Journal Description
Cancers
Cancers
is a peer-reviewed, open access journal of oncology, published semimonthly online by MDPI. The Irish Association for Cancer Research (IACR), Spanish Association for Cancer Research (ASEICA), Biomedical Research Centre (CIBM), British Neuro-Oncology Society (BNOS) and Spanish Group for Cancer Immuno-Biotherapy (GÉTICA) are affiliated with Cancers and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Oncology) / CiteScore - Q1 (Oncology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17.9 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 18 topical sections.
- Companion journals for Cancers include: Radiation and Onco.
Impact Factor:
5.2 (2022);
5-Year Impact Factor:
5.6 (2022)
Latest Articles
Regulation of RORα Stability through PRMT5-Dependent Symmetric Dimethylation
Cancers 2024, 16(10), 1914; https://doi.org/10.3390/cancers16101914 - 17 May 2024
Abstract
Retinoic acid receptor-related orphan receptor alpha (RORα), a candidate tumor suppressor, is prevalently downregulated or lost in malignant breast cancer cells. However, the mechanisms of how RORα expression is regulated in breast epithelial cells remain incompletely understood. Protein arginine N-methyltransferase 5 (PRMT5), a
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Retinoic acid receptor-related orphan receptor alpha (RORα), a candidate tumor suppressor, is prevalently downregulated or lost in malignant breast cancer cells. However, the mechanisms of how RORα expression is regulated in breast epithelial cells remain incompletely understood. Protein arginine N-methyltransferase 5 (PRMT5), a type II methyltransferase catalyzing the symmetric methylation of the amino acid arginine in target proteins, was reported to regulate protein stability. To study whether and how PRMT5 regulates RORα, we examined the direct interaction between RORα and PRMT5 by immunoprecipitation and GST pull-down assays. The results showed that PRMT5 directly bound to RORα, and PRMT5 mainly symmetrically dimethylated the DNA-binding domain (DBD) but not the ligand-binding domain (LBD) of RORα. To investigate whether RORα protein stability is regulated by PRMT5, we transfected HEK293FT cells with RORα and PRMT5-expressing or PRMT5-silencing (shPRMT5) vectors and then examined RORα protein stability by a cycloheximide chase assay. The results showed that PRMT5 increased RORα protein stability, while silencing PRMT5 accelerated RORα protein degradation. In PRMT5-silenced mammary epithelial cells, RORα protein expression was decreased, accompanied by an enhanced epithelial–mesenchymal transition morphology and cell invasion and migration abilities. In PRMT5-overexpressed mammary epithelial cells, RORα protein was accumulated, and cell invasion was suppressed. These findings revealed a novel mechanism by which PRMT5 regulates RORα protein stability.
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(This article belongs to the Section Tumor Microenvironment)
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A Preparatory Virtual Reality Experience Reduces Anxiety before Surgery in Gynecologic Oncology Patients: A Randomized Controlled Trial
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Bernd C. Schmid, Dominic Marsland, Eilish Jacobs and Günther A. Rezniczek
Cancers 2024, 16(10), 1913; https://doi.org/10.3390/cancers16101913 - 17 May 2024
Abstract
Perioperative anxiety is common among patients undergoing surgery, potentially leading to negative outcomes. Immersive virtual reality (VR) has shown promise in reducing anxiety in various clinical settings. This study aimed to evaluate the effectiveness of VR in reducing perioperative anxiety in patients undergoing
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Perioperative anxiety is common among patients undergoing surgery, potentially leading to negative outcomes. Immersive virtual reality (VR) has shown promise in reducing anxiety in various clinical settings. This study aimed to evaluate the effectiveness of VR in reducing perioperative anxiety in patients undergoing gynecological oncology surgery and was conducted as a single-center, double-arm, single-blinded randomized controlled trial at the Gold Coast University Hospital, Queensland, Australia. Participants were randomized into the VR intervention + care as usual (CAU) group (n = 39) and the CAU group (n = 41). Anxiety scores were assessed using a six-tier visual facial anxiety scale at baseline, after the intervention/CAU on the same day, and, several days up to weeks later, immediately before surgery. There was no significant difference in baseline anxiety scores, type of operation, or suspected cancer between the two groups. The VR intervention significantly reduced anxiety scores from baseline to preoperative assessment (p < 0.001). The median anxiety score in the VR intervention group decreased from 3 (interquartile range 2 to 5) at baseline to 2 (2 to 3) prior to surgery, while the control group’s scores were 4 (2 to 5) and 4 (3 to 5), respectively. Multivariate analysis showed that group assignment was the sole outcome predictor, not age, type of procedure, or the time elapsed until surgery. Thus, VR exposure was effective in reducing perioperative anxiety in patients undergoing gynecological oncology surgery. The use of VR as a preparation tool may improve patient experience and contribute to better surgical outcomes, warranting further research into exploring the potential benefits of VR in other surgical specialties and its long-term impact on patient recovery.
