franz Solomayer, Martin Ertz, Laura Schnöder, Bernd Holleczek, Walburgis Brenner, Annette Hasenburg, Mathias Wagner and Meletios P. Nigdelis

Cancers 2025, 17(10), 1718; https://doi.org/10.3390/cancers17101718 - 21 May 2025

Abstract

Background/Objectives: Several histopathological risk factors have been examined in vulvar cancer (VC) so far. However, the prognostic relevance of morphological biomarkers such as tumor budding (TB) and poorly defined clusters (PDCs) remains to be determined. Material and Methods: We histologically analyzed the formation of peritumoral and intratumoral TB and PDCs in a cohort of 157 patients with VC. We assessed their association with clinico-pathological features and evaluated their prognostic impact in terms of the risk of local recurrence and occurrence of metastasis (Fisher’s exact test) as well as overall survival (Log-rank test). Results: We determined a distinct prognostic relevance of peritumoral TB with regard to occurrence of metastasis (Fisher’s exact test; p = 0.0415) as well as a significant reduced risk of local recurrence in the group with absent intratumoral TB (Fisher’s exact test; p = 0.0004). Furthermore, we showed that patients without peritumoral budding formation had a significant superior prognosis in terms of overall survival (p = 0.0366, x² = 4.370). Conclusions: This study shows that several new histomorphological biomarkers may serve useful in predicting the clinical course of patients with VC, identifying patients at a lower risk of developing metastases/local recurrence as well as improved overall survival. Full article

(This article belongs to the Special Issue Biomarkers for Gynecological Cancers)

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17 pages, 1905 KiB

Open AccessSystematic Review

The Impact of Prophylactic Negative Wound Pressure Treatment (NWPT) on Surgical Site Occurrences After Gynecologic Cancer Surgery: A Meta-Analysis of Randomized Controlled and Observational Cohort Studies

by Maximos Frountzas, Ioannis Karavolias, Christina Nikolaou, Orsalia Toutouza, Vasilios Pergialiotis and Konstantinos G. Toutouzas

Cancers 2025, 17(10), 1717; https://doi.org/10.3390/cancers17101717 - 20 May 2025

Abstract

Background: Surgical site infections (SSIs) remain a serious problem following abdominal surgery due to gynecologic malignancies leading to increased hospitalization, high costs, and delays in adjuvant treatments; thus, SSIs affect overall survival. The aim of the present meta-analysis was to investigate the impact of closed incision–negative pressure wound treatment (ci-NPWT) systems on postoperative surgical site occurrences (SSOs) after gynecologic oncology surgery. Methods: The present meta-analysis was designed using the PRISMA guidelines. A search in several databases was conducted from inception until March 2025. Results: Overall, five studies were included; these studies enrolled 1174 patients in total, where 412 were treated with ci-NPWT systems and 762 were treated with conventional gauze. Patients treated with ci-NPWT systems presented with lower SSI rates (OR 0.40, 95% CI 0.15–1.10, p = 0.08), lower fascial dehiscence rates (OR 0.72, 95% CI 0.21–2.42, p = 0.59), and lower seroma formation rates (OR 0.70, 95% CI 0.25–1.93, p = 0.49), although statistical significance was not reached in all comparisons. On the other hand, patients treated with ci-NPWT systems also presented with higher postoperative hematoma formation rates (OR 1.38, 95% CI 0.32–5.99, p = 0.66), although statistical significance was not reached. Preoperative patient characteristics, operative parameters, and cancer characteristics were similar among the two study groups. Conclusions: The prophylactic use of ci-NPWT systems showed promising results in reducing postoperative SSOs after gynecologic cancer surgery. Nevertheless, prospectively designed studies are needed in the future to reach robust evidence that would enable the wide implementation of such devices in routine clinical practice. Full article

(This article belongs to the Special Issue Perioperative Care in Gynecologic Oncology: 2nd Edition)

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26 pages, 9951 KiB

Open AccessArticle

Establishment of Two Novel Ovarian Tumor Cell Lines with Characteristics of Mucinous Borderline Tumors or Dedifferentiated Carcinoma—Implications for Tumor Heterogeneity and the Complex Carcinogenesis of Mucinous Tumors

by Hasibul Islam Sohel, Umme Farzana Zahan, Tohru Kiyono, Masako Ishikawa, Sultana Razia, Kosuke Kanno, Hitomi Yamashita, Shahataj Begum Sonia, Kentaro Nakayama and Satoru Kyo

