Cancers

16 pages, 2063 KiB

Open AccessArticle

Multi-Modal Machine Learning for Evaluating the Predictive Value of Pelvimetric Measurements (Pelvimetry) for Anastomotic Leakage After Restorative Low Anterior Resection

by Ritch T. J. Geitenbeek, Simon C. Baltus, Mark Broekman, Sander N. Barendsen, Maike C. Frieben, Ilias Asaggau, Elina Thibeau-Sutre, Jelmer M. Wolterink, Matthijs C. Vermeulen, Can O. Tan, Ivo A. M. J. Broeders and Esther C. J. Consten

Cancers 2025, 17(6), 1051; https://doi.org/10.3390/cancers17061051 - 20 Mar 2025

Viewed by 331

Abstract

Background/Objectives: Anastomotic leakage (AL) remains a major complication after restorative rectal cancer surgery, with accurate preoperative risk stratification posing a significant challenge. Pelvic measurements derived from magnetic resonance imaging (MRI) have been proposed as potential predictors of AL, but their clinical utility [...] Read more.

Background/Objectives: Anastomotic leakage (AL) remains a major complication after restorative rectal cancer surgery, with accurate preoperative risk stratification posing a significant challenge. Pelvic measurements derived from magnetic resonance imaging (MRI) have been proposed as potential predictors of AL, but their clinical utility remains uncertain. Methods: This retrospective, multicenter cohort study analyzed rectal cancer patients undergoing restorative surgery between 2013 and 2021. Pelvic dimensions were assessed using MRI-based pelvimetry. Univariate and multivariate regression analyses identified independent risk factors for AL. Subsequently, machine Learning (ML) models—logistic regression, random forest classifier, and XGBoost—were developed to predict AL using preoperative clinical data alone and in combination with pelvimetry. Model performance was evaluated using F1 scores, with the area under the receiver operating characteristic (ROC-AUC) and precision–recall curves (AUC-PR) as primary metrics. Results: Among 487 patients, the overall AL rate was 14%. Multivariate regression analysis identified distance to the anorectal junction, pelvic inlet width, and interspinous distance as independent risk factors for AL (p < 0.05). The logistic regression model incorporating pelvimetry achieved the highest predictive performance, with a mean ROC-AUC of 0.70 ± 0.09 and AUC-PR of 0.32 ± 0.10. Although predictive models that included pelvic measurements demonstrated higher ROC-AUCs compared to those without pelvimetry, the improvement was not statistically significant. Conclusions: Pelvic dimensions, specifically pelvic inlet and interspinous distance, were independently associated with an increased risk of AL. While ML models incorporating pelvimetry showed only moderate predictive performance, these measurements should be considered in developing clinical prediction tools for AL to enhance preoperative risk stratification. Full article

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

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14 pages, 400 KiB

Open AccessReview

Daylight Photodynamic Therapy for Actinic Keratosis and Field Cancerization: A Narrative Review

by Elena Sotiriou, Dimitra Kiritsi, Nikolaos Chaitidis, Michael Arabatzis, Aimilios Lallas and Efstratios Vakirlis

Cancers 2025, 17(6), 1050; https://doi.org/10.3390/cancers17061050 - 20 Mar 2025

Viewed by 224

Abstract

Actinic keratoses (AKs), also known as solar keratoses, are rough, scaly lesions that appear as macules, papules, or plaques [...] Full article

(This article belongs to the Special Issue Skin Cancer and Environmental Exposure)

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16 pages, 705 KiB

Open AccessReview

The Role of 18F PSMA-1007 PET/CT in the Staging and Detection of Recurrence of Prostate Cancer, A Scoping Review

by David Armany, Lequang Vo, Duncan Self, Sriskanthan Baskaranathan, Tania Hossack, Simon Bariol, David Ende and Henry Hyunshik Woo

Cancers 2025, 17(6), 1049; https://doi.org/10.3390/cancers17061049 - 20 Mar 2025

Viewed by 417

Abstract

Background: To determine and review the currently available literature behind the staging capabilities of 18F-PSMA-1007 PET/CT in the setting of initial staging and detection of recurrent disease for patients with prostate cancer. Prostate cancer (PCa), one of the most diagnosed malignancies affecting adult [...] Read more.

Background: To determine and review the currently available literature behind the staging capabilities of 18F-PSMA-1007 PET/CT in the setting of initial staging and detection of recurrent disease for patients with prostate cancer. Prostate cancer (PCa), one of the most diagnosed malignancies affecting adult men worldwide, requires accurate staging and early detection of recurrent disease to guide treatment decisions and improve oncological outcomes. 18F-PSMA-1007 PET/CT is a novel radiotracer with favorable imaging characteristics suggesting an important role within the Prostate Cancer management landscape. Methods: The Arksey and O’Malley Framework was used to guide this review. PubMed/MEDLINE, EMBASE, EBSCO, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were used, and relevant titles were screened for eligibility. Results: 404 database results were returned; 343 titles were excluded due to irrelevance and duplicates. A total of 61 papers were included for title and abstract review with a subsequent 26 excluded due to not meeting the inclusion criteria. A total of 35 papers proceeded to full-text review and 35 papers were included in this review. Evidence was grouped under three major themes: (1) The role of 18F-PSMA-1007 PET/CT in Initial staging; (2) The role of 18F-PSMA-1007 PET/CT in the detection of recurrent Prostate Cancer and (3) The Role of 18F-PSMA-1007 PET/CT in Salvage Therapy. The findings suggest 18F-PSMA-1007 PET/CT has superior diagnostic accuracy and sensitivity for the initial staging of prostate cancer compared with conventional imaging and other commonly used radiotracers. Strengths included the detection of pelvic and locoregional disease. Limitations included poor specificity for the detection of bone lesions, inconsistent urinary excretion patterns, and high inter-reader variability. Conclusions: 18F-PSMA-1007 PET/CT demonstrates superior diagnostic accuracy and sensitivity in both initial staging and detection of prostate cancer recurrence; however, it is limited by poor specificity for bone lesions and inconsistent urinary excretion patterns. Prospective multicenter trials are required to clearly delineate its role in the initial staging of prostate cancer and detection of recurrent disease. Full article

(This article belongs to the Special Issue PSMA PET/CT in Prostate Cancer)

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27 pages, 2306 KiB

Open AccessArticle

Impact of Surgical Resection After Induction Gemcitabine Plus S-1-Based Chemoradiotherapy in Patients with Locally Advanced Pancreatic Ductal Adenocarcinoma: A Focus on UR-LA Cases

by Masashi Kishiwada, Shugo Mizuno, Aoi Hayasaki, Benson Kaluba, Takehiro Fujii, Daisuke Noguchi, Takahiro Ito, Yusuke Iizawa, Akihiro Tanemura, Yasuhiro Murata and Naohisa Kuriyama

Cancers 2025, 17(6), 1048; https://doi.org/10.3390/cancers17061048 - 20 Mar 2025

Viewed by 243

Abstract

Background: This study aimed to assess the safety and efficacy of gemcitabine plus S-1-based chemoradiotherapy (GS-CRT) among patients with locally advanced pancreatic ductal adenocarcinoma (PDAC), especially among those with unresectable locally advanced (UR-LA) cases. Methods: A total of 351 consecutive PDAC patients [...] Read more.

Background: This study aimed to assess the safety and efficacy of gemcitabine plus S-1-based chemoradiotherapy (GS-CRT) among patients with locally advanced pancreatic ductal adenocarcinoma (PDAC), especially among those with unresectable locally advanced (UR-LA) cases. Methods: A total of 351 consecutive PDAC patients were enrolled and prognostic predictors of disease-specific survival (DSS) were identified. Results: The treatment completion rate was 98.9% and Grade 3 or higher adverse events occurred in 181 cases (51.6%). Among 319 re-evaluated patients, pancreatectomy was performed in 184 (57.7%). Based on resectability, the 5-year DSS rates for the entire cohort were 39.6% (R), 43.8% (BR-PV), 21.2% (BR-A) and 13.3% (UR-LA), while the predictors of DSS were performance status (PS), hemoglobin (Hb) level, celiac artery (CA) involvement of ≥180 degrees and JPS 8th T category. In the resected cases, the predictors of DSS were preoperative PS, preoperative CA19-9 level, preoperative JPS-T factor, degree of histological response and adjuvant chemotherapy. In UR-LA resected patients, preoperative prognostic nutritional index (PNI), absence of pathological venous invasion and adjuvant chemotherapy were predictors of DSS. Conclusions: Even though Grade 3 or higher adverse events were encountered in about half of the cases, they were uneventfully managed. Therefore, GS-CRT is safe and highly tolerable with potential to improve patients‘ prognosis. Preoperative PS, CA19-9 levels and histological response are important prognostic factors, as well as adjuvant therapy. In UR-LA patients, prognostic nutritional index (PNI) and adjuvant chemotherapy were important for curative intent surgery. Full article

(This article belongs to the Special Issue Recent Advances in Hepatobiliary Cancers: From Diagnosis to Treatment (2nd Edition))

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19 pages, 2686 KiB

Open AccessArticle

Diagnostic Performance of Combined Conventional CT Imaging Features and Radiomics Signature in Differentiating Grade 1 Tumors from Higher-Grade Pancreatic Neuroendocrine Neoplasms

by Florent Tixier, Felipe Lopez-Ramirez, Alejandra Blanco, Ammar A. Javed, Linda C. Chu, Ralph H. Hruban, Mohammad Yasrab, Daniel Fadaei Fouladi, Shahab Shayesteh, Saeed Ghandili, Elliot K. Fishman and Satomi Kawamoto

Cancers 2025, 17(6), 1047; https://doi.org/10.3390/cancers17061047 - 20 Mar 2025

Viewed by 379

Abstract

Background/Objectives: Accurate identification of grade 1 (G1) pancreatic neuroendocrine tumors (PanNETs) is crucial due to their rising incidence and emerging nonsurgical management strategies. This study evaluated whether combining conventional CT imaging features, CT radiomics features, and clinical data improves differentiation of G1 PanNETs [...] Read more.