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(This article belongs to the Special Issue Evolving Trends in the Surgical Therapy of Patients with Gynecological Cancer)
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Open AccessArticle
Effect of a Long-Term Online Home-Based Supervised Exercise Program on Physical Fitness and Adherence in Breast Cancer Patients: A Randomized Clinical Trial
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María Elena Garcia-Roca, Ignacio Catalá-Vilaplana, Carlos Hernando, Pablo Baliño, Pablo Salas-Medina, Pilar Suarez-Alcazar, Ana Folch-Ayora and Eladio Collado Boira
Cancers 2024, 16(10), 1912; https://doi.org/10.3390/cancers16101912 - 17 May 2024
Abstract
The purpose of the present study was to analyze the effect of a synchronous-supervised online home-based exercise program (HBG) during 24 weeks on body composition, physical fitness and adherence compared to an exercise recommendation group (ERG) without supervision with patients undergoing breast cancer
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The purpose of the present study was to analyze the effect of a synchronous-supervised online home-based exercise program (HBG) during 24 weeks on body composition, physical fitness and adherence compared to an exercise recommendation group (ERG) without supervision with patients undergoing breast cancer treatment. Fifty-nine female breast cancer patients (31 in HBG and 28 in the ERG) undergoing cancer treatments participated in the present randomized clinical trial. The exercise program consisted of a 60 min combined resistance and aerobic supervised exercise session (6–8 points on Borg Scale CR-10, moderate intensity), twice a week during 24 weeks. The exercise recommendation group only received general recommendations to comply with the current ACSM guidelines. Body composition and physical fitness were assessed at baseline, 12 weeks and 24 weeks of the program. Adherence to the intervention was measured according to the minutes of exercise completed per session during each week. A general linear model of two-way repeated measures showed significant improvements (p < 0.05) in physical fitness that were observed in the home-based exercise group at the baseline, 12-week and 24-week assessments compared to the exercise recommendation group. Adherence was also higher in the home-based exercise group. However, no changes (p > 0.05) in body composition between groups and moments were observed. In this sense, supervised home-based exercise interventions can be an interesting strategy to improve physical fitness and adherence rates in breast cancer patients undergoing treatment.
Full article
(This article belongs to the Section Clinical Research of Cancer)
Open AccessArticle
The Utility of Contrast-Enhanced Ultrasound (CEUS) in Assessing the Risk of Malignancy in Thyroid Nodules
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Agnieszka Żyłka, Katarzyna Dobruch-Sobczak, Hanna Piotrzkowska-Wróblewska, Maciej Jędrzejczyk, Elwira Bakuła-Zalewska, Piotr Góralski, Jacek Gałczyński and Marek Dedecjus
Cancers 2024, 16(10), 1911; https://doi.org/10.3390/cancers16101911 - 17 May 2024
Abstract
Background: Ultrasonography is a primary method used in the evaluation of thyroid nodules, but no single feature of this method predicts malignancy with high accuracy. Therefore, this paper aims to assess the utility of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of thyroid
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Background: Ultrasonography is a primary method used in the evaluation of thyroid nodules, but no single feature of this method predicts malignancy with high accuracy. Therefore, this paper aims to assess the utility of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of thyroid nodules. Methods: The study group comprised 188 adult patients (155 women and 33 men) who preoperatively underwent CEUS of a thyroid nodule classified as Bethesda categories II–VI after fine-needle aspiration biopsy. During the CEUS examination, 1.5 mL of SonoVue contrast was injected intravenously, after which 15 qualitative CEUS enhancement patterns were analysed. Results: The histopathologic results comprised 65 benign thyroid nodules and 123 thyroid carcinomas. The dominant malignant CEUS features, such as hypo- and heterogeneous enhancement and slow wash-in phase, were evaluated, whereas high enhancement, ring enhancement, and a slow wash-out phase were assessed as predictors of benign lesions. Two significant combinations of B-mode and CEUS patterns were noted, namely, hypoechogenicity with heterogeneous enhancement and non-smooth margins with hypo- or iso-enhancement. Conclusions: The preliminary results indicate that CEUS is a useful tool in assessing the risk of malignancy of thyroid lesions. The combination of the qualitative enhancement parameters and B-mode sonographic features significantly increases the method’s usefulness.
Full article
(This article belongs to the Section Methods and Technologies Development)
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Open AccessCommentary
Need for Behavioral Interventions for Young Adults Living with Advanced Cancer in the U.S.
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Lisa M. Gudenkauf, Rina S. Fox, Brian D. Gonzalez, Heather S. L. Jim, John M. Salsman, David E. Victorson, Stacy D. Sanford and Laura B. Oswald
Cancers 2024, 16(10), 1910; https://doi.org/10.3390/cancers16101910 - 17 May 2024
Abstract
The population of young adults (YAs) aged 18–39 living with advanced cancer is growing and faces a compounded set of challenges at the intersection of age and disease. Despite these substantial challenges, behavioral interventions tailored to YAs living with advanced cancer remain scarce.
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The population of young adults (YAs) aged 18–39 living with advanced cancer is growing and faces a compounded set of challenges at the intersection of age and disease. Despite these substantial challenges, behavioral interventions tailored to YAs living with advanced cancer remain scarce. This commentary aims to (1) discuss the unmet psychological, social, and behavioral needs of YAs living with advanced cancer; (2) highlight the paucity of behavioral interventions tailored to this growing population; (3) offer recommendations for the development of behavioral interventions targeting the unique needs of YAs living with advanced cancer; and (4) describe potential far-reaching public health benefits of these targeted behavioral interventions.
