Cancers

12 pages, 2254 KiB

Open AccessSystematic Review

Impact of Physical Exercise on Breast Cancer-Related Lymphedema and Non-Invasive Measurement Tools: A Systematic Review

by Marta Arias-Crespo, Rubén García-Fernández, Natalia Calvo-Ayuso, Cristian Martín-Vázquez, Maria de Fátima da Silva Vieira Martins and Enedina Quiroga-Sánchez

Cancers 2025, 17(2), 333; https://doi.org/10.3390/cancers17020333 - 20 Jan 2025

Viewed by 1025

Abstract

Background/Objectives: Breast cancer-related lymphedema (BCRL) is a chronic disease with lasting effects, making it one of the most feared sequelae of breast cancer with significant personal and social impacts. Therapeutic exercises play a fundamental role in its treatment. This systematic review aims to [...] Read more.

Background/Objectives: Breast cancer-related lymphedema (BCRL) is a chronic disease with lasting effects, making it one of the most feared sequelae of breast cancer with significant personal and social impacts. Therapeutic exercises play a fundamental role in its treatment. This systematic review aims to provide the most up-to-date findings on the impact of physical exercise on the management of BCRL. Methods: Following the PRISMA statement guidelines, searches were conducted in the Web of Science, Scopus, and Science Direct databases. Results: Sixteen studies published between 2019 and 2024 were analyzed in detail. The combination of strength and aerobic exercises emerged as an effective strategy for both the treatment and prevention of lymphedema, also highlighting the innovative potential of virtual reality. Conclusions: It is essential to emphasize tailoring exercise programs to each patient individually. Additionally, the promising role of thermography as a non-invasive and safe tool for evaluating lymphedema progress is underscored. Full article

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

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19 pages, 3459 KiB

Open AccessArticle

Predicting the Progression from Asymptomatic to Symptomatic Multiple Myeloma and Stage Classification Using Gene Expression Data

by Nestoras Karathanasis and George M. Spyrou

Cancers 2025, 17(2), 332; https://doi.org/10.3390/cancers17020332 - 20 Jan 2025

Viewed by 944

Abstract

Background: The accurate staging of multiple myeloma (MM) is essential for optimizing treatment strategies, while predicting the progression of asymptomatic patients, also referred to as monoclonal gammopathy of undetermined significance (MGUS), to symptomatic MM remains a significant challenge due to limited data. This [...] Read more.

Background: The accurate staging of multiple myeloma (MM) is essential for optimizing treatment strategies, while predicting the progression of asymptomatic patients, also referred to as monoclonal gammopathy of undetermined significance (MGUS), to symptomatic MM remains a significant challenge due to limited data. This study aimed to develop machine learning models to enhance MM staging accuracy and stratify asymptomatic patients by their risk of progression. Methods: We utilized gene expression microarray datasets to develop machine learning models, combined with various data transformations. For multiple myeloma staging, models were trained on a single dataset and validated across five independent datasets, with performance evaluated using multiclass area under the curve (AUC) metrics. To predict progression in asymptomatic patients, we employed two approaches: (1) training models on a dataset comprising asymptomatic patients who either progressed or remained stable without progressing to multiple myeloma, and (2) training models on multiple datasets combining asymptomatic and multiple myeloma samples and then testing their ability to distinguish between asymptomatic and asymptomatic that progressed. We performed feature selection and enrichment analyses to identify key signaling pathways underlying disease stages and progression. Results: Multiple myeloma staging models demonstrated high efficacy, with ElasticNet achieving consistent multiclass AUC values of 0.9 across datasets and transformations, demonstrating robust generalizability. For asymptomatic progression, both modeling approaches yielded similar results, with AUC values exceeding 0.8 across datasets and algorithms (ElasticNet, Boosting, and Support Vector Machines), underscoring their potential in identifying progression risk. Enrichment analyses revealed key pathways, including PI3K-Akt, MAPK, Wnt, and mTOR, as central to MM pathogenesis. Conclusions: To the best of our knowledge, this is the first study to utilize gene expression datasets for classifying patients across different stages of multiple myeloma and to integrate multiple myeloma with asymptomatic cases to predict disease progression, offering a novel methodology with potential clinical applications in patient monitoring and early intervention. Full article

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

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Figure 1
Flowchart of the analysis. (A) The flowchart illustrates the process used for predicting the stage of multiple myeloma. The method encompasses multiple steps: data preprocessing, model training, and performance evaluation applied across various datasets. Preprocessing includes several data transformations and the training phase incorporates a variety of machine learning models. After predictions, the model’s key features were interpreted through enrichment analyses. In the figure, (ps) indicates per-sample preprocessing, (train) indicates that normalization was applied to training samples, and (test) refers to applying the parameters learned from training to the test set. (B) The flowchart outlines the process used for predicting the progression of MGUS to MM using machine learning techniques. The method involves preprocessing, model training, and performance evaluation using different datasets similar to A. The boxes with a black background indicate the use of the GSE235356 dataset for training and testing in a 10-fold nested cross-validation fashion. In contrast, gray background boxes represent training on various datasets and testing on the GSE235356 dataset. Full article ">Figure 2
Models’ multiclass auc in the external validation sets. (A) The performance of the external dataset used across all data transformations and machine learning algorithms. (B) The relation of performance to the data transformations across datasets generated in GLP96 or A.AFFY.34 platforms and all machine learning algorithms. (C) The relation of performance to the machine learning algorithms across datasets generated in GLP96 or A.AFFY.34 platforms and all data transformations. Full article ">Figure 3
The number of features utilized by each model across different data transformations. The plot shows the variation in feature selection for each model, highlighting the range of features used in the analysis. Full article ">Figure 4
Enrichment analysis for the selected probes. (Top): KEGG pathways associated with identified genes. This figure illustrates the KEGG pathways enriched for the genes identified by the machine learning models across different data transformations and training datasets. The pathways displayed are significantly associated with the probes selected by at least one model. Key pathways related to multiple myeloma, such as PI3K-Akt, MAPK, and Wnt signaling, are highlighted. (Bottom): Disease-related terms associated with identified genes. The figure illustrates the distribution of disease-related terms associated with the genes identified by the models. The chart highlights how different methods and data transformations reveal connections to various cancers, including multiple myeloma. Each term represents a disease category. In both figures, the size and color indicate the strength of the association and statistical significance. Full article ">Figure 5
Performance of machine learning algorithms on the GSE235356 dataset. The figure displays the distribution of the mean cross-validation AUC (auc_cvmean, shown in red) and the distribution of the AUC from the outer hold of the nested cross-validation (auc_test, shown in cyan) for each algorithm when the GSE235356 dataset was used for training and testing. The auc_cvmean represents the performance across the cross-validation folds, while the auc_test indicates the model’s generalizability on unseen data. The comparison of these distributions highlights the algorithm’s generalization and stability. Full article ">Figure 6
Model performance in differentiating MGUS from progressing MGUS across different datasets. The boxplots show the distribution of the mean cross-validation AUC for models trained to differentiate MGUS from progressing MGUS using the GSE235356 dataset. The colored points represent the performance of each algorithm–data transformation combination across various training datasets: models trained with the EMTAB317 dataset are shown in red; those trained with the GSE235356 dataset are in green; models trained with the GSE6477 dataset are shown in cyan; and those trained with the combined GSE6477 + GSE2113 + EMTAB316 + GSE13591 datasets are depicted in purple. Notably, in all cases except for the second (GSE235356), the models were specifically trained to distinguish MGUS from MM. Full article ">Figure 7
Disease-related terms associated with identified genes. The figure illustrates the distribution of disease-related terms associated with the genes identified by the models. The chart highlights how different methods across all data transformations and the different training datasets reveal connections to various cancers, including multiple myeloma. Each term represents a disease category. The size and color indicate the strength of the association and statistical significance. “all GLP96” refers to the combined dataset of GSE6477 + GSE2113 + EMTAB316 + GSE13591, and “GSE” to the GSE235356 dataset. Full article ">

12 pages, 3714 KiB

Open AccessArticle

A Machine Learning-Based Radiomics Model for the Differential Diagnosis of Benign and Malignant Thyroid Nodules in F-18 FDG PET/CT: External Validation in the Different Scanner

by Junchae Lee, Jinny Lee and Bong-Il Song

Cancers 2025, 17(2), 331; https://doi.org/10.3390/cancers17020331 - 20 Jan 2025

Viewed by 621

Abstract

Background/Objectives: Accurate diagnosis is essential to avoid unnecessary procedures for thyroid incidentalomas (TIs). Advances in radiomics and machine learning applied to medical imaging offer promise for assessing thyroid nodules. This study utilized radiomics analysis on F-18 FDG PET/CT to improve preoperative differential diagnosis [...] Read more.

Background/Objectives: Accurate diagnosis is essential to avoid unnecessary procedures for thyroid incidentalomas (TIs). Advances in radiomics and machine learning applied to medical imaging offer promise for assessing thyroid nodules. This study utilized radiomics analysis on F-18 FDG PET/CT to improve preoperative differential diagnosis of TIs. Methods: A total of 152 patient cases were retrospectively analyzed and split into training and validation sets (7:3) using stratification and randomization. Results: The least absolute shrinkage and selection operator (LASSO) algorithm identified nine radiomics features from 960 candidates to construct a radiomics signature predictive of malignancy. Performance of the radiomics score was evaluated using receiver operating characteristic (ROC) analysis and area under the curve (AUC). In the training set, the radiomics score achieved an AUC of 0.794 (95% CI: 0.703–0.885, p < 0.001). Validation was performed on internal and external datasets, yielding AUCs of 0.702 (95% CI: 0.547–0.858, p = 0.011) and 0.668 (95% CI: 0.500–0.838, p = 0.043), respectively. Conclusions: These results demonstrate that the selected nine radiomics features effectively differentiate malignant thyroid nodules. Overall, the radiomics model shows potential as a valuable predictive tool for thyroid cancer in patients with TIs, supporting improved preoperative decision-making. Full article