Cancers 2025, 17(10), 1716; https://doi.org/10.3390/cancers17101716 - 20 May 2025

Abstract

Background/objective: Mucinous borderline tumors of the ovary (MBOTs) are characterized by their unique histological features and intermediate malignant potential; however, the factors underlying their molecular carcinogenesis and tumor biology remain largely unknown. Developing cell lines from these tumors presents an ongoing challenge. The purpose of this study is to establish MBOT cell lines and characterize their biological features. Methods: Epithelial cells were collected and purified from surgically removed MBOT samples and then stably maintained with an extended life span by overexpressing CyclinD1/CDK4 in combination with human telomerase reverse transcriptase. The characterization of resulting cell lines was defined by morphology, growth kinetics, functional analysis, whole-exome sequencing, and tumorigenicity in mice. Results: Two independent cell lines, HMucBOT-1 and HMucBOT-2, were successfully established from the tissues of a patient with an MBOT, with the latter showing more aggressive growth capacity. In the patient-derived xenograft model, HMucBOT-1 cells retained the original morphological characteristics of the MBOT, whereas HMucBOT-2 cells displayed a transition to mucinous carcinoma accompanying undifferentiated carcinoma, suggestive of dedifferentiated carcinoma. Genetic analysis of the original tumor sample and HMucBOT-2 cells revealed shared oncogenic mutations. However, KRAS amplification and certain copy number alterations were uniquely observed in the HMucBOT-2 cells. Conclusions: The above results indicate that HMucBOT-1 can serve as a preclinical model for investigating the biological behavior of and potential targeted therapies for human MBOTs, with HMucBOT-2 serving as a valuable tool for studying the heterogeneity and genetic diversity of this tumor and explaining the potential causes of treatment failure or relapse. Full article

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

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12 pages, 1171 KiB

Open AccessArticle

Survival Outcomes of Luminal Metastatic Breast Cancer Patients According to Changes in Molecular Subtype at Re-Biopsy: Insights from the GIM-13—AMBRA Study

by Marina Elena Cazzaniga, Paolo Pronzato, Domenico Amoroso, Grazia Arpino, Francesco Atzori, Alessandra Beano, Laura Biganzoli, Giancarlo Bisagni, Livio Blasi, Cristina Capello, Rita Chiari, Alessia D’Alonzo, Michelino De Laurentiis, Angela Denaro, Alessandra Fabi, Daniele Farci, Francesco Ferraù, Elena Fiorio, Alessandra Gennari, Francesco Giotta, Filippo Giovanardi, Vanesa Gregorc, Lorenzo Livi, Emanuela Magnolfi, Anna Maria Mosconi, Raffaella Palumbo, Palma Pugliese, Carlo Putzu, Giuseppina Rosaria Rita Ricciardi, Ferdinando Riccardi, Laura Scortichini, Simon Spazzapan, Pierosandro Tagliaferri, Nicola Tinari, Giuseppe Tonini, Anna Maria Vandone and Giorgio Mustacchi Show full author list Hide full author list

Cancers 2025, 17(10), 1715; https://doi.org/10.3390/cancers17101715 - 20 May 2025

Abstract

Introduction: The treatment of MBC patients is guided by receptor status, with re-biopsy at relapse recommended to reassess hormone receptor (HR) status. Various treatment options are available for HER2-veMBC, including CDK4/6 inhibitors, PARP inhibitors, and checkpoint inhibitors. The study highlights the importance of determining receptor subtype for guiding treatment choices. Patients and Methods: The GIM 13 AMBRA study is a longitudinal cohort study involving 42 centers in Italy. It includes data from 939 HER2- MBC patients enrolled between May 2015 and September 2020. The study analyzes the impact of HR expression changes on clinical outcomes using Kaplan–Meier survival curves and other statistical methods. Results: Among the 939 patients, 588 were rebiopsied at first relapse. The study found no significant differences in disease-free survival (DFS), progression-free survival (PFS), or overall survival (OS) between patients whose tumors changed molecular subtype and those who did not. However, post-progression survival from first-line treatment (PPS1) was different between the two groups. Discussion: The study confirms the phenomenon of receptor discordance between primary tumors and metastases. It emphasizes the need for re-biopsy in recurrent MBC to guide treatment strategies. The findings align with previous studies and highlight the importance of understanding receptor changes for improving patient outcomes. Conclusions: The GIM 13 AMBRA study provides valuable insights into the impact of molecular subtype changes on survival outcomes in Luminal MBC patients. It underscores the importance of re-biopsy and personalized treatment strategies in managing metastatic breast cancer. Full article

