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
Therapeutic Parent–Child Communication and Health Outcomes in the Childhood Cancer Context: A Scoping Review
Cancers 2024, 16(11), 2152; https://doi.org/10.3390/cancers16112152 (registering DOI) - 6 Jun 2024
Abstract
Family communication has been thought to be an important area to support children’s adjustment to a cancer diagnosis. However, the characteristics of therapeutic parent–child communication that contribute to better patient outcomes and the specific patient health outcomes have been less explored. This current
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Family communication has been thought to be an important area to support children’s adjustment to a cancer diagnosis. However, the characteristics of therapeutic parent–child communication that contribute to better patient outcomes and the specific patient health outcomes have been less explored. This current review explored the characteristics of therapeutic parent–child communication and its physical and psychological health outcomes. A total of 5034 articles were initially identified, and only 10 articles remained for inclusion in this review after application of the exclusion criteria. Most studies used a cross-sectional design and measured verbal communication characteristics and its psychological outcomes, but no physical outcomes. The characteristics of therapeutic verbal communication (openness, maternal validation, quality of information shared, etc.) and nonverbal communication (eye contact, close physical distance, and acknowledging behaviors) were identified. The psychological health outcomes included less distress, a lower level of PTSS, less internalizing and externalizing of symptoms, increased levels of social emotional competencies, better peer relationships, and more cooperation during the procedure at the individual level. Increased family cohesion and family adaptation were family-level outcomes. Longitudinal studies are needed to identify what qualities of communication predict better psychological outcomes so that interventions can be developed and tested. In addition, physical outcomes should be evaluated.
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(This article belongs to the Special Issue Advances in Pediatric and Adolescent Psycho-Oncology)
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Open AccessCorrection
Correction: Nam et al. Identification of Thiazolo[5,4-b]pyridine Derivatives as c-KIT Inhibitors for Overcoming Imatinib Resistance. Cancers 2023, 15, 143
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Yunju Nam, Chan Kim, Junghee Han, SeongShick Ryu, Hanna Cho, Chiman Song, Nam Doo Kim, Namkyoung Kim and Taebo Sim
Cancers 2024, 16(11), 2151; https://doi.org/10.3390/cancers16112151 (registering DOI) - 6 Jun 2024
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The authors would like to make a correction to the previous article [...]
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Open AccessArticle
Exploring the Survival Determinants in Recurrent Ovarian Cancer: The Role of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
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Katarzyna Gęca, Jakub Litwiński, Tomasz Ostrowski, Izabela Świetlicka, Wojciech P. Polkowski and Magdalena Skórzewska
Cancers 2024, 16(11), 2150; https://doi.org/10.3390/cancers16112150 - 5 Jun 2024
Abstract
Background: Recurrent ovarian cancer (ROC) significantly challenges gynecological oncology due to its poor outcomes. This study assesses the impact of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) on ROC survival rates. Materials and Methods: Conducted at the Medical University of Lublin
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Background: Recurrent ovarian cancer (ROC) significantly challenges gynecological oncology due to its poor outcomes. This study assesses the impact of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) on ROC survival rates. Materials and Methods: Conducted at the Medical University of Lublin from April 2011 to November 2022, this retrospective observational study involved 71 patients with histologically confirmed ROC who underwent CRS and subsequent HIPEC. Results: The median overall survival (OS) was 41.1 months, with 3-year and 5-year survival rates post-treatment of 0.50 and 0.33, respectively. Patients undergoing radical surgery for primary ovarian cancer had a median OS of 61.9 months. The key survival-related factors included the Peritoneal Carcinomatosis Index (PCI) score, AGO score, platinum sensitivity, and ECOG status. Conclusions: The key factors enhancing ROC patients’ survival include radical surgery, optimal performance status, platinum sensitivity, a positive AGO score, and a lower PCI. This study highlights the predictive value of the platinum resistance and AGO score in patient outcomes, underlining their role in treatment planning. Further prospective research is needed to confirm these results and improve patient selection for this treatment approach.
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(This article belongs to the Section Cancer Survivorship and Quality of Life)
Open AccessArticle
A Clinical Perspective on Plasma Cell Leukemia: A Single-Center Experience
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Andrew Y. Li, Farin Kamangar, Noa G. Holtzman, Aaron P. Rapoport, Mehmet H. Kocoglu, Djordje Atanackovic and Ashraf Z. Badros
Cancers 2024, 16(11), 2149; https://doi.org/10.3390/cancers16112149 - 5 Jun 2024
Abstract
Circulating plasma cells (CPCs) are detected in most multiple myeloma (MM) patients, both at diagnosis and on relapse. A small subset, plasma cell leukemia (PCL), represents a different biology and has a poor prognosis. In this retrospective analysis, we evaluated patients with primary
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Circulating plasma cells (CPCs) are detected in most multiple myeloma (MM) patients, both at diagnosis and on relapse. A small subset, plasma cell leukemia (PCL), represents a different biology and has a poor prognosis. In this retrospective analysis, we evaluated patients with primary (pPCL, n = 35) or secondary (sPCL, n = 49), with ≥5% CPCs and a smaller subset with lower CPCs of 1–4% (n = 20). The median age was 61 years; 45% were men and 54% were Black. High-risk cytogenetics were found in 87% and extramedullary disease in 47%. For the entire cohort, 75% received a proteasome inhibitor, 70% chemotherapy, 54% an immunomodulatory drug, 24% a daratumumab-based regimen and 26% an autologous stem cell transplant (ASCT). The treatments marginally improved the overall survival (OS) for pPCL vs. sPCL (13 vs. 3.5 months p = 0.002). However, the 5-year survival for the whole cohort was dismal at 11%. High-risk cytogenetics, low platelets, extramedullary disease and high LDH were independently associated with poor outcomes. Further research is urgently needed to expand the treatment options and improve the outcomes in PCL.