Full article
(This article belongs to the Section Pediatric Oncology)
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Open AccessArticle
Deep Learning and High-Resolution Anoscopy: Development of an Interoperable Algorithm for the Detection and Differentiation of Anal Squamous Cell Carcinoma Precursors—A Multicentric Study
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Miguel Mascarenhas Saraiva, Lucas Spindler, Thiago Manzione, Tiago Ribeiro, Nadia Fathallah, Miguel Martins, Pedro Cardoso, Francisco Mendes, Joana Fernandes, João Ferreira, Guilherme Macedo, Sidney Nadal and Vincent de Parades
Cancers 2024, 16(10), 1909; https://doi.org/10.3390/cancers16101909 - 17 May 2024
Abstract
High-resolution anoscopy (HRA) plays a central role in the detection and treatment of precursors of anal squamous cell carcinoma (ASCC). Artificial intelligence (AI) algorithms have shown high levels of efficiency in detecting and differentiating HSIL from low-grade squamous intraepithelial lesions (LSIL) in HRA
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High-resolution anoscopy (HRA) plays a central role in the detection and treatment of precursors of anal squamous cell carcinoma (ASCC). Artificial intelligence (AI) algorithms have shown high levels of efficiency in detecting and differentiating HSIL from low-grade squamous intraepithelial lesions (LSIL) in HRA images. Our aim was to develop a deep learning system for the automatic detection and differentiation of HSIL versus LSIL using HRA images from both conventional and digital proctoscopes. A convolutional neural network (CNN) was developed based on 151 HRA exams performed at two volume centers using conventional and digital HRA systems. A total of 57,822 images were included, 28,874 images containing HSIL and 28,948 LSIL. Partial subanalyses were performed to evaluate the performance of the CNN in the subset of images acetic acid and lugol iodine staining and after treatment of the anal canal. The overall accuracy of the CNN in distinguishing HSIL from LSIL during the testing stage was 94.6%. The algorithm had an overall sensitivity and specificity of 93.6% and 95.7%, respectively (AUC 0.97). For staining with acetic acid, HSIL was differentiated from LSIL with an overall accuracy of 96.4%, while for lugol and after therapeutic manipulation, these values were 96.6% and 99.3%, respectively. The introduction of AI algorithms to HRA may enhance the early diagnosis of ASCC precursors, and this system was shown to perform adequately across conventional and digital HRA interfaces.
Full article
(This article belongs to the Special Issue Recent Advances in Deep Learning and Medical Imaging for Cancer Treatment (Volume II))
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Open AccessReview
The Dose/Fractionation Debate in Limited-Stage Small Cell Lung Cancer
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Kaixin Du, Xuehong Liao and Kazushi Kishi
Cancers 2024, 16(10), 1908; https://doi.org/10.3390/cancers16101908 - 17 May 2024
Abstract
To explore the most suitable dosage regimen for limited-stage small cell lung cancer (LS-SCLC) and provide references for clinical selection, strict inclusion criteria were applied, and studies were screened from Pubmed, Embase, and Web of Science. Subsequently, data on two-year overall survival rates
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To explore the most suitable dosage regimen for limited-stage small cell lung cancer (LS-SCLC) and provide references for clinical selection, strict inclusion criteria were applied, and studies were screened from Pubmed, Embase, and Web of Science. Subsequently, data on two-year overall survival rates and dosage regimens were collected, and scatter plots were constructed to provide a comprehensive perspective. The survival benefits of various dosage regimens were evaluated, and a linear quadratic equation was utilized to fit the relationship between the biologically effective dose (BED10) and the two-year overall survival rate. Among the five randomized controlled trials, the two-year overall survival rate of ConvTRT regimens with BED10 > 60 Gy (rough value) was only at or below the median of all ConvTRT regimens or all included study regimens, indicating that increasing the number and total dose of ConvTRT does not necessarily lead to better prognosis. In the exploration of HypoTRT regimens, there was a linear positive correlation between BED10 and the two-year overall survival rate (p < 0.0001), while the exploration of HyperTRT regimens was relatively limited, with the majority focused on the 45 Gy/30 F regimen. However, the current 45 Gy/30 F regimen is not sufficient to control LS-SCLC, resulting in a high local recurrence rate. High-dose ConvTRT regimens have long treatment durations and may induce tumor regrowth which may cause reduced efficacy. Under reasonable toxicity reactions, HyperTRT or HypoTRT with higher radiotherapy doses is recommended for treating LS-SCLC.