Background/Objectives: Accurate identification of grade 1 (G1) pancreatic neuroendocrine tumors (PanNETs) is crucial due to their rising incidence and emerging nonsurgical management strategies. This study evaluated whether combining conventional CT imaging features, CT radiomics features, and clinical data improves differentiation of G1 PanNETs from higher-grade tumors (G2/G3 PanNETs and pancreatic neuroendocrine carcinomas [PanNECs]) compared to using these features individually. Methods: A retrospective analysis included 133 patients with pathologically confirmed PanNETs or PanNECs (70 males, 63 females; mean age, 58.5 years) who underwent pancreas protocol CT. A total of 28 conventional imaging features, 4892 radiomics features, and clinical data (age, gender, and tumor location) were analyzed using a support vector machine (SVM) model. Data were divided into 70% training and 30% testing sets. Results: The SVM model using the top 10 conventional imaging features (e.g., suspicious lymph nodes and hypoattenuating tumors) achieved 75% sensitivity, 81% specificity, and 79% accuracy for identifying higher-grade tumors (G2/G3 PanNETs and PanNECs). The top 10 radiomics features yielded 94% sensitivity, 46% specificity, and 69% accuracy. Combining all features (imaging, radiomics, and clinical data) improved performance, with 94% sensitivity, 69% specificity, 79% accuracy, and an F1-score of 0.77. The radiomics score demonstrated an AUC of 0.85 in the training and 0.83 in the testing set. Conclusions: Conventional imaging features provided higher specificity, while radiomics offered greater sensitivity for identifying higher-grade tumors. Integrating all three features improved diagnostic accuracy, highlighting their complementary roles. This combined model may serve as a valuable tool for distinguishing higher-grade tumors from G1 PanNETs and potentially guiding patient management. Full article

(This article belongs to the Special Issue Updates in Neuroendocrine Neoplasms)

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12 pages, 7608 KiB

Open AccessArticle

Proton Craniospinal Irradiation for Patients with Solid Tumor Leptomeningeal Disease: Real-World Feasibility, Toxicity, and Outcome Analysis

by Omer Gal, Alonso La Rosa, Matthew D. Hall, Robert H. Press, Zachary Fellows, Andrew J. Wroe, Alonso N. Gutierrez, Yazmin Odia, Minesh P. Mehta and Rupesh Kotecha

Cancers 2025, 17(6), 1046; https://doi.org/10.3390/cancers17061046 - 20 Mar 2025

Viewed by 267

Abstract

Leptomeningeal disease (LMD) is a devastating clinical scenario in patients with metastatic cancer [...] Full article

(This article belongs to the Special Issue New Perspectives in the Management of Central Nervous System (CNS) Tumors)

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10 pages, 2218 KiB

Open AccessArticle

The Role and Potential of Modern Radiotherapy in the Treatment of Metastatic Prostate Cancer

by Robert Kwiatkowski, Anna M. Kłeczek, Jadwiga Gabor, Natalia Brzezińska and Andrzej S. Swinarew

Cancers 2025, 17(6), 1045; https://doi.org/10.3390/cancers17061045 - 20 Mar 2025

Viewed by 382

Abstract

Background/Objectives: Prostate cancer is one of the most prevalent cancers among men, with a significant proportion progressing to metastatic disease. Traditional treatments for metastatic prostate cancer have primarily been palliative, focusing on symptom relief. However, recent advances in radiotherapy have shown promise [...] Read more.

Background/Objectives: Prostate cancer is one of the most prevalent cancers among men, with a significant proportion progressing to metastatic disease. Traditional treatments for metastatic prostate cancer have primarily been palliative, focusing on symptom relief. However, recent advances in radiotherapy have shown promise in improving outcomes for these patients. Methods: This study presents a modern treatment plan for extensive metastatic prostate cancer. Pre-treatment imaging revealed extensive lymph node metastases and high metabolic activity in the prostate. The treatment regimen included bicalutamide, androgen deprivation therapy with leuprorelin, and six cycles of docetaxel chemotherapy, followed by a targeted radiotherapy regimen aimed at both the primary tumor and metastatic lymph nodes. Results: Following the comprehensive radiotherapy regimen, the patient’s PSA level dropped below the edge of detection, indicating complete biochemical remission. Follow-up imaging and clinical assessments confirmed the absence of active metastatic sites. Conclusions: The findings support the integration of radiotherapy into comprehensive treatment plans for metastatic prostate cancer, demonstrating that radiotherapy can achieve complete remission even in patients with extensive metastatic disease. This suggests a need for re-evaluating traditional approaches and exploring more personalized, multimodal treatment strategies. Enhanced imaging techniques, such as PET/PSMA scans, play a crucial role in accurately targeting metastatic sites, enabling more effective and individualized treatment. Full article

(This article belongs to the Special Issue Advances in Metastatic Prostate Cancer)

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19 pages, 1591 KiB

Open AccessReview

The Gut–Endometrium Axis: Exploring the Role of Microbiome in the Pathogenesis and Treatment of Endometrial Cancer—A Narrative Review

by Beibei Zhang, Nur Fatin Nabilah Mohd Sahardi, Wen Di, Xiaoran Long and Mohamad Nasir Shafiee

Cancers 2025, 17(6), 1044; https://doi.org/10.3390/cancers17061044 - 20 Mar 2025

Viewed by 509

Abstract

Background/Objectives: Endometrial cancer (EC) is a prevalent gynecological malignancy with an increasing incidence, particularly in developed countries. Recent research has demonstrated the significant involvement of gut and endometrial microbiomes in the pathogenesis and progression of EC. This review provides a comprehensive overview [...] Read more.

Background/Objectives: Endometrial cancer (EC) is a prevalent gynecological malignancy with an increasing incidence, particularly in developed countries. Recent research has demonstrated the significant involvement of gut and endometrial microbiomes in the pathogenesis and progression of EC. This review provides a comprehensive overview of the existing knowledge on the interactions between these microbial communities and their influence on EC. Methodology: A literature review was conducted using electronic databases including Google Scholar, Scopus, and PUBMED, covering the period from 2017 to 2024. The following keywords were used for the literature search: (1) gut microbiome and endometrial cancer, (2) endometrium microbiome and endometrial cancer, and (3) endometrial cancer and microbial dysbiosis. The selected articles were chosen based on inclusion and exclusion criteria. Scale for Assessment of Narrative Review Articles (SANRA) was used for evaluating and assessing the quality of articles. Results: The gut microbiome modulates systemic inflammation, immune responses, and estrogen metabolism, all of which are crucial factors in EC development. Dysbiosis is an imbalance in the composition of microbes that can cause chronic inflammation and hormonal imbalances, which can contribute to the EC. Similarly, the endometrial microbiome, while less extensively studied, has been implicated in EC through mechanisms involving local immune modulation and the production of harmful metabolites. Probiotics, prebiotics, fecal microbiota transplantation (FMT), and personalized microbiota-based therapies can be used as clinical interventions for EC management. This review emphasizes the need for further research to explore the gut–endometrium axis and its potential for innovative therapeutic approaches. Understanding these complex interactions will become a novel strategy to prevent and treat EC, ultimately enhancing patient outcomes. Full article

(This article belongs to the Section Cancer Pathophysiology)

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16 pages, 1251 KiB

Open AccessArticle

Mixed-Methods Approach: Impact of Clinical Consenter Diversity on Clinical Trials Enrollment

by Angelica Sanchez, Christina M. Vidal, Noé Rubén Chávez, Nikita Jinna, Jackelyn Alva-Ornelas, Vanessa Myriam Robles, Cristal Resto, Nancy Sanchez, Dana Aljaber, Margarita Monge, Alicia Ramirez, Angela Reyes, Ernest Martinez, Veronica C. Jones, Jerneja Tomsic, Kendrick A. Davis and Victoria L. Seewaldt

Cancers 2025, 17(6), 1043; https://doi.org/10.3390/cancers17061043 - 20 Mar 2025

Viewed by 300

Abstract

Background: Clinical trials should benefit all people. Consequently, the National Cancer Institute expects cancer centers to accrue individuals to clinical trials in proportion to the cancer burden experienced by populations that live in their respective catchment areas; unfortunately, many cancer centers fail to [...] Read more.