(This article belongs to the Special Issue New Perspectives in the Management of Breast Cancer)

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14 pages, 600 KiB

Open AccessSystematic Review

Active Surveillance in Non-Muscle Invasive Bladder Cancer: A Systematic Review

by Míriam Campistol, Fernando Lozano, Albert Carrion, Carles Xavier Raventós, Juan Morote and Enrique Trilla

Cancers 2025, 17(10), 1714; https://doi.org/10.3390/cancers17101714 - 20 May 2025

Abstract

Bladder cancer is the ninth most common cancer globally, with most cases classified as non-muscle-invasive bladder cancer (NMIBC). While transurethral resection of the bladder tumor (TURBT) remains the gold-standard treatment, its complications, high recurrence rates, and economic burden have prompted interest in alternative strategies like active surveillance (AS) for low-grade and low-grade NMBIC recurrences. AS minimizes surgical interventions and patient burden, but lacks standardized protocols for inclusion criteria and follow-up schedules. Most studies suggest intensive monitoring during the first year, with criteria often based on tumor size, number, and grade. Acquisition of evidence: A comprehensive literature search was conducted in December 2024 using Pubmed, Cochrane, and Trip databases to identify studies on AS for low-grade NMBIC recurrences. Only English studies were included, with Boolean operators used to refine the search. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Population, Intervention, Comparison and Outcomes (PICO) selection criteria were followed. The Newcastle–Ottawa quality assessment scale was used to analyze the quality of the included studies. Evidence synthesis: This systematic review included 11 studies evaluating AS for NMIBC. Early studies, such demonstrated AS as a feasible alternative to TURBT, with low progression rates. Subsequent research confirmed its safety in selected patients, with tumor growth and positive cytology being the main reasons for intervention. More recent investigations, further supported AS as a viable strategy, highlighting the low risk of stage and grade progression and its potential to reduce surgical interventions. Conclusions: AS may be considered an alternative approach for low-risk NMIBC recurrences. However, there is need for prospective studies and personalized approaches to optimize AS, addressing follow-up strategies, inclusion criteria and progression thresholds. Full article

(This article belongs to the Special Issue Systematic Reviews and Meta-Analyses of Genitourinary Cancers (2nd Edition))

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21 pages, 10416 KiB

Open AccessArticle

Combinational Radiotherapies Improve Brain Cancer Treatment at High Dose Rates In Vitro

by Michael Valceski, Elette Engels, Sarah Vogel, Jason Paino, Dylan Potter, Carolyn Hollis, Abass Khochaiche, Micah Barnes, Alice O’Keefe, Matthew Cameron, Kiarn Roughley, Anatoly Rosenfeld, Michael Lerch, Stéphanie Corde and Moeava Tehei

Cancers 2025, 17(10), 1713; https://doi.org/10.3390/cancers17101713 - 20 May 2025

Abstract

Background/objectives: Brain cancer remains difficult to treat, with survival statistics stagnant for decades. The resistance of glioblastoma brain tumours can greatly challenge the effectiveness of conventional cancer radiotherapy. However, high dose rate radiotherapy has unique effects that allow for normal tissue sparing whilst maintaining tumour control. The addition of targeted radiosensitisers, such as the chemotherapeutic drug methotrexate (MTX) or the high-Z halogenated pyrimidine drug iododeoxyuridine (IUdR), can improve radiotherapy outcomes. Combining these radiosensitiser agents with ultra-high dose rate (UHDR) synchrotron X-rays can bear synergistic effects to enhance the efficacy of these multi-modal UHDR therapies, providing a means to overcome the radioresistance of brain cancer. Methods: Here, we use controlled in vitro assays following treatment, including a clonogenic assay to determine long-term cell survival and γH2AX immunofluorescent confocal microscopy to quantify double-strand DNA breaks (DSBs). Results: We find significant enhancement for highly synergistic combinations of IUdR+MTX with synchrotron X-rays. Cell survival results demonstrate 5.4 times increased 9L gliosarcoma cell killing when these agents are combined with UHDR synchrotron X-rays compared with conventional X-rays alone at the same 5 Gy dose. The underlying mechanisms are unveiled using γH2AX imaging and reveal significant increases in DSBs and dying cells following exposure to UHDR radiation. Conclusions: Our results demonstrate that highly synergistic combination treatments using UHDR synchrotron radiation can yield significantly improved brain cancer killing compared with conventional radiotherapy. We anticipate that these additive, multi-modal combination therapies will provide options for more targeted and effective use of radiotherapies for the future treatment of brain cancer. Full article

