Cancers

16 pages, 2494 KiB

Open AccessArticle

Magrolimab Therapy in Conjunction with Conventional Chemotherapeutics Slows Disease Progression in Pediatric Acute Myeloid Leukemia Patient-Derived Xenograft Models

by Julia G. Kim, Sohani K. Sandhu, Ritesh V. Dontula, Josh J. Cooper, Jaden Sherman, Max Rochette, Rehan Siddiqui, Lana E. Kim, Michelle S. Redell and Alexandra M. Stevens

Cancers 2025, 17(9), 1509; https://doi.org/10.3390/cancers17091509 (registering DOI) - 29 Apr 2025

Abstract

Background/Objectives: Magrolimab (Magro) is a humanized naked anti-CD47 monoclonal antibody that blocks the SIRPα CD47 interaction, allowing macrophages to target and destroy cancer cells. To evaluate its preclinical efficacy in vivo, Magro was tested as a single agent and in combination with conventional [...] Read more.

Background/Objectives: Magrolimab (Magro) is a humanized naked anti-CD47 monoclonal antibody that blocks the SIRPα CD47 interaction, allowing macrophages to target and destroy cancer cells. To evaluate its preclinical efficacy in vivo, Magro was tested as a single agent and in combination with conventional chemotherapy drugs, Cytarabine (Ara-C) or Azacitidine (Aza), in three pediatric AML (pAML) patient-derived xenograft (PDX) models—AML006 (KMT2A::MLLT1), AML010 (+10, WT1), and AML013 (KMT2A::MLLT4). Methods: After PDX model establishment, mice were assigned to treatment groups hulgG4 (VC, vehicle control for Magro), Magro, Ara-C + VC, Aza + VC, Ara-C + Magro, and Aza + Magro, and then followed for survival. Mice that met humane euthanasia endpoints and at the culmination of experimental timelines had tissues harvested to measure disease burden. Results: Magro alone significantly improved survival in AML006 (p < 0.0001) and AML013 (p = 0.003) and decreased bone marrow (BM) disease burden in AML006 (p = 0.009) and AML013 (p = 0.002). Ara-C + Magro therapy led to significantly improved survival in all three models and significantly decreased BM disease burden in AML006 (p < 0.0001) and AML013 (p = 0.048). Aza + Magro therapy led to significantly improved survival in AML013 (p = 0.047) and AML010 (p = 0.017) and significantly lower BM disease burden in AML010 (p = 0.001). Conclusions: Interestingly, the two models that demonstrated improvement in survival with Magro harbored KMT2A rearrangements, suggesting a subset of patients that may be more responsive to the effects of CD47 blockade. As this drug is being evaluated for use in other malignancies, future studies may focus on investigating the importance of biomarker-based patient selection. Full article

(This article belongs to the Special Issue New Approaches to Biology and Treatment of Acute Leukemia)

► Show Figures

Figure 1

23 pages, 1215 KiB

Open AccessSystematic Review

Ossifying Fibromyxoid Tumor of Soft Parts in the Head and Neck: A Systematic Review Addressing Surgical Management and Adjuvant Therapies

by Gianluca Scalia, Valentina Zagardo, Zubayer Shams, Gianluca Ferini, Salvatore Marrone, Eliana Giurato, Francesca Graziano, Giancarlo Ponzo, Massimiliano Giuffrida, Massimo Furnari, Giuseppe Emmanuele Umana and Giovanni Federico Nicoletti

Cancers 2025, 17(9), 1508; https://doi.org/10.3390/cancers17091508 (registering DOI) - 29 Apr 2025

Abstract

Background: Ossifying fibromyxoid tumors (OFMTs) are rare mesenchymal neoplasms with behaviors ranging from benign to malignant. Although most occur in the extremities and trunk, 9–13% are found in the head and neck, such as the oral cavity, scalp, and calvarium. Diagnosis is [...] Read more.

Background: Ossifying fibromyxoid tumors (OFMTs) are rare mesenchymal neoplasms with behaviors ranging from benign to malignant. Although most occur in the extremities and trunk, 9–13% are found in the head and neck, such as the oral cavity, scalp, and calvarium. Diagnosis is challenging due to their rarity and histological similarity to other neoplasms. This review synthesizes evidence on the clinical presentation, diagnostic features, and treatment outcomes of OFMTs in the head and neck, focusing on surgical management and adjuvant therapies. Methods: A systematic review was conducted according to PRISMA guidelines, with searches in PubMed/MEDLINE, Embase, Scopus, and Web of Science. Studies from 1989 to 2024 reporting OFMTs in the head and neck with clinical, histopathological, and treatment data were included. Extracted data encompassed demographics, tumor features, surgical margins, adjuvant therapy, and outcomes. Results: Forty studies with 99 patients were included. Patient ages ranged from 3 weeks to 88 years (median 47), with a male predominance (63.64%). The most common presentation was a slow-growing, painless mass. Tumors were most often found in the neck, oral cavity, scalp, and calvarium. Histopathology revealed encapsulated tumors with fibromyxoid stroma, spindle-shaped cells, and a peripheral rim of metaplastic bone in 70% of cases. Immunohistochemistry showed positivity for S-100, vimentin, and SOX10. Surgical excision was the main treatment, used in 28.28% of cases, with recurrence in 9.09% and no metastases. Adjuvant therapies, mainly radiotherapy, were employed in 15.15% of cases. Conclusions: OFMTs of the head and neck are rare neoplasms requiring multidisciplinary care. Imaging, histopathology, and immunohistochemistry are key to diagnosis. Surgical excision with clear margins remains the primary treatment, with a low recurrence rate. Adjuvant therapy may be needed for malignant or incompletely excised cases. Further research is needed to optimize follow-up protocols and assess molecular profiling for risk stratification. Full article

(This article belongs to the Section Cancer Therapy)

14 pages, 550 KiB

Open AccessArticle

Clinical Outcomes and Prognostic Factors for Extramammary Paget’s Disease Treated with Radiation Therapy: A Multi-Institutional Observational Study

by Masanari Niwa, Natsuo Tomita, Hiromichi Ishiyama, Hijiri Kaneko, Yukihiko Oshima, Hirota Takano, Masayuki Matsuo, Mayu Kuno, Akifumi Miyakawa, Shinya Otsuka, Taiki Takaoka, Dai Okazaki, Akira Torii, Nozomi Kita, Seiya Takano, Motoki Nakamura, Hiroshi Kato, Akimichi Morita and Akio Hiwatashi

Cancers 2025, 17(9), 1507; https://doi.org/10.3390/cancers17091507 (registering DOI) - 29 Apr 2025

Abstract

Background: Extramammary Paget’s disease (EMPD) is a rare cutaneous carcinoma that typically affects the elderly and is frequently observed in genital and perianal regions. We analyzed the outcomes and prognostic factors for EMPD after radiation therapy (RT). Methods: We analyzed data [...] Read more.

Background: Extramammary Paget’s disease (EMPD) is a rare cutaneous carcinoma that typically affects the elderly and is frequently observed in genital and perianal regions. We analyzed the outcomes and prognostic factors for EMPD after radiation therapy (RT). Methods: We analyzed data from 81 patients with non-metastatic EMPD who received either RT alone or in combination with surgery and/or chemotherapy. The median radiation dose was 56 Gy in 28 fractions. Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were calculated using the Kaplan–Meier method. Multivariate analyses were performed using the Cox proportional hazards model. Late adverse events were evaluated by NCI-CTCAE version 5.0. Results: The median age was 78 years, and the median follow-up period was 36 months. The three-year LC, PFS, and OS rates were 75%, 52%, and 80%, respectively. Multivariate analyses identified the presence of lymph node (LN) metastasis, the absence of surgery, and the omission of elective nodal irradiation (i.e., local irradiation only) as significant factors for unfavorable LC (p = 0.01, 0.02, and 0.006) and PFS (p = 0.001, 0.04, and 0.03). LN metastasis was also a significant factor for unfavorable OS (p = 0.005). One patient developed grade 2 skin infection, and another developed grade 3 lymphedema; no grade 4 or higher toxicity was observed. Conclusion: The present results revealed prognostic factors for EMPD after RT and suggest that the absence of surgery and omission of elective nodal irradiation worsened outcomes. A prospective study is needed to establish an optimal treatment strategy for this rare malignancy, which is common in the elderly. Full article

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

13 pages, 821 KiB

Open AccessArticle

Assessment of p53 in Endometrial Carcinoma Biopsy and Corresponding Hysterectomy Cases in a Real-World Setting: Which Cases Need Molecular Work-Up?

by Marie-Lisa Eich, Janna Siemanowsk-Hrach, Uta Drebber, Nicolaus Friedrichs, Peter Mallmann, Christian Domröse, Dominik Ratiu, Sabine Merkelbach-Bruse, Reinhard Büttner, Alexander Quaas and Birgid Schömig-Markiefka

Cancers 2025, 17(9), 1506; https://doi.org/10.3390/cancers17091506 (registering DOI) - 29 Apr 2025

Abstract

Background/Objectives: The WHO classifies endometrial cancer into molecular subgroups, including tumors with abnormal p53 expression. In clinical practice, the p53 status can be assessed using either biopsy or hysterectomy samples. This study aimed to evaluate the correlation between p53 immunohistochemistry (IHC) and TP53 [...] Read more.