Background: Clinical trials should benefit all people. Consequently, the National Cancer Institute expects cancer centers to accrue individuals to clinical trials in proportion to the cancer burden experienced by populations that live in their respective catchment areas; unfortunately, many cancer centers fail to meet this expectation. The person who gives consent for individuals in clinical trials frequently has significant contact with potential trial participants. We hypothesized that the race, ethnicity, and language of the consenter may have an important bearing on whether an individual chooses to participate in a clinical trial. Methods: We used mixed methods to investigate the impact of the socio-cultural background of the consenter on the decision of a potential research subject to participate in a clinical trial. Between 01/2018 and 02/2020, 205 women were approached in the sequential order they appeared in our breast clinic; of the 181 participants who agreed to complete the survey questionnaire, 94 (52%) were Northern European, non-Hispanic White (NE White), and 87 (48%) were Women-of-Color (WOC); this category includes participants who self-identified as Asian, Black, Hispanic/Latina, or Native American. Results: There were statistically significant differences according to the importance of the consenter’s characteristics in the decision to enroll or decline participation in the BCT. No NE White enroller (0%, n = 0) reported that consenter race was important versus 11% (n = 9) of WOC enrollers (p = 0.0009). Similarly, none of the NE White enrollers rated the consenter “looking like people in my community” as important versus 12% (n = 10) of the WOC enrollers (p = 0.0004). Conclusions: We find that consenter race and ethnicity are important for clinical trial diversity. Larger studies are needed to evaluate the generalizability of this finding. Full article

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

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21 pages, 992 KiB

Open AccessReview

The Current Role of Circulating Cell-Free DNA in the Management of Hepatocellular Carcinoma

by Alkistis Papatheodoridi, Vasileios Lekakis, Antonios Chatzigeorgiou and George Papatheodoridis

Cancers 2025, 17(6), 1042; https://doi.org/10.3390/cancers17061042 - 20 Mar 2025

Viewed by 529

Abstract

Circulating cell-free DNA (cfDNA) has emerged as a compelling candidate of liquid biopsy markers for the diagnosis and prognosis of several cancers. We systematically reviewed data on the role of cfDNA markers in the diagnosis, prognosis and treatment of hepatocellular carcinoma (HCC). Early [...] Read more.

Circulating cell-free DNA (cfDNA) has emerged as a compelling candidate of liquid biopsy markers for the diagnosis and prognosis of several cancers. We systematically reviewed data on the role of cfDNA markers in the diagnosis, prognosis and treatment of hepatocellular carcinoma (HCC). Early studies suggested that levels of circulating cfDNA, mitochondrial DNA and cfDNA integrity are higher in patients with HCC than chronic liver diseases. In subsequent studies, methylation changes in circulating tumor DNA (ctDNA) as well as cfDNA fragmentation patterns and circulating nucleosomes were found to offer high sensitivity (>60%) and excellent specificity (>90%) for HCC diagnosis. The predictive role of cfDNA markers and ctDNA has been assessed in a few studies including untreated patients with HCC providing promising results for prediction of survival. However, port-hepatectomy detection of cfDNA/ctDNA markers or copy number variation indicators of cfDNA seem to reflect minimum residual disease and thus a high risk for HCC recurrence. The same markers can be useful for prediction after transarterial chemoembolization, radiofrequency ablation, radiotherapy and even systemic therapies. In conclusion, cfDNA markers can be useful in HCC surveillance, improving early diagnosis rates, as well as for monitoring treatment effectiveness and minimal residual disease post-treatment. Full article

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

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19 pages, 15956 KiB

Open AccessReview

Clinical Characteristics and Management of Ocular Metastases

by Karolina Gerba-Górecka, Bożena Romanowska-Dixon, Izabella Karska-Basta, Ewelina Cieplińska-Kechner and Michał S. Nowak

Cancers 2025, 17(6), 1041; https://doi.org/10.3390/cancers17061041 - 20 Mar 2025

Viewed by 274

Abstract

Intraocular metastases represent the most common type of intraocular tumors in adults. In most cases, the metastases originate from primary breast and lung cancers. Effective management of patients with intraocular metastatic disease requires a multidisciplinary approach involving ophthalmologists, oncologists, and radiation therapists. The [...] Read more.

Intraocular metastases represent the most common type of intraocular tumors in adults. In most cases, the metastases originate from primary breast and lung cancers. Effective management of patients with intraocular metastatic disease requires a multidisciplinary approach involving ophthalmologists, oncologists, and radiation therapists. The primary goals of treatment are disease control, maintenance of optimal quality of life, and preservation of functional vision. This article provides an in-depth overview of intraocular metastases, with special emphasis on the practical aspects of their diagnosis and treatment based on the most recent literature. Full article

(This article belongs to the Special Issue Advance in Treatment of Uveal Melanoma)

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19 pages, 806 KiB

Open AccessReview

Unlocking the Potential of ctDNA in Sarcomas: A Review of Recent Advances

by Sahana Aiyer, Tae-Hee Kim, Katharine Collier, Raphael Pollock, Claire Verschraegen, Daniel G. Stover and Gabriel Tinoco

Cancers 2025, 17(6), 1040; https://doi.org/10.3390/cancers17061040 - 20 Mar 2025

Viewed by 466

Abstract

Soft tissue sarcomas (STSs) constitute a group of tumors with heterogeneous alterations and different biological behavior. Genetic profiling techniques have immense potential to revolutionize sarcoma classification, detection, and treatment. Cell-free DNA (cfDNA) analysis offers a minimally invasive approach to profiling tumor alterations, including [...] Read more.

Soft tissue sarcomas (STSs) constitute a group of tumors with heterogeneous alterations and different biological behavior. Genetic profiling techniques have immense potential to revolutionize sarcoma classification, detection, and treatment. Cell-free DNA (cfDNA) analysis offers a minimally invasive approach to profiling tumor alterations, including tracking specific mutations or targeted panels of cancer-related genes via DNA sequencing methods. Circulating tumor DNA (ctDNA) platforms have gained popularity as a noninvasive alternative to tissue biopsies, offering a less invasive approach to tumor profiling. Nonetheless, ctDNA profiling in concordance with standard solid tumor comprehensive genomic profiling (CGP) is poorly characterized for STSs. Ultra-low-pass whole-genome sequencing and whole exome sequencing of cfDNA have yet to be fully leveraged in patients with sarcomas. This comprehensive review provides an overview of the application of ctDNA in STSs. Full article

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

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29 pages, 2013 KiB

Open AccessReview

CDK4/6 as a Therapeutic Target in HR+/HER2− Breast Cancer Cells—Current Treatment Status

by Kamila Krupa, Anna Liszcz-Tymoszuk, Natalia Czerw, Aleksandra Czerw, Katarzyna Sygit, Remigiusz Kozłowski, Andrzej Deptała and Anna Badowska-Kozakiewicz

Cancers 2025, 17(6), 1039; https://doi.org/10.3390/cancers17061039 - 20 Mar 2025

Viewed by 644

Abstract

Breast cancer is the most frequently diagnosed neoplasm in the world. It can be classified into four main subtypes, each of them showing differences in the expression of hormone receptor (HR), human epidermal growth factor receptor 2 (HER2), and in cell metabolism. Since [...] Read more.