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(This article belongs to the Section Clinical Research of Cancer)
Open AccessArticle
Spheno-Orbital Meningiomas: The Rationale behind the Decision-Making Process of Treatment Strategy
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Giuseppe Mariniello, Sergio Corvino, Giuseppe Corazzelli, Oreste de Divitiis, Giancarlo Fusco, Adriana Iuliano, Diego Strianese, Francesco Briganti and Andrea Elefante
Cancers 2024, 16(11), 2148; https://doi.org/10.3390/cancers16112148 - 5 Jun 2024
Abstract
Surgery stands as the primary treatment for spheno-orbital meningiomas, following a symptoms-oriented approach. We discussed the decision-making process behind surgical strategies through a review of medical records from 80 patients who underwent surgical resection at the University of Naples Federico II. Different surgical
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Surgery stands as the primary treatment for spheno-orbital meningiomas, following a symptoms-oriented approach. We discussed the decision-making process behind surgical strategies through a review of medical records from 80 patients who underwent surgical resection at the University of Naples Federico II. Different surgical approaches were employed based on the tumor’s location relative to the optic nerve’s long axis, categorized into lateral (type I), medial (type II), and diffuse (type III). We examined clinical, neuroradiological, surgical, pathological, and outcome factors. Proptosis emerged as the most frequent symptom (97%), followed by visual impairment (59%) and ocular motility issues (35%). Type I represented 20%, type II 43%, and type III 17%. Growth primarily affected the optic canal (74%), superior orbital fissure (65%), anterior clinoid (60%), and orbital apex (59%). The resection outcomes varied, with Simpson grades I and II achieved in all type I cases, 67.5% of type II, and 18% of type III. Recurrence rates were highest in type II (41.8%) and type III (59%). Improvement was notable in proptosis (68%) and visual function (51%, predominantly type I). Surgery for spheno-orbital meningiomas should be tailored to each patient, considering individual characteristics and tumor features to improve quality of life by addressing primary symptoms like proptosis and visual deficits.
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(This article belongs to the Section Molecular Cancer Biology)
Open AccessArticle
Prognostic Significance of CD163+ and/or CD206+ Tumor-Associated Macrophages Is Linked to Their Spatial Distribution and Tumor-Infiltrating Lymphocytes in Breast Cancer
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Canbin Fang, Maisy Y. Cheung, Ronald C. Chan, Ivan K. Poon, Conrad Lee, Curtis C. To, Julia Y. Tsang, Joshua Li and Gary M. Tse
Cancers 2024, 16(11), 2147; https://doi.org/10.3390/cancers16112147 - 5 Jun 2024
Abstract
Tumor-associated macrophages (TAMs) is a key element in the breast tumor microenvironment. CD163 and CD206 have been utilized for TAM identification, but the clinical implications of TAMs identified by these markers have not been thoroughly explored. This study conducted a comparative analysis of
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Tumor-associated macrophages (TAMs) is a key element in the breast tumor microenvironment. CD163 and CD206 have been utilized for TAM identification, but the clinical implications of TAMs identified by these markers have not been thoroughly explored. This study conducted a comparative analysis of CD163 and CD206 TAMs using digital image analysis, focusing on their spatial distribution and prognostic significance in relation to tumor-infiltrating lymphocytes (TILs). Distinct clinico-pathological and prognostic characteristics were noted between the two types of TAMs. CD163 TAMs were linked to high-grade tumors (p = 0.006), whereas CD206 TAMs were associated with a higher incidence of nodal metastasis (p = 0.033). CD206 TAMs were predominantly found in the stroma, with more cases being stromal CD206-high (sCD206-high) than tumoral CD206-high (tCD206-high) (p = 0.024). Regarding prognostication, patients stratified according to stromal and tumoral densities of CD163 showed different disease-free survival (DFS) time. Specifically, those that were sCD163-low but tCD163-high exhibited the poorest DFS (chi-square = 10.853, p = 0.013). Furthermore, a high sCD163-to-stromal-TILs ratio was identified as an independent predictor of unfavorable survival outcomes (DFS: HR = 3.477, p = 0.018). The spatial distribution and interactions with TILs enhanced the prognostic value of CD163 TAMs, while CD206 TAMs appeared to have limited prognostic utility in breast cancer cases.