Background/Objectives: The WHO classifies endometrial cancer into molecular subgroups, including tumors with abnormal p53 expression. In clinical practice, the p53 status can be assessed using either biopsy or hysterectomy samples. This study aimed to evaluate the correlation between p53 immunohistochemistry (IHC) and TP53 molecular status in both tissue types and assess interobserver variability among five pathologists. Methods: We analyzed 98 endometrial biopsies and 86 hysterectomy samples from 101 patients (83 matched cases). Five pathologists with varying experience independently assessed p53 IHC staining. Targeted panel sequencing was performed on 169 of 184 cases. Results: Pathologists recommended molecular TP53 analysis in 14.3–23% of biopsies and 3.5–32.6% of hysterectomy cases. For biopsy samples, kappa values for IHC-molecular agreement ranged from 0.61 to 0.94, while hysterectomy cases showed higher agreement (kappa 0.83–1.0). When all five pathologists agreed on the IHC p53 status, molecular analysis confirmed the same results in all evaluable cases (no mutation/wild-type: 42/42 biopsy, 42/42 hysterectomy; mutated: 3/3 biopsy, 5/5 hysterectomy). Conclusions: Despite variability in staining intensity between tissue types, p53 IHC showed complete agreement with TP53 molecular status when all pathologists concurred. Experienced pathologists demonstrated higher concordance with molecular results, though molecular testing was necessary in up to one-third of cases. Adequate training can improve IHC reliability, but molecular confirmation is essential for equivocal cases. Full article

(This article belongs to the Section Cancer Biomarkers)

12 pages, 503 KiB

Open AccessArticle

Risk Factors for Unplanned Early Implantable Port Catheter Removal in Adult Leukemia/Lymphoma Patients: Cancer Type or Different Degrees of Cytopenia?

by Ming-Shian Lu, Chih-Chen Chen, Che-Chia Chang, Chien-Chao Lin and Ching-Chuan Hsieh

Cancers 2025, 17(9), 1505; https://doi.org/10.3390/cancers17091505 (registering DOI) - 29 Apr 2025

Abstract

(1) Background: Implantable port catheters are vital for cancer treatment, but complications such as infections and mechanical failures pose challenges. Lymphoma and leukemia patients’ unique cellular abnormalities may influence these risks. This study aimed to determine whether the underlying disease or varying degrees [...] Read more.

(1) Background: Implantable port catheters are vital for cancer treatment, but complications such as infections and mechanical failures pose challenges. Lymphoma and leukemia patients’ unique cellular abnormalities may influence these risks. This study aimed to determine whether the underlying disease or varying degrees of cytopenia increase the risk of unplanned early port removal. (2) Methods: We conducted a single institution retrospective study that included 368 patients with lymphoma or leukemia who received implantable venous access ports between January 2015 and December 2022. Propensity score matching was employed to compare patients with and without early removals. (3) Results: Univariate analysis revealed statistically significant differences between early and non-early port removal for cancer, hemoglobin, and PG-SGA scores. Cox proportional hazard analysis demonstrated that leukemia patients exhibited a 4.5 times higher risk for unplanned early catheter removal than lymphoma patients did (HR 4.589, 95% CI 1.377–15.299, p = 0.013), while patients with normal nutrition, based on the PS-SGA, demonstrated a 75% lower risk of unplanned early catheter removal than those with any degree of malnutrition did (HR 0.258, 95% CI 0.116–0575, p < 0.001). Unplanned early catheter removal negatively impacted patient survival. (4) Conclusions: The type of cancer, rather than individual cytopenias, is an independent factor influencing clinical outcomes in lymphoma and leukemia patients. Full article

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

18 pages, 1368 KiB

Open AccessReview

⁶⁸Ga-Trivehexin: Current Status of αvβ6-Integrin Imaging and Perspectives

by Luca Urso, Rebecca Napolitano, Giorgia Speltri, Murat Tuncel, Ilham Badrane, Licia Uccelli, Francesca Porto, Petra Martini, Alessandro Niorettini, Corrado Cittanti, Mirco Bartolomei and Alessandra Boschi

Cancers 2025, 17(9), 1504; https://doi.org/10.3390/cancers17091504 - 29 Apr 2025

Abstract

Background/Objectives: Molecular imaging, especially PET, has advanced significantly, shifting from metabolic radiotracers like 2-deoxy-2-[¹⁸F]fluoro-D-glucose [¹⁸F]FDG to target-specific probes. Among these, αvβ6-integrin has emerged as a promising target in cancer and non-cancer diseases. This review focuses on the radiochemical properties [...] Read more.

Background/Objectives: Molecular imaging, especially PET, has advanced significantly, shifting from metabolic radiotracers like 2-deoxy-2-[¹⁸F]fluoro-D-glucose [¹⁸F]FDG to target-specific probes. Among these, αvβ6-integrin has emerged as a promising target in cancer and non-cancer diseases. This review focuses on the radiochemical properties and initial clinical applications of the [⁶⁸Ga]Ga-Trivehexin PET probe. Methods: The literature review on [⁶⁸Ga]Ga-Trivehexin systematically evaluated both preclinical and clinical studies, with particular emphasis on its radiochemical characteristics and preliminary clinical applications, while highlighting advancements, associated challenges, and the potential for future developments in the field. Results: This study highlights the significant advancements achieved with [⁶⁸Ga]Ga-Trivehexin in the field of molecular imaging. The optimized multimeric system has substantially enhanced the radiotracer’s pharmacokinetic properties, binding affinity, and selectivity for αvβ6 integrin, demonstrating up to an 18-fold improvement compared to previous monomeric tracers. The synthesis protocol has been refined to achieve high radiochemical purity (>95%), essential for safe clinical use. Preliminary clinical applications, particularly in head and neck cancer (HNC) and pancreatic ductal adenocarcinoma (PDAC), have shown promising results, with high detection rates and improved differential diagnosis compared to [¹⁸F]FDG. Furthermore, [⁶⁸Ga]Ga-Trivehexin PET/CT has shown potential in non-oncological conditions, such as idiopathic pulmonary fibrosis (IPF) and primary hyperthyroidism, suggesting broader clinical applicability. Conclusions: [⁶⁸Ga]Ga-Trivehexin is a promising PET probe for imaging αvβ6-integrin in cancers and non-oncological diseases like idiopathic pulmonary fibrosis (IPF) and primary hyperparathyroidism (PHP). Full article

(This article belongs to the Special Issue Advances in Imaging Techniques of Molecular Oncology)

22 pages, 2431 KiB

Open AccessPerspective

Safely Targeting Cancer, the Wound That Never Heals, Utilizing CBP/Beta-Catenin Antagonists

by Yusuke Higuchi, Jia-Ling Teo, Daniel Yi and Michael Kahn

Cancers 2025, 17(9), 1503; https://doi.org/10.3390/cancers17091503 - 29 Apr 2025

Abstract

Stem cells, both normal somatic (SSC) and cancer stem cells (CSC) exist in minimally two states, i.e., quiescent and activated. Regulation of these two states, including their reliance on different metabolic processes, i.e., FAO and glycolysis in quiescent versus activated stem cells respectively, [...] Read more.