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

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Flow diagram of patient selection. Of the 376 patients who have thyroid incidentaloma in the F-18 FDG PET/CT, the final cohort was divided into a training set (n = 106), an internal validation set (n = 46), and an external validation set (n = 58) for model development and validation. Full article ">Figure 2
LASSO (least absolute shrinkage and selection operator) regression analysis used for feature selection. (A) For 980 radiomics features, the LASSO coefficient profiles are shown. The coefficient profiles of the variables as a function of the regularization parameter (Log Lambda). (B) The mean-squared error (MSE) versus Log Lambda, with red dots representing the MSE for each value of Lambda and error bars indicating the standard deviation. The two vertical dashed lines mark the optimal Lambda values: the left line corresponds to the minimum MSE; while the right line represents the largest Lambda within one standard error of the minimum MSE. Full article ">Figure 3
Receiver operating characteristic (ROC) curve of the radiomics score. The radiomics score showed good performance in the training set with an area under the curve (AUC) of 0.794, an AUC of 0.702 in the internal validation set, and an AUC of 0.668 in the external validation set. Full article ">Figure 4
F-18 FDG PET/CT image of a 69-year-old female patient, highlighting a thyroid incidentaloma in the right lobe of the thyroid gland: (A) maximum intensity projection (MIP); (B) axial PET/CT image; and (C) coronal PET/CT image. The lesion demonstrates increased FDG uptake with a maximum standardized uptake value (SUVmax) of 9.2. Radiomic features include a log-sigma-2-0-mm-3D_glszm_SmallAreaEmphasis value of 0.553 (relatively low) and a wavelet-HLH_gldm_LargeDependenceLowGrayLevelEmphasis value of 33.814 (relatively high). Despite the high SUVmax, the final diagnosis confirmed the nodule to be benign. Full article ">Figure 5
F-18 FDG PET/CT image of a 56-year-old female patient, showing a thyroid incidentaloma located in the right lobe of the thyroid gland: (A) maximum intensity projection (MIP); (B) axial PET/CT image; and (C) coronal PET/CT image. The lesion exhibits elevated FDG uptake, with a maximum standardized uptake value (SUVmax) of 7.3. Radiomic analysis reveals a log-sigma-2-0-mm-3D_glszm_SmallAreaEmphasis value of 0.734 (relatively high) and a wavelet-HLH_gldm_LargeDependenceLowGrayLevelEmphasis value of 4.440 (relatively low). The final diagnosis confirmed that the nodule was malignant. Full article ">

19 pages, 1340 KiB

Open AccessReview

A Comprehensive Approach to Neoadjuvant Treatment of Locally Advanced Rectal Cancer

by Annalice Gandini, Stefania Sciallero, Valentino Martelli, Chiara Pirrone, Silvia Puglisi, Malvina Cremante, Massimiliano Grassi, Valeria Andretta, Giuseppe Fornarini, Francesco Caprioni, Danila Comandini, Annamaria Pessino, Serafina Mammoliti, Alberto Sobrero and Alessandro Pastorino

Cancers 2025, 17(2), 330; https://doi.org/10.3390/cancers17020330 - 20 Jan 2025

Viewed by 1188

Abstract

At the end of the past century, the introduction of Total Mesorectal Excision (TME), preceded by either short-course radiotherapy (SCRT) or chemoradiation (CRT), established the new standard of care for locally advanced rectal cancer (LARC). Recently, significant advancements were achieved for both dMMR/MSI [...] Read more.

At the end of the past century, the introduction of Total Mesorectal Excision (TME), preceded by either short-course radiotherapy (SCRT) or chemoradiation (CRT), established the new standard of care for locally advanced rectal cancer (LARC). Recently, significant advancements were achieved for both dMMR/MSI and pMMR/MSS LARC patients. For the 2–3% of dMMR/MSI LARCs, ablative immunotherapy emerged as a curative approach, offering the possibility of avoiding chemotherapy (CT), radiotherapy, and surgery altogether. In pMMR/MSS LARCs, the intensification of preoperative treatments with Total Neoadjuvant Treatment (TNT) afforded three outcomes: (a) a reduction of distant metastases, positively impacting on survival endpoints, (b) a significant increase of complete clinical response (cCR) rate, paving the way for non-operative management (NOM), and (c) the selective omission of radiotherapy following induction CT. The choice of the most appropriate therapeutic strategy can only be made through the shared decision-making process between physician and patient based on risk stratification and patient preferences. Full article

(This article belongs to the Special Issue Locally Advanced and Recurrent Rectal Cancer (2nd Edition))

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16 pages, 2179 KiB

Open AccessSystematic Review

Predictive Value of the Loss of pRb Expression in the Malignant Transformation Risk of Oral Potentially Malignant Disorders: A Systematic Review and Meta-Analysis

by María López-Ansio, Pablo Ramos-García and Miguel Ángel González-Moles

Cancers 2025, 17(2), 329; https://doi.org/10.3390/cancers17020329 - 20 Jan 2025

Viewed by 630

Abstract

Objective: The aim of this systematic review and meta-analysis was to qualitatively and quantitatively evaluate the current evidence on the significance of the loss of early stages of oral carcinogenesis in lesions diagnosed according to clinical and/or histopathological criteria and their evolution to [...] Read more.

Objective: The aim of this systematic review and meta-analysis was to qualitatively and quantitatively evaluate the current evidence on the significance of the loss of early stages of oral carcinogenesis in lesions diagnosed according to clinical and/or histopathological criteria and their evolution to oral cancer. Materials and Methods: We searched MEDLINE (through PubMed), Embase, Scopus and Web of Science for primary-level studies published before November 2024, designed as prospective or retrospective longitudinal cohorts, and not restricted by language or publication date. The risk of bias was critically assessed using the QUIPS tool. Meta-analyses, heterogeneity exploration, sensitivity and small-study effect analyses were conducted. Results: The inclusion criteria were met by six primary-level studies, which recruited 330 patients with OPMDs with follow-up data. The loss of pRb expression, assessed through immunohistochemistry, was significantly associated with a higher malignant transformation risk of OPMDs (RR = 1.92, 95%CI = 1.25–2.94, p = 0.003). The leukoplakia subgroup retained this significant association (p = 0.006), being the OPMD where the loss of pRb expression showed the best predictive value for malignant transformation (RR = 2.00, 95%CI = 1.22–3.29). Regarding the immunohistochemical technique and scoring methods, better performance and results were achieved by applying a cutoff point > 10% pRb-positive cells with nuclear staining (RR = 2.10, 95%CI = 1.30–3.38, 95%CI = 0.002). Conclussion: The present systematic review and meta-analysis supports that the loss of expression of the tumor suppressor pRb, assessed through immunohistochemistry, is a predictor of the malignant transformation risk of oral leukoplakias. Future studies are needed in other OPMDs following the recommendations provided based on current evidence gaps. Full article

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

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26 pages, 993 KiB

Open AccessArticle

Risk Factors for Treatment Toxicity and High Side Effect Burden Among Breast Cancer Survivors: A Retrospective Chart Review

by Muna Alkhaifi, Elwyn Zhang, Malika Peera, Katarzyna Jerzak, Gregory Czarnota, Andrea Eisen, Amanda Roberts, Carlos Amir Carmona-Gonzalez, Rosanna Pezo and Sonal Gandhi

Cancers 2025, 17(2), 328; https://doi.org/10.3390/cancers17020328 - 20 Jan 2025

Viewed by 920

Abstract

Background/Objectives: This study describes the sequelae, side effects, and toxicities experienced by Canadian breast cancer survivors at a breast cancer survivorship clinic at a tertiary academic cancer centre and identifies potential risk factors which may be associated with increased side effect burden. Methods: [...] Read more.

Background/Objectives: This study describes the sequelae, side effects, and toxicities experienced by Canadian breast cancer survivors at a breast cancer survivorship clinic at a tertiary academic cancer centre and identifies potential risk factors which may be associated with increased side effect burden. Methods: A retrospective chart review was performed of adult patients treated at the Sunnybrook Breast Cancer Survivorship Clinic from 6 July 2022, to 30 September 2023 (n = 435). Results: Most patients (72.6%) reported at least one side effect impacting their quality of life, and a smaller majority (55.4%) reported two or more side effects. The most common symptoms experienced were anxiety (29.4%), chronic pain (23.9%), hot flashes (21.4%), and fear of recurrence (19.8%). Older age was strongly correlated with a lower likelihood of experiencing greater side effect burden (p < 0.01). Patients who underwent chemotherapy were significantly more likely to experience higher side effect burden than patients who did not. Current smokers were more likely than nonsmokers or past smokers to have a higher burden, for both physical (p < 0.01) and psychological side effects (p < 0.01). The multivariate analysis demonstrated that younger age was strongly associated with greater side effect burden, higher likelihood of psychological and physical symptoms, and greater likelihood of requiring close follow-up. Conclusions: The results highlight the need for survivorship resources tailored to survivors under the age of 55 and the importance of referring smokers to smoking cessation programs. Additional research is required to explore the significant reluctance among patients regarding discharge. Future studies should examine the acute needs of younger breast cancer survivors and investigate the impact of smoking and treatment modalities on the side effect burden. Full article

(This article belongs to the Special Issue Beyond Cancer: Enhancing Quality of Life for Cancer Survivors)

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9 pages, 1103 KiB

Open AccessArticle

Proton Beam Therapy for Advanced Periocular Skin Cancer: An Eye-Sparing Approach

by Yingying Zhang, Isabela C. S. Lima, Alessandra A. Woo, Stephen Zieminski, Judith A. Adams, Megan A. Hughes and Annie W. Chan

Cancers 2025, 17(2), 327; https://doi.org/10.3390/cancers17020327 - 20 Jan 2025

Viewed by 914

Abstract

Background/Objectives: The management of periocular skin malignancies presents a unique challenge. Proton beam therapy, due to its sharp dose fall-off, allows for the delivery of a tumoricidal dose to the tumor while sparing adjacent normal tissues. Methods: Thirteen patients with a median age [...] Read more.

