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
C-Reactive Protein Is a Potential Prognostic Marker in Patient with Advanced or Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multi-Center Retrospective Study
Cancers 2024, 16(9), 1725; https://doi.org/10.3390/cancers16091725 (registering DOI) - 28 Apr 2024
Abstract
Background: In the EV-301 trial, enfortumab vedotin prolonged survival in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based therapy and programmed cell death 1/programmed death-ligand 1 inhibitor. However, real-world Asian data are limited, and potential prognostic markers are non-existent.
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Background: In the EV-301 trial, enfortumab vedotin prolonged survival in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based therapy and programmed cell death 1/programmed death-ligand 1 inhibitor. However, real-world Asian data are limited, and potential prognostic markers are non-existent. We aimed to investigate potential prognostic markers for enfortumab vedotin therapy in Asian patients. Methods: We retrospectively enrolled 61 Japanese patients treated with enfortumab vedotin therapy at our hospital and affiliated hospitals between January 2019 and September 2023. Results: Enrolled patients (38 men, 23 women; median age 74 [IQR: 68–79] years) had bladder cancer (26 patients) or upper-tract urothelial carcinoma (35 patients). Fifty-four patients reported adverse events (grade >3 in 12). Skin disorders, pruritus, and neuropathy were common adverse effects. The median overall survival was 17.1 months (95% confidence interval: 10.0–not applicable). In multivariate analysis, the C-reactive protein level was an independent marker predicting favorable overall survival with enfortumab vedotin. Patient characteristics did not differ between C-reactive protein-high and -low groups. Conclusions: Our study provides real-world data showing that enfortumab vedotin prolonged survival in Asian patients similar to the EV-301 trial. Additionally, the C-reactive protein level might be considered a prognostic marker of enfortumab vedotin therapy in such patients.
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(This article belongs to the Special Issue Identification of the Targets to Overcome Clinical Problems in Bladder Cancer)
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Taking a BiTE out of Lymphoma: Bispecific Antibodies in B-Cell Non-Hodgkin Lymphoma
by
Jonathan M. Weiss and Tycel J. Phillips
Cancers 2024, 16(9), 1724; https://doi.org/10.3390/cancers16091724 (registering DOI) - 28 Apr 2024
Abstract
B-cell non-Hodgkin’s lymphoma (NHL) refers to a heterogenous group of diseases, all of which have a wide range of treatment strategies and patient outcomes. There have been multiple novel, immune-based therapies approved in NHL in the last decade, including bispecific antibodies (BsAbs) and
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B-cell non-Hodgkin’s lymphoma (NHL) refers to a heterogenous group of diseases, all of which have a wide range of treatment strategies and patient outcomes. There have been multiple novel, immune-based therapies approved in NHL in the last decade, including bispecific antibodies (BsAbs) and chimeric antigen receptor therapy (CAR-T). With a host of new therapies, an important next step will be determining how these therapies should be sequenced in contemporary management strategies. This review seeks to offer a framework for the ways in which BsABs can be incorporated into the current management paradigm for NHL, with special attention paid to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL).
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(This article belongs to the Special Issue Evolution of B-Cell Malignancy Therapy and Treatment Resistance: Where Are We Headed?)
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Integration of Computational Pipeline to Streamline Efficacious Drug Nomination and Biomarker Discovery in Glioblastoma
by
Danielle Maeser, Robert F. Gruener, Robert Galvin, Adam Lee, Tomoyuki Koga, Florina-Nicoleta Grigore, Yuta Suzuki, Frank B. Furnari, Clark Chen and R. Stephanie Huang
Cancers 2024, 16(9), 1723; https://doi.org/10.3390/cancers16091723 (registering DOI) - 28 Apr 2024
Abstract
Glioblastoma multiforme (GBM) is the deadliest, most heterogeneous, and most common brain cancer in adults. Not only is there an urgent need to identify efficacious therapeutics, but there is also a great need to pair these therapeutics with biomarkers that can help tailor
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Glioblastoma multiforme (GBM) is the deadliest, most heterogeneous, and most common brain cancer in adults. Not only is there an urgent need to identify efficacious therapeutics, but there is also a great need to pair these therapeutics with biomarkers that can help tailor treatment to the right patient populations. We built patient drug response models by integrating patient tumor transcriptome data with high-throughput cell line drug screening data as well as Bayesian networks to infer relationships between patient gene expression and drug response. Through these discovery pipelines, we identified agents of interest for GBM to be effective across five independent patient cohorts and in a mouse avatar model: among them are a number of MEK inhibitors (MEKis). We also predicted phosphoglycerate dehydrogenase enzyme (PHGDH) gene expression levels to be causally associated with MEKi efficacy, where knockdown of this gene increased tumor sensitivity to MEKi and overexpression led to MEKi resistance. Overall, our work demonstrated the power of integrating computational approaches. In doing so, we quickly nominated several drugs with varying known mechanisms of action that can efficaciously target GBM. By simultaneously identifying biomarkers with these drugs, we also provide tools to select the right patient populations for subsequent evaluation.
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(This article belongs to the Collection Oncology: State-of-the-Art Research in the USA)
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Adverse Reactions in Relapsed/Refractory B-Cell Lymphoma Administered with Chimeric Antigen Receptor T Cell Alone or in Combination with Autologous Stem Cell Transplantation
by
Haolong Lin, Ting Deng, Lijun Jiang, Fankai Meng, Yang Cao, Yicheng Zhang, Renying Ge and Xiaojian Zhu
Cancers 2024, 16(9), 1722; https://doi.org/10.3390/cancers16091722 (registering DOI) - 28 Apr 2024
Abstract
(1) Background: The combination of CAR-T with ASCT has been observed to enhance the efficacy of CAR-T cell therapy. However, the impact of this combination on adverse reactions is still uncertain. (2) Methods: Between January 2019 and February 2023, 292 patients diagnosed with
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(1) Background: The combination of CAR-T with ASCT has been observed to enhance the efficacy of CAR-T cell therapy. However, the impact of this combination on adverse reactions is still uncertain. (2) Methods: Between January 2019 and February 2023, 292 patients diagnosed with r/r B-cell lymphoma received either CAR-T therapy alone or in combination with ASCT at our institution. We evaluated the incidence of CRS and CRES and utilized a logistic regression model to identify factors contributing to severe CRS (grade 3–4) and CRES (grade 3–4). (3) Results: The overall incidence of CRS and CRES was 78.9% and 8.2% in 147 patients receiving CAR-T alone, and 95.9% and 15.2% in 145 patients receiving CAR-T combined with ASCT, respectively. The incidence of overall CRS (p < 0.0001) and mild CRS (grade 1–2) (p = 0.021) was elevated in the ASCT combined with CAR-T group. No significant difference was observed in severe CRS and CRES between the groups. Among the 26 cases of lymphoma involving the central nervous system (CNS), 96.2% (25/26) developed CRS (15.4% grade 3–4), and 34.6% (9/26) manifested CRES (7.7% grade 3–4). Female patients had a lower incidence of severe CRS but a higher incidence of severe CRES. Lymphomas with CNS involvement demonstrated a higher risk of CRES compared to those without central involvement. (4) Conclusions: The combination of ASCT with CAR-T demonstrated a preferable option in r/r B-cell lymphoma without an increased incidence of severe CRS and CRES.
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(This article belongs to the Special Issue Immunotherapy in the Management of Hematologic Malignancy)
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Textbook Neoadjuvant Outcome—Novel Composite Measure of Oncological Outcomes among Gastric Cancer Patients Undergoing Multimodal Treatment
by
Zuzanna Pelc, Katarzyna Sędłak, Magdalena Leśniewska, Katarzyna Mielniczek, Katarzyna Chawrylak, Magdalena Skórzewska, Tomasz Ciszewski, Joanna Czechowska, Agata Kiszczyńska, Bas P. L. Wijnhoven, Johanna W. Van Sandick, Ines Gockel, Suzanne S. Gisbertz, Guillaume Piessen, Clarisse Eveno, Maria Bencivenga, Giovanni De Manzoni, Gian Luca Baiocchi, Paolo Morgagni, Riccardo Rosati, Uberto Fumagalli Romario, Andrew Davies, Yutaka Endo, Timothy M. Pawlik, Franco Roviello, Christiane Bruns, Wojciech P. Polkowski and Karol Rawicz-Pruszyńskiadd
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Cancers 2024, 16(9), 1721; https://doi.org/10.3390/cancers16091721 (registering DOI) - 28 Apr 2024
Abstract
The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival
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The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival rates remain poor, and further investigations should establish outcomes assessment of current clinical pathways. Individually assessed parameters have served as benchmarks for treatment quality in the past decades. The Outcome4Medicine Consensus Conference underscores the inadequacy of isolated metrics, leading to increased recognition and adoption of composite measures. One of the most simple and comprehensive is the “All or None” method, which refers to an approach where a specific set of criteria must be fulfilled for an individual to achieve the overall measure. This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome (TNO). TNO integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of GC patients undergoing NAC to identify the treatment- and patient-related data required to establish high-quality oncological care further. A key strength of this narrative review is the clinical feasibility and research background supporting the implementation of the first and novel composite measure representing the “ideal” and holistic care among patients with locally advanced esophago-gastric junction (EGJ) and GC in the preoperative period after NAC. Further analysis will correlate clinical outcomes with the prognostic factors evaluated within the TNO framework.
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(This article belongs to the Section Clinical Research of Cancer)
Open AccessArticle
Do Oncologists Recommend the “Pill” of Physical Activity in Their Practice? Answers from the Oncologist and Patients’ Perspectives
by
Aitor Martínez Aguirre-Betolaza, Ander Dobaran Amezua, Fatma Hilal Yagin, Jon Cacicedo, Jurgi Olasagasti-Ibargoien and Arkaitz Castañeda-Babarro
Cancers 2024, 16(9), 1720; https://doi.org/10.3390/cancers16091720 (registering DOI) - 28 Apr 2024
Abstract
Objectives: The purposes of this current questionnaire-based study were to analyse whether oncologists prescribed PA to their patients in Spain, as well as the type of exercise recommended, the variables that influence whether or not to recommend it and to compare these recommendations
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Objectives: The purposes of this current questionnaire-based study were to analyse whether oncologists prescribed PA to their patients in Spain, as well as the type of exercise recommended, the variables that influence whether or not to recommend it and to compare these recommendations with the values reported by their patients. Methods: Two online questionnaires were designed for this study. The first one, filled in by the oncologists (n = 93), contained aspects such as the attitude or barriers to promoting PA. The second was designed for patients with cancer (n = 149), which assessed PA levels and counselling received from oncologists, among other facets. Results: The majority of oncologists (97%) recommend PA during their consultations. Instead, only 62% of patients reported participating in exercise within the last 7 days. Walking was the most common form of exercise, reported by 50% of participants. Patients who received exercise recommendations from their oncologist walked for more days (p = 0.004; ES = 0.442) and more minutes per day (p = 0.022; ES = 0.410). The barriers most highlighted by patients were lack of time and not knowing how to perform PA. Conclusion: Oncologists and patients seem to be interested and able to participate in PA counselling and programmes. However, there was a discrepancy between what was reported by oncologists and expressed by patients in terms of recommendations for PA and the modality itself.
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(This article belongs to the Special Issue Implementation of Physical Activity Promotion in Cancer Care)
Open AccessReview
The Role of Surgery in Pleural Mesothelioma
by
Moshe Lapidot and Martin Sattler
Cancers 2024, 16(9), 1719; https://doi.org/10.3390/cancers16091719 (registering DOI) - 28 Apr 2024
Abstract
Surgery plays a central role in the diagnosis, staging, and management of pleural mesothelioma. Achieving an accurate diagnosis through surgical intervention and identifying the specific histologic subtype is crucial for determining the appropriate course of treatment. The histologic subtype guides decisions regarding the
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Surgery plays a central role in the diagnosis, staging, and management of pleural mesothelioma. Achieving an accurate diagnosis through surgical intervention and identifying the specific histologic subtype is crucial for determining the appropriate course of treatment. The histologic subtype guides decisions regarding the use of chemotherapy, immunotherapy, or multimodality treatment. The goal of surgery as part of multimodality treatment is to accomplish macroscopic complete resection with the eradication of grossly visible and palpable disease. Over the past two decades, many medical centers worldwide have shifted from performing extra-pleural pneumonectomy (EPP) to pleurectomy decortication (PD). This transition is motivated by the lower rates of short-term mortality and morbidity associated with PD and similar or even better long-term survival outcomes, compared to EPP. This review aims to outline the role of surgery in diagnosing, staging, and treating patients with pleural mesothelioma.
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(This article belongs to the Special Issue Mesothelioma—from Diagnosis to Treatment)
Open AccessArticle
Safety and Effectiveness of Perioperative Hyperthermic Intraperitoneal Chemotherapy with Gemcitabine in Patients with Resected Pancreatic Ductal Adenocarcinoma: Clinical Trial EudraCT 2016-004298-41
by
David Padilla-Valverde, Raquel Bodoque-Villar, Esther García-Santos, Susana Sanchez, Carmen Manzanares-Campillo, Marta Rodriguez, Lucia González, Alfonso Ambrós, Juana M. Cano, Maria Padilla-Marcote, Javier Redondo-Calvo, Jesus Martin and Leticia Serrano-Oviedo
Cancers 2024, 16(9), 1718; https://doi.org/10.3390/cancers16091718 (registering DOI) - 28 Apr 2024
Abstract
Background: Despite the improvement in therapies, pancreatic cancer represents one of the most cancer-related deaths. In our hypothesis, we propose that Hyperthermic Intraperitoneal Chemotherapy with gemcitabine after pancreatic cytoreductive surgery could reduce tumor progression by reducing residual neoplastic volume and residual pancreatic cancer
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Background: Despite the improvement in therapies, pancreatic cancer represents one of the most cancer-related deaths. In our hypothesis, we propose that Hyperthermic Intraperitoneal Chemotherapy with gemcitabine after pancreatic cytoreductive surgery could reduce tumor progression by reducing residual neoplastic volume and residual pancreatic cancer stem cells. Materials and methods: A randomized trial involving 42 patients. All patients were diagnosed with pancreatic ductal adenocarcinoma. Group I: R0 resection. Group II. R0 resection and HIPEC with gemcitabine (120 mg/m2 for 30 min). Effectiveness was measured with analysis of overall survival, disease-free survival, distant recurrence, locoregional recurrence, and measuring of pancreatic cancer stem cells (EpCAM+CXCR4+CD133+). Results: From 2017 to 2023, 63 patients were recruited for our clinical trial; 21 patients were included in each group, and 21 were excluded. Locoregional recurrence, p-value: 0.022, was lower in the experimental group. There were no significant differences between the two groups in hospital mortality, perioperative complications, or hospital costs. We found a significant decrease in pancreatic cancer stem cells in patients in the experimental group after treatment, p -value of 0.018. Conclusions: The use of HIPEC with gemcitabine after surgery in patients with resectable pancreatic ductal adenocarcinoma reduces locoregional recurrence and may be associated with a significant decrease in pancreatic cancer stem cells.
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(This article belongs to the Special Issue Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Cancer Therapy)
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Applications of Urinary Extracellular Vesicles in the Diagnosis and Active Surveillance of Prostate Cancer
by
Stephanie F. Smith, Daniel S. Brewer, Rachel Hurst and Colin S. Cooper
Cancers 2024, 16(9), 1717; https://doi.org/10.3390/cancers16091717 (registering DOI) - 28 Apr 2024
Abstract
Prostate cancer is the most common non-cutaneous cancer among men in the UK, causing significant health and economic burdens. Diagnosis and risk prognostication can be challenging due to the genetic and clinical heterogeneity of prostate cancer as well as uncertainties in our knowledge
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Prostate cancer is the most common non-cutaneous cancer among men in the UK, causing significant health and economic burdens. Diagnosis and risk prognostication can be challenging due to the genetic and clinical heterogeneity of prostate cancer as well as uncertainties in our knowledge of the underlying biology and natural history of disease development. Urinary extracellular vesicles (EVs) are microscopic, lipid bilayer defined particles released by cells that carry a variety of molecular cargoes including nucleic acids, proteins and other molecules. Urine is a plentiful source of prostate-derived EVs. In this narrative review, we summarise the evidence on the function of urinary EVs and their applications in the evolving field of prostate cancer diagnostics and active surveillance. EVs are implicated in the development of all hallmarks of prostate cancer, and this knowledge has been applied to the development of multiple diagnostic tests, which are largely based on RNA and miRNA. Common gene probes included in multi-probe tests include PCA3 and ERG, and the miRNAs miR-21 and miR-141. The next decade will likely bring further improvements in the diagnostic accuracy of biomarkers as well as insights into molecular biological mechanisms of action that can be translated into opportunities in precision uro-oncology.
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(This article belongs to the Special Issue Editorial Board Members’ Collection Series: The Functions of Extracellular Vesicles in Cancer)
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Direct Implantation of Patient Brain Tumor Cells into Matching Locations in Mouse Brains for Patient-Derived Orthotopic Xenograft Model Development
by
Lin Qi, Patricia Baxter, Mari Kogiso, Huiyuan Zhang, Frank K. Braun, Holly Lindsay, Sibo Zhao, Sophie Xiao, Aalaa Sanad Abdallah, Milagros Suarez, Zilu Huang, Wan Yee Teo, Litian Yu, Xiumei Zhao, Zhigang Liu, Yulun Huang, Jack M. Su, Tsz-Kwong Man, Ching C. Lau, Laszlo Perlaky, Yuchen Du and Xiao-Nan Liadd
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Cancers 2024, 16(9), 1716; https://doi.org/10.3390/cancers16091716 (registering DOI) - 28 Apr 2024
Abstract
Background: Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models. Methods: We have developed
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Background: Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models. Methods: We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice. Results: Using this technique, we successfully developed 188 PDOX models from 408 brain tumor patient samples (both high-and low-grade) with a success rate of 72.3% in high-grade glioma, 64.2% in medulloblastoma, 50% in ATRT, 33.8% in ependymoma, and 11.6% in low-grade gliomas. Detailed characterization confirmed their replication of the histopathological and genetic abnormalities of the original patient tumors. Conclusions: The protocol is easy to follow, without a sterotactic frame, in order to generate large cohorts of tumor-bearing mice to meet the needs of biological studies and preclinical drug testing.
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(This article belongs to the Section Methods and Technologies Development)
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Clinical Theranostics in Recurrent Gliomas: A Review
by
Austin R. Hoggarth, Sankar Muthukumar, Steven M. Thomas, James Crowley, Jackson Kiser and Mark R. Witcher
Cancers 2024, 16(9), 1715; https://doi.org/10.3390/cancers16091715 (registering DOI) - 28 Apr 2024
Abstract
Gliomas represent the most commonly occurring tumors in the central nervous system and account for approximately 80% of all malignant primary brain tumors. With a high malignancy and recurrence risk, the prognosis of high-grade gliomas is poor, with a mean survival time of
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Gliomas represent the most commonly occurring tumors in the central nervous system and account for approximately 80% of all malignant primary brain tumors. With a high malignancy and recurrence risk, the prognosis of high-grade gliomas is poor, with a mean survival time of 12–18 months. While contrast-enhanced MRI serves as the standard diagnostic imaging modality for gliomas, it faces limitations in the evaluation of recurrent gliomas, failing to distinguish between treatment-related changes and tumor progression, and offers no direct therapeutic options. Recent advances in imaging modalities have attempted to address some of these limitations, including positron emission tomography (PET), which has demonstrated success in delineating tumor margins and guiding the treatment of recurrent gliomas. Additionally, with the advent of theranostics in nuclear medicine, PET tracers, when combined with therapeutic agents, have also evolved beyond a purely diagnostic modality, serving both diagnostic and therapeutic roles. This review will discuss the growing involvement of theranostics in diagnosing and treating recurrent gliomas and address the associated impact on quality of life and functional recovery.
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(This article belongs to the Special Issue Functional Neuro-Oncology—Volume II)
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Deep Learning Reconstruction for DWIs by EPI and FASE Sequences for Head and Neck Tumors
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Hirotaka Ikeda, Yoshiharu Ohno, Kaori Yamamoto, Kazuhiro Murayama, Masato Ikedo, Masao Yui, Yunosuke Kumazawa, Yurika Shimamura, Yui Takagi, Yuhei Nakagaki, Satomu Hanamatsu, Yuki Obama, Takahiro Ueda, Hiroyuki Nagata, Yoshiyuki Ozawa, Akiyoshi Iwase and Hiroshi Toyama
Cancers 2024, 16(9), 1714; https://doi.org/10.3390/cancers16091714 (registering DOI) - 28 Apr 2024
Abstract
Background: Diffusion-weighted images (DWI) obtained by echo-planar imaging (EPI) are frequently degraded by susceptibility artifacts. It has been suggested that DWI obtained by fast advanced spin-echo (FASE) or reconstructed with deep learning reconstruction (DLR) could be useful for image quality improvements. The purpose
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Background: Diffusion-weighted images (DWI) obtained by echo-planar imaging (EPI) are frequently degraded by susceptibility artifacts. It has been suggested that DWI obtained by fast advanced spin-echo (FASE) or reconstructed with deep learning reconstruction (DLR) could be useful for image quality improvements. The purpose of this investigation using in vitro and in vivo studies was to determine the influence of sequence difference and of DLR for DWI on image quality, apparent diffusion coefficient (ADC) evaluation, and differentiation of malignant from benign head and neck tumors. Methods: For the in vitro study, a DWI phantom was scanned by FASE and EPI sequences and reconstructed with and without DLR. Each ADC within the phantom for each DWI was then assessed and correlated for each measured ADC and standard value by Spearman’s rank correlation analysis. For the in vivo study, DWIs obtained by EPI and FASE sequences were also obtained for head and neck tumor patients. Signal-to-noise ratio (SNR) and ADC were then determined based on ROI measurements, while SNR of tumors and ADC were compared between all DWI data sets by means of Tukey’s Honest Significant Difference test. Results: For the in vitro study, all correlations between measured ADC and standard reference were significant and excellent (0.92 ≤ ρ ≤ 0.99, p < 0.0001). For the in vivo study, the SNR of FASE with DLR was significantly higher than that of FASE without DLR (p = 0.02), while ADC values for benign and malignant tumors showed significant differences between each sequence with and without DLR (p < 0.05). Conclusion: In comparison with EPI sequence, FASE sequence and DLR can improve image quality and distortion of DWIs without significantly influencing ADC measurements or differentiation capability of malignant from benign head and neck tumors.
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(This article belongs to the Section Cancer Informatics and Big Data)
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Ex Vivo Confocal Laser Scanning Microscopy in Rare Skin Diseases
by
Luis Messner, Maximilian Deußing, Michaela Maurer, Lisa Buttgereit, Lara Stärr, Lars E. French and Daniela Hartmann
Cancers 2024, 16(9), 1713; https://doi.org/10.3390/cancers16091713 (registering DOI) - 28 Apr 2024
Abstract
While ex vivo confocal laser scanning microscopy has previously demonstrated its utility in most common skin diseases, its use in the assessment of dermatological entities with lower incidence remains unexplored in most cases. We therefore aimed to evaluate the diagnostic efficacy of some
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While ex vivo confocal laser scanning microscopy has previously demonstrated its utility in most common skin diseases, its use in the assessment of dermatological entities with lower incidence remains unexplored in most cases. We therefore aimed to evaluate the diagnostic efficacy of some rare skin tumors as well as a few inflammatory skin diseases, that have not yet been studied in ex vivo confocal laser scanning microscopy. A total of 50 tissue samples comprising 10 healthy controls, 10 basal cell carcinoma, 10 squamous cell carcinoma, and 20 rare skin conditions were imaged using the newest generation ex vivo confocal microscopy (Vivascope 2500 M-G4, Vivascope GmbH, Munich, Germany). Three blinded investigators were asked to identify characteristic features of rare skin disorders and distinguish them from more common skin diseases in the ex vivo confocal microscopy images. Our findings present the capability of ex vivo confocal microscopy to display distinctive morphologic patterns in common and rare skin diseases. As might be expected, we found a strong correlation between imaging experience and diagnostic accuracy. While the imaging inexperienced dermatohistopathologist reached 60% concordance, the imaging-trained dermatologist obtained 88% agreement with dermatohistopathology. The imaging-trained dermatohistopathologist achieved concordance up to 92% with gold-standard dermatohistopathology. This study highlights the potential of ex vivo confocal laser scanning microscopy as a promising adjunct to conventional dermatohistopathology for the early and precise identification of rare dermatological disorders.
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(This article belongs to the Special Issue Advances in Skin Cancer Diagnostics and Therapy: Research and Clinical Studies)
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A Systematic Review and Meta-Analysis on the Diagnostic and Prognostic Values of 18F-FDG PET in Uveal Melanoma and Its Hepatic Metastasis
by
Seyed Ali Mirshahvalad, Nazanin Zamani-Siahkali, Christian Pirich and Mohsen Beheshti
Cancers 2024, 16(9), 1712; https://doi.org/10.3390/cancers16091712 (registering DOI) - 28 Apr 2024
Abstract
In this systematic review and meta-analysis (PRISMA-compliant), we tried to investigate diagnostic and prognostic values of 18F-FDG PET in uveal melanoma. A systematic search was conducted on the main medical literature databases to include studies that evaluated 18F-FDG PET as the
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In this systematic review and meta-analysis (PRISMA-compliant), we tried to investigate diagnostic and prognostic values of 18F-FDG PET in uveal melanoma. A systematic search was conducted on the main medical literature databases to include studies that evaluated 18F-FDG PET as the imaging modality to evaluate patients with uveal melanoma. Overall, 27 studies were included. Twelve had data about the detection rate of 18F-FDG PET in primary intra-ocular tumours. The pooled sensitivity was 45% (95%CI: 41–50%). Furthermore, studies showed that the larger the primary tumour, the higher its uptake. Among the included studies, 13 assessed 18F-FDG PET in detecting metastasis. The pooled sensitivity and specificity were 96% (95%CI: 81–99%) and 100% (95%CI: 94–100%), respectively. Regarding liver metastasis, they were 95% (95%CI: 79–99%) and 100% (95%CI: 91–100%), respectively. Noteworthy, the level of 18F-FDG uptake was a strong predictor of patient survival. Lastly, 18F-FDG PET could characterise lesions from the histopathology perspective, distinguishing high-risk from low-risk diseases. Overall, although not reliable in detecting primary intra-ocular tumours, 18F-FDG PET is highly accurate for diagnosing metastatic uveal melanomas. It can also be a highly valuable modality in terms of patient prognostication. Thus, 18F-FDG PET can be recommended in patients diagnosed with uveal melanoma to enhance decision-making and patient management.
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(This article belongs to the Special Issue Advances in Skin Cancer Diagnostics and Therapy: Research and Clinical Studies)
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The Role of Phytonutrient Kaempferol in the Prevention of Gastrointestinal Cancers: Recent Trends and Future Perspectives
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Tejveer Singh, Deepika Sharma, Rishabh Sharma, Hardeep Singh Tuli, Shafiul Haque, Seema Ramniwas, Darin Mansor Mathkor and Vikas Yadav
Cancers 2024, 16(9), 1711; https://doi.org/10.3390/cancers16091711 (registering DOI) - 27 Apr 2024
Abstract
In recent years, kaempferol, a natural flavonoid present in various fruits and vegetables, has received significant attention in gastrointestinal cancer research due to its varied therapeutic effects. Kaempferol has been proven to alter several molecular mechanisms and pathways, such as the PI3/Akt, mTOR,
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In recent years, kaempferol, a natural flavonoid present in various fruits and vegetables, has received significant attention in gastrointestinal cancer research due to its varied therapeutic effects. Kaempferol has been proven to alter several molecular mechanisms and pathways, such as the PI3/Akt, mTOR, and Erk/MAPK pathway involved in cancer progression, showing its inhibitory effects on cell proliferation, survival, angiogenesis, metastasis, and migration. Kaempferol is processed in the liver and small intestine, but limited bioavailability has been a major concern in the clinical implications of kaempferol. Nano formulations have been proven to enhance kaempferol’s efficacy in cancer prevention. The synergy of nanotechnology and kaempferol has shown promising results in in vitro studies, highlighting the importance for more in vivo research and clinical trials to determine safety and efficacy. This review aims to focus on the role of kaempferol in various types of gastrointestinal cancer and how the combination of kaempferol with nanotechnology helps in improving therapeutic efficacy in cancer treatment.
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(This article belongs to the Special Issue Advances in Esophagogastric Cancer)
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Tumor Location Is An Independent Prognostic Factor in Completely Resected Pathological Stage I Non-Small Cell Lung Cancer: A Multicenter Retrospective Study
by
Wei-Ke Kuo, Po-Ju Chen, Mei-Hsuan Wu, Henry Hsin-Chung Lee, Jiun-Kai Fan, Pang-Hung Hsu and Ching-Fu Weng
Cancers 2024, 16(9), 1710; https://doi.org/10.3390/cancers16091710 (registering DOI) - 27 Apr 2024
Abstract
Previous studies suggested that the location of the primary tumor in non-small cell lung cancer (NSCLC) is associated with clinical features and prognosis, but results are conflicting. The purpose of this study was to explore tumor location as an independent risk factor of
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Previous studies suggested that the location of the primary tumor in non-small cell lung cancer (NSCLC) is associated with clinical features and prognosis, but results are conflicting. The purpose of this study was to explore tumor location as an independent risk factor of survival for patients with completely resected pathological stage I NSCLC. This was a multicenter retrospective study conducted in Taiwan. Included patients were diagnosed with stage I NSCLC and had undergone primary tumor resection. Variables including tumor location, pathological stage, histological differentiation, and International Association for the Study of Lung Cancer (IASLC) grade were evaluated for predictive ability for disease-free survival (DFS) and overall survival (OS). A total of 208 patients were included, with 123 (59.1%) patients having a primary tumor in the upper and middle lobes. The median duration of follow-up for survivors was 60.5 months. Compared to patients with IASLC Grade 3 disease, patients with Grade 1 disease had significantly longer DFS. Tumor location and IASLC grade were independent predictors for OS in multivariate analysis. Specifically, patients with NSCLC in the lower lobe and patients who are histologically classified as IASLC Grade 3 may have poorer prognosis and require greater attention to improve outcomes.
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(This article belongs to the Collection Diagnosis and Treatment of Primary and Secondary Lung Cancers)
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Immune System Disorder and Cancer-Associated Cachexia
by
Lingbing Zhang and Philip D. Bonomi
Cancers 2024, 16(9), 1709; https://doi.org/10.3390/cancers16091709 (registering DOI) - 27 Apr 2024
Abstract
Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, that is unresponsive to nutritional support and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores
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Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, that is unresponsive to nutritional support and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like the neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed the weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy.
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(This article belongs to the Topic Inflammatory Tumor Immune Microenvironment)
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Prognosis and Treatment of Gastric Cancer: A 2024 Update
by
Claudia Burz, Vlad Pop, Ciprian Silaghi, Iulia Lupan and Gabriel Samasca
Cancers 2024, 16(9), 1708; https://doi.org/10.3390/cancers16091708 (registering DOI) - 27 Apr 2024
Abstract
Due to the high death rate associated with gastric cancer, a great deal of research has been conducted on this disease. The goal of this paper was to start a trimestral review of 2024 for the year that had just started. The scientific
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Due to the high death rate associated with gastric cancer, a great deal of research has been conducted on this disease. The goal of this paper was to start a trimestral review of 2024 for the year that had just started. The scientific literature from 1 January 2024 was chosen with consideration of the the guidelines of the European Society of Medical Oncology (ESMO), which are updated with new findings but not systematically reviewed annually. We used the search term “gastric cancer” to find the most current publications in the PubMed database related to the prognosis and treatment of gastric cancer. As previously said, the only articles that satisfied the inclusion criteria were those from 2024. Articles with case reports were eliminated since they had nothing to do with our research. The treatment of gastric cancer is the focus of the majority of articles from 2024. The primary research axes include surgery and immunonutrition, immunotherapy and Helicobacter pylori, and therapeutic targets. Patients with GC may experience less psychological, social, and financial hardship if the recently identified markers discovered in circulation are better assessed and validated. This could be achieved by either including the markers in an artificial intelligence-based diagnostic score or by using them in conjunction with traditional diagnostic methods. Due to the rising death rate associated with GC, funding for research into diagnosis, prognosis, therapy, and therapeutic targets is essential.
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(This article belongs to the Special Issue Advances in the Prognosis of Gastrointestinal Cancers)
Open AccessArticle
Utility of Clinical Next Generation Sequencing Tests in KIT/PDGFRA/SDH Wild-Type Gastrointestinal Stromal Tumors
by
Ryan A. Denu, Cissimol P. Joseph, Elizabeth S. Urquiola, Precious S. Byrd, Richard K. Yang, Ravin Ratan, Maria Alejandra Zarzour, Anthony P. Conley, Dejka M. Araujo, Vinod Ravi, Elise F. Nassif Haddad, Michael S. Nakazawa, Shreyaskumar Patel, Wei-Lien Wang, Alexander J. Lazar and Neeta Somaiah
Cancers 2024, 16(9), 1707; https://doi.org/10.3390/cancers16091707 (registering DOI) - 27 Apr 2024
Abstract
Objective: The vast majority of gastrointestinal stromal tumors (GISTs) are driven by activating mutations in KIT, PDGFRA, or components of the succinate dehydrogenase (SDH) complex (SDHA, SDHB, SDHC, and SDHD genes). A small fraction of GISTs lack
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Objective: The vast majority of gastrointestinal stromal tumors (GISTs) are driven by activating mutations in KIT, PDGFRA, or components of the succinate dehydrogenase (SDH) complex (SDHA, SDHB, SDHC, and SDHD genes). A small fraction of GISTs lack alterations in KIT, PDGFRA, and SDH. We aimed to further characterize the clinical and genomic characteristics of these so-called “triple-negative” GISTs. Methods: We extracted clinical and genomic data from patients seen at MD Anderson Cancer Center with a diagnosis of GIST and available clinical next generation sequencing data to identify “triple-negative” patients. Results: Of the 20 patients identified, 11 (55.0%) had gastric, 8 (40.0%) had small intestinal, and 1 (5.0%) had rectal primary sites. In total, 18 patients (90.0%) eventually developed recurrent or metastatic disease, and 8 of these presented with de novo metastatic disease. For the 13 patients with evaluable response to imatinib (e.g., neoadjuvant treatment or for recurrent/metastatic disease), the median PFS with imatinib was 4.4 months (range 0.5–191.8 months). Outcomes varied widely, as some patients rapidly developed progressive disease while others had more indolent disease. Regarding potential genomic drivers, four patients were found to have alterations in the RAS/RAF/MAPK pathway: two with a BRAF V600E mutation and two with NF1 loss-of-function (LOF) mutations (one deletion and one splice site mutation). In addition, we identified two with TP53 LOF mutations, one with NTRK3 fusion (ETV6-NTRK3), one with PTEN deletion, one with FGFR1 gain-of-function (GOF) mutation (K654E), one with CHEK2 LOF mutation (T367fs*), one with Aurora kinase A fusion (AURKA-CSTF1), and one with FANCA deletion. Patients had better responses with molecularly targeted therapies than with imatinib. Conclusions: Triple-negative GISTs comprise a diverse cohort with different driver mutations. Compared to KIT/PDGFRA-mutant GIST, limited benefit was observed with imatinib in triple-negative GIST. In depth molecular profiling can be helpful in identifying driver mutations and guiding therapy.
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(This article belongs to the Special Issue Genome Sequencing of Cancer: Identifying Targets and Biomarkers for Therapy)
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Open AccessReview
Dissecting the Puzzling Roles of FAM46C: A Multifaceted Pan-Cancer Tumour Suppressor with Increasing Clinical Relevance
by
Giancarlo Lai, Federica De Grossi, Ilaria Catusi, Elisa Pesce and Nicola Manfrini
Cancers 2024, 16(9), 1706; https://doi.org/10.3390/cancers16091706 (registering DOI) - 27 Apr 2024
Abstract
FAM46C is a well-established tumour suppressor with a role that is not completely defined or universally accepted. Although FAM46C expression is down-modulated in several tumours, significant mutations in the FAM46C gene are only found in multiple myeloma (MM). Consequently, its tumour suppressor activity
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FAM46C is a well-established tumour suppressor with a role that is not completely defined or universally accepted. Although FAM46C expression is down-modulated in several tumours, significant mutations in the FAM46C gene are only found in multiple myeloma (MM). Consequently, its tumour suppressor activity has primarily been studied in the MM context. However, emerging evidence suggests that FAM46C is involved also in other cancer types, namely colorectal, prostate and gastric cancer and squamous cell and hepatocellular carcinoma, where FAM46C expression was found to be significantly reduced in tumoural versus non-tumoural tissues and where FAM46C was shown to possess anti-proliferative properties. Accordingly, FAM46C was recently proposed to function as a pan-cancer prognostic marker, bringing FAM46C under the spotlight and attracting growing interest from the scientific community in the pathways modulated by FAM46C and in its mechanistic activity. Here, we will provide the first comprehensive review regarding FAM46C by covering (1) the intracellular pathways regulated by FAM46C, namely the MAPK/ERK, PI3K/AKT, β-catenin and TGF-β/SMAD pathways; (2) the models regarding its mode of action, specifically the poly(A) polymerase, intracellular trafficking modulator and inhibitor of centriole duplication models, focusing on connections and interdependencies; (3) the regulation of FAM46C expression in different environments by interferons, IL-4, TLR engagement or transcriptional modulators; and, lastly, (4) how FAM46C expression levels associate with increased/decreased tumour cell sensitivity to anticancer agents, such as bortezomib, dexamethasone, lenalidomide, pomalidomide, doxorubicin, melphalan, SK1-I, docetaxel and norcantharidin.
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(This article belongs to the Special Issue Unique Perspectives in Cancer Signaling)
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