(This article belongs to the Section Cancer Therapy)

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11 pages, 451 KiB

Open AccessArticle

The Role of Social Support in Buffering the Financial Toxicity of Breast Cancer: A Qualitative Study of Patient Experiences

by Ramona G. Olvera, Sara P. Myers, Alice A. Gaughan, Willi L. Tarver, Sandy Lee, Karen Shiu, Laura J. Rush, Tessa Blevins, Samilia Obeng-Gyasi and Ann Scheck McAlearney

Cancers 2025, 17(10), 1712; https://doi.org/10.3390/cancers17101712 - 20 May 2025

Abstract

Background/Objectives: Financial distress from the direct and indirect costs of cancer treatment is a critical issue for many patients with breast cancer, particularly those from underserved populations who may be more vulnerable to financial hardship and its negative impacts on quality of life and clinical outcomes (i.e., financial toxicity). Few investigations, however, focus on protective factors that safeguard against financial toxicity. This study explores how social support might reduce financial toxicity among patients with breast cancer who are at high risk for financial hardship. Methods: We analyzed interviews with 41 adult women treated for stage I-IV breast cancer that had been conducted between December 2021 and March 2022. Our study specifically sampled women considered to be at elevated risk for financial toxicity: young adults aged 18–40 years old, Black women, women with lower incomes, and those residing in rural communities. We used deductive and inductive coding to identify themes related to social support. Results: Interviewees reported receiving support from family, friends, and their communities during their treatments. They noted how this social support helped with direct and indirect costs, encouraged emotional wellbeing, and safeguarded against economizing behaviors that offset spending (e.g., financial tradeoffs that jeopardize their treatment plan). Conclusions: Patients with breast cancer from groups vulnerable to financial toxicity often rely on the support of family, friends, and their communities to help buffer financial distress from the costs of treatment. These data highlight social support as an area for future studies exploring strategies to mitigate financial toxicity. Full article

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

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20 pages, 1969 KiB

Open AccessArticle

Early Immune Checkpoint Inhibitor Administration Increases the Risk of Radiation-Induced Pneumonitis in Patients with Stage III Unresectable NSCLC Undergoing Chemoradiotherapy

by Yiwei Qin, You Mo, Pengwei Li, Xinyi Liang, Jinming Yu and Dawei Chen

Cancers 2025, 17(10), 1711; https://doi.org/10.3390/cancers17101711 - 20 May 2025

Abstract

Background/Objectives: The PACIFIC trial showed that immune checkpoint inhibitors (ICI) administered after concurrent chemoradiotherapy (cCRT) significantly improve survival in stage III unresectable non-small cell lung cancer (NSCLC). However, the optimal timing of ICI administration with cCRT is still debated, with concerns about increased risks of adverse effects, particularly radiation-induced pneumonitis (RP), from combining radiotherapy and immunotherapy. Methods: A search of multiple databases identified studies on stage III unresectable NSCLC patients receiving cCRT and ICI. A meta-analysis was performed utilizing the meta package in R software. Furthermore, data from 170 patients treated at Shandong Cancer Hospital and Institute between 2019 and 2023 were analyzed to assess RP following cCRT and ICI treatment. Results: The meta-analysis revealed that the incidences of ≥grade 2 RP were 25.3%, 24.3%, and 45.3% in the ICI following cCRT group, the ICI concurrent with cCRT group, and the ICI prior to cCRT group, respectively. The ICI prior to cCRT group exhibited significantly elevated rates. In the clinical retrospective study, ≥grade 2 RP was more prevalent in the ICI concurrent with cCRT group (HR: 2.258, 95% CI: 1.135–4.492, p = 0.020) and the ICI prior to cCRT group (HR: 2.843, 95% CI: 1.453–5.561, p = 0.002) compared with the ICI following cCRT group. Furthermore, a shorter interval between treatments correlates with an increased incidence of RP. Conclusions: Advancing the timing of ICI administration is associated with an increased incidence of ≥grade 2 RP following cCRT in patients with stage III unresectable NSCLC. Full article

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

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