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(This article belongs to the Section Cancer Therapy)
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Open AccessReview
Hyaluronic Acid Interacting Molecules Mediated Crosstalk between Cancer Cells and Microenvironment from Primary Tumour to Distant Metastasis
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Yali Xu, Johannes Benedikt and Lin Ye
Cancers 2024, 16(10), 1907; https://doi.org/10.3390/cancers16101907 - 16 May 2024
Abstract
Hyaluronic acid (HA) is a prominent component of the extracellular matrix, and its interactions with HA-interacting molecules (HAIMs) play a critical role in cancer development and disease progression. This review explores the multifaceted role of HAIMs in the context of cancer, focusing on
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Hyaluronic acid (HA) is a prominent component of the extracellular matrix, and its interactions with HA-interacting molecules (HAIMs) play a critical role in cancer development and disease progression. This review explores the multifaceted role of HAIMs in the context of cancer, focusing on their influence on disease progression by dissecting relevant cellular and molecular mechanisms in tumour cells and the tumour microenvironment. Cancer progression can be profoundly affected by the interactions between HA and HAIMs. They modulate critical processes such as cell adhesion, migration, invasion, and proliferation. The TME serves as a dynamic platform in which HAIMs contribute to the formation of a unique niche. The resulting changes in HA composition profoundly influence the biophysical properties of the TME. These modifications in the TME, in conjunction with HAIMs, impact angiogenesis, immune cell recruitment, and immune evasion. Therefore, understanding the intricate interplay between HAIMs and HA within the cancer context is essential for developing novel therapeutic strategies. Targeting these interactions offers promising avenues for cancer treatment, as they hold the potential to disrupt critical aspects of disease progression and the TME. Further research in this field is imperative for advancing our knowledge and the treatment of cancer.
Full article
(This article belongs to the Special Issue Cancer Cells Fostered Microenvironment in Metastasis)
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Open AccessArticle
‘The Reports of My Death Are Greatly Exaggerated’—Evaluating the Effect of Necrosis on MGMT Promoter Methylation Testing in High-Grade Glioma
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Laveniya Satgunaseelan, Maggie Lee, Sebastian Iannuzzi, Susannah Hallal, Kristine Deang, Kristian Stanceski, Heng Wei, Sofia Mason, Brindha Shivalingam, Hao-Wen Sim, Michael E. Buckland and Kimberley L. Alexander
Cancers 2024, 16(10), 1906; https://doi.org/10.3390/cancers16101906 - 16 May 2024
Abstract
(1) Background: MGMT (O-6-methylguanine-DNA methyltransferase) promoter methylation remains an important predictive biomarker in high-grade gliomas (HGGs). The influence of necrosis on the fidelity of MGMT promoter (MGMTp) hypermethylation testing is currently unknown. Therefore, our study aims to evaluate the effect of
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(1) Background: MGMT (O-6-methylguanine-DNA methyltransferase) promoter methylation remains an important predictive biomarker in high-grade gliomas (HGGs). The influence of necrosis on the fidelity of MGMT promoter (MGMTp) hypermethylation testing is currently unknown. Therefore, our study aims to evaluate the effect of varying degrees of necrosis on MGMTp status, as determined by pyrosequencing, in a series of primary and recurrent HGGs; (2) Methods: Within each case, the most viable blocks (assigned as ‘true’ MGMTp status) and the most necrotic block were determined by histopathology review. MGMTp status was determined by pyrosequencing. Comparisons of MGMTp status were made between the most viable and most necrotic blocks. (3) Results: 163 samples from 64 patients with HGGs were analyzed. MGMTp status was maintained in 84.6% of primary and 78.3% of recurrent HGGs between the most viable and necrotic blocks. A threshold of ≥60% tumor cellularity was established at which MGMTp status was unaltered, irrespective of the degree of necrosis. (4) Conclusions: MGMTp methylation status, as determined by pyrosequencing, does not appear to be influenced by necrosis in the majority of cases at a cellularity of at least 60%. Further investigation into the role of intratumoral heterogeneity on MGMTp status will increase our understanding of this predictive marker.
Full article
(This article belongs to the Special Issue Molecular Pathology of Brain Tumors)
Open AccessReview
Role of 18F-FDG PET/CT in Head and Neck Squamous Cell Carcinoma: Current Evidence and Innovative Applications
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Carmelo Caldarella, Marina De Risi, Mariangela Massaccesi, Francesco Miccichè, Francesco Bussu, Jacopo Galli, Vittoria Rufini and Lucia Leccisotti
Cancers 2024, 16(10), 1905; https://doi.org/10.3390/cancers16101905 - 16 May 2024
Abstract
This article provides an overview of the use of 18F-FDG PET/CT in various clinical scenarios of head–neck squamous cell carcinoma, ranging from initial staging to treatment-response assessment, and post-therapy follow-up, with a focus on the current evidence, debated issues, and innovative applications.
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This article provides an overview of the use of 18F-FDG PET/CT in various clinical scenarios of head–neck squamous cell carcinoma, ranging from initial staging to treatment-response assessment, and post-therapy follow-up, with a focus on the current evidence, debated issues, and innovative applications. Methodological aspects and the most frequent pitfalls in head–neck imaging interpretation are described. In the initial work-up, 18F-FDG PET/CT is recommended in patients with metastatic cervical lymphadenectomy and occult primary tumor; moreover, it is a well-established imaging tool for detecting cervical nodal involvement, distant metastases, and synchronous primary tumors. Various 18F-FDG pre-treatment parameters show prognostic value in terms of disease progression and overall survival. In this scenario, an emerging role is played by radiomics and machine learning. For radiation-treatment planning, 18F-FDG PET/CT provides an accurate delineation of target volumes and treatment adaptation. Due to its high negative predictive value, 18F-FDG PET/CT, performed at least 12 weeks after the completion of chemoradiotherapy, can prevent unnecessary neck dissections. In addition to radiomics and machine learning, emerging applications include PET/MRI, which combines the high soft-tissue contrast of MRI with the metabolic information of PET, and the use of PET radiopharmaceuticals other than 18F-FDG, which can answer specific clinical needs.