Breast cancer is the most frequently diagnosed neoplasm in the world. It can be classified into four main subtypes, each of them showing differences in the expression of hormone receptor (HR), human epidermal growth factor receptor 2 (HER2), and in cell metabolism. Since 2015, when The U.S. Food and Drug Administration (FDA) approved the first cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor that regulates the cell cycle, treatment of HR+/HER2− BC has become much more effective. Currently, palbociclib, ribociclib, and abemaciclib are more often used both in combination with endocrine therapy as well as in monotherapy. Their application has been extensively verified in many clinical trials such as PALOMA-1,2,3, MONALEESA-1,2,3,7, and MONARCH-1,2,3, which allowed the verification of differences in their effectiveness, dosage, and adverse effects. Subsequent studies, MonarchE and NATALEE, examined the role of these inhibitors as adjuvant therapy, as well as at verifying their safety. Moreover, dalpiciclib is being investigated in HR+/HER2− BC treatment. This article will summarize clinical efficacy, recommendations, and differences in toxicity profile between palbociclib, ribociclib, and abemaciclib and will also discuss the possibility of using dalpiciclib in the treatment of breast cancer. Full article

(This article belongs to the Section Molecular Cancer Biology)

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12 pages, 596 KiB

Open AccessArticle

Design of a Phase I Drug Combination Study with Adaptive Allocation Based on Dose-Limiting Toxicity Attribution

by Nolan A. Wages, Bethany J. Horton, Li Liu, Enrica Marchi and Gina R. Petroni

Cancers 2025, 17(6), 1038; https://doi.org/10.3390/cancers17061038 - 20 Mar 2025

Viewed by 278

Abstract

Background: This article describes the adaptation of a Phase I drug combination method to incorporate dose-limiting toxicity (DLT) attribution in dose assignments. The study is motivated by the Embolden trial (NCT03240211), a Phase Ib, multicenter trial at the UVA Comprehensive Cancer Center evaluating [...] Read more.

Background: This article describes the adaptation of a Phase I drug combination method to incorporate dose-limiting toxicity (DLT) attribution in dose assignments. The study is motivated by the Embolden trial (NCT03240211), a Phase Ib, multicenter trial at the UVA Comprehensive Cancer Center evaluating pembrolizumab with pralatrexate (Arm A), decitabine (Arm C), or both (Arm B) in relapsed/refractory peripheral and cutaneous T cell lymphomas. Methods: While Arms A and C used monotherapy dose escalation, Arm B required simultaneous escalation of both agents, integrating drug-specific DLT attribution to guide dosing. Results: We adapted the partial order continual reassessment method (POCRM) to incorporate this attribution, ensuring appropriate de-escalation of the offending agent. Given the trial’s complexity, software modifications were necessary to evaluate design performance through simulations. Conclusions: This work underscores the importance of novel dose-finding strategies in early-phase trials and aims to promote their broader adoption for improved trial efficiency and transparency. Full article

(This article belongs to the Special Issue Advances in Clinical Trials: Outcome, Innovations, Challenges, and Ethical Practice in Cancer Research 2024–2025)

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17 pages, 3123 KiB

Open AccessArticle

Loss of ING3 in the Prostate Leads to Activation of DNA Damage Repair Markers

by Viktor Lang, Lisa Barones, ShiTing Misaki Hu, Fatemeh Hashemi, Karen Blote, Karl Riabowol and Dieter Fink

Cancers 2025, 17(6), 1037; https://doi.org/10.3390/cancers17061037 - 20 Mar 2025

Viewed by 333

Abstract

Background/Objectives: The inhibitor of growth family member 3 (ING3) acts as an epigenetic reader through physical interactions with histone-modifying enzymes and subsequent chromatin remodelling processes. It is involved in various cellular functions, such as cell cycle control, cell growth, and apoptosis. Although ING3 [...] Read more.

Background/Objectives: The inhibitor of growth family member 3 (ING3) acts as an epigenetic reader through physical interactions with histone-modifying enzymes and subsequent chromatin remodelling processes. It is involved in various cellular functions, such as cell cycle control, cell growth, and apoptosis. Although ING3 was assigned tumour suppressor candidate status in some types of cancers, including prostate cancer, some studies suggest it acts to promote growth. To address these contradictory reports regarding its role in the initiation and progression of prostate cancer, we specifically addressed the question of whether ablation of ING3 in the mouse prostate is sufficient to initiate malignant transformation of the prostate and support its (candidate) tumour suppressor status. Methods: To generate the prostate-specific Ing3 knockout mouse, paternal inheritance of the PB-Cre4 transgene was used, while for the generation of a global knockout control, a female mouse harbouring the PB-Cre4 transgene was utilized. To determine the recombination efficiency of the Cre-LoxP system in the prostate at the Ing3 locus, a duplex probe-based digital PCR assay capable of counting undisrupted Ing3 copies was designed. The impact of DNA recombination on the protein level was investigated by immunohistochemical staining of prostate tissue samples. Results: In the prostate-specific knockout, digital PCR analysis revealed mosaic gene deletion. We found recombination efficiencies in the anterior, dorsolateral, and ventral prostate lobes ranging from approximately 15 to 30%. ING3 staining in the prostate was faint with no detectable differences in signal intensity between the knockout specimen and wild-type controls. This low ING3 expression in the prostate is consistent with observations of X-gal staining of an Ing3-LacZ reporter allele. Immunohistochemistry showed increased expression of DNA-damage-associated markers γH2AX and 53BP1. However, no gross anatomical abnormalities or prostate intraepithelial neoplasia (PIN) lesions in the prostate of tissue-specific knockout animals compared to wild-type controls were observed. Conclusions: Altogether, our data provide evidence that disruption of ING3 expression in prostate cells does not lead to malignant transformation and challenges the idea that ING3 acts primarily in a tumour-suppressive manner. Furthermore, this work supports the crucial role of ING3 in maintaining genomic stability, and we confirmed the embryonic lethal phenotype of homozygous Ing3 null mice that is rescued by ectopic expression of ING3. Full article

(This article belongs to the Special Issue CelebratING 25 Years of the ING Family Proteins as Epigenetic Regulators in Cancer)

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18 pages, 12086 KiB

Open AccessArticle

Temporal Validation of an FDG-PET-Radiomic Model for Distant-Relapse-Free-Survival After Radio-Chemotherapy for Pancreatic Adenocarcinoma

by Monica Maria Vincenzi, Martina Mori, Paolo Passoni, Roberta Tummineri, Najla Slim, Martina Midulla, Gabriele Palazzo, Alfonso Belardo, Emiliano Spezi, Maria Picchio, Michele Reni, Arturo Chiti, Antonella del Vecchio, Claudio Fiorino and Nadia Gisella Di Muzio

Cancers 2025, 17(6), 1036; https://doi.org/10.3390/cancers17061036 - 20 Mar 2025

Viewed by 349

Abstract

Background/Objectives: Pancreatic cancer is a very aggressive disease with a poor prognosis, even when diagnosed at an early stage. This study aimed to validate and refine a radiomic-based [¹⁸F]FDG-PET model to predict distant relapse-free survival (DRFS) in patients with unresectable [...] Read more.

Background/Objectives: Pancreatic cancer is a very aggressive disease with a poor prognosis, even when diagnosed at an early stage. This study aimed to validate and refine a radiomic-based [¹⁸F]FDG-PET model to predict distant relapse-free survival (DRFS) in patients with unresectable locally advanced pancreatic cancer (LAPC). Methods: A Cox regression model incorporating two radiomic features (RFs) and cancer stage (III vs. IV) was temporally validated using a larger cohort (215 patients treated between 2005–2022). Patients received concurrent chemoradiotherapy with capecitabine and hypo-fractionated Intensity Modulated Radiotherapy (IMRT). Data were split into training (145 patients, 2005–2017) and validation (70 patients, 2017–2022) groups. Seventy-eight RFs were extracted, harmonized, and analyzed using machine learning to develop refined models. Results: The model incorporating Statistical-Percentile10, Morphological-ComShift, and stage demonstrated moderate predictive accuracy (training: C-index = 0.632; validation: C-index = 0.590). When simplified to include only Statistical-Percentile10, performance improved slightly in the validation group (C-index = 0.601). Adding GLSZM3D-grayLevelVariance to Statistical-Percentile10, while excluding Morphological-ComShift, further enhanced accuracy (training: C-index = 0.654; validation: C-index = 0.623). Despite these refinements, all versions showed similar moderate ability to stratify patients into risk classes. Conclusions: [¹⁸F]FDG-PET radiomic features are robust predictors of DRFS after chemoradiotherapy in LAPC. Despite moderate performance, these models hold promise for patient risk stratification. Further validation with external cohorts is ongoing. Full article

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

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22 pages, 5571 KiB

Open AccessArticle

Trends in Endometrial Cancer Incidence Among Premenopausal and Postmenopausal Women in the United States Between 2001 and 2021

by Fangjian Guo, Victor Adekanmbi, Christine D. Hsu, Thao N. Hoang, Pamela T. Soliman, Jacques G. Baillargeon and Abbey B. Berenson

Cancers 2025, 17(6), 1035; https://doi.org/10.3390/cancers17061035 - 20 Mar 2025

Viewed by 400

Abstract

Background: Endometrial cancer incidence has been rising in the United States. We assessed trends in endometrial cancer incidence among both premenopausal and postmenopausal women in the US from 2001 to 2021. We also compared the incidence during 2019–2021 to assess the impact of [...] Read more.