Background/Objectives: The management of periocular skin malignancies presents a unique challenge. Proton beam therapy, due to its sharp dose fall-off, allows for the delivery of a tumoricidal dose to the tumor while sparing adjacent normal tissues. Methods: Thirteen patients with a median age of 76.5 years received protons at our institution to a median dose of 66.6 Gy (RBE). Sixty-four percent of the lesions were basal cell carcinoma, and 22% were squamous cell carcinoma. Eighty-six percent of patients underwent biopsy only or partial resection. Fifty-seven percent of the lesions were located in the medial or lateral canthus. There was orbital invasion in 93% of the cases. Locoregional control probability and overall survival were estimated with the Kaplan–Meier method. Treatment toxicity was scored using the CTCAE 4.0. Results: At a median follow-up of 96 months, there was no local recurrence. The rate of orbital preservation was 100%. Functional vision was maintained in all the patients. There was no acute or late grade 3 or higher toxicity. Conclusions: Protons allow for long-term tumor control with eye preservation in patients with locally advanced periocular skin cancers. Larger prospective multi-institutional trials with standardized ophthalmological assessments are needed to confirm our findings. Full article

(This article belongs to the Special Issue Advances in Proton Pencil Beam Scanning Therapy)

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36 pages, 1669 KiB

Open AccessReview

Immune-Based and Novel Therapies in Variant Histology Renal Cell Carcinomas

by Justin W. Miller, Jeffrey S. Johnson, Christopher Guske, Gowtam Mannam, Firas Hatoum, Michelle Nassar, Marine Potez, Adnan Fazili, Philippe E. Spiess and Jad Chahoud

Cancers 2025, 17(2), 326; https://doi.org/10.3390/cancers17020326 - 20 Jan 2025

Viewed by 1614

Abstract

Renal cell carcinoma (RCC) is a heterogeneous disease that represents the most common type of kidney cancer. The classification of RCC is primarily based on distinct morphological and molecular characteristics, with two broad categories: clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC). [...] Read more.

Renal cell carcinoma (RCC) is a heterogeneous disease that represents the most common type of kidney cancer. The classification of RCC is primarily based on distinct morphological and molecular characteristics, with two broad categories: clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC). Clear cell RCC is the predominant subtype, representing about 70–80% of all RCC cases, while non-clear cell subtypes collectively make up the remaining 20–30%. Non-clear cell RCC encompasses many histopathological variants, each with unique biological and clinical characteristics. Additionally, any RCC subtype can undergo sarcomatoid dedifferentiation, which is associated with poor prognosis and rapid disease progression. Recent advances in molecular profiling have also led to the identification of molecularly defined variants, further highlighting the complexity of this disease. While immunotherapy has shown efficacy in some RCC variants and subpopulations, significant gaps remain in the treatment of rare subtypes. This review explores the outcomes of immunotherapy across RCC subtypes, including rare variants, and highlights opportunities for improving care through novel therapies, biomarker-driven approaches, and inclusive clinical trial designs. Full article

(This article belongs to the Special Issue Immune Landscape of Renal Cell Carcinoma)

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Timeline and summary of results for key clinical trials evaluating first-line immune therapies in non-clear cell renal cell carcinoma (nccRCC). RCC: renal cell carcinoma; SWOG: Southwest Oncology Group. Full article ">Figure 2
An overview of key strategies shaping the landscape of variant histology renal cell carcinoma treatment. These include advancements in biomarker development, inclusive clinical trial eligibility criteria, immune checkpoint blockade, novel targeted therapies and antibody–drug conjugates (ADCs), engineered cellular therapies (including CAR-T, CAR-NK, and cellular vaccines), tumor-infiltrating and adoptive immune cells, artificial intelligence integration, and the incorporation of real-world data into clinical trials. These interconnected approaches aim to optimize outcomes across diverse histologic subtypes and patient populations. Full article ">Figure 3
Distribution of RCC histologic variants by race/ethnicity from two independent cohorts. (A) Lichtensztajn et al. analyzed 40,016 RCC cases from the California Cancer Registry, showing racial/ethnic distribution within histologically confirmed clear cell renal cell carcinoma (ccRCC, N = 25,051), papillary RCC (N = 4363), and chromophobe RCC (N = 2372) cases. The remaining cases were classified as “other” variants or were not otherwise specified [<a href="#B113-cancers-17-00326" class="html-bibr">113</a>]. (B) Lipworth et al. analyzed 1532 consecutive cases from a single academic medical center demonstrating the distribution of RCC variants between Black and White patients. The ‘Other Variants’ category includes collecting duct carcinoma (CDC, 3.1% in Black vs. 0.3% in White patients), mixed RCC, unclassified RCC, translocation RCC (tRCC), and other rare variants [<a href="#B114-cancers-17-00326" class="html-bibr">114</a>]. NL = Non-Latino; PI = Pacific Islander. Sample sizes (N) for each racial/ethnic group are indicated in parentheses. Full article ">

2 pages, 840 KiB

Open AccessCorrection

Correction: Alaei et al. Therapeutic Potential of Targeting the Cytochrome P450 Enzymes Using Lopinavir/Ritonavir in Colorectal Cancer: A Study in Monolayers, Spheroids and In Vivo Models. Cancers 2023, 15, 3939

by Maryam Alaei, Seyedeh Elnaz Nazari, Ghazaleh Pourali, AliReza Asadnia, Mehrdad Moetamani-Ahmadi, Hamid Fiuji, Hamid Tanzadehpanah, Fereshteh Asgharzadeh, Fatemeh Babaei, Fatemeh Khojasteh-Leylakoohi, Ibrahim Saeed Gataa, Mohammad Ali Kiani, Gordon A. Ferns, Alfred King-yin Lam, Seyed Mahdi Hassanian, Majid Khazaei, Elisa Giovannetti and Amir Avan

Cancers 2025, 17(2), 325; https://doi.org/10.3390/cancers17020325 - 20 Jan 2025

Viewed by 606

Abstract

Error in Figure and Text [...] Full article

(This article belongs to the Special Issue 3D Cell Culture Cancer Models: Development and Applications 2.0)

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20 pages, 7803 KiB

Open AccessArticle

Impact of Hyaluronic Acid on the Cutaneous T-Cell Lymphoma Microenvironment: A Novel Anti-Tumor Mechanism of Bexarotene

by Tetsuya Ikawa, Emi Yamazaki, Ryo Amagai, Yumi Kambayashi, Mana Sekine, Takuya Takahashi, Yoshihide Asano and Taku Fujimura

Cancers 2025, 17(2), 324; https://doi.org/10.3390/cancers17020324 - 20 Jan 2025

Viewed by 797

Abstract

Background: Cutaneous T-cell lymphoma (CTCL) is a type of non-Hodgkin’s lymphoma that primarily affects the skin, rich in hyaluronic acid (HA). HA is a component of the extracellular matrix in the dermis and likely affects the development of CTCL, but the mechanism is [...] Read more.

Background: Cutaneous T-cell lymphoma (CTCL) is a type of non-Hodgkin’s lymphoma that primarily affects the skin, rich in hyaluronic acid (HA). HA is a component of the extracellular matrix in the dermis and likely affects the development of CTCL, but the mechanism is poorly understood. Here we show that low-molecular-weight HA (LMWHA) possibly exacerbates CTCL, and bexarotene, already used in CTCL treatment, decreases HA production. Methods: We conducted immunohistochemistry, qRT-PCR, immunoblotting, and HA quantification using both mouse and human specimens to evaluate the impact of HA on CTCL. Additionally, we assessed the effect of bexarotene, which is already used for CTCL treatment, on HA metabolism. Results: HA expression was higher in patients’ serum and skin sections than in healthy controls. HA extracted from the skin of mice inoculated with tumors showed an increase in LMWHA. LMWHA increased lymphoma cell proliferation in vitro and accelerated tumor formation in mice in vivo. LMWHA also created a favorable environment for tumor cells by affecting fibroblasts, vascular endothelial cells, and tumor-associated macrophages. Thus, increased levels of HA, mainly LMWHA, exacerbate CTCL progression by affecting tumor cells and their microenvironment. Bexarotene treatment reduced the amount of total HA in murine tumor-inoculated skin, as well as the supernatant of cultured normal human dermal fibroblasts (NHDFs) and HuT78 cells. Detailed in vitro analyses showed that bexarotene treatment decreased HA synthase (HAS)1 and HAS2 expression in NHDFs and HAS1 and HAS3, and CEMIP expression in HuT78 cells. Chromatin immunoprecipitation assays revealed that bexarotene reduced retinoid X receptor-α binding to the HAS1 and HAS2 promoters in NHDFs. Conclusions: Bexarotene potentially exerts its anti-tumor effect by reducing HA levels through decreased expression of HAS. These findings provide new insights into the process of CTCL development and additional insights regarding bexarotene treatment. Full article

(This article belongs to the Special Issue Immunomodulation in Cancer Treatment)

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18 pages, 307 KiB

Open AccessReview

Lymphangioleiomyomatosis and Pregnancy—Do We Have All the Answers for a Woman Who Desires to Conceive?—Literature Review

by Ancuta-Alina Constantin, Andreea Dumitrita Gaburici, Andreea Nicoleta Malaescu, Ana-Luiza Iorga, Christiana Diana Maria Dragosloveanu, Mircea-Octavian Poenaru, Gabriel-Petre Gorecki, Mihaela Amza, Mihai-Teodor Georgescu, Ramona-Elena Dragomir, Mihai Popescu and Romina-Marina Sima

Cancers 2025, 17(2), 323; https://doi.org/10.3390/cancers17020323 - 20 Jan 2025

Viewed by 980

Abstract

Lymphangioleiomyomatosis (LAM) is a rare, progressive, and poor-prognosis systemic disorder that primarily affects women of reproductive age, with a higher prevalence among individuals of Caucasian origin. However, there are limited reliable data on the prevalence of LAM during pregnancy. The fulminant respiratory clinical [...] Read more.

Lymphangioleiomyomatosis (LAM) is a rare, progressive, and poor-prognosis systemic disorder that primarily affects women of reproductive age, with a higher prevalence among individuals of Caucasian origin. However, there are limited reliable data on the prevalence of LAM during pregnancy. The fulminant respiratory clinical presentation that often includes progressive dyspnea on exertion, cough, or hemoptysis, frequently complicated by pneumothorax, and the increased risk of spontaneous abortion due to increased estrogen and progesterone production during gestation, are arguments that most often make the diagnosed woman avoid pregnancy. Elevated levels of vascular endothelial growth factor D (VEGF-D), decline in respiratory function, and radiological findings are sufficient arguments in favor of the diagnosis in the pregnant woman. Sirolimus, an mTOR inhibitor, has demonstrated effectiveness in slowing the decline of lung function. Although sirolimus treatment is often recommended to be discontinued before conception due to the increased risk of fetal growth restriction, maintaining a dose level of <5 pcg/mL, with serum drug levels of 3–5 pcg/L, has been considered safe. Given the potential risks, individualized decisions about pregnancy are advised for patients with LAM. For those who choose to proceed, close monitoring by a multidisciplinary team is essential to manage complications effectively. Ongoing research aims to provide clearer guidance to optimize outcomes for both mother and child. Full article

(This article belongs to the Special Issue Pregnancy and Cancer: Special Considerations on Maternal and Fetal Implications)

17 pages, 5761 KiB

Open AccessArticle

Computed Tomography-Image-Based Glioma Grading Using Radiomics and Machine Learning: A Proof-of-Principle Study

by Melike Bilgin, Sabriye Sennur Bilgin, Burak Han Akkurt, Walter Heindel, Manoj Mannil and Manfred Musigmann

Cancers 2025, 17(2), 322; https://doi.org/10.3390/cancers17020322 - 20 Jan 2025

Viewed by 647

Abstract

Background/Objectives: In recent years, numerous studies have been published on determining the WHO grade of central nervous system (CNS) tumors using machine learning algorithms. These studies are usually based on magnetic resonance imaging (MRI) and sometimes also on positron emission tomography (PET) images. [...] Read more.