Full article
(This article belongs to the Special Issue Clinical and Translational Research in Head and Neck Cancer)
Open AccessArticle
Financial Toxicity in Japanese Patients with Metastatic Renal Cell Carcinoma: A Cross-Sectional Study
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Go Kimura, Yasuhisa Fujii, Kazunori Honda, Takahiro Osawa, Yosuke Uchitomi, Miki Kondo, Ariko Otani, Tetsuya Wako, Daisuke Kawai, Yoshihide Mitsuda, Naotaka Sakashita and Nobuo Shinohara
Cancers 2024, 16(10), 1904; https://doi.org/10.3390/cancers16101904 - 16 May 2024
Abstract
Information on the financial toxicity experienced by Japanese patients with metastatic renal cell carcinoma (mRCC) is lacking, even though Japan has its own unique public health insurance system. Thus, a web-based survey was conducted to evaluate the financial toxicity experienced by Japanese mRCC
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Information on the financial toxicity experienced by Japanese patients with metastatic renal cell carcinoma (mRCC) is lacking, even though Japan has its own unique public health insurance system. Thus, a web-based survey was conducted to evaluate the financial toxicity experienced by Japanese mRCC patients using the COmprehensive Score for financial Toxicity (COST) tool. This study enrolled Japanese patients who underwent, or were undergoing, systemic therapy for mRCC. The outcomes evaluated were the distribution of COST scores, the correlation between COST and quality of life (QOL) assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) scale, and demographic factors associated with financial toxicity. The median (range) COST score was 19.0 (3.0–36.0). The Pearson correlation coefficient for COST and FACT-G total scores was 0.40. Univariate analysis revealed that not having private health insurance and lower household income per year were significantly associated with lower COST scores. Multivariate analyses showed that age < 65 years and not having private health insurance were significantly associated with lower COST scores. This study revealed that Japanese mRCC patients experience adverse financial impacts even under the universal health insurance coverage system available in Japan, and financial toxicity negatively affects their QOL.
Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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Open AccessArticle
Navigating the Maze: Exploring Non-Oncological Complexities in Non-Small-Cell Lung Cancer
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Angela-Ștefania Marghescu, Silviu Vlăsceanu, Mădălina Preda, Mirela Țigău, Ștefan Dumitrache-Rujinski, Diana Gabriela Leonte, Elena Doina Măgheran, Adrian Tudor, Ioana Anca Bădărău, Livia Georgescu and Mariana Costache
Cancers 2024, 16(10), 1903; https://doi.org/10.3390/cancers16101903 - 16 May 2024
Abstract
Pulmonary oncological pathologies are an important public health problem and the association with other pulmonary lesions may pose difficulties in diagnosis and staging or require different treatment options. To address this complexity, we conducted a retrospective observational study at the Marius Nasta Institute
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Pulmonary oncological pathologies are an important public health problem and the association with other pulmonary lesions may pose difficulties in diagnosis and staging or require different treatment options. To address this complexity, we conducted a retrospective observational study at the Marius Nasta Institute of Pneumophthisiology, Bucharest, Romania. Our study focused on patients admitted in 2019 with non-small-cell lung carcinoma and associated pulmonary lesions identified through surgical resection specimens. Among the 314 included patients, multiple pulmonary nodules were observed on macroscopic examination, with 12% (N = 37) exhibiting nonmalignant etiologies upon microscopic examination. These findings underscore the challenge of preoperative staging. Patients with coexisting nonmalignant lesions were similar in age, smoking habits, and professional or environmental exposure by comparison with those who presented only malignant lesions. The presentation of coexisting malignant and nonmalignant lesions may pose difficulties in diagnosing and staging pulmonary cancer.
Full article
(This article belongs to the Special Issue Pathology, Diagnosis and Treatment in Non-small Cell Lung Cancer)
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Open AccessArticle
An Anti-VEGF-B Antibody Reduces Abnormal Tumor Vasculature and Enhances the Effects of Chemotherapy
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Peter W. Janes, Adam C. Parslow, Diana Cao, Angela Rigopoulos, Fook-Thean Lee, Sylvia J. Gong, Glenn A. Cartwright, Ingrid J. G. Burvenich, Ulf Eriksson, Terrance G. Johns, Fiona E. Scott and Andrew M. Scott
Cancers 2024, 16(10), 1902; https://doi.org/10.3390/cancers16101902 - 16 May 2024
Abstract
The vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key regulators of blood vessel formation, including in tumors, where their deregulated function can promote the production of aberrant, leaky blood vessels, supporting tumor development. Here we investigated the VEGFR1 ligand VEGF-B,
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The vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key regulators of blood vessel formation, including in tumors, where their deregulated function can promote the production of aberrant, leaky blood vessels, supporting tumor development. Here we investigated the VEGFR1 ligand VEGF-B, which we demonstrate to be expressed in tumor cells and in tumor stroma and vasculature across a range of tumor types. We examined the anti-VEGF-B-specific monoclonal antibody 2H10 in preclinical xenograft models of breast and colorectal cancer, in comparison with the anti-VEGF-A antibody bevacizumab. Similar to bevacizumab, 2H10 therapy was associated with changes in tumor blood vessels and intra-tumoral diffusion consistent with normalization of the tumor vasculature. Accordingly, treatment resulted in partial inhibition of tumor growth, and significantly improved the response to chemotherapy. Our studies indicate the importance of VEGF-B in tumor growth, and the potential of specific anti-VEGF-B treatment to inhibit tumor development, alone or in combination with established chemotherapies.