Stem cells, both normal somatic (SSC) and cancer stem cells (CSC) exist in minimally two states, i.e., quiescent and activated. Regulation of these two states, including their reliance on different metabolic processes, i.e., FAO and glycolysis in quiescent versus activated stem cells respectively, involves the analysis of a complex array of factors (nutrient and oxygen levels, adhesion molecules, cytokines, etc.) to initiate the epigenetic changes to either depart or enter quiescence. Quiescence is a critical feature of SSC that is required to maintain the genomic integrity of the stem cell pool, particularly in long lived complex organisms. Quiescence in CSC, whether they are derived from mutations arising in SSC, aberrant microenvironmental regulation, or via dedifferentiation of more committed progenitors, is a critical component of therapy resistance and disease latency and relapse. At the beginning of vertebrate evolution, approximately 450 million years ago, a gene duplication generated the two members of the Kat3 family, CREBBP (CBP) and EP300 (p300). Despite their very high degree of homology, these two Kat3 coactivators play critical and non-redundant roles at enhancers and super-enhancers via acetylation of H3K27, thereby controlling stem cell quiescence versus activation and the cells metabolic requirements. In this review/perspective, we discuss the unique regulatory roles of CBP and p300 and how specifically targeting the CBP/β-catenin interaction utilizing small molecule antagonists, can correct lineage infidelity and safely eliminate quiescent CSC. Full article

(This article belongs to the Section Molecular Cancer Biology)

► Show Figures

Figure 1

14 pages, 221 KiB

Open AccessArticle

Neighborhood Disadvantage, Built Environment, and Breast Cancer Outcomes: Disparities in Tumor Aggressiveness and Survival

by Jie Shen, Yufan Guan, Supraja Gururaj, Kai Zhang, Qian Song, Xin Liu, Harry D. Bear, Bernard F. Fuemmeler, Roger T. Anderson and Hua Zhao

Cancers 2025, 17(9), 1502; https://doi.org/10.3390/cancers17091502 - 29 Apr 2025

Abstract

Background: Breast cancer disparities persist globally, with growing evidence implicating neighborhood and built environmental factors in disease outcomes. Methods: This study investigates the associations between neighborhood disadvantage, environmental exposures, and breast tumor characteristics and survival among 3041 stage I–III breast cancer patients treated [...] Read more.

Background: Breast cancer disparities persist globally, with growing evidence implicating neighborhood and built environmental factors in disease outcomes. Methods: This study investigates the associations between neighborhood disadvantage, environmental exposures, and breast tumor characteristics and survival among 3041 stage I–III breast cancer patients treated at the University of Virginia Comprehensive Cancer Center (2014–2024). Neighborhood disadvantage was assessed via the Area Deprivation Index (ADI), while environmental exposures included PM2.5, green space (NDVI), and food indices (modified retail food environment index (mRFEI), retail food activity index (RFAI)). Multivariable regression and Cox models adjusted for demographic, socioeconomic, and clinical covariates were employed. Results: A higher ADI score was associated with aggressive tumor characteristics, including advanced stage (Odds Ratio (OR) = 1.06, 95% Confidence Interval (CI):1.01–1.11), poor differentiation (OR = 1.07, 1.01–1.15), ER-negative status (OR = 1.06, 1.01–1.12), and triple-negative breast cancer (TNBC) (OR = 1.08, 1.02–1.16), as well as younger diagnosis age (β = −0.22, −0.36 to −0.09). PM2.5 exposure was correlated with advanced tumor stage (OR = 1.24, 1.09–1.40 for stage III) but paradoxically predicted improved survival (Hazard Ratio (HR) = 0.71, 0.63–0.82). The food environment indices showed subtype-specific survival benefits: higher mRFEI and RFAI scores were linked to reduced mortality in ER-negative (HR = 0.45, 0.23–0.85 and HR = 0.61, 0.38–0.97) and TNBC (HR = 0.40, 0.18–0.90 and HR = 0.48, 0.26–0.87) patients. NDVI scores exhibited no significant associations. Conclusion: Our findings underscore the dual role of neighborhood disadvantage and the built environmental in breast cancer outcomes. While neighborhood disadvantage and PM2.5 exposure elevate tumor aggressiveness, survival disparities may be mediated by other factors. Improved food environments may enhance survival in aggressive subtypes, highlighting the need for integrated interventions addressing socioeconomic inequities, environmental risks, and nutritional support needs. Full article

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

14 pages, 2021 KiB

Open AccessSystematic Review

Locoregional and Surgical Treatment of Single-Nodule Hepatocellular Carcinoma Recurrence After Liver Transplantation: A Systematic Review and a Meta-Analysis

by Marco Maria Pascale, Camilla Marandola, Francesco Frongillo, Erida Nure and Salvatore Agnes

Cancers 2025, 17(9), 1501; https://doi.org/10.3390/cancers17091501 - 29 Apr 2025

Abstract

Background: Liver transplantation (LT) is regarded as a curative approach for patients with hepatocellular carcinoma (HCC), especially those with underlying advanced liver disease. However, the recurrence of HCC post-LT poses significant challenges, with reported rates of 15–20% within the first two years following [...] Read more.

Background: Liver transplantation (LT) is regarded as a curative approach for patients with hepatocellular carcinoma (HCC), especially those with underlying advanced liver disease. However, the recurrence of HCC post-LT poses significant challenges, with reported rates of 15–20% within the first two years following surgery. Effective management of single-nodule recurrence is critical to improving patient outcomes. Methods: This meta-analysis evaluates the efficacy of surgical resection versus locoregional therapies (LRT) in patients with localized HCC recurrence after LT. We adhered to the PRISMA Statement in conducting a thorough search of relevant studies published from 2009 to 2024, ultimately including ten studies that met our eligibility criteria. Results: The results indicate that patients undergoing surgical treatment displayed superior one-year overall survival (OS) rates compared to those receiving LRT (71% vs. 62%, p = 0.038), as well as higher one-year disease-free survival (DFS) rates (60% vs. 54%, p = 0.042). Notably, patients in the LRT group presented with more advanced HCC characteristics prior to transplantation, including higher rates of microvascular invasion and elevated alpha-fetoprotein levels. Conclusions: Our findings suggest that while surgical resection is associated with better survival outcomes, the choice between surgical and locoregional approaches must be individualized based on tumor characteristics and liver function. The ongoing development of standardized guidelines with the inclusion of immunotherapy or targeted agents will be essential in refining treatment pathways and improving outcomes for patients experiencing HCC recurrence following LT. Full article

(This article belongs to the Special Issue Hepatocellular Carcinoma: Current Treatment Strategies for Advanced Disease and Recurrence: 2nd Edition)

► Show Figures

Figure 1

16 pages, 1873 KiB

Open AccessArticle

Rising Incidence and Mortality of Early-Onset Colorectal Cancer in Young Cohorts Associated with Delayed Diagnosis

by Yazan Abboud, Anand Shah, Madison Fraser, Eric M. Montminy, Chun-Wei Pan, Kaveh Hajifathalian, Paul J. Gaglio and Ahmed Al-Khazraji

Cancers 2025, 17(9), 1500; https://doi.org/10.3390/cancers17091500 - 29 Apr 2025

Abstract

Background and Aims: Prior data showed an increasing incidence of early-onset colorectal cancer (EO-CRC) in the US. However, there are limited comprehensive data on recent EO-CRC incidence and mortality per different age cohorts and tumor characteristics. We aimed to evaluate EO-CRC incidence [...] Read more.

Background and Aims: Prior data showed an increasing incidence of early-onset colorectal cancer (EO-CRC) in the US. However, there are limited comprehensive data on recent EO-CRC incidence and mortality per different age cohorts and tumor characteristics. We aimed to evaluate EO-CRC incidence and mortality in different populations. Methods: Age-adjusted EO-CRC incidence rates were calculated from the USCS database between 2001 and 2021. Age-adjusted EO-CRC mortality rates were calculated from the NCHS database between 2000 and 2022 and the SEER database between 2004 and 2021. The age groups were 20–44 years and 45–54 years. Tumors were categorized by anatomical location (right, transverse, left, and proximal) and stage at diagnosis (early and late). The annual and average annual percentage changes (AAPC) were estimated using joinpoint regression. Age-specific pairwise comparison was conducted. Results: A total of 474,601 patients were diagnosed with EO-CRC between 2001 and 2021. The EO-CRC incidence increased in patients aged 20–44 years faster than in those aged 45–54 years (AAPC = 1.51 vs. 0.73; AAPC difference = 0.78, p = 0.001). This was most notable in proximal colon tumors (AAPC difference = 0.88, p < 0.001). While the incidence of early-stage tumors decreased in recent years across all anatomical locations, late-stage tumors increased, mostly in the proximal colon (AAPC = 2.44). A total of 147,026 patients died from EO-CRC between 2000 and 2022. Mortality increased in patients aged 20–44 years faster than in patients aged 45–54 years, who had a stable trend (AAPC difference = 0.85, p < 0.001). The increase in mortality was noted in both early- and late-stage tumors. Conclusions: Our study provides epidemiologic evidence showing an alarming increase in EO-CRC incidence and mortality among patients aged 20–44 years compared to those aged 45–54 years, which is associated with delayed diagnosis, and mostly in proximal colon tumors. Expanding screening efforts to younger populations and addressing healthcare disparities are essential for improving early detection and outcomes for younger patients. Full article