Background/Objectives: In recent years, numerous studies have been published on determining the WHO grade of central nervous system (CNS) tumors using machine learning algorithms. These studies are usually based on magnetic resonance imaging (MRI) and sometimes also on positron emission tomography (PET) images. To date, however, there are virtually no corresponding studies based on routinely generated computed tomography (CT) images. The aim of our proof-of-concept study is to investigate whether machine learning-based tumor diagnosis is also possible using CT images. Methods: We investigate the differentiability of histologically confirmed low-grade and high-grade gliomas. Three conventional machine learning algorithms and a neural net are tested. In addition, we analyze which of the common imaging methods (MRI or CT) appears to be best suited for the diagnostic question under investigation when machine learning algorithms are used. For this purpose, we compare our results based on CT images with numerous studies based on MRI scans. Results: Our best-performing model includes six features and is obtained using univariate analysis for feature preselection and a Naive Bayes approach for model construction. Using independent test data, this model yields a mean AUC of 0.903, a mean accuracy of 0.839, a mean sensitivity of 0.807 and a mean specificity of 0.864. Conclusions: Our results demonstrate that low-grade and high-grade gliomas can be differentiated with high accuracy using machine learning algorithms, not only based on the usual MRI scans, but also based on CT images. In the future, such CT-image-based models can help to further accelerate brain tumor diagnostics and to reduce the number of necessary biopsies. Full article

(This article belongs to the Special Issue Application of Advanced Biomedical Imaging in Cancer Treatment)

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Case of low-grade glioma (LGG). Patient aged 45 years old with oligodendroglioma localized in left frontal lobe. Images (a–c): original CT images before segmentation. Images (d–f): semi-automatic segmentation with 3D Slicer (areas marked in green). Full article ">Figure 2
Case of high-grade glioma (HGG). Patient aged 49 years old with astrocytoma localized in left parietal lobe. Images (a–c): original CT images before segmentation. Images (d–f): semi-automatic segmentation with 3D Slicer (areas marked in green). Full article ">Figure 3
Flowchart describing the methodological approach to distinguish between LGGs and HGGs based on contrast-enhanced CT images. Three different feature preselection algorithms are tested, in combination with four different machine learning algorithms for subsequent model development (see text for a detailed description). Full article ">Figure 4
(a) AUC, (b) accuracy, (c) sensitivity and (d) specificity for independent test samples using univariate analysis for feature preselection. All values are calculated as means of 100 repetitions. Full article ">Figure 5
(a) AUC, (b) accuracy, (c) sensitivity and (d) specificity for independent test samples, using Naïve Bayes algorithm for feature preselection. All values are calculated as means of 100 repetitions. Full article ">Figure 6
(a) AUC, (b) accuracy, (c) sensitivity and (d) specificity for independent test samples, using Ridge regression for feature preselection. All values are calculated as means of 100 repetitions. Full article ">

11 pages, 746 KiB

Open AccessArticle

Determining ED90 of Flumazenil for Selective Respiratory Distress Improvement Using Remimazolam During Endoscopic Submucosal Dissection of Gastric Neoplasms: A Prospective Study

by Hyun Il Kim, Da Hyun Jung, Sung Jin Lee, Namo Kim, Seung Hyun Kim, Yu Jun Ji, Hyo-Jin Byon and Sung Kwan Shin

Cancers 2025, 17(2), 321; https://doi.org/10.3390/cancers17020321 - 20 Jan 2025

Viewed by 589

Abstract

Background: Patients undergoing endoscopic submucosal dissection under monitored anesthesia care (MAC) with remimazolam may develop respiratory distress during the procedure. In these cases, low doses of flumazenil improved respiratory distress without completely reversing sedation, which is a novel phenomenon. This study aimed to [...] Read more.

Background: Patients undergoing endoscopic submucosal dissection under monitored anesthesia care (MAC) with remimazolam may develop respiratory distress during the procedure. In these cases, low doses of flumazenil improved respiratory distress without completely reversing sedation, which is a novel phenomenon. This study aimed to explore the ED90 of flumazenil to selectively improve respiratory distress in patients with MAC treated with remimazolam. Methods: Flumazenil dose determination followed a biased-coin up-and-down design. Starting with a dose of 5 mcg, if respiratory distress improved, the biased-coin method was used to give the same dose in the next patient with a probability of 8/9, and a decreased dose of 5 mcg in the next patient with a probability of 1/9. Any improvement in respiratory distress within 30 s of flumazenil administration was recorded. After the procedure, patients were asked whether they had any memory recall during the procedure. Centered isotonic regression was used to determine the ED90 of flumazenil. Results: Sixty patients were included in the study. The estimated ED90 was 76.72 mcg (95% CI: 68.07–102.62). Memory recall occurred in two of thirteen patients (15%) near the ED90 dose range (75 mcg and 80 mcg). None of the patients developed major postoperative complications (bleeding, perforation, or aspiration) within the 2-day postoperative period. Conclusions: This study determined that the ED90 of flumazenil for effectively alleviating respiratory distress in patients undergoing MAC with remimazolam was 76.7 mcg, without reversing consciousness. These findings provide valuable guidance for the care of patients undergoing sedation. Full article

(This article belongs to the Section Cancer Therapy)

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34 pages, 6832 KiB

Open AccessReview

From Genes to Clinical Practice: Exploring the Genomic Underpinnings of Endometrial Cancer

by Thulo Molefi, Lloyd Mabonga, Rodney Hull, Motshedisi Sebitloane and Zodwa Dlamini

Cancers 2025, 17(2), 320; https://doi.org/10.3390/cancers17020320 - 20 Jan 2025

Viewed by 1119

Abstract

Endometrial cancer (EC), a prevalent gynecological malignancy, presents significant challenges due to its genetic complexity and heterogeneity. The genomic landscape of EC is underpinned by genetic alterations, such as mutations in PTEN, PIK3CA, and ARID1A, and chromosomal abnormalities. The identification of molecular subtypes—POLE [...] Read more.

Endometrial cancer (EC), a prevalent gynecological malignancy, presents significant challenges due to its genetic complexity and heterogeneity. The genomic landscape of EC is underpinned by genetic alterations, such as mutations in PTEN, PIK3CA, and ARID1A, and chromosomal abnormalities. The identification of molecular subtypes—POLE ultramutated, microsatellite instability (MSI), copy number low, and copy number high—illustrates the diverse genetic profiles within EC and underscores the need for subtype-specific therapeutic strategies. The integration of multi-omics technologies such as single-cell genomics and spatial transcriptomics has revolutionized our understanding and approach to studying EC and offers a holistic perspective that enhances the ability to identify novel biomarkers and therapeutic targets. The translation of these multi-omics findings into personalized medicine and precision oncology is increasingly feasible in clinical practice. Targeted therapies such as PI3K/AKT/mTOR inhibitors have demonstrated the potential for improved treatment efficacy tailored to specific genetic alterations. Despite these advancements, challenges persist in terms of variability in patient responses, the integration of genomic data into clinical workflows, and ethical considerations. This review explores the genomic underpinnings of EC, from genes to clinical practice. It highlights the ongoing need for multidisciplinary research and collaboration to address the complexities of EC and improve diagnosis, treatment, and patient outcomes. Full article

(This article belongs to the Section Cancer Pathophysiology)

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18 pages, 6443 KiB

Open AccessArticle

Transcriptional Pathways Predisposing to Cancer Oxidative Stress Sensitivity and Resistance Are Shared Between Hydrogen Peroxide and Cold Gas Plasma but Not Hypochlorous Acid

by Debora Singer and Sander Bekeschus

Cancers 2025, 17(2), 319; https://doi.org/10.3390/cancers17020319 - 20 Jan 2025

Viewed by 750

Abstract

Oxidative stress is universal to all cell types, including cancer. It is elicited by a surplus of reactive oxygen species (ROS) or a reduced cellular ability to defend against those. At low levels (oxidative eustress), this induces altered cellular signaling, while at higher [...] Read more.

Oxidative stress is universal to all cell types, including cancer. It is elicited by a surplus of reactive oxygen species (ROS) or a reduced cellular ability to defend against those. At low levels (oxidative eustress), this induces altered cellular signaling, while at higher levels (oxidative distress), cellular toxicity and non-specific redox signaling become apparent. While oxidation-induced cell death is a hallmark of many cancer therapies, including ROS-producing radiotherapy, some chemotherapies and targeted therapies, photodynamic therapy, and recently emerging physical modalities such as medical gas plasma (a multi-ROS generating technology), less is known about the transcriptional profiles predisposing cancer cells to oxidative demise. In particular, which genes are associated with resistance or sensitivity to ROS overload and subsequent toxicity has not been systematically investigated. Moreover, it is unclear if there are differences between oxidant types, such as hydrogen peroxide and hypochlorous acid. To this end, we here employed 35 cell lines of various origins (e.g., adenocarcinoma, melanoma, leukemia, squamous cell carcinoma, and neuroblastoma). We first performed in-house transcriptomic analysis to assess baseline transcriptional profiles. Second, all cell lines were exposed to four different ROS concentrations of either hydrogen peroxide, hypochlorous, or gas plasma exposure. Third, correlation analysis was performed to identify genes associated with (i) oxidative stress sensitivity, (ii) oxidative stress resistance, and (iii) similarities and/or differences between the different oxidative stress inducers. Intriguingly, distinct gene sets were found for all treatments, and there was a striking difference between hydrogen peroxide and hypochlorous acid, suggesting different modes of action of both oxidants. Full article

(This article belongs to the Special Issue Oxidative Stress and Cancer: Possible Beneficial and Antioxidant Strategies (2nd Edition))

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29 pages, 3188 KiB

Open AccessReview

Unlocking the Therapeutic Potential of Algae-Derived Compounds in Hematological Malignancies

by Tamara Vujović, Tina Paradžik, Sanja Babić Brčić and Roberto Piva

Cancers 2025, 17(2), 318; https://doi.org/10.3390/cancers17020318 - 20 Jan 2025

Viewed by 1220

Abstract

Algae are a rich source of bioactive compounds that have a wide range of beneficial effects on human health and can show significant potential in the treatment of hematological malignancies such as leukemia, lymphoma, and multiple myeloma. These diseases often pose a therapeutic [...] Read more.