Full article
(This article belongs to the Section Cancer Therapy)
Open AccessArticle
Sex Matters–Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer
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Benjamin Schulz, Emily Leitner, Tim Schreiber, Tobias Lindner, Rico Schwarz, Nadine Aboutara, Yixuan Ma, Hugo Murua Escobar, Rupert Palme, Burkhard Hinz, Brigitte Vollmar and Dietmar Zechner
Cancers 2024, 16(10), 1901; https://doi.org/10.3390/cancers16101901 - 16 May 2024
Abstract
Preclinical studies rarely test the efficacy of therapies in both sexes. The field of oncology is no exception in this regard. In a model of syngeneic, orthotopic, metastasized pancreatic ductal adenocarcinoma we evaluated the impact of sex on pathological features of this disease
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Preclinical studies rarely test the efficacy of therapies in both sexes. The field of oncology is no exception in this regard. In a model of syngeneic, orthotopic, metastasized pancreatic ductal adenocarcinoma we evaluated the impact of sex on pathological features of this disease as well as on the efficacy and possible adverse side effects of a novel, small molecule-based therapy inhibiting KRAS:SOS1, MEK1/2 and PI3K signaling in male and female C57BL/6J mice. Male mice had less tumor infiltration of CD8-positive cells, developed bigger tumors, had more lung metastasis and a lower probability of survival compared to female mice. These more severe pathological features in male animals were accompanied by higher distress at the end of the experiment. The evaluated inhibitors BI-3406, trametinib and BKM120 showed synergistic effects in vitro. This combinatorial therapy reduced tumor weight more efficiently in male animals, although the drug concentrations were similar in the tumors of both sexes. These results underline the importance of sex-specific preclinical research and at the same time provide a solid basis for future studies with the tested compounds.
Full article
(This article belongs to the Special Issue Sex Differences in Cancer)
Open AccessArticle
Prediction of Lymph Node Metastasis in T1 Colorectal Cancer Using Artificial Intelligence with Hematoxylin and Eosin-Stained Whole-Slide-Images of Endoscopic and Surgical Resection Specimens
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Joo Hye Song, Eun Ran Kim, Yiyu Hong, Insuk Sohn, Soomin Ahn, Seok-Hyung Kim and Kee-Taek Jang
Cancers 2024, 16(10), 1900; https://doi.org/10.3390/cancers16101900 - 16 May 2024
Abstract
According to the current guidelines, additional surgery is performed for endoscopically resected specimens of early colorectal cancer (CRC) with a high risk of lymph node metastasis (LNM). However, the rate of LNM is 2.1–25.0% in cases treated endoscopically followed by surgery, indicating a
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According to the current guidelines, additional surgery is performed for endoscopically resected specimens of early colorectal cancer (CRC) with a high risk of lymph node metastasis (LNM). However, the rate of LNM is 2.1–25.0% in cases treated endoscopically followed by surgery, indicating a high rate of unnecessary surgeries. Therefore, this study aimed to develop an artificial intelligence (AI) model using H&E-stained whole slide images (WSIs) without handcrafted features employing surgically and endoscopically resected specimens to predict LNM in T1 CRC. To validate with an independent cohort, we developed a model with four versions comprising various combinations of training and test sets using H&E-stained WSIs from endoscopically (400 patients) and surgically resected specimens (881 patients): Version 1, Train and Test: surgical specimens; Version 2, Train and Test: endoscopic and surgically resected specimens; Version 3, Train: endoscopic and surgical specimens and Test: surgical specimens; Version 4, Train: endoscopic and surgical specimens and Test: endoscopic specimens. The area under the curve (AUC) of the receiver operating characteristic curve was used to determine the accuracy of the AI model for predicting LNM with a 5-fold cross-validation in the training set. Our AI model with H&E-stained WSIs and without annotations showed good performance power with the validation of an independent cohort in a single center. The AUC of our model was 0.758–0.830 in the training set and 0.781–0.824 in the test set, higher than that of previous AI studies with only WSI. Moreover, the AI model with Version 4, which showed the highest sensitivity (92.9%), reduced unnecessary additional surgery by 14.2% more than using the current guidelines (68.3% vs. 82.5%). This revealed the feasibility of using an AI model with only H&E-stained WSIs to predict LNM in T1 CRC.