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

► Show Figures

Figure 1

17 pages, 1328 KiB

Open AccessArticle

Lung Cancer Risk Prediction in Patients with Persistent Pulmonary Nodules Using the Brock Model and Sybil Model

by Hui Li, Morteza Salehjahromi, Myrna C. B. Godoy, Kang Qin, Courtney M. Plummer, Zheng Zhang, Lingzhi Hong, Simon Heeke, Xiuning Le, Natalie Vokes, Bingnan Zhang, Haniel A. Araujo, Mehmet Altan, Carol C. Wu, Mara B. Antonoff, Edwin J. Ostrin, Don L. Gibbons, John V. Heymach, J. Jack Lee, David E. Gerber, Jia Wu and Jianjun Zhang Show full author list Hide full author list

Cancers 2025, 17(9), 1499; https://doi.org/10.3390/cancers17091499 - 29 Apr 2025

Abstract

Background/Objectives: Persistent pulmonary nodules are at higher risk of developing into lung cancers. Assessing their future cancer risk is essential for successful interception. We evaluated the performance of two risk prediction models for persistent nodules in hospital-based cohorts: the Brock model, based on [...] Read more.

Background/Objectives: Persistent pulmonary nodules are at higher risk of developing into lung cancers. Assessing their future cancer risk is essential for successful interception. We evaluated the performance of two risk prediction models for persistent nodules in hospital-based cohorts: the Brock model, based on clinical and radiological characteristics, and the Sybil model, a novel deep learning model for lung cancer risk prediction. Methods: Patients with persistent pulmonary nodules—defined as nodules detected on at least two computed tomography (CT) scans, three months apart, without evidence of shrinkage—were included in the retrospective (n = 130) and prospective (n = 301) cohorts. We analyzed the correlations between demographic factors, nodule characteristics, and Brock scores and assessed the performance of both models. We also built machine learning models to refine the risk assessment for our cohort. Results: In the retrospective cohort, Brock scores ranged from 0% to 85.82%. In the prospective cohort, 62 of 301 patients were diagnosed with lung cancer, displaying higher median Brock scores than those without lung cancer diagnosis (18.65% vs. 4.95%, p < 0.001). Family history, nodule size ≥10 mm, part-solid nodule types, and spiculation were associated with the risks of lung cancer. The Brock model had an AUC of 0.679, and Sybil’s AUC was 0.678. We tested five machine learning models, and the logistic regression model achieved the highest AUC at 0.729. Conclusions: For patients with persistent pulmonary nodules in real-world cancer hospital-based cohorts, both the Brock and Sybil models had values and limitations for lung cancer risk prediction. Optimizing predictive models in this population is crucial for improving early lung cancer detection and interception. Full article

(This article belongs to the Special Issue Predictive Biomarkers for Lung Cancer)

► Show Figures

Figure 1

15 pages, 1475 KiB

Open AccessArticle

Negative Effect of Intravenous Antibiotics on Survival in Patients with Triple-Negative Breast Cancer

by Stefan Lukac, Visnja Fink, Davut Dayan, Brigitte Rack, Wolfgang Janni, Krisztian Lato, Kristina Veselinovic, Sabine Heublein, Thomas Wolfram Paul Friedl and Elena Leinert

Cancers 2025, 17(9), 1498; https://doi.org/10.3390/cancers17091498 - 29 Apr 2025

Abstract

Background: The anti-tumor response of the immune system is pivotal for treating triple-negative breast cancer (TNBC), particularly as targeted therapies are limited. However, the impact of immune-modulating factors such as the application of granulocyte-stimulating factors (G-CSFs) or infections, including febrile neutropenia, prophylactic or [...] Read more.

Background: The anti-tumor response of the immune system is pivotal for treating triple-negative breast cancer (TNBC), particularly as targeted therapies are limited. However, the impact of immune-modulating factors such as the application of granulocyte-stimulating factors (G-CSFs) or infections, including febrile neutropenia, prophylactic or therapeutical application of oral antibiotics (OABs), and the need for intravenous antibiotics (IABs), on survival outcomes remains unclear. Methods: 1583 patients with early-stage TNBC enrolled in the SUCCESS A or C study underwent primary surgery, adjuvant chemotherapy, and radiotherapy if indicated. All patients had Eastern Cooperative Oncology Group (ECOG) status ≤ 2. The effects of G-CSF, OAB, and IAB application on overall survival (OS), invasive disease-free survival (iDFS), breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) were assessed. Results: Only IAB treatment was significantly associated with decreased survival in univariable analyses (OS: p = 0.003; iDFS: p = 0.036; BCSS: p = 0.011; DDFS: p = 0.044), while G-CSF and OAB administration were not. Adjusted multivariable Cox regressions including febrile neutropenia and dose reduction/shift, ECOG, age of patients, and other clinicopathological parameters confirmed a significant negative effect of IABs on OS (p = 0.020), BCSS (p = 0.018), and DDFS (p = 0.044). Conclusions: In summary, IABs during adjuvant chemotherapy seems to be a risk factor for inferior OS, BCSS, and DDFS in TNBC patients, possibly by affecting microbiome-related immune response modulation. Hence, preventive measures to avoid the need for IABs should be considered in these patients. Full article

(This article belongs to the Section Cancer Therapy)

► Show Figures

Figure 1

11 pages, 1620 KiB

Open AccessReview

Super-Superselective Level VB Neck Dissection for Papillary Thyroid Cancer

by Dana M. Hartl, Davide Lombardi, Ricard Simo, Radu Mihai, Aleix Rovira, Enyi Ofo and Iain J. Nixon

Cancers 2025, 17(9), 1497; https://doi.org/10.3390/cancers17091497 - 29 Apr 2025

Abstract

Objective: Therapeutic lateral neck dissection is recommended for papillary thyroid cancer with metastatic lymph nodes detected on palpation or on preoperative imaging. Current guidelines recommend systematic dissection of levels IIA, III, IV and VB in these patients. Despite this recommendation, management of level [...] Read more.

Objective: Therapeutic lateral neck dissection is recommended for papillary thyroid cancer with metastatic lymph nodes detected on palpation or on preoperative imaging. Current guidelines recommend systematic dissection of levels IIA, III, IV and VB in these patients. Despite this recommendation, management of level V remains controversial due to a varying degree of clinical and occult lymph node involvement reported in published retrospective studies, but also due to the functional risk involved in level V dissection in which the spinal accessory nerve may be temporarily or permanently injured. The aim of this review was to address the issues involved in level VB dissection and to provide our view of surgical management of level VB. Method: Narrrative review. Result: We propose a new concept of a partial or “super-superselective” level VB dissection in patients with clinical disease in levels IIA, III and IV. Full article

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

► Show Figures

Figure 1

6 pages, 200 KiB

Open AccessCommunication

A Comparison of Surgical and Functional Outcomes in Prostate Cancer Patients with Overweight and Obesity Participating in a Presurgical Weight Loss Trial

by Madeline F. Morgan, Andrew D. Frugé, Wendy Demark-Wahnefried, Jeffrey W. Nix and Soroush Rais-Bahrami

Cancers 2025, 17(9), 1496; https://doi.org/10.3390/cancers17091496 - 29 Apr 2025

Abstract

Background/Objectives: Obesity and abdominal adiposity are associated with worse surgical and functional outcomes in prostate cancer (PCa) patients. This exploratory study assessed whether reductions in total body fat mass (TFM) among overweight and obese PCa patients enrolled in a diet and exercise weight [...] Read more.