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(This article belongs to the Section Tumor Microenvironment)
Open AccessArticle
Lung Cancer and Air Quality in a Large Urban County in the United States
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Hollis Hutchings, Qiong Zhang, Sue C. Grady, Jessica Cox, Andrew Popoff, Carl P. Wilson, Shangrui Zhu and Ikenna Okereke
Cancers 2024, 16(11), 2146; https://doi.org/10.3390/cancers16112146 - 5 Jun 2024
Abstract
Lung cancer is the leading cancer-related killer in the United States. The incidence varies geographically and may be affected by environmental pollutants. Our goal was to determine associations within time series for specific air pollutants and lung cancer cases over a 33-year period
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Lung cancer is the leading cancer-related killer in the United States. The incidence varies geographically and may be affected by environmental pollutants. Our goal was to determine associations within time series for specific air pollutants and lung cancer cases over a 33-year period in Wayne County, Michigan, controlling for population change. Lung cancer data for Wayne County were queried from the Michigan Cancer Registry from 1985 to 2018. Air pollutant data were obtained from the United States Environmental Protection Agency from 1980 to 2018. Autoregressive distributed lag (ARDL) models were estimated to investigate time lags in years between specific air pollution levels and lung cancer development. A total of 58,866 cases of lung cancer were identified. The mean age was 67.8 years. Females accounted for 53 percent of all cases in 2018 compared to 44 percent in 1985. Three major clusters of lung cancer incidence were detected with the most intense clusters in downtown Detroit and the heavily industrialized downriver area. Sulfur dioxide (SO2) had the strongest statistically significant relationship with lung cancer, showing both short- and long-term effects (lag range, 1–15 years). Particulate matter (PM2.5) (lag range, 1–3 years) and nitrogen dioxide (NO2) (lag range, 2–4 years) had more immediate effects on lung cancer development compared to carbon monoxide (CO) (lag range, 5–6 years), hazardous air pollutants (HAPs) (lag range, 9 years) and lead (Pb) (lag range, 10–12 years), which had more long-term effects on lung cancer development. Areas with poor air quality may benefit from targeted interventions for lung cancer screening and reductions in environmental pollution.
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(This article belongs to the Special Issue Advances in Cancer Data and Statistics)
Open AccessArticle
Type Disparity in Sodium–Glucose Cotransporter-2 Inhibitors in Incidences of Renal Cell Carcinoma: A Propensity-Score-Matched Cohort Study
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Tsung-Kun Lin, Wei-Yao Wang, Tsung-Yuan Yang and Gwo-Ping Jong
Cancers 2024, 16(11), 2145; https://doi.org/10.3390/cancers16112145 - 5 Jun 2024
Abstract
(1) Background: Recently, sodium–glucose cotransporter-2 inhibitors (SGLT2Is) have been reported to significantly reduce renal cell carcinoma (RCC) risk. However, the effect between individual SGLT2Is on RCC incidence in patients with type 2 diabetes (T2D) or heart failure is unclear. We conducted an observational
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(1) Background: Recently, sodium–glucose cotransporter-2 inhibitors (SGLT2Is) have been reported to significantly reduce renal cell carcinoma (RCC) risk. However, the effect between individual SGLT2Is on RCC incidence in patients with type 2 diabetes (T2D) or heart failure is unclear. We conducted an observational analysis to explore type disparity in the prescription of SGLT2Is on RCC risk. (2) Methods: A nationwide retrospective cohort study using the Health and Welfare Data Science Center database (2016–2021) was conducted. Patients aged ≥40 years who took SGLT2Is were designated as the SGLT2I group, whereas propensity score 1:1-matched randomly selected patients without SGLT2Is were assigned to the non-SGLT2I group. The primary outcome was the risk of incident RCC between individual SGLT2Is. Multiple Cox regression modeling was conducted to analyze the association between individual SGLT2I use and RCC risk. (3) Results: After a 5.5-year follow-up, SGLT2I use was associated with a significantly lower risk of incident RCC (hazard: 0.62; 95% confidence interval [CI]: 0.44–0.89). Compared with non-users and after adjusting for the index year, sex, age, comorbidities, concurrent medication, and the risk of developing RCC, the hazard ratios of dapagliflozin, canagliflozin, and empagliflozin were 0.66 (95% CI: 0.53–0.83), 0.84 (95% CI: 0.46–1.30), and 0.71 (95% CI: 0.56–0.90), respectively. (4) Conclusions: Our data show a type-based effect of SGLT2Is on RCC risk. The type-based effect of SGLT2Is should be further studied for better clinical management information and for reducing RCC incidence in patients with T2D.