Full article
(This article belongs to the Topic AI in Medical Imaging and Image Processing)
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Open AccessArticle
MR Imaging of Adverse Effects and Ocular Growth Decline after Selective Intra-Arterial Chemotherapy for Retinoblastoma
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Christiaan M. de Bloeme, Sabien van Elst, Paolo Galluzzi, Robin W. Jansen, Joeka de Haan, Sophia Göricke, Annette C. Moll, Joseph C. J. Bot, Francis L. Munier, Maja Beck-Popovic, Francesco Puccinelli, Isabelle Aerts, Theodora Hadjistilianou, Selma Sirin, Mériam Koob, Hervé J. Brisse, Liesbeth Cardoen, Philippe Maeder, Marcus C. de Jong and Pim de Graaf
Cancers 2024, 16(10), 1899; https://doi.org/10.3390/cancers16101899 - 16 May 2024
Abstract
This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring
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This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research.
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(This article belongs to the Special Issue Current Progress and Research Trends in Ocular Oncology)
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Open AccessCommentary
Reimagining Colorectal Cancer Screening: Innovations and Challenges with Dr. Aasma Shaukat
by
Viviana Cortiana, Muskan Joshi, Harshal Chorya, Harshitha Vallabhaneni, Shreevikaa Kannan, Helena S. Coloma, Chandler H. Park and Yan Leyfman
Cancers 2024, 16(10), 1898; https://doi.org/10.3390/cancers16101898 - 16 May 2024
Abstract
Colorectal cancer (CRC) currently ranks as the third most common cancer and the second leading cause of cancer-related deaths worldwide, posing a significant global health burden to the population. Recent studies have reported the emergence of a new clinical picture of the disease,
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Colorectal cancer (CRC) currently ranks as the third most common cancer and the second leading cause of cancer-related deaths worldwide, posing a significant global health burden to the population. Recent studies have reported the emergence of a new clinical picture of the disease, with a notable increase in CRC rates in younger populations of <50 years of age. The American Cancer Society (ACS) now recommends CRC screening starting at age 45 for average-risk individuals. Dr. Aasma Shaukat’s Keynote Conference highlights the critical need for updated screening strategies, with an emphasis on addressing the suboptimal adherence rates and the effective management of the growing burden of CRC. Lowering the adenoma detection screening age can facilitate early identification of adenomas in younger asymptomatic patients, altering the epidemiologic landscape. However, its implications may not be as profound unless a drastic shift in the age distribution of CRC is observed. Currently, various screening options are available in practice, including stool-based tests like multitarget stool DNA (mtDNA) tests, fecal immunochemical testing (FIT), and imaging-based tests. In addition to existing screening methods, blood-based tests are now emerging as promising tools for early CRC detection. These tests leverage innovative techniques along with AI and machine learning algorithms, aiding in tumor detection at a significantly earlier stage, which was not possible before. Medicare mandates specific criteria for national coverage of blood-based tests, including sensitivity ≥ 74%, specificity ≥ 90%, FDA approval, and inclusion in professional society guidelines. Ongoing clinical trials, such as Freenome, Guardant, and CancerSEEK, offer hope for further advancements in blood-based CRC screening. The development of multicancer early detection tests like GRAIL demonstrates a tremendous potential for detecting various solid tumors and hematologic malignancies. Despite these breakthroughs, the question of accessibility and affordability still stands. The ever-evolving landscape of CRC screening reflects the strength of the scientific field in light of an altered disease epidemiology. Lowering screening age along with the integration of blood-based tests with existing screening methods holds great potential in reducing the CRC-related burden. At the same time, it is increasingly important to address the challenges of adaptation of the healthcare system to this change in the epidemiologic paradigm.
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(This article belongs to the Collection Commentaries from MedNews Week)
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Open AccessReview
Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography-Derived Radiomic Models in Prostate Cancer Prognostication
by
Linda My Huynh, Shea Swanson, Sophia Cima, Eliana Haddadin and Michael Baine
Cancers 2024, 16(10), 1897; https://doi.org/10.3390/cancers16101897 - 16 May 2024
Abstract
The clinical integration of prostate membrane specific antigen (PSMA) positron emission tomography and computed tomography (PET/CT) scans represents potential for advanced data analysis techniques in prostate cancer (PC) prognostication. Among these tools is the use of radiomics, a computer-based method of extracting and
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The clinical integration of prostate membrane specific antigen (PSMA) positron emission tomography and computed tomography (PET/CT) scans represents potential for advanced data analysis techniques in prostate cancer (PC) prognostication. Among these tools is the use of radiomics, a computer-based method of extracting and quantitatively analyzing subvisual features in medical imaging. Within this context, the present review seeks to summarize the current literature on the use of PSMA PET/CT-derived radiomics in PC risk stratification. A stepwise literature search of publications from 2017 to 2023 was performed. Of 23 articles on PSMA PET/CT-derived prostate radiomics, PC diagnosis, prediction of biopsy Gleason score (GS), prediction of adverse pathology, and treatment outcomes were the primary endpoints of 4 (17.4%), 5 (21.7%), 7 (30.4%), and 7 (30.4%) studies, respectively. In predicting PC diagnosis, PSMA PET/CT-derived models performed well, with receiver operator characteristic curve area under the curve (ROC-AUC) values of 0.85–0.925. Similarly, in the prediction of biopsy and surgical pathology results, ROC-AUC values had ranges of 0.719–0.84 and 0.84–0.95, respectively. Finally, prediction of recurrence, progression, or survival following treatment was explored in nine studies, with ROC-AUC ranging 0.698–0.90. Of the 23 studies included in this review, 2 (8.7%) included external validation. While explorations of PSMA PET/CT-derived radiomic models are immature in follow-up and experience, these results represent great potential for future investigation and exploration. Prior to consideration for clinical use, however, rigorous validation in feature reproducibility and biologic validation of radiomic signatures must be prioritized.