Background/Objectives: Obesity and abdominal adiposity are associated with worse surgical and functional outcomes in prostate cancer (PCa) patients. This exploratory study assessed whether reductions in total body fat mass (TFM) among overweight and obese PCa patients enrolled in a diet and exercise weight loss intervention prior to robotic-assisted radical prostatectomy (RARP) improved outcomes. Methods: In this secondary analysis of an NIH-funded randomized controlled trial (NCT01886677) conducted 2012–2015, twenty-nine patients with newly diagnosed, pathology-confirmed PCa who participated and underwent RARP were evaluated for percent change in TFM and divided into High Fat Losers who lost ≥1% TFM per week and Low Fat Losers who lost <1% TFM per week. High versus Low Fat Losers were compared on operative time (OT), estimated blood loss (EBL), length of hospital stay (LOS), incidence of surgical or postoperative complications, and incontinence and impotence scores at first postoperative follow-up. Results: There was a statistically significant difference between High versus Low Fat Losers with respect to overall complications (p = 0.027); 28.6% of High Fat Losers experienced one or more complications by first postoperative follow-up, compared to 73.3% of Low Fat Losers. However, no differences were observed for each individual complication analyzed, or with respect to OT, EBL, LOS, or incontinence or impotence scores. Conclusions and Relevance: Findings implicate the potential benefit of healthy weight loss as an adjunct to surgery, and support the need for larger trials to elucidate a clearer relationship between improvements in body composition and effects on specific surgical complications and functional outcomes. Full article

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

12 pages, 4516 KiB

Open AccessArticle

Expression Characteristics of 3-Marker Panel (PAX2, PTEN, and β-Catenin) in Benign Interval and Secretory Endometrium and Secretory Endometrial Precancer

by Shuang Niu, Kyle Molberg, Jackson Chen, Lesley Conrad, Elena Lucas and Hao Chen

Cancers 2025, 17(9), 1495; https://doi.org/10.3390/cancers17091495 - 29 Apr 2025

Abstract

Background/Objectives: Despite advancements in treatment options, endometrial cancer remains a significant threat to women, underscoring the importance of early detection of atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), the widely accepted histological precursor to endometrial carcinoma. Even with refinements in morphological criteria for the [...] Read more.

Background/Objectives: Despite advancements in treatment options, endometrial cancer remains a significant threat to women, underscoring the importance of early detection of atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), the widely accepted histological precursor to endometrial carcinoma. Even with refinements in morphological criteria for the diagnosis of AH/EIN, accurate diagnosis remains challenging for pathologists, particularly in cases with secretory changes. Morphological alterations resulting from secretory-related changes further complicate the application of diagnostic criteria, emphasizing the need for reliable biomarkers. Previous studies have demonstrated that a panel consisting of three immunohistochemical markers, PAX2, PTEN, and β-catenin, can be effectively utilized for the identification of AH/EIN in various non-secretory scenarios. Methods: In this study, a total of 69 AH/EIN within secretory endometrium were analyzed using this panel. Benign interval endometrium (n = 57) and secretory phase endometrium (n = 71) were also analyzed for PAX2, PTEN, and β-catenin expression as controls. Results: The 3-marker panel successfully identified 93% of secretory AH/EIN, comparable to its performance in identifying non-secretory bona fide AH/EIN (92.8%) and AH/EIN within endometrial polyps (92.4%). Of note, β-catenin expression in benign interval endometrium commonly displayed weak nuclear staining (67%), which could pose a diagnostic pitfall when using the 3-marker panel. Overall, the results demonstrate the diagnostic utility of the 3-marker panel in clinical practice in identifying AH/EIN within challenging secretory phase endometrium cases. Conclusions: Combined with previous research highlighting its effectiveness in other challenging contexts—such as AH/EIN in polyps, small-sized EIN (subdiagnostic EIN), and progestin-treated EIN—this study provides strong evidence supporting the panel’s broad applicability in resolving major diagnostic challenges related to the precise diagnosis of AH/EIN. Full article

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

► Show Figures

Figure 1

22 pages, 2971 KiB

Open AccessReview

Advances and Emerging Techniques in Y-90 Radioembolization for Hepatocellular Carcinoma

by Elliott L. Fite and Mina S. Makary

Cancers 2025, 17(9), 1494; https://doi.org/10.3390/cancers17091494 - 29 Apr 2025

Abstract

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer deaths worldwide. Despite the high incidence of HCC, mortality remains high, with an estimated 5-year survival rate of less than 20%. Surgical resection represents a potential curative treatment for HCC; however, less than [...] Read more.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer deaths worldwide. Despite the high incidence of HCC, mortality remains high, with an estimated 5-year survival rate of less than 20%. Surgical resection represents a potential curative treatment for HCC; however, less than 20% of patients with HCC are candidates for surgical resection. In patients with unresectable HCC, Yttrium-90 (Y90) transarterial radioembolization (TARE) has emerged as an innovative treatment option. This locoregional therapy delivers high doses of radiation directly to liver tumors via intra-arterial injection, allowing for the targeted destruction of malignant cells while sparing surrounding healthy tissue. In this review, we will explore the latest advances in Y90 TARE for the treatment of HCC, focusing on key developments such as the following: (1) improvements in radiation lobectomy and segmentectomy techniques, (2) the introduction of personalized dosimetry, (3) the integration of combination therapies, (4) the use of imageable microspheres, (5) pressure-enabled Y90 delivery systems, and (6) the application of Y90 surrogates. Full article

(This article belongs to the Special Issue Interventional Oncology: Advances in Cancer Care)

► Show Figures

Figure 1

23 pages, 2020 KiB

Open AccessReview

Targeting c-MET Alterations in Cancer: A Review of Genetic Drivers and Therapeutic Implications

by Michelle Ji, Shridar Ganesan, Bing Xia and Yanying Huo

Cancers 2025, 17(9), 1493; https://doi.org/10.3390/cancers17091493 - 29 Apr 2025

Abstract

Background: Recent research has increasingly highlighted alterations in the proto-oncogene MET, whose abnormal activation has been implicated in multiple cancers. MET encodes c-MET, a receptor tyrosine kinase critical for cellular growth, survival, and migration. Aberrant c-MET signaling, driven by mutations or gene [...] Read more.

Background: Recent research has increasingly highlighted alterations in the proto-oncogene MET, whose abnormal activation has been implicated in multiple cancers. MET encodes c-MET, a receptor tyrosine kinase critical for cellular growth, survival, and migration. Aberrant c-MET signaling, driven by mutations or gene amplification, promotes proliferation and invasion, contributing to tumorigenesis. Scope of the Review: While MET mutations are most often observed in non-small cell lung cancer (NSCLC), they also occur in other malignancies, including breast and gastric cancers. This review highlights key MET alterations, such as gene amplification, gene fusions, and exon 14 skipping deletions, and examines their prevalence across various tumor types. Major Conclusions: We discuss the clinical significance of c-MET as a therapeutic target and identify gaps in knowledge that could inform the development of alternative treatment strategies. Full article

(This article belongs to the Section Molecular Cancer Biology)

► Show Figures

Figure 1

17 pages, 1283 KiB

Open AccessArticle

Association Between Epstein–Barr Virus Infection and PD-L1 Expression in Gastric Cancer: Prevalence, Clinicopathological Features, and Prognostic Implications

by Jirapat Wonglhow, Jarukit Tantipisit, Panu Wetwittayakhlang, Patrapim Sunpaweravong, Chirawadee Sathitruangsak, Kanet Kanjanapradit, Phatcharaporn Thongwatchara and Arunee Dechaphunkul

Cancers 2025, 17(9), 1492; https://doi.org/10.3390/cancers17091492 - 29 Apr 2025

Abstract

Background: Epstein–Barr virus-associated gastric cancer (EBVaGC) represents a distinct molecular subgroup with potential responsiveness to immunotherapy approved for programmed death-ligand 1 (PD-L1)-positive gastric cancer. This retrospective study aimed to assess the prevalence and association between EBVaGC and PD-L1 positivity among patients with gastric [...] Read more.