Background: Endometrial cancer incidence has been rising in the United States. We assessed trends in endometrial cancer incidence among both premenopausal and postmenopausal women in the US from 2001 to 2021. We also compared the incidence during 2019–2021 to assess the impact of the COVID-19 pandemic. Methods: We used data from the United States Cancer Statistics 2001–2021 database to assess the incidence trends among adult females. Endometrial cancer incidence was corrected for hysterectomy prevalence and age, adjusted to the 2000 US standard population. Results: From 2001 to 2021, the incidence of endometrial cancer rose from 86.8 cases to 113.8 cases per 1,000,000 persons among women aged 20–49 years (APC 1.5, 95% CI 1.2–1.8), while in women 70 and older, it increased from 1326.4 cases to 1339.4 cases per 1,000,000 persons (APC 0.3, 95% CI 0.1–0.6). The incidence has recently decreased among women aged 50–69 years (APC from 2001 to 2016 0.3, 95% CI 0.1–0.9; APC from 2016 to 2021 −1.3, 95% CI −2.2–−0.3). Endometrial cancer incidence sharply increased from 2001 to 2021 among non-Hispanic Blacks, non-Hispanic Asians or Pacific Islanders, and women in the South. Endometrial cancer incidence sharply decreased from 2019 to 2020, and the proportion of metastatic cancer at diagnosis increased across all age groups. In 2021, the incidence returned to 2019 levels. Conclusions: Endometrial cancer incidence rates are rising, particularly among premenopausal women. During the beginning of the COVID-19 pandemic, the incidence rates decreased, but the proportion of metastatic cancer increased. Full article

(This article belongs to the Special Issue Endometrial Cancer Prevention, Early Diagnosis and Treatment: Advances and Challenges)

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23 pages, 1652 KiB

Open AccessArticle

Exploring the Expression of CD73 in Lung Adenocarcinoma with EGFR Genomic Alterations

by Elodie Long-Mira, Christophe Bontoux, Guylène Rignol, Véronique Hofman, Sandra Lassalle, Jonathan Benzaquen, Jacques Boutros, Salomé Lalvée-Moret, Katia Zahaf, Virginie Lespinet-Fabre, Olivier Bordone, Sophia Maistre, Christelle Bonnetaud, Charlotte Cohen, Jean-Philippe Berthet, Charles-Hugo Marquette, Valerie Vouret-Craviari, Marius Ilié and Paul Hofman

Cancers 2025, 17(6), 1034; https://doi.org/10.3390/cancers17061034 - 20 Mar 2025

Viewed by 420

Abstract

Background/Objectives: Immune checkpoint inhibitors (ICIs) benefit some lung cancer patients, but their efficacy is limited in advanced lung adenocarcinoma (LUAD) with EGFR mutations (EGFRm), largely due to a non-immunogenic tumour microenvironment (TME). Furthermore, EGFRm LUAD patients often experience increased toxicity with [...] Read more.

Background/Objectives: Immune checkpoint inhibitors (ICIs) benefit some lung cancer patients, but their efficacy is limited in advanced lung adenocarcinoma (LUAD) with EGFR mutations (EGFRm), largely due to a non-immunogenic tumour microenvironment (TME). Furthermore, EGFRm LUAD patients often experience increased toxicity with ICIs. CD73, an ectonucleotidase involved in adenosine production, promotes tumour immune evasion and could represent a novel therapeutic target. This study investigates CD73 expression in LUAD with EGFR alterations and its clinico-pathological correlations. Methods: CD73 expression in tumour (CD73_TC) and stromal (CD73_SC) cells was assessed in 76 treatment-naive LUAD patients using immunohistochemistry (IHC) (D7F9A clone) alongside IHC PD-L1 (22C3 clone). EGFR alterations were identified by molecular sequencing and FISH. Event-free survival (EFS) was analysed based on CD73_TC expression. Results: CD73_TC expression was observed in 66% of cases, with high expression (Tumour Proportion Score > 50%) correlating with improved EFS (p = 0.045). CD73_TC and PD-L1 expression were not significantly correlated (p = 0.44), although a weak inverse trend was observed. CD73_SC expression was detected in 18% of cases, predominantly in early-stage (p = 0.037), PD-L1-negative (p = 0.030), and non-EGFR-amplified (p = 0.0018) tumours. No significant associations were found with disease stage, histological subtype, EGFR mutation type, and amplification. Conclusions: CD73 expression in EGFRm LUAD is heterogeneous and associated with diverse TME profiles. These findings support the potential of CD73 as a predictive biomarker and therapeutic target, highlighting its clinical relevance in EGFRm LUAD. Full article

(This article belongs to the Special Issue New Advances in Lung Cancer: Diagnosis, Pathophysiology and Emerging Treatments. A Selection of Papers from the 4th Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))

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10 pages, 220 KiB

Open AccessArticle

The Impact of Surgical Conization of the Cervix and Loop Electrosurgical Excision Procedure on Female Sexual Function

by Paweł Bartnik, Joanna Kacperczyk-Bartnik, Anna Różańska-Walędziak, Andrzej Wróbel, Christopher Kobierzycki, Krzysztof Czajkowski and Ewa Romejko-Wolniewicz

Cancers 2025, 17(6), 1033; https://doi.org/10.3390/cancers17061033 - 20 Mar 2025

Viewed by 278

Abstract

Objectives: The aim of the study was to analyze and compare the possible effect of cervical conization and the loop electrosurgical excision procedure (LEEP) on female sexual function up to one year after intervention, as existing studies provide incoherent results. Methods: [...] Read more.

Objectives: The aim of the study was to analyze and compare the possible effect of cervical conization and the loop electrosurgical excision procedure (LEEP) on female sexual function up to one year after intervention, as existing studies provide incoherent results. Methods: This prospective cohort study enrolled patients who underwent either LEEP (n = 35) or surgical conization of the cervix (n = 44). Patients completed the questionnaire before the intervention and at three, six, and twelve months after the end of the postoperative period. The questionnaire included the Polish version of the Female Sexual Function Index (FSFI) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire of Cancer Patients with the module Cervix-24. Results: In the LEEP group, significant deterioration was observed in the FSFI orgasm subscale after three and six months in comparison to the baseline (3.98 ± 2.08 vs. 3.19 ± 2.29 vs. 3.09 ± 2.24; p < 0.02). The difference in the orgasm subscale compared to the baseline score was not reported after twelve months of follow-up. In the surgical conization group, significant deterioration was observed in the general FSFI score between the baseline and three months after (22.37 ± 12.38 vs. 20.82 ± 12.02; p < 0.003) and in the arousal subscale between the baseline and three months after (3.69 ± 2.14 vs. 3.01 ± 2.02; p < 0.001). In the orgasm subscale, there was a significant improvement between three and twelve months of observation (3.05 ± 2.22 vs. 3.63 ± 2.29; p < 0.003). A significant deterioration was observed in the sexual activity subscale of the EORTC QLQ-C30 + CX24 between baseline and after three months (49.42 ± 36.12 vs. 39.09 ± 36.81; p < 0.03). All reported deteriorations had a tendency to resolve within twelve months of observation. Conclusions: Both LEEP and surgical conization of the cervix seem to have a mild, transient negative impact on female sexual function, which normalizes one year after the procedure. Long-term consequences of both procedures are similar. Further research with larger sample sizes is necessary to confirm these findings. Full article

(This article belongs to the Special Issue Cervical Cancer: Study on Molecular Landscape and Protein Biomarkers. Current Diagnostic and Therapeutic Capabilities)

18 pages, 3049 KiB

Open AccessReview

Camptothein-Based Anti-Cancer Therapies and Strategies to Improve Their Therapeutic Index

by Jue Gong, Wenqiu Zhang and Joseph P. Balthasar

Cancers 2025, 17(6), 1032; https://doi.org/10.3390/cancers17061032 - 20 Mar 2025

Viewed by 525

Abstract

Camptothecin and its derivatives (CPTs) are potent antineoplastic agents that exert their effects by inhibiting DNA topoisomerase I, leading to apoptosis during cell proliferation. Since their discovery in the 1960s, CPTs have faced challenges such as low water solubility, pH-dependent lactone ring instability, [...] Read more.

Camptothecin and its derivatives (CPTs) are potent antineoplastic agents that exert their effects by inhibiting DNA topoisomerase I, leading to apoptosis during cell proliferation. Since their discovery in the 1960s, CPTs have faced challenges such as low water solubility, pH-dependent lactone ring instability, and severe off-target toxicities. Despite extensive research, only two CPTs, irinotecan and topotecan, have received health authority approval. Ongoing clinical trials continue to explore the use of CPTs in combination with targeted therapies and immunotherapies to expand their clinical use. Drug delivery systems, including liposomes and antibody–drug conjugates (ADCs), have significantly enhanced the therapeutic index of CPTs. Liposomal irinotecan (Onivyde^®, Ipsen, Paris, France) and two ADCs delivering CPT payloads, trastuzumab deruxtecan (Enhertu^®, Daiichi Sankyo, Tokyo, Japan) and sacituzumab govitecan (Trodelvy^®, Gilead Sciences, Inc., Foster City, CA, USA), have demonstrated substantial efficacy and safety. There is promise that novel strategies such as inverse targeting and co-dosing with anti-idiotypic distribution enhancers may expand the utility of CPT ADCs. This review highlights CPT therapies in clinical use and discusses approaches to further enhance their therapeutic selectivity. Full article

(This article belongs to the Special Issue Advances in Drug Delivery for Cancer Therapy)

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11 pages, 4235 KiB

Open AccessArticle

The Use of PI-FAB Score in Evaluating mpMRI After Focal Ablation of Prostate Cancer: Is It Reliable? Inter-Reader Agreement in a Tertiary Care Referral University Hospital

by Elena Bertelli, Michele Vizzi, Martina Legato, Rossella Nicoletti, Sebastiano Paolucci, Ron Ruzga, Simona Giovannelli, Francesco Sessa, Sergio Serni, Lorenzo Masieri, Riccardo Campi, Emanuele Neri, Simone Agostini and Vittorio Miele

Cancers 2025, 17(6), 1031; https://doi.org/10.3390/cancers17061031 - 20 Mar 2025

Viewed by 246

Abstract

Background/Purpose: to assess the inter-reader agreement of the PIFAB (Prostate Imaging after Focal Ablation) score, a new MRI-based standardized system for evaluating post-focal therapy prostate mpMRI, among radiologists in a single large cohort of patients treated with focal therapy (HIFU) in a tertiary [...] Read more.

Background/Purpose: to assess the inter-reader agreement of the PIFAB (Prostate Imaging after Focal Ablation) score, a new MRI-based standardized system for evaluating post-focal therapy prostate mpMRI, among radiologists in a single large cohort of patients treated with focal therapy (HIFU) in a tertiary care referral University Hospital. Methods: In total, 68 consecutive patients who underwent HIFU were included in this single-center retrospective observational study. A total of 109 post-HIFU follow-up mpMRIs were evaluated by three radiologists with varying levels of experience (12, 8, and 3 years, respectively). All patients underwent their first follow-up mpMRI at 6 months post-treatment, with 30 patients receiving additional evaluations at 18 months and 11 at 30 months. Results: The patients had a mean age of 70.6 ± 8.31 years, a mean pre-treatment PSA (prostate-specific antigen) of 7.85 ± 1.21 ng/mL, and a mean post-treatment PSA of 4.64 ± 4.2 ng/mL. The inter-reader agreement for PI-FAB among the three radiologists showed a Gwet’s AC2 value of 0.941 (95% confidence interval: 0.904–0.978, p < 0.0001). For the most experienced radiologist, at the 6-month follow-up 64 (94.14%) patients were scored as PI-FAB 1, 1 (1.47%) as PI-FAB 2, and 3 (4.41%) as PI-FAB 3. At the 18-month and 30-month follow-ups all patients were scored as PI-FAB 1 (no suspicion of recurrence). Conclusions: Our study demonstrates excellent inter-reader agreement among radiologists with varying levels of experience, confirming that the PI-FAB score is highly reproducible when evaluating post-treatment mpMRI scans. The low rate of PI-FAB 2 and PI-FAB 3 lesions observed at the first follow-up, coupled with the absence of significant recurrence in subsequent evaluations, suggests that HIFU is a reliable technique for prostate cancer treatment in selected patients. Full article

(This article belongs to the Special Issue Molecular Imaging in Oncology: Recent Advances)

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18 pages, 877 KiB

Open AccessArticle

Physical Activity, Fitness, and Health-Related Quality of Life in Children and Adolescent Cancer Survivors: A Cross-Sectional Study (iBoneFIT Project)

by Andrés Redondo-Tébar, Andrea Rodriguez-Solana, Luis Gracia-Marco, Andres Marmol-Perez, José J. Gil-Cosano, Cristina Cadenas-Sánchez, Francisco J. Llorente-Cantarero, Juan Francisco Pascual-Gázquez, María Herrada-Robles, Mairena Sánchez-López and Esther Ubago-Guisado

Cancers 2025, 17(6), 1030; https://doi.org/10.3390/cancers17061030 - 19 Mar 2025

Viewed by 429

Abstract

Background/Objectives: This study aims to evaluate the health-related quality of life (HRQoL) of children and adolescent cancer survivors in relation to previously published normative values for typically developing children and adolescents, as well as to analyze the differences in HRQoL based on [...] Read more.

Background/Objectives: This study aims to evaluate the health-related quality of life (HRQoL) of children and adolescent cancer survivors in relation to previously published normative values for typically developing children and adolescents, as well as to analyze the differences in HRQoL based on their levels of physical activity and fitness. Methods: Cross-sectional study with 116 cancer survivors (12.1 ± 3.3 years, 57.8% boys) from two pediatric oncology units in Andalusia (Spain). HRQoL was assessed using PedsQL 4.0 Generic Core Scales. Physical activity was measured with accelerometers, and fitness was evaluated using self-reported and objective tests for muscular fitness. Independent samples t-tests to compare HRQoL between our sample and the normative values published for typically developing children and adolescents of the same age and analysis of covariance (ANCOVA) were conducted to assess differences in HRQoL according to physical activity and fitness categories in our sample. Results: Children and adolescent cancer survivors had lower HRQoL scores compared to typically developing children’s and adolescents’ normative values, except for social functioning. Higher levels of moderate-to-vigorous physical activity were associated with better total, physical, and psychosocial HRQoL scores. Children and adolescent cancer survivors with better levels of cardiorespiratory fitness, motor fitness, and flexibility reported better HRQoL scores in total and psychosocial domains. However, muscular fitness (self-reported and objectively measured) did not show a significant difference in HRQoL. Conclusions: Children and adolescent cancer survivors experience lower HRQoL than their typically developing counterparts. Engaging in at least 30 min of moderate-to-vigorous physical activity per day is associated with fewer HRQoL impairments. Improved fitness, particularly cardiorespiratory fitness, motor fitness, and flexibility, are associated with better HRQoL outcomes. These findings highlight the association between physical activity, fitness levels, and HRQoL in children and adolescent cancer survivors, suggesting the potential benefits of promoting physical activity and enhancing fitness levels. Full article

(This article belongs to the Section Pediatric Oncology)

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42 pages, 19095 KiB

Open AccessReview

Pheochromocytomas and Paragangliomas—Current Management

by Adam Brewczyński, Agnieszka Kolasińska-Ćwikła, Beata Jabłońska and Lucjan Wyrwicz

Cancers 2025, 17(6), 1029; https://doi.org/10.3390/cancers17061029 - 19 Mar 2025

Viewed by 578

Abstract

Pheochromocytomas and paragangliomas (PPGLs) are infrequent neuroendocrine hypervascular neoplasms arising within different sites of the paraganglion system. They are divided into sympathetic (including pheochromocytomas and extraadrenal paragangliomas) and parasympathetic extraadrenal tumors. These tumors are usually not malignant and grow slowly; about 90% of [...] Read more.

Pheochromocytomas and paragangliomas (PPGLs) are infrequent neuroendocrine hypervascular neoplasms arising within different sites of the paraganglion system. They are divided into sympathetic (including pheochromocytomas and extraadrenal paragangliomas) and parasympathetic extraadrenal tumors. These tumors are usually not malignant and grow slowly; about 90% of them are found in the adrenal paraganglia (pheochromocytomas). Extraadrenal tumors are most frequently located in the abdominal cavity (85%), followed by the thoracic cavity (12%), and head and neck (3%). About 25% of PPGLs are related to germline mutations, which are risk factors for multifocal and metastatic disease. In PPGL diagnostics, laboratory, biochemical, and imaging (anatomical and functional) examinations are used. Surgery is the standard management choice for locoregional disease. For patients who are not candidates for surgery and who have stable, not-growing, or slow-growing tumors, active observation or other less invasive techniques (i.e., stereotactic surgery, hypofractionated stereotactic radiotherapy) are considered. In metastatic disease, systemic therapies (tyrosine kinase inhibitors [TKIs], mTORC1 inhibitor everolimus, immunotherapy, cold somatostatin analogs [biotherapy], and radioligand therapy) are used. The prognosis for PPGLs is quite good, and the 5-year survival rate is >90%. The goal of this paper is to review knowledge on the etiopathogenesis, current diagnostics, and therapy for PPGL patients. Our paper is particularly focused on the current management of PPGLs. Full article

(This article belongs to the Special Issue Neuroendocrine Neoplasms: Pathogenesis, Diagnostics, and Therapy)

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18 pages, 2940 KiB

Open AccessArticle

Development of an Intratumoral Holmium Microsphere Injection Method in Ex Vivo Human Pancreatic Ductal Adenocarcinoma: A Preclinical Feasibility Study

by Coen Ysbrand Willink, Sjoerd Franciscus Maria Jenniskens, Nienke Johanna Maria Klaassen, Martijn Willem Jan Stommel, Cornelis Johannes Henricus Martinus van Laarhoven, Jurgen J. Fütterer and Johannes Frank Wilhelmus Nijsen

Cancers 2025, 17(6), 1028; https://doi.org/10.3390/cancers17061028 - 19 Mar 2025

Viewed by 307

Abstract

Background/Objectives: Patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) have a poor prognosis. Local therapy may enhance tumor control and increase resectability. Intratumoral injection of radioactive holmium-166 microspheres presents a promising and minimally invasive treatment with multimodality imaging capabilities (SPECT, CT, MRI). However, holmium-166 [...] Read more.

Background/Objectives: Patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) have a poor prognosis. Local therapy may enhance tumor control and increase resectability. Intratumoral injection of radioactive holmium-166 microspheres presents a promising and minimally invasive treatment with multimodality imaging capabilities (SPECT, CT, MRI). However, holmium-166 microspheres are not commonly used for intratumoral injections, and PDAC is notorious for its high intratumoral pressure. This study developed an intratumoral injection method with nonradioactive holmium-165 microspheres in ex vivo human PDAC specimens using a novel injection system for suspension homogenization. Methods: An injection system was developed and validated in a laboratory setting. Thereafter, intratumoral injections in surgically removed ex vivo PDACs were performed, and parameters were established to optimize feasibility, defined by the ability to inject and control the microsphere distribution. Also, injection limitations and cutoff values were determined. The distribution was assessed by visual confirmation, CT, MRI, ultrasound, and histopathology. Results: With a validated injection system, intratumoral injections were performed in ten ex vivo PDAC samples. Feasible injection guidelines include but are not limited to ultrasound or CT needle guidance, a maximum injection volume of <20.0% from the tumor volume, ≤3 needle positions, and an injection volume of 0.3–1.0 mL per needle position. Conclusions: Intratumoral injection of holmium-165 microspheres in ex vivo pancreatic ductal adenocarcinoma was feasible with adherence to injection parameters necessary for effective intratumoral deposition and minimal leakage. The injection system and parameters developed here provide a foundation for future studies on holmium-166 microsphere injections in pancreatic cancer patients, with the aim to improve local tumor control as a part of a multimodal therapy. Full article

(This article belongs to the Special Issue Multimodal Treatment for Pancreatic Cancer)

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26 pages, 2013 KiB

Open AccessReview

Tumor Heterogeneity and the Immune Response in Non-Small Cell Lung Cancer: Emerging Insights and Implications for Immunotherapy

by Michael S. Oh, Jensen Abascal, Austin K. Rennels, Ramin Salehi-Rad, Steven M. Dubinett and Bin Liu

Cancers 2025, 17(6), 1027; https://doi.org/10.3390/cancers17061027 - 19 Mar 2025

Viewed by 627

Abstract

Resistance to immune checkpoint inhibitors (ICIs) represents a major challenge for the effective treatment of non-small cell lung cancer (NSCLC). Tumor heterogeneity has been identified as an important mechanism of treatment resistance in cancer and has been increasingly implicated in ICI resistance. The [...] Read more.

Resistance to immune checkpoint inhibitors (ICIs) represents a major challenge for the effective treatment of non-small cell lung cancer (NSCLC). Tumor heterogeneity has been identified as an important mechanism of treatment resistance in cancer and has been increasingly implicated in ICI resistance. The diversity and clonality of tumor neoantigens, which represent the target epitopes for tumor-specific immune cells, have been shown to impact the efficacy of immunotherapy. Advances in genomic techniques have further enhanced our understanding of clonal landscapes within NSCLC and their evolution in response to therapy. In this review, we examine the role of tumor heterogeneity during immune surveillance in NSCLC and highlight its spatial and temporal evolution as revealed by modern technologies. We explore additional sources of heterogeneity, including epigenetic and metabolic factors, that have come under greater scrutiny as potential mediators of the immune response. We finally discuss the implications of tumor heterogeneity on the efficacy of ICIs and highlight potential strategies for overcoming therapeutic resistance. Full article

(This article belongs to the Special Issue Immunotherapy in Non-Small Cell Lung Cancers)

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18 pages, 991 KiB

Open AccessSystematic Review

Primary or Interval Debulking Surgery for Advanced Endometrial Cancer with Carcinosis: A Systematic Review and Individual Patient Data Meta-Analysis of Survival Outcomes

by Giulia Mantovani, Camelia Alexandra Coada, Stella Di Costanzo, Francesco Mezzapesa, Lucia Genovesi, Giorgio Bogani, Francesco Raspagliesi, Alessio Giuseppe Morganti, Pierandrea De Iaco and Anna Myriam Perrone

Cancers 2025, 17(6), 1026; https://doi.org/10.3390/cancers17061026 - 19 Mar 2025

Viewed by 382

Abstract

Objective. To compare the survival outcomes of primary debulking surgery and platinum-based adjuvant chemotherapy versus interval debulking surgery after platinum-based neoadjuvant chemotherapy in patients with stage IVb endometrial cancer and peritoneal carcinosis. Methods. The online search included the following data sources: PubMed, Scopus, [...] Read more.

Objective. To compare the survival outcomes of primary debulking surgery and platinum-based adjuvant chemotherapy versus interval debulking surgery after platinum-based neoadjuvant chemotherapy in patients with stage IVb endometrial cancer and peritoneal carcinosis. Methods. The online search included the following data sources: PubMed, Scopus, WOS, and the Cochrane Library from 1990 to 2024 (PROSPERO registration code: CRD42023438602). A total of 3230 studies were identified, with the inclusion of 16. Individual patient data on survival outcomes, disease distribution, and residual tumors, as well as details of neoadjuvant chemotherapy and adjuvant treatment, were extracted. Results. A total of 285 patients were included: 197 (69%) underwent primary debulking surgery and 88 (31%) underwent interval debulking surgery. The pooled analysis revealed a median progression-free survival in the primary debulking surgery group of 18.0 months compared to 12.0 months in the interval debulking surgery group (p = 0.028; log-rank test), and a median overall survival of 30.92 months versus 28.73 months (p = 0.400; log-rank test). Among the 134 patients with available information on the residual tumor after primary debulking surgery or interval debulking surgery, 110 (82%) had no macroscopic residual tumor (residual tumor = 0). The median progression-free survival was 18.9 months in the residual tumor = 0 group compared to 6.19 months in the residual tumor > 0 group (p < 0.001; log-rank test); the median overall survival was 40.6 months versus 21 months (p = 0.028; log-rank test). Conclusions. These results indicate that primary debulking surgery should be considered the preferred treatment approach for advanced endometrial cancer with carcinosis, especially in carefully selected patients where complete cytoreduction is achievable. Further prospective studies are warranted to confirm these results and to establish standardized criteria for patient selection, incorporating molecular-integrated risk profiles for endometrial cancer. Full article

(This article belongs to the Special Issue Advancements in Surgical Approaches for Gynecological Cancers)

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28 pages, 3557 KiB

Open AccessReview

Dermoscopy of Basal Cell Carcinoma Part 3: Differential Diagnosis, Treatment Monitoring and Novel Technologies

by Irena Wojtowicz and Magdalena Żychowska

Cancers 2025, 17(6), 1025; https://doi.org/10.3390/cancers17061025 - 19 Mar 2025

Viewed by 516

Abstract

Introduction: Basal cell carcinoma (BCC) is the most frequently diagnosed skin cancer globally. Despite the well-established dermoscopic features of BCC, overlapping characteristics with other benign and malignant skin conditions cause challenges in differential diagnosis. Part III of this review highlights the role of [...] Read more.

Introduction: Basal cell carcinoma (BCC) is the most frequently diagnosed skin cancer globally. Despite the well-established dermoscopic features of BCC, overlapping characteristics with other benign and malignant skin conditions cause challenges in differential diagnosis. Part III of this review highlights the role of dermoscopy in differential diagnosis, treatment planning, therapy monitoring and the integration of novel technologies including ultraviolet-induced fluorescence dermoscopy (UVFD) and optical super-high magnification dermoscopy (OSHMD). Methods: A search of the PubMed database was conducted for studies reporting on advances in the dermoscopic assessment of BCC, including differential diagnosis, treatment, monitoring and novel diagnostic technologies. Results: Even entities with well-defined dermoscopic features distinguishing them from BCC can sometimes mimic BCC. Additionally, rare lesions such as neurothekeoma, reticulohistiocytoma, solitary circumscribed neuroma, dermal leiomyosarcoma and various adnexal tumors often remain dermoscopically indistinguishable from BCC, which underscores the importance of histopathology as the diagnostic gold standard. Dermoscopy aids in delineating the tumor margins, optimizing Mohs micrographic surgery (MMS) and traditional excision. It may also help to monitor therapeutic effects by detecting the disappearance of BCC patterns, the presence of residual tumor or recurrences. Dermoscopy may aid in the prediction of therapeutic responses to imiquimod, photodynamic therapy or vismodegib. UVFD and OSHMD appear to be valuable complementary diagnostic techniques for detecting BCC. UVFD seems to be particularly valuable for the detection of small tumors (<5 mm), facial lesions and nodular or non-pigmented BCC subtypes, while OSHMD is useful for the assessment of superficial and non-pigmented BCCs. Three-dimensional total-body photography enhances diagnostic precision but, so far, only when used in combination with traditional dermoscopy. Conclusions: Dermoscopy is valuable for margin delineation, therapy monitoring and differential diagnosis but can be inconclusive, which highlights the role of histopathology as the gold standard. Modifications in dermoscopy technique may further enhance its accuracy. Full article

(This article belongs to the Special Issue Dermoscopy in Skin Cancer)

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12 pages, 501 KiB

Open AccessArticle

The Effect of Lifestyle on the Quality of Life of Vulvar Cancer Survivors

by Marleen S. Boonstra, Anke Smits, Viktor Cassar, Ruud L. M. Bekkers, Yvonne Anderson, Nithya Ratnavelu and Tineke F. M. Vergeldt

Cancers 2025, 17(6), 1024; https://doi.org/10.3390/cancers17061024 - 18 Mar 2025

Viewed by 366

Abstract

Introduction: Vulvar cancer affects approximately 47,000 women annually worldwide. With most studies focusing on oncological outcomes, quality of life is often overlooked. There is a lack of knowledge on the influence of modifiable factors such as lifestyle on the quality of life [...] Read more.

Introduction: Vulvar cancer affects approximately 47,000 women annually worldwide. With most studies focusing on oncological outcomes, quality of life is often overlooked. There is a lack of knowledge on the influence of modifiable factors such as lifestyle on the quality of life of vulvar cancer survivors. This study evaluated the association between lifestyle factors and the quality of life of vulvar cancer survivors. Methods: This was a cross-sectional survey study of women who received surgical treatment for vulvar cancer ≥FIGO stage 1B at the Northern Gynecological Oncology Centre, UK, between 2013 and 2022. Baseline and clinical characteristics were collected from patient records. Godin Leisure-Time Exercise questionnaires were used to assess physical activity. BMI was assessed using self-reported height and weight. Quality of life was measured using the validated European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and the vulvar cancer-specific module (VU-34). An analysis was performed using Mann–Whitney-U and Kruskal–Wallis tests. Results: Of the 299 women, 139 were eligible for participation, of whom 58 participated (41.7%). Twenty participants had a sedentary (40.8%), eight a moderately active (16.3%), and seventeen an active (34.7%) lifestyle. Active participants reported higher overall quality of life and higher functioning in all domains but not for vulvar-related symptoms or sexual functioning. Forty-nine participants disclosed their BMI, which was not associated with quality of life outcomes. Conclusions: A higher level of physical activity was associated with higher quality of life. No association was found between BMI and quality of life. Full article

(This article belongs to the Special Issue Long-Term Cancer Survivors: Rehabilitation and Quality of Life)

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36 pages, 1237 KiB

Open AccessReview

Describing the Core Attributes and Impact of Comprehensive Cancer Centers Internationally: A Chronological Scoping Review

by Carla Thamm, Elise Button, Jolyn Johal, Reegan Knowles, Catherine Paterson, Michael T. Halpern, Andreas Charalambous, Alexandre Chan, Sanchia Aranda, Carolyn Taylor and Raymond J. Chan

Cancers 2025, 17(6), 1023; https://doi.org/10.3390/cancers17061023 - 18 Mar 2025

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Abstract

Background/Objectives: Comprehensive cancer centers (CCCs) remain at the forefront of cancer control efforts. Limited clarity and variation exist around the models, scope, characteristics, and impacts of CCCs around the globe. This scoping review systematically searched and synthesized the international literature, describing core [...] Read more.

Background/Objectives: Comprehensive cancer centers (CCCs) remain at the forefront of cancer control efforts. Limited clarity and variation exist around the models, scope, characteristics, and impacts of CCCs around the globe. This scoping review systematically searched and synthesized the international literature, describing core attributes and anticipated and realized impacts of CCCs, detailing changes over time. Methods: Searches for English language sources were conducted across PubMed, Cochrane CENTRAL, Epistemonikos, and the gray literature from January 2002 to April 2024. Data were extracted and appraised by two authors. Results were narratively synthesized. Results: Of 3895 database records and 843 gray literature sources screened, 81 sources were included. Papers were predominantly opinion-based, from the USA and Europe, and published between 2011 and 2020. Internationally, the interconnected attributes of CCCs included (1) clinical service provision; (2) research, data, and innovation; (3) education and clinical support; (4) networks and leadership; (5) health equity and inclusiveness; and (6) accountability and governance. Largely anticipated impacts were synergistic and included delivery of optimal, person-centered, complex care; development of a highly qualified cancer workforce; greater research activity and funding; effective, strategic alliances; and reduction in cancer-related inequalities. Limited evidence was found demonstrating measurable broad outcomes of CCCs. The early literature highlighted the establishment, development, and accreditation of CCCs. The ongoing literature has reflected the evolution of cancer care, key areas for growth, and limitations of CCCs. Recently, the CCC literature has increased exponentially and focused on the need for CCCs to drive networks and leadership to address health equity and inclusiveness. Conclusions: Results suggest that CCCs are yet to reach their full potential, with future efforts ideally focusing on accountability, effective networking, and health equity at a local, national, and international level. CCCs must generate evidence of impact, and continue to evolve in line with contemporary healthcare, to fulfil their role in cancer control efforts. Full article

(This article belongs to the Section Cancer Therapy)

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Bone Marrow CD34+/lin− Cells of Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) After 12 Months of Nilotinib Treatment Exhibit a Different Gene Expression Signature Compared to the Diagnosis and the Corresponding Cells from Healthy Subjects

by Alessandra Trojani, Ester Pungolino, Barbara Di Camillo, Luca Emanuele Bossi, Cassandra Palumbo, Mariella D’adda, Alessandra Perego, Mauro Turrini, Chiara Elena, Lorenza Maria Borin, Alessandra Iurlo, Simona Malato, Francesco Spina, Maria Luisa Latargia, Pierangelo Spedini, Salvatore Artale, Michela Anghilieri, Maria Cristina Carraro, Cristina Bucelli, Alessandro Beghini and Roberto Cairoli Show full author list Hide full author list

Cancers 2025, 17(6), 1022; https://doi.org/10.3390/cancers17061022 - 18 Mar 2025

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Abstract

Background: Chronic-Phase Chronic Myeloid Leukemia (C-PCML) is defined by the presence of the BCR-ABL1 fusion gene, which encodes a tyrosine kinase protein that drives the uncontrolled proliferation and survival of leukemic stem cells (LSCs). Nilotinib, a tyrosine kinase inhibitor, targets the activity of [...] Read more.

Background: Chronic-Phase Chronic Myeloid Leukemia (C-PCML) is defined by the presence of the BCR-ABL1 fusion gene, which encodes a tyrosine kinase protein that drives the uncontrolled proliferation and survival of leukemic stem cells (LSCs). Nilotinib, a tyrosine kinase inhibitor, targets the activity of BCR-ABL1 by reducing aberrant signaling pathways, which drive the regeneration of LSCs. Despite nilotinib’s action, a population of resilient LSCs persist in the bone marrow (BM) and can indeed drive relapse and progression in CML patients. Methods: Our study investigated the gene expression profiling (GEP) of BM CD34+/lin− cells from 79 CP-CML patients at diagnosis, compared to the BM CD34+/lin− cells from the same patients after 12 months of nilotinib treatment and to the normal counterpart cells from 10 donors (CTRLs). Results: GEP analyses identified 3012 significantly differentially expressed genes across these comparisons. Among these, we focused on certain key genes associated with eight crucial KEGG pathways: CML, cell cycle, JAK-STAT, PI3K-Akt, MAPK, Ras, NF-kB, and ABC transporters. Within these pathways, we observed the up-regulation of several genes at diagnosis compared to both 12 months of nilotinib treatment and the CTRLs. Conclusions: We observed that certain transcriptome features present at diagnosis persisted after 12 months of nilotinib treatment, compared to CTRLs. This suggests that nilotinib may exert selective pressure, potentially supporting the survival and self-renewal of LSCs. Future insights into these pathways could help identify therapeutic targets to improve outcomes in CML. Full article

(This article belongs to the Special Issue Exploring the Genetic and Epigenetic Factors in Leukemia and Lymphoma)

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