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(This article belongs to the Special Issue Imaging and Liquid Biopsy Biomarkers for Cancer Diagnosis and Treatment)
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Open AccessSystematic Review
Uncommon Adverse Events of Immune Checkpoint Inhibitors in Small Cell Lung Cancer: A Systematic Review of Case Reports
by
Eunso Lee, Jeong Yun Jang and Jinho Yang
Cancers 2024, 16(10), 1896; https://doi.org/10.3390/cancers16101896 - 16 May 2024
Abstract
Background: This study aimed to systematically review case reports documenting rare adverse events in patients with small cell lung cancer (SCLC) following the administration of immune checkpoint inhibitors (ICIs). Methods: A systematic literature review was conducted to identify case reports detailing previously unreported
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Background: This study aimed to systematically review case reports documenting rare adverse events in patients with small cell lung cancer (SCLC) following the administration of immune checkpoint inhibitors (ICIs). Methods: A systematic literature review was conducted to identify case reports detailing previously unreported adverse drug reactions to ICIs in patients with SCLC. The scope of the literature reviewed was restricted to case studies on SCLC published up to 31 December 2023. Results: We analyzed twenty-four studies on ICI use for patients with SCLC. There were six reports on atezolizumab, four on durvalumab, and three on adverse events from monotherapy with nivolumab. Reports involving combination treatments were the most frequent, with a total of six, predominantly involving using nivolumab in combination with ipilimumab. Additionally, there was one report each on using pembrolizumab, nofazinilimab, sintilimab, tislelizumab, and toripalimab. We collected detailed information on the clinical course, including patient and disease characteristics, symptoms, treatment for each adverse event, and recovery status. Among the patients included in the case reports, 21 out of 24 (87.5%) had extensive-stage SCLC when initiating ICI therapy, with only 1 patient diagnosed with limited-stage SCLC. Respiratory system adverse events were most common, with seven cases, followed by neurological, endocrinological, and gastroenterological events. Three case reports documented adverse events across multiple systems in a single patient. In most cases, patients showed symptom improvement; however, four studies reported cases where patients either expired without symptom improvement or experienced sequelae. Conclusions: Efforts to develop reliable biomarkers for predicting irAEs continue, with ongoing research to enhance predictive precision. Immunotherapy presents diverse and unpredictable adverse events, underscoring the need for advanced diagnostic tools and a multidisciplinary approach to improve patient management.
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(This article belongs to the Section Cancer Immunology and Immunotherapy)
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Open AccessArticle
Tumor Budding, p53, and DNA Mismatch Repair Markers in Sinonasal Intestinal-Type Adenocarcinoma: A Retrospective Study Supports the Adverse Prognostic Impact of Tumor Budding
by
Sebastiano Puccio, Giuseppe Azzarello, Valeria Maffeis, Licia Laurino, Edoardo Mairani, Federica Conte, Nicola Tessari, Diego Cazzador, Elisabetta Zanoletti, Doriano Politi, Enzo Emanuelli, Giacomo Spinato and Simonetta Ausoni
Cancers 2024, 16(10), 1895; https://doi.org/10.3390/cancers16101895 - 16 May 2024
Abstract
Sinonasal intestinal-type adenocarcinoma (ITAC) is a very rare, closely occupational-related tumor with strong histological similarities to colorectal cancer (CRC). In the latter, tumor budding (TB) is widely recognized as a negative prognostic parameter. The aim of this study was to evaluate the prognostic
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Sinonasal intestinal-type adenocarcinoma (ITAC) is a very rare, closely occupational-related tumor with strong histological similarities to colorectal cancer (CRC). In the latter, tumor budding (TB) is widely recognized as a negative prognostic parameter. The aim of this study was to evaluate the prognostic role of TB in ITAC and to correlate it with other established or emerging biomarkers of the disease, such as p53 and deficient DNA mismatch repair (MMR) system status/microsatellite instability (MSI). We retrospectively analyzed 32 consecutive specimens of patients with ITAC diagnosis treated in two institutions in Northern Italy. We reviewed surgical specimens for TB evaluation (low-intermediate/high); p53 expression and MMR proteins were evaluated via immunohistochemistry. Results were retrospectively stratified using clinical data and patients’ outcomes. According to bud counts, patients were stratified into two groups: intermediate/high budding (>4 TB) and low budding (≤4 TB). Patients with high TB (>4) have an increased risk of recurrence and death compared to those with low TB, with a median survival of 13 and 54 months, respectively. On multivariate analysis, considering TB, therapy, and stage as covariates, TB emerged as an independent prognostic factor net of the stage of disease or type of therapy received. No impact of p53 status as a biomarker of prognosis was observed and no alterations regarding MMR proteins were identified. The results of the present work provide further significant evidence on the prognostic role of TB in ITAC and underline the need for larger multicenter studies to implement the use of TB in clinical practice.
Full article
(This article belongs to the Special Issue Rare Cancers, Diagnostic Challenges and Personalized Therapeutic Approaches in the 21st Century)
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