Background: Epstein–Barr virus-associated gastric cancer (EBVaGC) represents a distinct molecular subgroup with potential responsiveness to immunotherapy approved for programmed death-ligand 1 (PD-L1)-positive gastric cancer. This retrospective study aimed to assess the prevalence and association between EBVaGC and PD-L1 positivity among patients with gastric adenocarcinoma treated at a university hospital in Southern Thailand from January 2017 to October 2023. Methods: The EBV status of the patients and PD-L1 expression were determined using in situ hybridization and immunohistochemistry, respectively. Results: The prevalence of EBVaGC was 4.5% among 132 patients, whereas 9.1% of patients exhibited a PD-L1 combined positive score (CPS) of ≥1, with no significant association observed between them. EBVaGC was more prevalent in males, non-antral tumors, diffuse/mixed histologic subtypes, and poorly differentiated tumors. Median overall survival for patients with EBVaGC and PD-L1 CPS ≥ 1 was 9.48 and 14.19 months, respectively, compared with 10.32 and 9.79 months for those with non-EBVaGC (hazard ratio: 1.24; 95% CI: 0.50–3.04; p = 0.645) and PD-L1 CPS < 1 (hazard ratio: 0.82; 95% CI: 0.40–1.69; p = 0.590), respectively. Conclusions: Our findings revealed a low prevalence of EBVaGC and PD-L1 positivity in Thailand, with no significant association or survival impact observed. These findings highlight the regional variation in these biomarkers and support EBV as an independent biomarker from PD-L1. However, further research, particularly studies evaluating immunotherapy outcomes, is warranted to clarify the predictive and clinical significance of EBV in gastric cancer. Full article

(This article belongs to the Special Issue Epstein–Barr Virus (EBV) Associated Cancers)

► Show Figures

Figure 1

12 pages, 727 KiB

Open AccessPerspective

The Role of the Extracellular Matrix in Cancer Prevention

by Stuart G. Baker and Edward R. Sauter

Cancers 2025, 17(9), 1491; https://doi.org/10.3390/cancers17091491 - 29 Apr 2025

Abstract

The extracellular matrix (ECM) is a major driver of tumorigenesis, yet its role in cancer prevention has received relatively little attention. Here, we discuss studies linking the ECM to cancer initiation with an emphasis on ECM stiffness and remodeling, pericytes, and hyaluronan (hyaluronic [...] Read more.

The extracellular matrix (ECM) is a major driver of tumorigenesis, yet its role in cancer prevention has received relatively little attention. Here, we discuss studies linking the ECM to cancer initiation with an emphasis on ECM stiffness and remodeling, pericytes, and hyaluronan (hyaluronic acid). We then share our thoughts on how an ECM viewpoint could lead to new insights and directions in cancer-prevention research. Topics discussed include mouse experiments, clinical studies, risk factors, biomarkers for risk prediction or the early detection of cancer, surrogate endpoints, and targets for preventive interventions. Full article

(This article belongs to the Special Issue Prevention, Screening and Early Detection of Cancer)

► Show Figures

Figure 1

8 pages, 510 KiB

Open AccessArticle

Café-Au-Lait Macules in Neurofibromatosis Type 1: Birthmark or Biomarker?

by Andrea Santangelo, Cristina Chelleri, Marco Tomasino, Mattia Pasquinucci, Francesca Cappozzo, Pasquale Striano, Maria Cristina Diana and Marcello Scala

Cancers 2025, 17(9), 1490; https://doi.org/10.3390/cancers17091490 - 29 Apr 2025

Abstract

Background: Neurofibromatosis type 1 (NF1) is a rare multisystem disorder characterized by variable expressivity and increased tumor risk. Café-au-lait macules (CALMs) are a hallmark of the disease, often representing one of the earliest clinical manifestations and allowing a clinical NF1 diagnosis if six [...] Read more.

Background: Neurofibromatosis type 1 (NF1) is a rare multisystem disorder characterized by variable expressivity and increased tumor risk. Café-au-lait macules (CALMs) are a hallmark of the disease, often representing one of the earliest clinical manifestations and allowing a clinical NF1 diagnosis if six or more are present. In this study, we aimed to investigate the prognostic value of CALMs at birth in NF1 patients. Methods: We conducted a retrospective study in patients aged ≥ 4 years presenting with CALMs at our Institution between 2020 and 2021, with a minimum follow-up of four years. We retrospectively collected data on CALMs at birth and other clinical manifestations associated with NF1. Results: Among 208 patients evaluated, including 147 with a confirmed diagnosis of NF1, 110 did not show CALMs at birth, and 98 had at least one. The absence of CALMs at birth did not correlate with a lower likelihood of NF1. In contrast, the CALM number at birth directly correlated with the likelihood of NF1, up to 95% in patients with ≥5 macules. Additionally, a higher number of CALMs correlated with a greater prevalence of plexiform neurofibromas (p < 0.001). Conclusions: Our findings suggest that a higher number of CALMs may indicate a more severe form of NF1, with an increased risk of plexiform neurofibromas. These results emphasize the importance of a comprehensive evaluation of patients with CALMs, especially in case of multiple lesions, aiming at implementing early NF1 diagnosis, follow-up strategies, and overall patient management. Full article

(This article belongs to the Special Issue Neurofibromatosis)

► Show Figures

Figure 1

10 pages, 204 KiB

Open AccessArticle

The Early Detection of Malignant Transformation of Potentially Malignant Disorders: Oral Lichen Planus

by Camilla Lüdecke, Heinrich Neumann and Torsten W. Remmerbach

Cancers 2025, 17(9), 1489; https://doi.org/10.3390/cancers17091489 - 28 Apr 2025

Abstract

Background: The aim of this study was to evaluate the usefulness of close clinical surveillance intervals combined with oral brush biopsies to enable the early detection of malignant transformations in patients with oral lichen planus (OLP) performed in our oral medicine clinic. Methods: [...] Read more.

Background: The aim of this study was to evaluate the usefulness of close clinical surveillance intervals combined with oral brush biopsies to enable the early detection of malignant transformations in patients with oral lichen planus (OLP) performed in our oral medicine clinic. Methods: This retrospective study was carried out on 414 patients suffering from OLP, based on pre-established clinical and histopathological criteria, who received long-term follow-up between 1993–2022 (ranging from 6 months to 22.2 years). Results: A total of 297 patients were included in this study. Four people developed an oral squamous cell carcinoma (OSCC) during the observation period. Patients with close follow-up intervals were detected at early stages (two cases showed histologically SIN III and one patient was classified as having a pT1N0M0 tumour). One case was dropped in the consultation hour during the COVID19 pandemic and appeared again two years later, staged as a pT3N1M0 tumour based on an OLP. Three of the cases were clinically doubtful, which led to brush biopsies. Afterwards, additional DNA-image cytometry was performed, in which all the specimens of brush biopsies showed aneuploidy as a marker for malignancy, regarding both stem line and single cell aneuploidy. Conclusions: A careful surveillance programme consisting of check-ups every 3–4 months, oral brush biopsies, and static DNA image cytometry in cytologically diagnosed doubtful or suspicious cases assures the early detection of malignant transformation in the cancer’s early intraepithelial and microinvasive stages. Full article

(This article belongs to the Special Issue Oral Potentially Malignant Disorders and Oral Cavity Cancer)

14 pages, 244 KiB

Open AccessArticle

The Effect of Chemotherapy Treatment on Cognitive Impairment and Clinical Symptoms in Hodgkin Lymphoma Patients

by Dan Fayette, Veronika Juríčková, Iveta Fajnerová, Jiří Horáček and Tomáš Kozák

Cancers 2025, 17(9), 1488; https://doi.org/10.3390/cancers17091488 - 28 Apr 2025

Viewed by 32

Abstract

Background/Objectives: Cancer- or chemotherapy-related cognitive deficit is a common side effect occurring in patients with Hodgkin lymphoma. No previous study compared the influence of different types of treatment on the onset and development of chemotherapy cognitive impairment in longitudinal design. The aim of [...] Read more.