Algae are a rich source of bioactive compounds that have a wide range of beneficial effects on human health and can show significant potential in the treatment of hematological malignancies such as leukemia, lymphoma, and multiple myeloma. These diseases often pose a therapeutic challenge despite recent advances in treatment (e.g., the use of immunomodulatory drugs, proteasome inhibitors, CD38 monoclonal antibodies, stem cell transplant, and targeted therapy). A considerable number of patients experience relapses or resistance to the applied therapies. Algal compounds, alone or in combination with chemotherapy or other more advanced therapies, have exhibited antitumor and immunomodulatory effects in preclinical studies that may improve disease outcomes. These include the ability to induce apoptosis, inhibit tumor growth, and improve immune responses. However, most of these studies are conducted in vitro, often without in vivo validation or clinical trials. This paper summarizes the current evidence on the in vitro effects of algae extracts and isolated compounds on leukemia, lymphoma, and myeloma cell lines. In addition, we address the current advances in the application of algae-derived compounds as targeted drug carriers and their synergistic potential against hematologic malignancies. Full article

(This article belongs to the Special Issue Natural Compounds in Cancers)

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17 pages, 887 KiB

Open AccessReview

The Role of the Tumor Microenvironment in T-Cell Redirecting Therapies of Large B-Cell Lymphoma: Lessons Learned from CAR-T to Bispecific Antibodies

by Kirill V. Lepik and Vladislav V. Markelov

Cancers 2025, 17(2), 317; https://doi.org/10.3390/cancers17020317 - 20 Jan 2025

Viewed by 1165

Abstract

T-cell redirecting therapies, which include chimeric antigen receptor T-cells (CAR-Ts) and bispecific antibodies (BSAs), have revolutionized the treatment of relapsed\refractory large B-cell lymphoma (LBCL). Expanding clinical experience with these advanced therapies shows the potential for the optimization of their use with combination or [...] Read more.

T-cell redirecting therapies, which include chimeric antigen receptor T-cells (CAR-Ts) and bispecific antibodies (BSAs), have revolutionized the treatment of relapsed\refractory large B-cell lymphoma (LBCL). Expanding clinical experience with these advanced therapies shows the potential for the optimization of their use with combination or consolidation strategies, which necessitates the prognostic stratification of patients. While traditional clinical prognostic factors identified in the era of chemotherapy are characterized by limited value, the tumor microenvironment (TME) is becoming a new prognostic cluster. We examine how the heterogeneity of LBCL, characterized by variations in tumor parameters and differences in TME immune cell composition, immune checkpoint expression, and cytokine milieu, correlates with both positive responses and resistance to treatment. While classical parameters such as histological subtype, cell of origin, and target antigen expression lack proven prognostic value for T-cell redirecting therapies, the density and functional state of tumor-infiltrating lymphocytes, tumor-associated macrophages, and immune checkpoint molecules are shown to be critical determinants of therapeutic success, particularly in CAR-T therapy. We identify several gaps in the current knowledge and suggest that the insights gained from CAR-T experience could be instrumental in refining BSA applications. This report also highlights limitations in the current knowledge, as TME data derive from a limited number of registrational trials with varying methodologies, complicating cross-study comparisons and often focusing on immediate response metrics rather than long-term outcomes. By dissecting the complex interactions within the TME, this review aims to identify new prognostic factors and targets, ultimately fostering more effective and tailored treatment strategies for LBCL patients. Full article

(This article belongs to the Special Issue CAR T Cells in Lymphoma and Multiple Myeloma)

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16 pages, 1357 KiB

Open AccessReview

Urogenital Cancer Epidemiology in Poland (1980–2020): A Narrative Review

by Iwona Wnętrzak, Joanna Didkowska, Roman Sosnowski, Mateusz Czajkowski, Dawid Sigorski, Bartosz Małkiewicz, Piotr Marczyński, Jarosław Jaskulski, Piotr Kania, Adam Ostrowski, Artur Sieczych, Grzegorz Kade, Piotr Purpurowicz, Stanisław Szempliński and Robert Nowakowski

Cancers 2025, 17(2), 316; https://doi.org/10.3390/cancers17020316 - 20 Jan 2025

Viewed by 986

Abstract

Despite advances in prophylaxis, early diagnosis, and treatment, urogenital cancers represent a significant challenge to public health in Poland due to their relatively high prevalence and mortality rates. This narrative review aims to explore contemporary evidence on the epidemiology of urogenital cancers in [...] Read more.

Despite advances in prophylaxis, early diagnosis, and treatment, urogenital cancers represent a significant challenge to public health in Poland due to their relatively high prevalence and mortality rates. This narrative review aims to explore contemporary evidence on the epidemiology of urogenital cancers in Poland, such as prostate cancer, bladder cancer, kidney cancer, testicular cancer, and penile cancer, focusing on current and historical status and trends in the broader context of healthcare delivery. The literature consistently indicates that urogenital cancer continues to be a significant contributor to cancer incidence and mortality rates in Poland. Although the body of evidence is expanding, its quantity remains limited, primarily attributable to the scarcity of top-notch epidemiological investigations targeting particular forms of cancer, such as testicular and penile cancers, which are characterized by sporadic occurrences. Full article

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

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12 pages, 1620 KiB

Open AccessArticle

Deep Learning-Based Glioma Segmentation of 2D Intraoperative Ultrasound Images: A Multicenter Study Using the Brain Tumor Intraoperative Ultrasound Database (BraTioUS)

by Santiago Cepeda, Olga Esteban-Sinovas, Vikas Singh, Prakash Shetty, Aliasgar Moiyadi, Luke Dixon, Alistair Weld, Giulio Anichini, Stamatia Giannarou, Sophie Camp, Ilyess Zemmoura, Giuseppe Roberto Giammalva, Massimiliano Del Bene, Arianna Barbotti, Francesco DiMeco, Timothy Richard West, Brian Vala Nahed, Roberto Romero, Ignacio Arrese, Roberto Hornero and Rosario Sarabia Show full author list Hide full author list

Cancers 2025, 17(2), 315; https://doi.org/10.3390/cancers17020315 - 19 Jan 2025

Viewed by 1059

Abstract

Background: Intraoperative ultrasound (ioUS) provides real-time imaging during neurosurgical procedures, with advantages such as portability and cost-effectiveness. Accurate tumor segmentation has the potential to substantially enhance the interpretability of ioUS images; however, its implementation is limited by persistent challenges, including noise, artifacts, and [...] Read more.

Background: Intraoperative ultrasound (ioUS) provides real-time imaging during neurosurgical procedures, with advantages such as portability and cost-effectiveness. Accurate tumor segmentation has the potential to substantially enhance the interpretability of ioUS images; however, its implementation is limited by persistent challenges, including noise, artifacts, and anatomical variability. This study aims to develop a convolutional neural network (CNN) model for glioma segmentation in ioUS images via a multicenter dataset. Methods: We retrospectively collected data from the BraTioUS and ReMIND datasets, including histologically confirmed gliomas with high-quality B-mode images. For each patient, the tumor was manually segmented on the 2D slice with its largest diameter. A CNN was trained using the nnU-Net framework. The dataset was stratified by center and divided into training (70%) and testing (30%) subsets, with external validation performed on two independent cohorts: the RESECT-SEG database and the Imperial College NHS Trust London cohort. Performance was evaluated using metrics such as the Dice similarity coefficient (DSC), average symmetric surface distance (ASSD), and 95th percentile Hausdorff distance (HD95). Results: The training cohort consisted of 197 subjects, 56 of whom were in the hold-out testing set and 53 in the external validation cohort. In the hold-out testing set, the model achieved a median DSC of 0.90, ASSD of 8.51, and HD95 of 29.08. On external validation, the model achieved a DSC of 0.65, ASSD of 14.14, and HD95 of 44.02 on the RESECT-SEG database and a DSC of 0.93, ASSD of 8.58, and HD95 of 28.81 on the Imperial-NHS cohort. Conclusions: This study supports the feasibility of CNN-based glioma segmentation in ioUS across multiple centers. Future work should enhance segmentation detail and explore real-time clinical implementation, potentially expanding ioUS’s role in neurosurgical resection. Full article

(This article belongs to the Special Issue Development, Validation and Application of Advanced Biomarkers in Cerebral Tumours)

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Schematic representation of the workflow followed in this study. Full article ">Figure 2
Representative examples of patients from the different datasets and centers included in the study. Tumor segmentations, considered the ground truth, are highlighted with red contours. Full article ">Figure 3
Performance metrics of the glioma segmentation model across different centers. Each subplot represents a key evaluation metric: (A) Dice similarity coefficient, (B) Jaccard index, (C) average symmetric surface distance, (D) 95th percentile Hausdorff distance, (E) precision, and (F) recall. Boxplots illustrate the distribution of metric scores for each center, with the blue horizontal line indicating the median value for each center. Outliers are represented as individual points outside the whiskers. Full article ">Figure 4
Examples of model predictions and Dice similarity score (DSC) values for the hold-out test cohorts (A,B,E,F), as well as the external validation cohorts (C,G) (RESECT-SEG) and (D,H) (Imperial-NHS). The top panels show cases with good performance, whereas the bottom panels illustrate cases with poor performance. The ground truth tumor segmentations are delineated in red contours, whereas predicted segmentations are shown in green. Full article ">

15 pages, 1014 KiB

Open AccessArticle

Initial Use Experience of Durvalumab Plus Gemcitabine and Cisplatin for Advanced Biliary Tract Cancer in a Japanese Territory Center

by Kento Shionoya, Atsushi Sofuni, Shuntaro Mukai, Yoshiya Yamauchi, Takayoshi Tsuchiya, Reina Tanaka, Ryosuke Tonozuka, Kenjiro Yamamoto, Kazumasa Nagai, Yukitoshi Matsunami, Hiroyuki Kojima, Hirohito Minami, Noriyuki Hirakawa, Qiang Zhan and Takao Itoi

Cancers 2025, 17(2), 314; https://doi.org/10.3390/cancers17020314 - 19 Jan 2025

Viewed by 952

Abstract

Background: Biliary tract cancers (BTCs), including gallbladder and bile duct cancers, have a poor prognosis. Recent advances in chemotherapy, such as using targeted drugs for specific gene mutations, have improved outcomes. Gemcitabine plus cisplatin chemotherapy has been the standard of care for the [...] Read more.

Background: Biliary tract cancers (BTCs), including gallbladder and bile duct cancers, have a poor prognosis. Recent advances in chemotherapy, such as using targeted drugs for specific gene mutations, have improved outcomes. Gemcitabine plus cisplatin chemotherapy has been the standard of care for the primary treatment of BTCs, but secondary treatment had not been established until recently. In recent years, durvalumab plus gemcitabine and cisplatin (GCD) chemotherapy is emerging as a promising regimen, although more evidence is needed for its effectiveness. Methods: This retrospective single-center study involved 44 patients receiving GCD treatment between January 2023 and March 2024 with a median follow-up of 10 months. Outcomes focused on overall survival (OS), progression-free survival (PFS), response rates, and adverse events (AEs). Results: The overall response rate (ORR) was 23%, and the disease control rate (DCR) was 82%. The overall median OS and PFS were 15.3 and 8.0 months, respectively, with patients receiving primary chemotherapy experiencing longer survival compared to a control group. Patients who did not undergo bile duct drainage had statistically different better OS and PFS. Grade 3 or higher AEs occurred in 54.5% of patients, with neutropenia and biliary infections being common. Conclusions: GCD chemotherapy shows potential as an effective treatment for BTCs. The favorable treatment outcome was the response rate, particularly in primary therapy or those cases with no metastasis. Bile duct management is crucial for improving patient outcomes. GCD chemotherapy has a high response rate, PFS, and OS compared to other forms of chemotherapy. Full article

(This article belongs to the Special Issue The Evaluation of Cancer Treatment Patterns and Quality of Care across the World)

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Durvalumab plus gemcitabine and cisplatin (GCD) chemotherapy administration schedule. Full article ">Figure 2
Survival curves of durvalumab plus gemcitabine and cisplatin chemotherapy. Survival curves of the overall results following durvalumab plus gemcitabine and cisplatin administration. The median overall survival (OS) was 15.3 months (95% confidence interval (CI): 9.8–20.7), and the median progression-free survival (PFS) was 8.0 months (95% CI: 5.2–10.9). Full article ">Figure 3
Subgroup analysis of the survival curves of durvalumab plus gemcitabine and cisplatin chemotherapy. (a) Survival curves of durvalumab plus gemcitabine and cisplatin according to primary chemotherapy. The probability of OS in the primary therapy group was greater than 0.5. The primary chemotherapy group exhibited a significantly longer OS than the second and subsequent chemotherapy groups (p = 0.014). For patients treated with primary chemotherapy, the median PFS was 8.7 months, whereas it was 3.0 months for those who received subsequent therapies (p = 0.076). (b) Survival curves of durvalumab plus gemcitabine and cisplatin by requirement for biliary drainage. The group requiring bile duct drainage demonstrated inferior OS compared to those who did not require drainage (p = 0.003). Additionally, the group requiring drainage had a significantly worse PFS (p = 0.029). (c) Survival curves of durvalumab plus gemcitabine and cisplatin according to metastasis status. When comparing locally advanced cases, postoperative recurrent cases, and metastatic cases, the probability of OS in non-metastatic cases was greater than 0.5, and there was no statistical difference observed (p = 0.47). Furthermore, there was no statistically significant difference in PFS among the locally advanced, postoperative recurrent, and metastatic cases (p = 0.062). Full article ">

16 pages, 1180 KiB

Open AccessArticle

Evaluating Treatment Preferences and the Efficacy of Capsaicin 179 mg Patch vs. Pregabalin in a Randomized Trial for Postsurgical Neuropathic Pain in Breast Cancer: CAPTRANE

by Denis Dupoiron, Florent Bienfait, Valérie Seegers, François-Xavier Piloquet, Yves-Marie Pluchon, Marie Pechard, Karima Mezaib, Gisèle Chvetzoff, Jésus Diaz, Abesse Ahmeidi, Valérie Mauriès-Saffon, Nathalie Lebrec and Sabrina Jubier-Hamon

Cancers 2025, 17(2), 313; https://doi.org/10.3390/cancers17020313 - 19 Jan 2025

Viewed by 1032

Abstract

Background/Objectives: CAPTRANE evaluated the efficacy and tolerability of high-concentration capsaicin patch (HCCP) vs. oral pregabalin for the treatment of postsurgical neuropathic pain (PSNP) following breast cancer surgery. The study was designed with the aim of demonstrating noninferiority of one HCCP against daily pregabalin. [...] Read more.

Background/Objectives: CAPTRANE evaluated the efficacy and tolerability of high-concentration capsaicin patch (HCCP) vs. oral pregabalin for the treatment of postsurgical neuropathic pain (PSNP) following breast cancer surgery. The study was designed with the aim of demonstrating noninferiority of one HCCP against daily pregabalin. Methods: This was a multicenter, randomized, parallel-arm, open-label study conducted across nine centers in France. The primary endpoint was a change from baseline in the Numeric Pain Rating Scale (NPRS) score after 2 months. Results: Recruitment challenges resulted in the randomization of 140 patients (versus 644 planned); the per-protocol population comprised 107 patients (HCCP: n = 65; pregabalin: n = 42). Baseline characteristics were similar between the two groups. In the per-protocol analysis, the mean (standard deviation) change versus baseline in NPRS score was −1.926 (2.554) with HCCP and −1.634 (2.498) with pregabalin. The prespecified analysis showed that HCCP was not inferior to pregabalin: the lower bound of the 90% confidence interval for the between-arm difference was −0.889 and the upper bound was +0.260 (i.e., below the predefined clinical threshold of +0.4). Patient-reported outcomes showed no statistically significant differences between treatments. The painful area size decreased significantly more with HCCP. Tolerability profiles differed, with HCCP mostly causing application-site reactions. While >50% of patients switched from pregabalin to HCCP, none switched from HCCP to pregabalin. Conclusions: This comparative study in PSNP post breast cancer surgery, evaluating a single treatment of HCCP, shows a noninferior reduction in pain intensity, a superior reduction in painful area size, and a patient preference for HCCP compared with pregabalin. Despite limitations, it contributes valuable initial data for PSNP management in breast cancer care. Full article

(This article belongs to the Special Issue Palliative Care and Pain Management in Cancer)

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14 pages, 498 KiB

Open AccessReview

A Review of Neoadjuvant Therapy for Localized and Locally Advanced Renal Cell Carcinoma

by Qian Qin, Isamu Tachibana, Vitaly Margulis, Jeffrey A. Cadeddu and Tian Zhang

Cancers 2025, 17(2), 312; https://doi.org/10.3390/cancers17020312 - 19 Jan 2025

Viewed by 891

Abstract

The introduction of vascular endothelial growth factor receptor-tyrosine kinases (VEGFR-TKIs) and immune checkpoint inhibitors (IOs) have drastically altered the treatment landscape for kidney cancer, with doublet combination immunotherapy (IO/IO or IO/VEGFR-TKI) now set as the standard front-line treatment for advanced renal cell carcinoma [...] Read more.

The introduction of vascular endothelial growth factor receptor-tyrosine kinases (VEGFR-TKIs) and immune checkpoint inhibitors (IOs) have drastically altered the treatment landscape for kidney cancer, with doublet combination immunotherapy (IO/IO or IO/VEGFR-TKI) now set as the standard front-line treatment for advanced renal cell carcinoma (RCC). However, the roles of VEGFR-TKIs and IOs in the neoadjuvant setting for locoregional/locally advanced RCC remain undefined, where the goals may be primary tumor downsizing/downstaging and potentially eradicating micrometastatic disease. This review will examine VEGFR-TKI monotherapy, IO monotherapy, and VEGFR-TKI/IO combination regimens in a preoperative setting with a focus on the efficacy, toxicity, surgical, and long-term implications. Full article

(This article belongs to the Special Issue Immune Landscape of Renal Cell Carcinoma)

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18 pages, 3115 KiB

Open AccessArticle

Cancer Therapy-Induced Cardiotoxicity: Results of the Analysis of the UK DEFINE Database

by Stefanie Ho Yi Chan, Raymond W. Fitzpatrick, Deborah Layton, Sherael Webley and Sam Salek

Cancers 2025, 17(2), 311; https://doi.org/10.3390/cancers17020311 - 19 Jan 2025

Viewed by 920

Abstract

Background: The accelerated development of novel cancer therapies necessitates a thorough understanding of the associated cardiotoxicity profiles, due to their significant implications for the long-term health and quality of life of cancer survivors. Objectives: The aim of this study was to determine the [...] Read more.

Background: The accelerated development of novel cancer therapies necessitates a thorough understanding of the associated cardiotoxicity profiles, due to their significant implications for the long-term health and quality of life of cancer survivors. Objectives: The aim of this study was to determine the association between cardiotoxicity and non-small cell lung cancer (NSCLC) treatments using a hospital medicines usage database in England. Methods: An observational study based on a retrospective design using real-world data from the UK DEFINE database was performed. Monthly secondary data of 40 shortlisted drugs from April 2017 to July 2022 were extracted. Results: The cardiology drug that was associated with most oncology drugs was apixaban. Atezolizumab, bevacizumab, nintedanib, osimertinib, paclitaxel, pembrolizumab, gemcitabine and vincristine were all mostly associated with apixaban, which indicated association with atrial fibrillation. Afatinib, erlotinib and methotrexate were mostly associated with atenolol, hence suggesting the association with ischaemia or hypertension. Docetaxel and epirubicin were associated with verapamil, which indicated association with arrhythmia or hypertension. Conclusions: From the correlation and regression analyses, it can be concluded that hypertension was the most associated cardiovascular disease with the 20 shortlisted oncology drugs. The findings of this study have provided a better understanding of the association between each NSCLC–Cardio drug pair. Full article

(This article belongs to the Special Issue New Era of Cancer Research: From Large-Scale Cohorts to Big-Data)

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11 pages, 554 KiB

Open AccessArticle

Comparison of Outcomes of Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide in Older Versus Younger Patients

by Giacomo Adoncecchi, Ambuj Kumar, Krishnakar Mogili, Rawan Faramand, Hien Liu, Farhad Khimani, Asmita Mishra, Michael Nieder, Taiga Nishihori, Doris Hansen, Michael Jain, Aleksandr Lazaryan, Lia Perez, Joseph Pidala, Frederick Locke, Claudio Anasetti, Nelli Bejanyan and Hany Elmariah

Cancers 2025, 17(2), 310; https://doi.org/10.3390/cancers17020310 - 19 Jan 2025

Viewed by 754

Abstract

Background: Previous studies have shown that allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA haploidentical (haplo) donor followed by graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) results in lower relapse rates and improved DFS when compared to haplo bone marrow [...] Read more.

Background: Previous studies have shown that allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA haploidentical (haplo) donor followed by graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) results in lower relapse rates and improved DFS when compared to haplo bone marrow transplant (BMT) with PTCy. However, PBSCT leads to higher rates of GVHD. It is unknown whether the benefits of haplo PBSCT may be nullified in older patients (>60 years) by a higher susceptibility to GVHD and transplant related toxicity. Thus, we sought to determine if older patients receiving haplo PBSCT with PTCy experience significantly worse outcomes than younger patients. Methods: We evaluated 121 adult patients with hematologic malignancies treated at the Moffitt Cancer Center with allogeneic haplo PBSCT followed by PTCy and compared outcomes of patients ≥60 years (n = 55) versus patients <60 years (n = 66). Results: The cumulative incidence of non-relapse mortality (NRM) from the competing risk regression analysis was worse for the older patient group (SHR = 4.05, 95% CI: 1.43–11.47, p = 0.008). However, there was no significant difference between groups in graft-versus-host disease (GVHD), relapse, disease-free survival (DFS), or overall survival (OS). Instead, hematopoietic comorbidity index (HCT-CI) ≥ 3 was associated with worse DFS (HR = 1.87, 95% CI: 1.04–3.34, p = 0.035) and OS (HR = 1.98, 95% CI: 1.03–3.84, p-value = 0.042). Subgroup analysis of patients ≥60 years showed a trend toward improved 2-year OS with fludarabine/cyclophosphamide/total body irradiation (Flu/Cy/TBI) versus fludarabine/busulfan: 71% versus 53% (HR = 0.47, p = 0.121). In patients over 70 years (n = 14), NRM was 8% and OS was 76% at 1 year. Conclusion: Given similar OS and DFS between patients aged >60 years and those <60, haplo PBSCT with PTCy appears to be an appropriate transplant platform for older patients. Full article

(This article belongs to the Section Transplant Oncology)

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14 pages, 2960 KiB

Open AccessArticle

Trans-Arterial Embolization for Liver Metastases of Gastroenteropancreatic Neuroendocrine Tumors: Response Indicates Survival Benefit?

by Luohai Chen, Dequan Yang, Yueriguli Yusufu, Haikuan Liu, Man Liu, Yuan Lin, Yanji Luo, Qiao He, Minhu Chen, Zhirong Zeng, Ning Zhang and Yu Wang

Cancers 2025, 17(2), 309; https://doi.org/10.3390/cancers17020309 - 19 Jan 2025

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Abstract

Objective: To determine the impact of trans-arterial embolization (TAE) on overall survival (OS) in patients with liver metastases from gastroenteropancreatic neuroendocrine tumors (LM-GEP-NETs) and to identify factors that may influence tumor response to TAE treatment. Methods: This study included patients with histologically and [...] Read more.

Objective: To determine the impact of trans-arterial embolization (TAE) on overall survival (OS) in patients with liver metastases from gastroenteropancreatic neuroendocrine tumors (LM-GEP-NETs) and to identify factors that may influence tumor response to TAE treatment. Methods: This study included patients with histologically and radiologically confirmed LM-GEP-NETs who received TAE treatment at The First Affiliated Hospital, Sun Yat-sen University, between November 2016 and January 2023. Imaging responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria. Tumor response was defined as complete or partial remission. Results: In total, 267 patients with LM-GEP-NETs were included. Patients with liver tumor burdens <25%, 25–50%, and ≥50% had progressively worse OS (p < 0.005). According to the RECIST criteria, 65.9% of patients exhibited tumor responses. Using the mRECIST criteria, 77.5% of patients showed tumor responses. Survival analyses with log-rank tests indicated that patients with tumor responses assessed using either the RECIST or mRECIST criteria had significantly better OS (p = 0.015 and p = 0.023, respectively). Further logistic regression analyses showed that early TAE (within 4 months after diagnosis of liver metastases) was associated with tumor responses assessed using RECIST or mRECIST. These results were further verified using propensity score matching and inverse probability treatment weighting adjusted datasets. Conclusions: A higher liver tumor burden was associated with poorer OS in patients with LM-GEP-NETs. Tumor response after TAE indicates survival benefits. Early TAE (within 4 months of diagnosis) was associated with better treatment responses. Full article

(This article belongs to the Special Issue Treatment Options and Risk Factors of Pancreatic Neuroendocrine Neoplasms)

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(A) Survival analysis of patient with different liver tumor burdens. (B) Comparison of survival of patients with different tumor response after TAE treatments assessed using RECIST criteria. (C) Comparison of survival of patients with different tumor response after TAE treatments assessed using mRECIST criteria. (D) Comparison of survival of patients with different tumor response after TAE treatments assessed using RECIST and mRECIST criteria. Both CR/PR and both SD/PD means consistent CR/PR and SD/PD, respectively, using these two criteria. While discordant CR/PR means CR/PR using mRECIST criteria but SD/PD using RECIST criteria. Full article ">Figure 2
(A) Baseline CT image from a 56-year-old male patient with liver metastases of a WHO Grade 3 pancreatic neuroendocrine tumor. The longest diameter of one target lesion of liver metastasis was 61.5 mm. (B) After two procedures of TAE treatment, the longest diameter of this target lesion decreased to 48.9 mm. The longest diameter of the enhanced tumor region decreased to 25.9 mm. The general tumor response assessment for this patient was SD using RECIST criteria but partial response using mRECIST criteria. (C) Baseline CT image of liver metastases from a 66-year-old female patient with liver metastases with a WHO Grade 2 pancreatic neuroendocrine tumor. (D) After one procedure of TAE treatment, the patient had PD. Full article ">Figure 3
(A) Relationship between tumor response assessed using RECIST criteria and latency to TAE. (B) Relationship between tumor response assessed using mRECIST criteria and latency to TAE. (C) Comparison of tumor response rates assessed using RECIST criteria between patients with early (<4 months) and late (≥4 months) TAE treatments. (D) Comparison of tumor response rates assessed using mRECIST criteria between patients with early (<4 months) and late (≥4 months) TAE treatments. Full article ">

13 pages, 1220 KiB

Open AccessArticle

The Clinical Utility of a Next-Generation Sequencing-Based Approach to Detecting Circulating HPV DNA in Patients with Advanced Anal Cancer

by Deepak Bhamidipati, Jay R. Johnson, Kangyu Lin, Helene Pelicano, Cathy Eng, Ryan Huey, Robert A. Wolff, Daniel M. Halperin, Michael F. Frumovitz, Ignacio I. Wistuba, Dzifa Y. Duose, Saradhi Mallampati, Rajyalakshmi Luthra and Van K. Morris

Cancers 2025, 17(2), 308; https://doi.org/10.3390/cancers17020308 - 19 Jan 2025

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Abstract

Background: To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal [...] Read more.

Background: To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA). Methods: ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4 Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types. The HPV type, copy number (CN), and integration sites were determined using a bioinformatic pipeline. Results: A total of 77 plasma samples from 28 patients with HPV-related SCCA were retrospectively analyzed. HPV ctDNA was detected in 26 cases (93%) (including uncommon subtypes). The median HPV CN was higher in metastatic versus locally recurrent/unresectable SCCA (p = 0.043). Changes in the HPV CN were concordant with the radiographic response (p = 0.027). An integration event was detected in 23 patients (82%), with presumed episomal HPV DNA present in the remaining patients. Higher HPV integration (a mean of ≥1 integration across samples) was associated with a worse overall survival from the start of immunotherapy (13.6 months versus 36.0 months; p = 0.003). Conclusions: Using HPV-informed next-generation sequencing of the ctDNA, we found changes in the HPV CN correlated with the treatment response and that HPV integration detected in the ctDNA is an unfavorable prognostic biomarker. Full article

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

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HPV copy number and clinical endpoints. (A) displays the highest HPV copy number detected among patients with locoregional and distant metastatic disease (the bar represents the median and each dot represents a patient). (B) Percentage change in HPV copy number for paired samples according to radiographic response. * One value with a 1692% increase is not depicted. rDecrease = radiographic decrease and rIncrease = radiographic increase. Full article ">Figure 2
Integration hotspots and concordance. (A) The distribution of HPV integration breakpoints in the human genome among all patients with detectable HPV (n = 26). In the outer circle, each chromosome is represented, with the DNA numbering in millions of bases. In the inner circle, each red bar depicts the frequency of HPV integration, where the histogram axis units represent the number of samples. The tumor-associated genes located <500 kb from high rates of integration breakpoints are marked. (B) The number of unique integration events detected across multiple blood samples for patients with ≥2 samples. Each bar represents an individual patient, and the x-axis refers to the number of distinct integration loci. The color code denotes whether the integration loci were detected at an individual time point or at multiple time points. TP = time point. Full article ">Figure 3
Survival according to HPV integration status. Survival according to HPV integration status: The PFS (A) and OS (B) according to all systemic treatments; PFS (C) and OS (D) after the initiation of immunotherapy. I = integration group; NI = non-integration group. Full article ">

13 pages, 1256 KiB

Open AccessReview

Lung Cancers Associated with Cystic Airspaces

by Clara Valsecchi, Francesco Petrella, Stefania Freguia, Milo Frattini, Gianluca Argentieri, Carla Puligheddu, Giorgio Treglia and Stefania Rizzo

Cancers 2025, 17(2), 307; https://doi.org/10.3390/cancers17020307 - 18 Jan 2025

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Abstract

Lung cancer, the second most common malignancy in both men and women, poses a significant health burden. Early diagnosis remains pivotal in reducing lung cancer mortality. Given the escalating number of computed tomography (CT) examinations in both outpatient and inpatient settings, radiologists play [...] Read more.

Lung cancer, the second most common malignancy in both men and women, poses a significant health burden. Early diagnosis remains pivotal in reducing lung cancer mortality. Given the escalating number of computed tomography (CT) examinations in both outpatient and inpatient settings, radiologists play a crucial role in identifying early-stage pulmonary cancers, particularly non-nodular cancers. Screening programs have been instituted to achieve this goal, and they have raised attention within the scientific community to lung cancers associated with cystic airspaces. These cancers, although they have been known for at least a decade, remain understudied. Limited investigations with small sample sizes have estimated their prevalence and explored their radiological and pathological features. Lung cancers associated with cystic airspaces exhibit varying complexities within their cystic components and demonstrate suspicious changes over time. Adenocarcinoma is the predominant histological type, often with a peripheral location. Differential diagnosis on CT scans includes inflammatory processes or emphysema-related changes. Unfortunately, prospective studies specifically analyzing the prevalence of cystic airspace-associated lung cancers are lacking. However, it is estimated that they constitute approximately one-fourth of delayed radiological diagnoses. Increased awareness among radiologists could lead to more timely identification and potentially reduce lung cancer mortality in a cost-effective manner. Full article

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

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17 pages, 2532 KiB

Open AccessArticle

The Homeobox Transcription Factor NKX3.1 Displays an Oncogenic Role in Castration-Resistant Prostate Cancer Cells

by Audris Budreika, John T. Phoenix, Raymond J. Kostlan, Carleen D. Deegan, Marina G. Ferrari, Kristen S. Young, Sean W. Fanning and Steven Kregel

Cancers 2025, 17(2), 306; https://doi.org/10.3390/cancers17020306 - 18 Jan 2025

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Abstract

Background/Objectives: Prostate cancer (PCa) is the second leading cause of cancer-related death in men. The increase in incidence rates of more advanced and aggressive forms of the disease year-to-year fuels urgency to find new therapeutic interventions and bolster already established ones. PCa is [...] Read more.

Background/Objectives: Prostate cancer (PCa) is the second leading cause of cancer-related death in men. The increase in incidence rates of more advanced and aggressive forms of the disease year-to-year fuels urgency to find new therapeutic interventions and bolster already established ones. PCa is a uniquely targetable disease in that it is fueled by male hormones (androgens) that drive tumorigenesis via the androgen receptor or AR. Current standard-of-care therapies directly target AR and its aberrant signaling axis but resistance to these therapies commonly arises, and the mechanisms behind the onset of therapy-resistance are still elusive. Research has shown that even with resistant disease, AR remains the main driver of growth and survival of PCa, and AR target genes and cofactors may help mediate resistance to therapy. Here, we focused on a homeobox transcription factor that exhibits a close relationship with AR—NKX3.1. Though NKX3.1 is traditionally thought of as a tumor suppressor, it has been previously reported to promote cancer cell survival by cooperating with AR. The role of NKX3.1 as a tumor suppressor perhaps in early-stage disease also contradicts its profile as a diagnostic biomarker for advanced prostate cancer. Methods: We investigated the physical interaction between NKX3.1 and AR, a modulated NKX3.1 expression in prostate cancer cells via overexpression and knockdown and assayed subsequent viability and downstream target gene expression. Results: We find that the expression of NKX3.1 is maintained in advanced PCa, and it is often elevated because of aberrant AR activity. Transient knockdown experiments across various PCa cell line models reveal NKX3.1 expression is necessary for survival. Similarly, stable overexpression of NKX3.1 in PCa cell lines reveals an androgen insensitive phenotype, suggesting NKX3.1 is sufficient to promote growth in the absence of an AR ligand. Conclusions: Our work provides new insight into NKX3.1’s oncogenic influence on PCa and the molecular interplay of these transcription factors in models of late-stage prostate cancer. Full article

(This article belongs to the Special Issue New Insights into Urologic Oncology)

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18 pages, 3219 KiB

Open AccessArticle

Treatment Patterns and Outcomes in Patients with Advanced Biliary Tract Cancers Treated with Gemcitabine-Based Chemotherapy: A Retrospective Study

by Farshid Dayyani, Heide A. Stirnadel-Farrant, Jenny Hu, Yian Lin, Nehemiah Kebede, Stephen J. Valerio and Daniel H. Ahn

Cancers 2025, 17(2), 305; https://doi.org/10.3390/cancers17020305 - 18 Jan 2025

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Abstract

Background: Historically, the standard of care for advanced biliary tract cancers (aBTCs) was gemcitabine plus cisplatin (GemCis). Immunotherapy plus GemCis is now recommended as a first-line treatment for aBTCs. Whether patients can tolerate eight cycles of GemCis in clinical practice, as per the [...] Read more.

Background: Historically, the standard of care for advanced biliary tract cancers (aBTCs) was gemcitabine plus cisplatin (GemCis). Immunotherapy plus GemCis is now recommended as a first-line treatment for aBTCs. Whether patients can tolerate eight cycles of GemCis in clinical practice, as per the Advanced Biliary Cancer (ABC)-02 study, remains to be assessed. We performed a retrospective observational cohort study to assess real-world treatment patterns and overall survival (OS) in patients with de novo or recurrent aBTCs treated with first-line gemcitabine-based chemotherapy in the United States. Methods: This retrospective observational cohort study used Optum’s de-identified Market Clarity Data (Market Clarity). Adults diagnosed with de novo or recurrent aBTCs in the United States who began first-line gemcitabine-based chemotherapy from January 2016–March 2022 were identified and followed from index until death, the end of continuous enrolment, or the end of study period. Treatment patterns and OS were assessed. Results: Overall, 559 patients were included (de novo, n = 462; recurrent, n = 97). GemCis was the most common first-line therapy received (de novo: 73.8%; recurrent: 57.7%). Most patients received approximately five cycles of GemCis; median (95% CI) time to discontinuation was 4.6 (4.3–5.1) months. Most patients died over the follow-up period (de novo: 70.3%; recurrent: 62.9%). Median OS (95% CI) was 14.2 (12.1–16.1) months (de novo) and 18.5 (15.6–26.9) months (recurrent). Conclusions: GemCis was the most common first-line therapy received during the study period; most patients were unable to receive eight cycles of GemCis. Survival was limited over the follow-up period, highlighting the need for new treatments for aBTCs. Future studies are warranted to understand the real-world impact of first-line immunotherapy plus GemCis for patients with aBTCs. Full article

(This article belongs to the Section Cancer Drug Development)

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Graphical abstract

Graphical abstract
Full article ">Figure 1
Treatment regimens administered during follow-up in patients with de novo advanced biliary tract cancer. * Regimens administered to <5 patients. Gem, gemcitabine; GemCis, gemcitabine plus cisplatin; nab, nanoparticle albumin-bound. Full article ">Figure 2
Treatment regimens administered during follow-up inpatients with recurrent advanced biliary tract cancer. * Regimens administered to <5 patients. Gem, gemcitabine; GemCis, gemcitabine plus cisplatin. Full article ">Figure 3
Time to discontinuation or death with first-line gemcitabine plus cisplatin. (a) Kaplan–Meier curve of time to discontinuation or death with first-line gemcitabine plus cisplatin in all patients included in this study. (b) Kaplan–Meier curves of time to discontinuation or death with first-line gemcitabine plus cisplatin in subgroups of patients with de novo or recurrent advanced biliary tract cancer. aBTC, advanced biliary tract cancer; CI, confidence interval; GemCis, gemcitabine plus cisplatin; KM, Kaplan–Meier. Full article ">Figure 4
Time from index to death or end of follow-up. (a) Kaplan–Meier curve of time from index to death or end of follow-up for all patients included in this study. (b) Kaplan–Meier curves of time from index to death or end of follow-up in subgroups of patients with de novo or recurrent advanced biliary tract cancer. aBTC, advanced biliary tract cancer; CI, confidence interval; KM, Kaplan–Meier. Full article ">Figure 5
Time from index to death or end of follow-up for all patients with advanced biliary tract cancer stratified by the number of gemcitabine-based chemotherapy cycles received in first-line. Two patients treated with first-line gemcitabine monotherapy were excluded from this analysis as their gemcitabine records were within 7 days of each other. 1L, first-line; CI, confidence interval; KM, Kaplan–Meier. Full article ">

14 pages, 551 KiB

Open AccessArticle

Feasibility and Acceptability of Integrating Acupuncture for Management of Multiple Symptoms in Medically Underserved Breast Cancer Survivors

by Hongjin Li, Ardith Z. Doorenbos, Zhengjia Chen, Hannah Choi, Weiwei Ma, Oana Danciu, Crystal L. Patil, Shuang Gao, Natalie Lif and Judith M. Schlaeger

Cancers 2025, 17(2), 304; https://doi.org/10.3390/cancers17020304 - 18 Jan 2025

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Abstract

Background/Objectives: Breast cancer survivors undergoing long-term endocrine therapy often experience multiple symptoms, including pain, fatigue, sleep disturbance, hot flashes, anxiety, and depression. This study explored the feasibility and acceptability of integrating acupuncture for symptom management in medically underserved breast cancer survivors. Methods: This [...] Read more.

Background/Objectives: Breast cancer survivors undergoing long-term endocrine therapy often experience multiple symptoms, including pain, fatigue, sleep disturbance, hot flashes, anxiety, and depression. This study explored the feasibility and acceptability of integrating acupuncture for symptom management in medically underserved breast cancer survivors. Methods: This randomized controlled trial was conducted at two clinics serving medically underserved populations. Breast cancer survivors (N = 62) were randomized to receive acupuncture (n = 31) or usual care (n = 31). The acupuncture group underwent 10 sessions over 5 weeks. Symptoms were assessed at baseline and Weeks 6 and 12. Results: The majority of participants (55%) were Black, mean age was 55.2 ± 9.3 years, and 62.9% had a household income below $55,000. Retention (90.3%), engagement (93.1%), and acceptability (92.8%) rates were high, demonstrating that integrating acupuncture into care for medically underserved breast cancer survivors is both feasible and acceptable. At Week 6, the acupuncture group showed significant reduction compared to the usual care group in pain, fatigue, sleep disturbance, depression, anxiety, and the symptom cluster score. All improvements persisted to Week 12 except for those in anxiety. Conclusions: Integrating acupuncture for symptom management in medically underserved breast cancer survivors is both feasible and acceptable. This approach offers potential benefits for reducing multiple symptoms and addressing health disparities. Full article

(This article belongs to the Special Issue Symptom Burden in Cancer: Assessment and Management)

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Cancers, Volume 17, Issue 2 (January-2 2025) – 174 articles

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