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(This article belongs to the Section Cancer Survivorship and Quality of Life)
Open AccessArticle
Three-Dimension Epithelial Segmentation in Optical Coherence Tomography of the Oral Cavity Using Deep Learning
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Chloe Hill, Jeanie Malone, Kelly Liu, Samson Pak-Yan Ng, Calum MacAulay, Catherine Poh and Pierre Lane
Cancers 2024, 16(11), 2144; https://doi.org/10.3390/cancers16112144 - 5 Jun 2024
Abstract
This paper aims to simplify the application of optical coherence tomography (OCT) for the examination of subsurface morphology in the oral cavity and reduce barriers towards the adoption of OCT as a biopsy guidance device. The aim of this work was to develop
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This paper aims to simplify the application of optical coherence tomography (OCT) for the examination of subsurface morphology in the oral cavity and reduce barriers towards the adoption of OCT as a biopsy guidance device. The aim of this work was to develop automated software tools for the simplified analysis of the large volume of data collected during OCT. Imaging and corresponding histopathology were acquired in-clinic using a wide-field endoscopic OCT system. An annotated dataset (n = 294 images) from 60 patients (34 male and 26 female) was assembled to train four unique neural networks. A deep learning pipeline was built using convolutional and modified u-net models to detect the imaging field of view (network 1), detect artifacts (network 2), identify the tissue surface (network 3), and identify the presence and location of the epithelial–stromal boundary (network 4). The area under the curve of the image and artifact detection networks was 1.00 and 0.94, respectively. The Dice similarity score for the surface and epithelial–stromal boundary segmentation networks was 0.98 and 0.83, respectively. Deep learning (DL) techniques can identify the location and variations in the epithelial surface and epithelial–stromal boundary in OCT images of the oral mucosa. Segmentation results can be synthesized into accessible en face maps to allow easier visualization of changes.
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(This article belongs to the Special Issue Image Analysis and Machine Learning in Cancers)
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Open AccessArticle
Treatment Patterns and Outcomes by Age in Metastatic Urinary Tract Cancer: A Retrospective Tertiary Cancer Center Analysis
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Nishita Tripathi, Georges Gebrael, Beverly Chigarira, Kamal Kant Sahu, Ishwarya Balasubramanian, Constance Caparas, Vinay Mathew Thomas, Jessica N. Cohan, Kaitlyn Pelletier, Benjamin L. Maughan, Neeraj Agarwal, Umang Swami and Sumati Gupta
Cancers 2024, 16(11), 2143; https://doi.org/10.3390/cancers16112143 - 5 Jun 2024
Abstract
Metastatic urinary tract cancer (mUTC) is challenging to treat in older adults due to comorbidities. We compared the clinical courses of younger and older (≥70 years) adults with mUTC receiving first-line (1L) systemic therapy in a tertiary cancer center. Baseline clinical characteristics, treatments
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Metastatic urinary tract cancer (mUTC) is challenging to treat in older adults due to comorbidities. We compared the clinical courses of younger and older (≥70 years) adults with mUTC receiving first-line (1L) systemic therapy in a tertiary cancer center. Baseline clinical characteristics, treatments received, tolerability, and survival outcomes were analyzed. Among 212 patients (103 older vs. 109 younger), the older patients had lower hemoglobin at baseline (84% vs. 71%, p = 0.03), the majority were cisplatin-ineligible (74% vs. 45%, p < 0.001), received more immunotherapy-based treatments in the 1L (52% vs. 36%, p = 0.01), received fewer subsequent lines of treatment (median 0 vs. 1, p = 0.003), and had lower clinical trial participation (30% vs. 18%, p = 0.05) compared to the younger patients. When treated with 1L chemotherapy, older patients required more dose adjustments (53.4% vs. 23%, p = 0.001) and received fewer cycles of chemotherapy (median 4 vs. 5, p= 0.01). Older patients had similar OS (11.2 months vs. 14 months, p = 0.06) and similar rates of treatment-related severe toxicity and healthcare visits, independent of the type of systemic treatment received, compared to younger patients. We conclude that select older adults with mUTC can be safely treated with immunotherapy and risk-adjusted regimens of chemotherapy with tangible survival benefits.
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(This article belongs to the Special Issue Multidisciplinary Approaches in Bladder Cancer)
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Open AccessArticle
Sentinel Lymph Node Mapping by Retroperitoneal vNOTES for Uterus-Confined Malignancies: A Standardized 10-Step Approach
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Daniela Huber and Yannick Hurni
Cancers 2024, 16(11), 2142; https://doi.org/10.3390/cancers16112142 - 5 Jun 2024
Abstract
(1) Background: Sentinel lymph node (SLN) mapping represents an accurate and feasible technique for the surgical staging of endometrial and cervical cancer. This is commonly performed by conventional laparoscopy or robotic-assisted laparoscopy, but in recent years, a new retroperitoneal transvaginal natural orifice transluminal
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(1) Background: Sentinel lymph node (SLN) mapping represents an accurate and feasible technique for the surgical staging of endometrial and cervical cancer. This is commonly performed by conventional laparoscopy or robotic-assisted laparoscopy, but in recent years, a new retroperitoneal transvaginal natural orifice transluminal endoscopic surgery (vNOTES) approach has been described and developed by Jan Baekelandt. This technique provides easy visualization of lymphatic afferent vessels and pelvic lymph nodes, early SLN assessment, and a coherent mapping methodology following the lymphatic flow from caudal to cranial. However, only a few publications have reported it. Following the IDEAL (Idea Development Exploration Assessment Long-term follow-up) framework, research concerning this technique is in Stage 2a, with only small case series as evidence of its feasibility. Its standardized description appears necessary to provide the surgical homogeneity required to move further. (2) Methods: Description of a standardized approach for retroperitoneal pelvic SLN mapping by vNOTES. (3) Results: We describe a 10-step approach to successfully perform retroperitoneal vNOTES SLN mapping, including pre-, intra-, and postoperative management. (4) Conclusions: This IDEAL Stage 2a study could help other surgeons approach this new technique, and it proposes a common methodology necessary for evolving through future IDEAL Stage 2b (multi-center studies) and Stage 3 (randomized controlled trials) studies.
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(This article belongs to the Special Issue Unlocking Precision and Minimizing Morbidity: Sentinel Lymph Node Mapping in Gynecological Cancer)
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Open AccessReview
Magnetic Resonance Spectroscopy for Cervical Cancer: Review and Potential Prognostic Applications
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Zohaib Iqbal, Kevin Albuquerque and Kimberly L. Chan
Cancers 2024, 16(11), 2141; https://doi.org/10.3390/cancers16112141 - 5 Jun 2024
Abstract
This review article investigates the utilization of MRS in the setting of cervical cancer. A variety of different techniques have been used in this space including single-voxel techniques such as point-resolved spectroscopy (PRESS) and stimulated echo acquisition mode spectroscopy (STEAM). Furthermore, the experimental
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This review article investigates the utilization of MRS in the setting of cervical cancer. A variety of different techniques have been used in this space including single-voxel techniques such as point-resolved spectroscopy (PRESS) and stimulated echo acquisition mode spectroscopy (STEAM). Furthermore, the experimental parameters for these acquisitions including field strength, repetition times (TR), and echo times (TE) vary greatly. This study critically examines eleven MRS studies that focus on cervical cancer. Out of the eleven studies, ten studies utilized PRESS acquisition, while the remaining study used STEAM acquisition. These studies generally showed that the choline signal is altered in cervical cancer (4/11 studies), the lipid signal is generally increased in cervical cancer or the lipid distribution is changed (5/11 studies), and that diffusion-weighted imaging (DWI) can quantitatively detect lower apparent diffusion coefficient (ADC) values in cervical cancer (2/11 studies). Two studies also investigated the role of MRS for monitoring treatment response and demonstrated mixed results regarding choline signal, and one of these studies showed increased lipid signal for non-responders. There are several new MRS technologies that have yet to be implemented for cervical cancer including advanced spectroscopic imaging and artificial intelligence, and those technologies are also discussed in the article.
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(This article belongs to the Special Issue Cervical Cancer: Study on Molecular Landscape and Protein Biomarkers. Current Diagnostic and Therapeutic Capabilities)
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Open AccessArticle
The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study
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Ayaka Asakawa, Ryoto Yoshimoto, Maki Kobayashi, Nanae Izumi, Takanori Maejima, Tsuneo Deguchi, Kazuishi Kubota, Hisashi Takahashi, Miyuki Yamada, Sachiko Ishibashi, Iichiroh Onishi, Yuko Kinowaki, Morito Kurata, Masashi Kobayashi, Hironori Ishibashi, Kenichi Okubo, Kenichi Ohashi, Masanobu Kitagawa and Kouhei Yamamoto
Cancers 2024, 16(11), 2140; https://doi.org/10.3390/cancers16112140 - 4 Jun 2024
Abstract
Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and
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Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and significance of B7-H3 in the tumor microenvironment (TME) and its relationship with other immune checkpoint molecules have not yet been investigated in detail. We used high-throughput quantitative multiplex immunohistochemistry to examine B7-H3 expression in the TME. We investigated the relationship between B7-H3 expression and prognosis as well as changes in the TME with B7-H3 expression using 110 surgically resected pathological specimens retrospectively. We examined the correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells. High B7-H3 expression in tumor cells was associated with a better prognosis and a significant increase in the number of CD163+PD-L1+ macrophages. Quantitative analysis revealed that there is a positive correlation between B7-H3 and PD-L1 expression in tumor and stromal cells, as well as in intratumoral tumor-infiltrating lymphocytes and tumor-associated macrophages in the same cells. CD68+, CD163+, and CK+ cells with PD-L1+ phenotypes had higher B7-H3 expression compared to PD-L1− cells. Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies.
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(This article belongs to the Special Issue Latest Breakthroughs in Tumor Immune Microenvironment: From Cellular Discovery to Cutting-Edge Technology)
Open AccessArticle
Functional Investigation of IGF1R Mutations in Multiple Myeloma
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Sofia Catalina Heredia-Guerrero, Marietheres Evers, Sarah Keppler, Marlene Schwarzfischer, Viktoria Fuhr, Hilka Rauert-Wunderlich, Anne Krügl, Theodora Nedeva, Tina Grieb, Julia Pickert, Hanna Koch, Torsten Steinbrunn, Otto-Jonas Bayrhof, Ralf Christian Bargou, Andreas Rosenwald, Thorsten Stühmer and Ellen Leich
Cancers 2024, 16(11), 2139; https://doi.org/10.3390/cancers16112139 - 4 Jun 2024
Abstract
High expression of the receptor tyrosine kinase (RTK) insulin-like growth factor-1 receptor (IGF1R) and RTK mutations are associated with high-risk/worse prognosis in multiple myeloma (MM). Combining the pIGF1R/pINSR inhibitor linsitinib with the proteasome inhibitor (PI) bortezomib seemed promising in a clinical
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High expression of the receptor tyrosine kinase (RTK) insulin-like growth factor-1 receptor (IGF1R) and RTK mutations are associated with high-risk/worse prognosis in multiple myeloma (MM). Combining the pIGF1R/pINSR inhibitor linsitinib with the proteasome inhibitor (PI) bortezomib seemed promising in a clinical trial, but IGF1R expression was not associated with therapy response. Because the oncogenic impact of IGF1R mutations is so far unknown, we investigated the functional impact of IGF1R mutations on survival signaling, viability/proliferation and survival response to therapy. We transfected four human myeloma cell lines (HMCLs) with IGF1RWT, IGF1RD1146N and IGF1RN1129S (Sleeping Beauty), generated CRISPR-Cas9 IGF1R knockouts in the HMCLs U-266 (IGF1RWT) and L-363 (IGF1RD1146N) and tested the anti-MM activity of linsitinib alone and in combination with the second-generation PI carfilzomib in seven HMCLs. IGF1R knockout entailed reduced proliferation. Upon IGF1R overexpression, survival signaling was moderately increased in all HCMLs and slightly affected by IGF1RN1129S in one HMCL, whereby the viability remained unaffected. Expression of IGF1RD1146N reduced pIGF1R-Y1135, especially under serum reduction, but did not impact downstream signaling. Linsitinib and carfilzomib showed enhanced anti-myeloma activity in six out of seven HMCL irrespective of the IGF1R mutation status. In conclusion, IGF1R mutations can impact IGF1R activation and/or downstream signaling, and a combination of linsitinib with carfilzomib might be a suitable therapeutic approach for MM patients potentially responsive to IGF1R blockade.
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(This article belongs to the Section Molecular Cancer Biology)
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Open AccessReview
Transfer Learning in Cancer Genetics, Mutation Detection, Gene Expression Analysis, and Syndrome Recognition
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Hamidreza Ashayeri, Navid Sobhi, Paweł Pławiak, Siamak Pedrammehr, Roohallah Alizadehsani and Ali Jafarizadeh
Cancers 2024, 16(11), 2138; https://doi.org/10.3390/cancers16112138 - 4 Jun 2024
Abstract
Artificial intelligence (AI), encompassing machine learning (ML) and deep learning (DL), has revolutionized medical research, facilitating advancements in drug discovery and cancer diagnosis. ML identifies patterns in data, while DL employs neural networks for intricate processing. Predictive modeling challenges, such as data labeling,
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Artificial intelligence (AI), encompassing machine learning (ML) and deep learning (DL), has revolutionized medical research, facilitating advancements in drug discovery and cancer diagnosis. ML identifies patterns in data, while DL employs neural networks for intricate processing. Predictive modeling challenges, such as data labeling, are addressed by transfer learning (TL), leveraging pre-existing models for faster training. TL shows potential in genetic research, improving tasks like gene expression analysis, mutation detection, genetic syndrome recognition, and genotype–phenotype association. This review explores the role of TL in overcoming challenges in mutation detection, genetic syndrome detection, gene expression, or phenotype–genotype association. TL has shown effectiveness in various aspects of genetic research. TL enhances the accuracy and efficiency of mutation detection, aiding in the identification of genetic abnormalities. TL can improve the diagnostic accuracy of syndrome-related genetic patterns. Moreover, TL plays a crucial role in gene expression analysis in order to accurately predict gene expression levels and their interactions. Additionally, TL enhances phenotype–genotype association studies by leveraging pre-trained models. In conclusion, TL enhances AI efficiency by improving mutation prediction, gene expression analysis, and genetic syndrome detection. Future studies should focus on increasing domain similarities, expanding databases, and incorporating clinical data for better predictions.
Full article
(This article belongs to the Topic Artificial Intelligence in Cancer Pathology and Prognosis)
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Open AccessArticle
Prognostic Impact and Clinical Implications of Adverse Tumor Grade in Very Favorable Low- and Intermediate-Risk Prostate Cancer Patients Treated with Robot-Assisted Radical Prostatectomy: Experience of a Single Tertiary Referral Center
by
Antonio Benito Porcaro, Alberto Bianchi, Sebastian Gallina, Andrea Panunzio, Alessandro Tafuri, Emanuele Serafin, Rossella Orlando, Giovanni Mazzucato, Paola Irene Ornaghi, Francesco Cianflone, Francesca Montanaro, Francesco Artoni, Alberto Baielli, Francesco Ditonno, Filippo Migliorini, Matteo Brunelli, Salvatore Siracusano, Maria Angela Cerruto and Alessandro Antonelli
Cancers 2024, 16(11), 2137; https://doi.org/10.3390/cancers16112137 - 4 Jun 2024
Abstract
Objectives: To assess the prognostic impact and predictors of adverse tumor grade in very favorable low- and intermediate-risk prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP). Methods: Data of low- and intermediate PCa risk-class patients were retrieved from a prospectively maintained
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Objectives: To assess the prognostic impact and predictors of adverse tumor grade in very favorable low- and intermediate-risk prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP). Methods: Data of low- and intermediate PCa risk-class patients were retrieved from a prospectively maintained institutional database. Adverse tumor grade was defined as pathology ISUP grade group > 2. Disease progression was defined as a biochemical recurrence event and/or local recurrence and/or distant metastases. Associations were assessed by Cox’s proportional hazards and logistic regression model. Results: Between January 2013 and October 2020, the study evaluated a population of 289 patients, including 178 low-risk cases (61.1%) and 111 intermediate-risk subjects (38.4%); unfavorable tumor grade was detected in 82 cases (28.4%). PCa progression, which occurred in 29 patients (10%), was independently predicted by adverse tumor grade and biopsy ISUP grade group 2, with the former showing stronger associations (hazard ratio, HR = 4.478; 95% CI: 1.840–10.895; p = 0.001) than the latter (HR = 2.336; 95% CI: 1.057–5.164; p = 0.036). Older age and biopsy ISUP grade group 2 were independent clinical predictors of adverse tumor grade, associated with larger tumors that eventually presented non-organ-confined disease. Conclusions: In a very favorable PCa patient population, adverse tumor grade was an unfavorable prognostic factor for disease progression. Active surveillance in very favorable intermediate-risk patients is still a hazard, so molecular and genetic testing of biopsy specimens is needed.
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(This article belongs to the Special Issue Robot-Assisted Radical Prostatectomy for Urologic Cancer: State of the Art)
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Open AccessArticle
Site-Specific Response and Resistance Patterns in Patients with Advanced Non-Small-Cell Lung Cancer Treated with First-Line Systemic Therapy
by
Lauren Julia Brown, Julie Ahn, Bo Gao, Harriet Gee, Adnan Nagrial, Eric Hau and Inês Pires da Silva
Cancers 2024, 16(11), 2136; https://doi.org/10.3390/cancers16112136 - 4 Jun 2024
Abstract
Patients with advanced NSCLC have heterogenous responses to immune checkpoint inhibitors (ICIs) with or without chemotherapy. In NSCLC, the impact of the distribution of metastatic sites and the response to systemic therapy combinations remain poorly understood. In a retrospective cohort study of patients
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Patients with advanced NSCLC have heterogenous responses to immune checkpoint inhibitors (ICIs) with or without chemotherapy. In NSCLC, the impact of the distribution of metastatic sites and the response to systemic therapy combinations remain poorly understood. In a retrospective cohort study of patients with unresectable stage III/IV NSCLC who received first-line systemic therapy, we sought to assess the association between the site of metastases with patterns of response and progression. Data regarding demographics, tumour characteristics (including site, size, and volume of metastases), treatment, and outcomes were examined at two cancer care centres. The endpoints included organ site-specific response rate, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Two-hundred and eighty-five patients were included in the analysis. In a multivariate analysis, patients with bone metastases had a reduced ORR, PFS, and OS. Primary resistance was also more likely in patients with bone metastases. Patients with bone or liver metastases had a shorter OS when receiving ICIs with or without chemotherapy, but not with chemotherapy alone, suggesting an immunological basis for therapeutic resistance. A directed assessment of the tumour microenvironment in these locations and a deeper understanding of the drivers of organ-specific resistance to immunotherapy are critical to optimise novel combination therapies and sequencing in these patients.
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(This article belongs to the Special Issue Immunotherapy with Checkpoint Inhibitors for Non-small Cell Lung Cancer)
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Open AccessReview
Topical and Intralesional Immunotherapy for the Management of Basal Cell Carcinoma
by
Aurora Fernández-Galván, Pedro Rodríguez-Jiménez, Beatriz González-Sixto, María Teresa Abalde-Pintos and Beatriz Butrón-Bris
Cancers 2024, 16(11), 2135; https://doi.org/10.3390/cancers16112135 - 4 Jun 2024
Abstract
Basal Cell Carcinoma (BCC) is the most common type of cancer among the white population. Individuals with fair skin have an average lifetime risk of around 30% for developing BCC, and there is a noticeable upward trend in its incidence rate. The principal
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Basal Cell Carcinoma (BCC) is the most common type of cancer among the white population. Individuals with fair skin have an average lifetime risk of around 30% for developing BCC, and there is a noticeable upward trend in its incidence rate. The principal treatment objectives for BCC involve achieving the total excision of the tumor while maximizing the preservation of function and cosmesis. Surgery is considered the treatment of choice for BCC for two main reasons: it allows for the highest cure rates and facilitates histological control of resection margins. However, in the subgroup of patients with low-risk recurrence or medical contraindications for surgery, new non-surgical treatment alternatives can provide an excellent oncological and cosmetic outcome. An evident and justified instance of these local therapies occurred during the COVID-19 pandemic, a period when surgical interventions carried out in hospital settings were not a viable option.
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(This article belongs to the Special Issue Topical and Intralesional Immunotherapy for Skin Cancer)
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Open AccessReview
Prevention of Brain Metastases: A New Frontier
by
Alessia Pellerino, Tara Marie Davidson, Shreyas S. Bellur, Manmeet S. Ahluwalia, Hussein Tawbi, Roberta Rudà and Riccardo Soffietti
Cancers 2024, 16(11), 2134; https://doi.org/10.3390/cancers16112134 - 4 Jun 2024
Abstract
This review discusses the topic of prevention of brain metastases from the most frequent solid tumor types, i.e., lung cancer, breast cancer and melanoma. Within each tumor type, the risk of brain metastasis is related to disease status and molecular subtype (i.e., EGFR-mutant
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This review discusses the topic of prevention of brain metastases from the most frequent solid tumor types, i.e., lung cancer, breast cancer and melanoma. Within each tumor type, the risk of brain metastasis is related to disease status and molecular subtype (i.e., EGFR-mutant non-small cell lung cancer, HER2-positive and triple-negative breast cancer, BRAF and NRAF-mutant melanoma). Prophylactic cranial irradiation is the standard of care in patients in small cell lung cancer responsive to chemotherapy but at the price of late neurocognitive decline. More recently, several molecular agents with the capability to target molecular alterations driving tumor growth have proven as effective in the prevention of secondary relapse into the brain in clinical trials. This is the case for EGFR-mutant or ALK-rearranged non-small cell lung cancer inhibitors, tucatinib and trastuzumab–deruxtecan for HER2-positive breast cancer and BRAF inhibitors for melanoma. The need for screening with an MRI in asymptomatic patients at risk of brain metastases is emphasized.
Full article
(This article belongs to the Section Cancer Metastasis)
Open AccessArticle
A Phase II Trial of Bevacizumab in Patients with Recurrent/Progressive Solid Tumor Brain Metastases That Have Progressed Following Whole-Brain Radiation Therapy
by
Karan Dixit, Lauren Singer, Sean Aaron Grimm, Rimas V. Lukas, Margaret A. Schwartz, Alfred Rademaker, Hui Zhang, Masha Kocherginsky, Sofia Chernet, Laura Sharp, Valerie Nelson, Jeffrey J. Raizer and Priya Kumthekar
Cancers 2024, 16(11), 2133; https://doi.org/10.3390/cancers16112133 - 4 Jun 2024
Abstract
Patients with solid tumor brain metastases that progress after whole-brain radiation have limited options. This prospective trial investigated the efficacy, safety, and tolerability of bevacizumab as salvage therapy in this population. Eligible patients received bevacizumab 10 mg/kg intravenously every 2 weeks until progression.
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Patients with solid tumor brain metastases that progress after whole-brain radiation have limited options. This prospective trial investigated the efficacy, safety, and tolerability of bevacizumab as salvage therapy in this population. Eligible patients received bevacizumab 10 mg/kg intravenously every 2 weeks until progression. The primary endpoint was radiologic response using Response Assessment in Neuro-Oncology (RANO) criteria. The secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response, and safety. Quality of life (QOL) was studied using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) scale. Twenty-seven patients were enrolled, with twenty-four having evaluable data for response. The majority of histologies (n = 21, 78%) were breast cancer. The remaining histologies were non-small-cell lung cancer (n = 4, 15%), neuroendocrine cancer (n = 1, 3%), and papillary fallopian serous adenocarcinoma (n = 1, 3%). Eighteen patients had radiologic response, with two patients demonstrating partial response (8.33%) and sixteen patients demonstrating stable disease (66.7%). The median duration of response was 203 days. PFS at 6 months was 46%, median PFS was 5.3 m, and median OS was 9.5 m. Treatment was well tolerated, with six patients experiencing grade 3 lymphopenia and hypertension. There was one grade 3 thromboembolism. QOL was not negatively impacted. Bevacizumab is a safe and feasible salvage treatment with durable response and favorable overall survival for patients with progressive brain metastases after whole-brain radiation.
Full article
(This article belongs to the Special Issue Brain Metastases: Diagnosis and Treatment)
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