Background/Objectives: Cancer- or chemotherapy-related cognitive deficit is a common side effect occurring in patients with Hodgkin lymphoma. No previous study compared the influence of different types of treatment on the onset and development of chemotherapy cognitive impairment in longitudinal design. The aim of this study was to assess whether a more intensive form of chemotherapy causes greater cognitive impairment. Methods: Forty-four patients at three different stages of the disease and with three different treatments (ABVD + 30 Gy, BEACOPPesc, or ABVD + 30 Gy plus BEACOPPesc) completed the neuropsychological battery and psychological measures of affective distress and quality of life. We compared their cognitive performance before, immediately after, and 6 months after the treatment. Results: Whether or not we divided the total number of people with Hodgkin lymphoma into two groups (mild and moderate disease versus severe disease) or three groups (mild, moderate, and advanced disease), we found no statistically significant difference between the groups in cognitive performance or other psychological factors or experienced quality of life. Conclusions: Our results did not show that disease stage or treatment protocol had an effect on the depth of cognitive impairment in cancer or chemotherapy. We hypothesize that, in terms of brain health, intensive forms of chemotherapy (6 × BEA-COPPesc) do not pose a greater risk than milder forms (4 × ABVD + 30 Gy IF RT and 2 × BEACOPPesc + 4 × ABVD + 30 Gy IF RT) of cancer treatment for Hodgkin lymphoma. However, a limitation of our study is the small number of participants in the study, so it would be advisable to repeat the study on a larger sample of patients. Confirmation of our results could be beneficial in that neither patients nor physicians need to worry that intensive chemotherapy will worsen cognitive deficits. Full article

(This article belongs to the Special Issue Blood Stem Cell and Hematological Malignancies)

12 pages, 1953 KiB

Open AccessArticle

[⁶⁸Ga]-DOTATOC PET/CT Volumetric Parameters Reflect Metastatic Potential in Pancreatic Neuroendocrine Tumors

by So Jeong Kim, Jongtae Cha, Hee Seung Lee, Moon Jae Chung, Jeong Youp Park, Seungmin Bang, Seung Woo Park, Si Young Song, Arthur Cho and Jung Hyun Jo

Cancers 2025, 17(9), 1487; https://doi.org/10.3390/cancers17091487 - 28 Apr 2025

Viewed by 47

Abstract

Background: [⁶⁸Ga]-DOTATOC PET/CT is a valuable technique for identifying neuroendocrine tumors overexpressing somatostatin receptors; however, its diagnostic and prognostic utility for WHO low-grade pancreatic neuroendocrine tumors remains unclear. Therefore, we aimed to evaluate [⁶⁸Ga]-DOTATOC uptake in well-differentiated pancreatic neuroendocrine [...] Read more.

Background: [⁶⁸Ga]-DOTATOC PET/CT is a valuable technique for identifying neuroendocrine tumors overexpressing somatostatin receptors; however, its diagnostic and prognostic utility for WHO low-grade pancreatic neuroendocrine tumors remains unclear. Therefore, we aimed to evaluate [⁶⁸Ga]-DOTATOC uptake in well-differentiated pancreatic neuroendocrine tumors and determine its predictive capability for metastasis. Methods: Patients with pathologically diagnosed well-differentiated, non-functional pancreatic neuroendocrine tumors who underwent [⁶⁸Ga]-DOTATOC PET/CT between 2015 and 2021 were included. Medical records and [⁶⁸Ga]-DOTATOC PET/CT indices (maximal and mean standardized uptake values, somatostatin receptor-expressing tumor volume, and total lesion somatostatin receptor expression in pancreatic tumors) were retrospectively reviewed. Correlations between indices were analyzed to determine their collective diagnostic significance. Results: Among 93 patients who were pathologically diagnosed with pancreatic neuroendocrine tumors and underwent [⁶⁸Ga]-DOTATOC PET/CT, 48 with well-differentiated, non-functional pancreatic neuroendocrine tumors without accompanying genetic syndromes were included. The pancreatic neuroendocrine tumors were classified as WHO grade 1 (n = 30, 62.5%) and grade 2 (n = 18, 37.5%), with tumors in 25% of the patients exhibiting initial metastases. A higher incidence of metastasis was observed in larger metabolically active tumors (somatostatin receptor-expressing tumor volume, p < 0.001; total lesion somatostatin receptor expression, p < 0.001). Conclusions: Volumetric parameters derived from [⁶⁸Ga]-DOTATOC PET/CT correlates with initial metastasis in well-differentiated pancreatic neuroendocrine tumors. Full article

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

► Show Figures

Figure 1

16 pages, 2907 KiB

Open AccessArticle

Well-Differentiated Jejunoileal Neuroendocrine Tumors and Corresponding Liver Metastases: Mesenteric Fibrogenesis and Extramural Vascular Invasion in Tumor Progression

by Jacob M. Ranot, Jemila S. Hamid, Azita Montazeri, Kelly Harper, Christopher McCudden and Terence N. Moyana

Cancers 2025, 17(9), 1486; https://doi.org/10.3390/cancers17091486 - 28 Apr 2025

Viewed by 39

Abstract

Background: Patients with jejunoileal neuroendocrine tumors (JINETs) can live for many years despite liver metastases. Evidence suggests that tumor heterogeneity is prognostically important, hence the selection of Ki67 hotspots for tumor grading. According to the stepwise metastasis model, clonal hotspots should predominate in [...] Read more.

Background: Patients with jejunoileal neuroendocrine tumors (JINETs) can live for many years despite liver metastases. Evidence suggests that tumor heterogeneity is prognostically important, hence the selection of Ki67 hotspots for tumor grading. According to the stepwise metastasis model, clonal hotspots should predominate in the metastases. However, an alternative view holds that the polyclonality of metastases is consistent with origin from genetically heterogeneous clusters of disseminated cells. The shortcomings of Ki67 grading are also being recognized, thus renewing the search for other prognostic parameters. Methods: A 20-year retrospective study that paired JINETs and hepatic metastases was conducted by analyzing them for various parameters. Results: There were 43 patients (mean follow-up of 7.234 years); 14 were dead due to the disease, 22 were alive with the disease, and 7 were alive with no evidence of the disease. Most JI NETs (22/30) were grade 1, eight were grade 2, and none were grade 3. Tumor grades for both the primaries and liver metastases were not prognostic (p-values = 0.1260 and 0.2566, respectively). Seventeen of the 41 JI NETs showed mesenteric fibrogenesis (MF), and 18 had EMVI, with a high level of agreement between these parameters (92.68%) (kappa value 0.85), and both were strongly associated with poor outcomes. Conclusions: JINETs and their liver metastases tend to have low proliferation rates. However, an important mechanism in the metastatic cascade appears to be mesenteric fibrogenesis. It encases vessels, which enhances extramural vascular invasion, thereby conveying clusters of tumor cells to the liver. This supports the polyclonal nature of tumor progression rather than origin from hotspot aberrant clones. Full article

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

► Show Figures

Figure 1

21 pages, 918 KiB

Open AccessReview

A Systematic Analysis of Expression and Function of RAS GTPase-Activating Proteins (RASGAPs) in Urological Cancers: A Mini-Review

by Hao Song, Guojing Wang, Guoqiang Gao, Huayu Xia, Lianying Jiao and Kaijie Wu

Cancers 2025, 17(9), 1485; https://doi.org/10.3390/cancers17091485 - 28 Apr 2025

Viewed by 65

Abstract

The RAS signaling pathway is one of the most commonly dysregulated pathways in urological cancers. This pathway can be regulated by RASGAPs, which catalyze the hydrolysis of RAS-GTP to RAS-GDP. As such, the loss of RASGAPs can promote the activation of the RAS [...] Read more.

The RAS signaling pathway is one of the most commonly dysregulated pathways in urological cancers. This pathway can be regulated by RASGAPs, which catalyze the hydrolysis of RAS-GTP to RAS-GDP. As such, the loss of RASGAPs can promote the activation of the RAS signaling pathway. Dysregulation of RASGAPs significantly contributes to the progression of urological cancers, including prostate cancer, bladder cancer, and renal cell carcinoma. Furthermore, alterations in RASGAP expression may influence sensitivity to chemotherapy, radiotherapy, and targeted therapies, suggesting their potential as therapeutic targets. Despite the challenges involved, a deeper understanding of the complexity of the RAS signaling network, along with the evolution of personalized medicine, holds promise for delivering more precise and effective treatment options targeting RASGAPs in urological cancers. Full article

(This article belongs to the Special Issue RAS Signaling Pathway in Cancer Therapy)

► Show Figures

Figure 1

18 pages, 998 KiB

Open AccessReview

Inflammation, Immunosuppression, and Immunotherapy in Pancreatic Cancer—Where Are We Now?

by Marta Fudalej, Kamila Krupa, Anna Badowska-Kozakiewicz and Andrzej Deptała

Cancers 2025, 17(9), 1484; https://doi.org/10.3390/cancers17091484 - 28 Apr 2025

Viewed by 60

Abstract

Pancreatic cancer (PC) is one of the most commonly diagnosed and deadliest neoplasms in the modern world. Over the past few years, the incidence of PC has risen with only a slight improvement in overall survival. Moreover, the improvement in survival is primarily [...] Read more.

Pancreatic cancer (PC) is one of the most commonly diagnosed and deadliest neoplasms in the modern world. Over the past few years, the incidence of PC has risen with only a slight improvement in overall survival. Moreover, the improvement in survival is primarily driven by diagnoses in the localized stage of the disease, rather than by new treatment methods. The inflammatory process is a key mediator of PC development, yet PC is also one of the most immune-resistant tumors. Patients rarely benefit from monotherapy with immune checkpoint inhibitors; nevertheless, the latest biological findings on the complexity of the pancreatic tumor microenvironment might be translated into designing new clinical studies that combine various approaches to overcome single-agent immunotherapy resistance. On the other hand, focusing on inflammation may lead to the development of new inflammation-based prognostic markers for patients. This review aims to describe the current state of knowledge regarding the complex relationships between systemic and local inflammation, immune response, immunosuppression, and therapeutic options in PC. Full article

(This article belongs to the Special Issue Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment 2nd Edition)

► Show Figures

Figure 1

5 pages, 170 KiB

Open AccessEditorial

Emerging Trends in Global Cancer Epidemiology

by Syed Ahsan Raza

Cancers 2025, 17(9), 1483; https://doi.org/10.3390/cancers17091483 - 28 Apr 2025

Viewed by 53

Abstract

Cancer continues to be one of the most pressing global public health challenges, with an increasing number of new cases and deaths each year [...] Full article

(This article belongs to the Special Issue Emerging Trends in Global Cancer Epidemiology)

21 pages, 310 KiB

Open AccessReview

Gene Expression Signatures for Guiding Initial Therapy in ER+/HER2- Early Breast Cancer

by Sara Marín-Liébana, Paula Llor, Lucía Serrano-García, María Leonor Fernández-Murga, Ana Comes-Raga, Dolores Torregrosa, José Manuel Pérez-García, Javier Cortés and Antonio Llombart-Cussac

Cancers 2025, 17(9), 1482; https://doi.org/10.3390/cancers17091482 - 28 Apr 2025

Viewed by 154

Abstract

In triple-negative (TNBC) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer patients, neoadjuvant systemic therapy is the standard recommendation for tumors larger than 2 cm. Monitoring the response to primary systemic therapy allows for the assessment of treatment effects, the need [...] Read more.

In triple-negative (TNBC) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer patients, neoadjuvant systemic therapy is the standard recommendation for tumors larger than 2 cm. Monitoring the response to primary systemic therapy allows for the assessment of treatment effects, the need for breast-conserving surgery (BCS), and the achievement of pathological complete responses (pCRs). In estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer, the benefit of neoadjuvant strategies is controversial, as they have shown lower tumor downstaging and pCR rates compared to other breast cancers. In recent decades, several gene expression assays have been developed to tailor adjuvant treatments in ER+/HER2- early breast cancer (EBC) to identify the patients that will benefit the most from adjuvant chemotherapy (CT) and those at low risk who could be spared from undergoing CT. It is still a challenge to identify patients who will benefit from neoadjuvant systemic treatment (CT or endocrine therapy (ET)). Here, we review the published data on the most common gene expression signatures (MammaPrint (MP), BluePrint (BP), Oncotype Dx, PAM50, the Breast Cancer Index (BCI), and EndoPredict (EP)) and their ability to predict the response to neoadjuvant treatment, as well as the possibility of using them on core needle biopsies. Additionally, we review the changes in the gene expression signatures after neoadjuvant treatment, and the ongoing clinical trials related to the utility of gene expression signatures in the neoadjuvant setting. Full article

(This article belongs to the Collection The Molecular Predictive and Prognostic Biomarkers in Breast Cancer)

17 pages, 679 KiB

Open AccessReview

Epstein–Barr Infection, Hodgkin’s Lymphoma, and the Immune System: Insights into the Molecular Mechanisms Facilitating Immune Evasion

by Eleni Tsotridou and Emmanouel Hatzipantelis

Cancers 2025, 17(9), 1481; https://doi.org/10.3390/cancers17091481 - 28 Apr 2025

Viewed by 184

Abstract

Epstein–Barr virus (EBV) constitutes a very common pathogen and a well-characterized carcinogen. EBV has the ability to establish a chronic latent infection, during which only a subset of the viral genes is expressed. EBV is implicated in multiple malignancies, including Hodgkin’s lymphoma (HL). [...] Read more.

Epstein–Barr virus (EBV) constitutes a very common pathogen and a well-characterized carcinogen. EBV has the ability to establish a chronic latent infection, during which only a subset of the viral genes is expressed. EBV is implicated in multiple malignancies, including Hodgkin’s lymphoma (HL). HL mainly affects adolescents and young adults and has an overall favorable prognosis. However, relapsed or refractory disease still poses a therapeutic challenge. EBV does not only induce malignant transformation but also hinders the detection and clearance of the neoplastic cells by the immune system. The proteins and non-coding RNAs expressed in latency IIa, which is associated with HL, employ a variety of mechanisms to target different steps of innate and adaptive immunity, to take advantage of the immunosuppressant effect of immune checkpoints, and to shape the microenvironment to support the survival and proliferation of malignant cells. They suppress the expression or promote the degradation of pattern-recognition receptors, interfere with type I interferon and proinflammatory cytokine mediated signaling, and hinder the effector function of natural killer cells. The processing and presentation of peptides to CD4 and CD8 T cells are also hampered. EBV induces the expression of immune checkpoints, the secretion of immunosuppressive cytokines, and the efflux of regulatory T cells in the tumor microenvironment. The current review provides a comprehensive overview of the molecular mechanisms underlying this complex interplay between EBV and the immune system in HL with focus on clinical data from the pediatric population, which is the key for developing novel, effective therapeutic interventions. Full article

(This article belongs to the Special Issue Infectious Agents and Cancer in Children and Adolescents)

► Show Figures

Figure 1

16 pages, 940 KiB

Open AccessArticle

Elastography Enhances the Diagnostic Performance of Conventional Ultrasonography in Differentiating Benign from Malignant Superficial Lymphadenopathies

by Novella Pugliese, Marco Picardi, Claudia Giordano, Annamaria Vincenzi, Rosaria Cappiello, Massimo Mascolo and Fabrizio Pane

Cancers 2025, 17(9), 1480; https://doi.org/10.3390/cancers17091480 - 28 Apr 2025

Viewed by 125

Abstract

Background/Objectives: Lymph node (LN) evaluation is critical in diagnosing, staging, and managing various diseases, particularly lymphoma and metastatic cancer. Although conventional ultrasound (US) is widely used for this purpose, its limitations in reliably differentiating between benign and malignant LNs persist. Ultrasound elastography (US-E), [...] Read more.

Background/Objectives: Lymph node (LN) evaluation is critical in diagnosing, staging, and managing various diseases, particularly lymphoma and metastatic cancer. Although conventional ultrasound (US) is widely used for this purpose, its limitations in reliably differentiating between benign and malignant LNs persist. Ultrasound elastography (US-E), which evaluates tissue stiffness, has emerged as a promising adjunct to improve diagnostic accuracy. This study aims to evaluate the diagnostic performance of conventional US, power Doppler US, and strain elastography (SE) in distinguishing malignant from benign superficial lymph nodes. Methods: In this prospective study, 214 consecutive patients referred for US of enlarged LNs were enrolled. Conventional B-mode US, power Doppler, and SE were performed, and the strain ratio (SR) was calculated as a measure of LN stiffness. Histopathological examination was used as the reference standard. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis, and multivariable logistic regression models were applied to determine the independent predictive role of SR. Results: Among the 214 LNs (one for each patient), 74 (34.6%) were benign and 140 (65.4%) were malignant. The SR showed a significant association with malignancy (p < 0.001). For hematological malignancies, SR demonstrated high sensitivity (79–85%) and specificity (81–96%), with an overall area under the curve (AUC) of 0.91. Multivariable analysis confirmed that SR was an independent predictor of malignancy (continuous and dichotomous), with a 14% gain in predictive accuracy when treated as a continuous variable (p < 0.0001). Conclusions: US-E, particularly SR, is a valuable tool in the differentiation of benign and malignant superficial LNs. SR provides significant diagnostic value, especially in hematological neoplasms like Hodgkin lymphoma, and can serve as an independent predictor of malignancy. This technique, when used in combination with conventional US features, offers enhanced diagnostic performance for LN evaluation. Full article

(This article belongs to the Special Issue Insights from the Editorial Board Member)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Cancers, Volume 17, Issue 9 (May-1 2025) – 127 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI