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Cancers, Volume 15, Issue 18 (September-2 2023) – 249 articles

Cover Story (view full-size image): Primary tumor invasiveness and metastasis formation at distant sites strongly impact the prognosis and quality of life of cancer patients. A better understanding of these mechanisms and the development of new therapies are urgently needed. Extracellular vesicles (EVs) are lipid-enveloped particles involved in inter-tissue and inter-cell communication. This review article focuses on the impact of EVs released by tumor cells, specifically on cancer cell migration and metastasis and on the development of EV-based therapeutic approaches. Moreover, we propose EV sorting as a route alternative to secretion or cell membrane binding, influencing downstream signaling and the final effect on target cells, with strong implications for tumorigenesis. View this paper
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23 pages, 3664 KiB  
Review
An Observatory for the MET Oncogene: A Guide for Targeted Therapies
by Dogus M. Altintas and Paolo M. Comoglio
Cancers 2023, 15(18), 4672; https://doi.org/10.3390/cancers15184672 - 21 Sep 2023
Viewed by 1248
Abstract
The MET proto-oncogene encodes a pivotal tyrosine kinase receptor, binding the hepatocyte growth factor (HGF, also known as scatter factor, SF) and governing essential biological processes such as organogenesis, tissue repair, and angiogenesis. The pleiotropic physiological functions of MET explain its diverse role [...] Read more.
The MET proto-oncogene encodes a pivotal tyrosine kinase receptor, binding the hepatocyte growth factor (HGF, also known as scatter factor, SF) and governing essential biological processes such as organogenesis, tissue repair, and angiogenesis. The pleiotropic physiological functions of MET explain its diverse role in cancer progression in a broad range of tumors; genetic/epigenetic alterations of MET drive tumor cell dissemination, metastasis, and acquired resistance to conventional and targeted therapies. Therefore, targeting MET emerged as a promising strategy, and many efforts were devoted to identifying the optimal way of hampering MET signaling. Despite encouraging results, however, the complexity of MET’s functions in oncogenesis yields intriguing observations, fostering a humbler stance on our comprehension. This review explores recent discoveries concerning MET alterations in cancer, elucidating their biological repercussions, discussing therapeutic avenues, and outlining future directions. By contextualizing the research question and articulating the study’s purpose, this work navigates MET biology’s intricacies in cancer, offering a comprehensive perspective. Full article
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14 pages, 1302 KiB  
Article
Outcomes of Chimeric Antigen Receptor (CAR) T-Cell Therapy in Patients with Large B-Cell Lymphoma (LBCL): A Single-Institution Experience
by Aaron Trando, Anna Ter-Zakarian, Phillip Yeung, Aaron M. Goodman, Ayad Hamdan, Michael Hurley, Ah-Reum Jeong and Dimitrios Tzachanis
Cancers 2023, 15(18), 4671; https://doi.org/10.3390/cancers15184671 - 21 Sep 2023
Viewed by 1374
Abstract
Chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionized the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We describe the real-world baseline characteristics, efficacy, safety, and post-relapse outcomes of adult patients with R/R LBCL who received CAR T-cell therapy at the University [...] Read more.
Chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionized the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We describe the real-world baseline characteristics, efficacy, safety, and post-relapse outcomes of adult patients with R/R LBCL who received CAR T-cell therapy at the University of California San Diego. A total of 66 patients with LBCL were treated with tisagenlecleucel or axicabtagene ciloleucel. The median age was 59.5, and 21% were over 70 years old. Additionally, 20% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance score of ≥2. Cytokine release syndrome incidence was 88%; immune effector cell-associated neurotoxicity syndrome incidence was 56%. All-grade infection occurred in 48% of patients and in 79% of patients > 70 years old. Complete response (CR) was achieved in 53% and partial response in 14%. Median progression-free survival (PFS) was 10.3 months; median overall survival (OS) was 28.4 months. Patients who relapsed post-CAR T-cell therapy had poor outcomes, with a median OS2 of 4.8 months. Upon multivariate analysis, both ECOG (HR 2.65, 95% CI: 1.30–5.41; p = 0.007) and ≥2 sites of extranodal involvement (HR 2.22, 95% CI: 1.15–4.31; p = 0.018) were significant predictors of PFS. Twenty-six patients were R/R to CAR T-cell therapy; six patients were in remission at the time of data cut off, one of whom received allogeneic transplant. Overall, older patients can safely undergo CAR T-cell therapy, despite the increased risk of all-grade infection. In our cohort, ECOG performance score and ≥2 sites of extranodal disease are significant predictors of PFS. Full article
(This article belongs to the Special Issue CAR T-cell Therapy for Lymphoma Research)
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14 pages, 581 KiB  
Article
Predicting Risk of Severe Toxicity and Early Death in Older Adult Patients Treated with Chemotherapy
by Jaime Feliu, Ana Belén Custodio, Alvaro Pinto-Marín, Oliver Higuera, Miriam Pérez-González, Laura del Pino, Leticia Ruiz-Jiménez, Darío Sánchez-Cabero, Isabel Viera, Ana Jurado and Enrique Espinosa
Cancers 2023, 15(18), 4670; https://doi.org/10.3390/cancers15184670 - 21 Sep 2023
Viewed by 1014
Abstract
Background: Determining the risk of grade 3–5 toxicity and early death (ED) is important to plan chemotherapy in older adult patients with cancer. Our objective was to identify factors predicting these complications at the time of treatment initiation. Methods: 234 patients aged ≥70 [...] Read more.
Background: Determining the risk of grade 3–5 toxicity and early death (ED) is important to plan chemotherapy in older adult patients with cancer. Our objective was to identify factors predicting these complications at the time of treatment initiation. Methods: 234 patients aged ≥70 were subjected to a geriatric assessment and variables related to the tumor and the treatment were also collected. Logistic regression multivariable analysis was used to relate these factors with the appearance of grade 3–5 toxicity and ED. Predictive scores for both toxicity and ED were then developed. Results: Factors related to grade 3–5 toxicity were hemoglobin, MAX2 index, ADL, and the CONUT score. Factors related to ED were tumor stage and the GNRI score. Two predictive scores were developed using these variables. ROC curves for the prediction of toxicity and ED were 0.71 (95% CI: 0.64–0.78) and 0.73 (95% CI: 0.68–0.79), respectively. Conclusions: Two simple and reliable scores were developed to predict grade 3–5 toxicity and ED in older adult patients with cancer. This may be helpful in treatment planning. Full article
(This article belongs to the Special Issue Combination Therapy in Geriatric Population with Cancer)
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20 pages, 918 KiB  
Review
Trial Design for Cancer Immunotherapy: A Methodological Toolkit
by Everardo D. Saad, Elisabeth Coart, Vaiva Deltuvaite-Thomas, Leandro Garcia-Barrado, Tomasz Burzykowski and Marc Buyse
Cancers 2023, 15(18), 4669; https://doi.org/10.3390/cancers15184669 - 21 Sep 2023
Viewed by 1200
Abstract
Immunotherapy with checkpoint inhibitors (CPIs) and cell-based products has revolutionized the treatment of various solid tumors and hematologic malignancies. These agents have shown unprecedented response rates and long-term benefits in various settings. These clinical advances have also pointed to the need for new [...] Read more.
Immunotherapy with checkpoint inhibitors (CPIs) and cell-based products has revolutionized the treatment of various solid tumors and hematologic malignancies. These agents have shown unprecedented response rates and long-term benefits in various settings. These clinical advances have also pointed to the need for new or adapted approaches to trial design and assessment of efficacy and safety, both in the early and late phases of drug development. Some of the conventional statistical methods and endpoints used in other areas of oncology appear to be less appropriate in immuno-oncology. Conversely, other methods and endpoints have emerged as alternatives. In this article, we discuss issues related to trial design in the early and late phases of drug development in immuno-oncology, with a focus on CPIs. For early trials, we review the most salient issues related to dose escalation, use and limitations of tumor response and progression criteria for immunotherapy, the role of duration of response as an endpoint in and of itself, and the need to conduct randomized trials as early as possible in the development of new therapies. For late phases, we discuss the choice of primary endpoints for randomized trials, review the current status of surrogate endpoints, and discuss specific statistical issues related to immunotherapy, including non-proportional hazards in the assessment of time-to-event endpoints, alternatives to the Cox model in these settings, and the method of generalized pairwise comparisons, which can provide a patient-centric assessment of clinical benefit and be used to design randomized trials. Full article
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24 pages, 2044 KiB  
Review
Can Exercise Enhance the Efficacy of Checkpoint Inhibition by Modulating Anti-Tumor Immunity?
by Christina Brummer, Tobias Pukrop, Joachim Wiskemann, Christina Bruss, Ines Ugele and Kathrin Renner
Cancers 2023, 15(18), 4668; https://doi.org/10.3390/cancers15184668 - 21 Sep 2023
Cited by 2 | Viewed by 1722
Abstract
Immune checkpoint inhibition (ICI) has revolutionized cancer therapy. However, response to ICI is often limited to selected subsets of patients or not durable. Tumors that are non-responsive to checkpoint inhibition are characterized by low anti-tumoral immune cell infiltration and a highly immunosuppressive tumor [...] Read more.
Immune checkpoint inhibition (ICI) has revolutionized cancer therapy. However, response to ICI is often limited to selected subsets of patients or not durable. Tumors that are non-responsive to checkpoint inhibition are characterized by low anti-tumoral immune cell infiltration and a highly immunosuppressive tumor microenvironment. Exercise is known to promote immune cell circulation and improve immunosurveillance. Results of recent studies indicate that physical activity can induce mobilization and redistribution of immune cells towards the tumor microenvironment (TME) and therefore enhance anti-tumor immunity. This suggests a favorable impact of exercise on the efficacy of ICI. Our review delivers insight into possible molecular mechanisms of the crosstalk between muscle, tumor, and immune cells. It summarizes current data on exercise-induced effects on anti-tumor immunity and ICI in mice and men. We consider preclinical and clinical study design challenges and discuss the role of cancer type, exercise frequency, intensity, time, and type (FITT) and immune sensitivity as critical factors for exercise-induced impact on cancer immunosurveillance. Full article
(This article belongs to the Special Issue The Role of Immunity in the Tumor Microenvironment)
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13 pages, 862 KiB  
Article
Daratumumab, Bortezomib, and Dexamethasone for Treatment of Patients with Relapsed or Refractory Multiple Myeloma and Severe Renal Impairment: Results from the Phase 2 GMMG-DANTE Trial
by Lisa B. Leypoldt, Maria Gavriatopoulou, Britta Besemer, Hans Salwender, Marc S. Raab, Axel Nogai, Cyrus Khandanpour, Volker Runde, Anna Jauch, Manola Zago, Peter Martus, Hartmut Goldschmidt, Carsten Bokemeyer, Meletios A. Dimopoulos and Katja C. Weisel
Cancers 2023, 15(18), 4667; https://doi.org/10.3390/cancers15184667 - 21 Sep 2023
Viewed by 1225
Abstract
Renal function impairment (RI) is a common complication in multiple myeloma (MM). However, limited data exist on the safety and efficacy of anti-MM regimens in patients with severe RI, as these patients are frequently excluded from clinical trials. This investigator-initiated multicentric phase II [...] Read more.
Renal function impairment (RI) is a common complication in multiple myeloma (MM). However, limited data exist on the safety and efficacy of anti-MM regimens in patients with severe RI, as these patients are frequently excluded from clinical trials. This investigator-initiated multicentric phase II GMMG-DANTE trial evaluated daratumumab, bortezomib, and dexamethasone (DVd) in relapsed or refractory (r/r) MM patients with severe RI. r/rMM patients with ≥1 prior treatment line and a GFR <30 mL/min/1.73 m2 or undergoing hemodialysis were eligible and received eight cycles of DVd followed by daratumumab maintenance. The trial closed prematurely after 22/36 planned patients. The primary endpoint was overall response rate (ORR). Median age of patients was 70 (range 55–89) years, with a median GFR of 20.1 mL/min/1.73 m2 (interquartile range, 9.4–27.3 mL/min/1.73 m2), and eight patients under hemodialysis. Median number of prior lines was two (range 1–10). The trial was successful, albeit with premature termination, as it met its primary endpoint, with an ORR of 67% (14/21). The rates of partial response, very good partial response, and complete response were 29%, 29%, and 10%, respectively (n = 6, 6, and 2). Fourteen patients (67%) achieved renal response. After median follow-up of 28 months, median progression-free survival was 10.4 months; median overall survival was not reached. Higher-grade toxicity was mainly hematologic, and non-hematologic toxicities ≥Grade 3 were mostly infections (24%). The prospective GMMG-DANTE trial investigating DVd exclusively in r/rMM patients with severe RI showed efficacy and safety to be comparable to data from patients without RI. Full article
(This article belongs to the Special Issue Novel Therapeutic Targets for the Treatment of Multiple Myeloma)
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32 pages, 6038 KiB  
Review
Image-Guided Precision Medicine in the Diagnosis and Treatment of Pheochromocytomas and Paragangliomas
by Gildas Gabiache, Charline Zadro, Laura Rozenblum, Delphine Vezzosi, Céline Mouly, Matthieu Thoulouzan, Rosine Guimbaud, Philippe Otal, Lawrence Dierickx, Hervé Rousseau, Christopher Trepanier, Laurent Dercle and Fatima-Zohra Mokrane
Cancers 2023, 15(18), 4666; https://doi.org/10.3390/cancers15184666 - 21 Sep 2023
Cited by 2 | Viewed by 1261
Abstract
In this comprehensive review, we aimed to discuss the current state-of-the-art medical imaging for pheochromocytomas and paragangliomas (PPGLs) diagnosis and treatment. Despite major medical improvements, PPGLs, as with other neuroendocrine tumors (NETs), leave clinicians facing several challenges; their inherent particularities and their diagnosis [...] Read more.
In this comprehensive review, we aimed to discuss the current state-of-the-art medical imaging for pheochromocytomas and paragangliomas (PPGLs) diagnosis and treatment. Despite major medical improvements, PPGLs, as with other neuroendocrine tumors (NETs), leave clinicians facing several challenges; their inherent particularities and their diagnosis and treatment pose several challenges for clinicians due to their inherent complexity, and they require management by multidisciplinary teams. The conventional concepts of medical imaging are currently undergoing a paradigm shift, thanks to developments in radiomic and metabolic imaging. However, despite active research, clinical relevance of these new parameters remains unclear, and further multicentric studies are needed in order to validate and increase widespread use and integration in clinical routine. Use of AI in PPGLs may detect changes in tumor phenotype that precede classical medical imaging biomarkers, such as shape, texture, and size. Since PPGLs are rare, slow-growing, and heterogeneous, multicentric collaboration will be necessary to have enough data in order to develop new PPGL biomarkers. In this nonsystematic review, our aim is to present an exhaustive pedagogical tool based on real-world cases, dedicated to physicians dealing with PPGLs, augmented by perspectives of artificial intelligence and big data. Full article
(This article belongs to the Special Issue Cancer: Updates on Imaging and Machine Learning)
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22 pages, 4318 KiB  
Article
Identification of Potentially Novel Molecular Targets of Endometrial Cancer Using a Non-Biased Proteomic Approach
by Anthony H. Taylor, Justin C. Konje and Thangesweran Ayakannu
Cancers 2023, 15(18), 4665; https://doi.org/10.3390/cancers15184665 - 21 Sep 2023
Viewed by 1019
Abstract
The present study was aimed at identifying novel proteins in endometrial cancer (EC), employing proteomic analysis of tissues obtained after surgery. A differential MS-based proteomic analysis was conducted from whole tissues dissected from biopsies from post-menopausal women, histologically confirmed as endometrial cancer (two [...] Read more.
The present study was aimed at identifying novel proteins in endometrial cancer (EC), employing proteomic analysis of tissues obtained after surgery. A differential MS-based proteomic analysis was conducted from whole tissues dissected from biopsies from post-menopausal women, histologically confirmed as endometrial cancer (two endometrioid and two serous; n = 4) or normal atrophic endometrium (n = 4), providing 888 differentially expressed proteins with 246 of these previously documented elsewhere as expressed in EC and 372 proteins not previously demonstrated to be expressed in EC but associated with other types of cancer. Additionally, 33 proteins not recorded previously in PubMed as being expressed in any forms of cancer were also identified, with only 26 of these proteins having a publication associated with their expression patterns or putative functions. The putative functions of the 26 proteins (GRN, APP, HEXA, CST3, CAD, QARS, SIAE, WARS, MYH8, CLTB, GOLIM4, SCARB2, BOD1L1, C14orf142, C9orf142, CCDC13, CNPY4, FAM169A, HN1L, PIGT, PLCL1, PMFBP1, SARS2, SCPEP1, SLC25A24 and ZC3H4) in other tissues point towards and provide a basis for further investigation of these previously unrecognised novel EC proteins. The developmental biology, disease, extracellular matrix, homeostatic, immune, metabolic (both RNA and protein), programmed cell death, signal transduction, molecular transport, transcriptional networks and as yet uncharacterised pathways indicate that these proteins are potentially involved in endometrial carcinogenesis and thus may be important in EC diagnosis, prognostication and treatment and thus are worthy of further investigation. Full article
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10 pages, 5327 KiB  
Article
Proximal Tibia Tumour Location and Curettage Are Major Risk Factors of Local Recurrence in Giant Cell Tumour of Bone
by Michal Mahdal, Tomáš Tomáš, Vasileios Apostolopoulos, Dagmar Adámková, Peter Múdry, Iva Staniczková Zambo and Lukáš Pazourek
Cancers 2023, 15(18), 4664; https://doi.org/10.3390/cancers15184664 - 21 Sep 2023
Viewed by 853
Abstract
Giant cell tumour of bone (GCTB) is one of the most common local aggressive tumourous lesions with a wide variety of biological behaviour. However, there are no clear indicative criteria when choosing the type of procedure and the complication rates remain high, especially [...] Read more.
Giant cell tumour of bone (GCTB) is one of the most common local aggressive tumourous lesions with a wide variety of biological behaviour. However, there are no clear indicative criteria when choosing the type of procedure and the complication rates remain high, especially in terms of local recurrence. The purpose of the study was to (1) identify the main risk factors for local recurrence, (2) evaluate the recurrence-free survival in dependence on neoadjuvant denosumab use and the type of procedure, and (3) compare the functional outcomes after curettage and en bloc resection. The group included 102 patients with GCTB treated between 2006 and 2020. The mean age of patients was 34.4 years (15–79). The follow-up period was 8.32 years (2–16) on average. Local recurrence occurred in 14 patients (29.8%) who underwent curettage and in 5 patients (10.6%) after en bloc resection. Curettage was shown to be a factor in increasing recurrence rates (OR = 3.64 [95% CI: 1.19–11.15]; p = 0.023). Tibial location was an independent risk factor for local recurrence regardless of the type of surgery (OR = 3.22 [95% CI: 1.09–9.48]; p = 0.026). The recurrence-free survival rate of patients treated with resection and denosumab was higher compared to other treatments at five years postoperatively (p = 0.0307). Functional ability and pain as reported by patients at the latest follow-up were superior after curettage compared to resection for upper and lower extremity (mean difference: −4.00 [95% CI: –6.81 to −1.18]; p < 0.001 and mean difference: −5.36 [95% CI: −3.74 to −6.97]; p < 0.001, respectively). Proximal tibia tumour location and curettage were shown to be major risk factors for local recurrence in GCTB regardless of neoadjuvant denosumab treatment. The recurrence-free survival rate of patients treated with resection and denosumab was higher compared to other treatments. The functional outcome of patients after curettage was better compared to en bloc resection. Full article
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11 pages, 2490 KiB  
Article
Polo-like Kinase 4: A Multifaceted Marker Linking Tumor Aggressiveness and Unfavorable Prognosis, and Insights into Therapeutic Strategies
by Youngtaek Kim, Joon Yeon Hwang, Dong Kwon Kim, Kwangmin Na, Seul Lee, Sujeong Baek, Seong-san Kang, Seung Min Yang, Mi Hyun Kim, Heekyung Han, Chai Young Lee, Yu Jin Han, Min Hee Hong, Jii Bum Lee, Sun Min Lim, Byoung Chul Cho, Youngjoon Park and Kyoung-Ho Pyo
Cancers 2023, 15(18), 4663; https://doi.org/10.3390/cancers15184663 - 21 Sep 2023
Viewed by 1104
Abstract
(1) Background: This study investigated whether polo-like kinase 4 (PLK4) is a suitable therapeutic target or biomarker for lung adenocarcinoma (LUAD). (2) Methods: We acquired LUAD data from The Cancer Genome Atlas (TCGA) database through the UCSC Xena data portal. Gene expression, clinical, [...] Read more.
(1) Background: This study investigated whether polo-like kinase 4 (PLK4) is a suitable therapeutic target or biomarker for lung adenocarcinoma (LUAD). (2) Methods: We acquired LUAD data from The Cancer Genome Atlas (TCGA) database through the UCSC Xena data portal. Gene expression, clinical, survival, and mutation data from multiple samples were analyzed. Gene enrichment analysis, unsupervised clustering of PLK4-related pathways, and differential gene expression analyses were performed. Additionally, correlations, t-tests, survival analyses, and statistical analyses were performed. (3) Results: PLK4 expression was higher in LUAD tissues than in normal tissues and was associated with poor prognosis for both overall and progression-free survival in LUAD. PLK4 was highly correlated with cell-proliferation-related pathways using Gene Ontology (GO) biological process terms. PLK4 expression and pathways that were highly correlated with PLK4 expression levels were upregulated in patients with LUAD with the TP53 mutation. (4) Conclusions: PLK4 expression affects the survival of patients with LUAD and is a potential therapeutic target for LUAD with TP53 mutations. Full article
(This article belongs to the Section Cancer Biomarkers)
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16 pages, 4449 KiB  
Article
MRI Assessment of Changes in Tumor Vascularization during Neoadjuvant Anti-Angiogenic Treatment in Locally Advanced Breast Cancer Patients
by Torgeir Mo, Siri Helene Bertelsen Brandal, Oliver Marcel Geier, Olav Engebråten, Line Brennhaug Nilsen, Vessela N. Kristensen, Knut Håkon Hole, Tord Hompland, Thomas Fleischer and Therese Seierstad
Cancers 2023, 15(18), 4662; https://doi.org/10.3390/cancers15184662 - 21 Sep 2023
Viewed by 882
Abstract
Anti-VEGF (vascular endothelial growth factor) treatment improves response rates, but not progression-free or overall survival in advanced breast cancer. It has been suggested that subgroups of patients may benefit from this treatment; however, the effects of adding anti-VEGF treatment to a standard chemotherapy [...] Read more.
Anti-VEGF (vascular endothelial growth factor) treatment improves response rates, but not progression-free or overall survival in advanced breast cancer. It has been suggested that subgroups of patients may benefit from this treatment; however, the effects of adding anti-VEGF treatment to a standard chemotherapy regimen in breast cancer patients are not well studied. Understanding the effects of the anti-vascular treatment on tumor vasculature may provide a selection of patients that can benefit. The aim of this study was to study the vascular effect of bevacizumab using clinical dynamic contrast-enhanced MRI (DCE-MRI). A total of 70 women were randomized to receive either chemotherapy alone or chemotherapy with bevacizumab for 25 weeks. DCE-MRI was performed at baseline and at 12 and 25 weeks, and in addition 25 of 70 patients agreed to participate in an early MRI after one week. Voxel-wise pharmacokinetic analysis was performed using semi-quantitative methods and the extended Tofts model. Vascular architecture was assessed by calculating the fractal dimension of the contrast-enhanced images. Changes during treatment were compared with baseline and between the treatment groups. There was no significant difference in tumor volume at any point; however, DCE-MRI parameters revealed differences in vascular function and vessel architecture. Adding bevacizumab to chemotherapy led to a pronounced reduction in vascular DCE-MRI parameters, indicating decreased vascularity. At 12 and 25 weeks, the difference between the treatment groups is severely reduced. Full article
(This article belongs to the Special Issue Imaging the Tumor Microenvironment)
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16 pages, 6135 KiB  
Article
Radiomics Features on Magnetic Resonance Images Can Predict C5aR1 Expression Levels and Prognosis in High-Grade Glioma
by Zijun Wu, Yuan Yang and Yunfei Zha
Cancers 2023, 15(18), 4661; https://doi.org/10.3390/cancers15184661 - 21 Sep 2023
Cited by 1 | Viewed by 744
Abstract
Background: The complement component C5a receptor 1 (C5aR1) regulates cancer immunity. This retrospective study aimed to assess its prognostic value in high-grade glioma (HGG) and predict C5aR1 expression using a radiomics approach. Methods: Among 298 patients with HGG, 182 with MRI data were [...] Read more.
Background: The complement component C5a receptor 1 (C5aR1) regulates cancer immunity. This retrospective study aimed to assess its prognostic value in high-grade glioma (HGG) and predict C5aR1 expression using a radiomics approach. Methods: Among 298 patients with HGG, 182 with MRI data were randomly divided into training and test groups for radiomics analysis. We examined the association between C5aR1 expression and prognosis through Kaplan–Meier and Cox regression analyses. We used maximum relevance–minimum redundancy and recursive feature elimination algorithms for radiomics feature selection. We then built a support vector machine (SVM) and a logistic regression model, investigating their performances using receiver operating characteristic, calibration curves, and decision curves. Results: C5aR1 expression was elevated in HGG and was an independent prognostic factor (hazard ratio = 3.984, 95% CI: 2.834–5.607). Both models presented with >0.8 area under the curve values in the training and test datasets, indicating efficient discriminatory ability, with SVM performing marginally better. The radiomics score calculated using the SVM model correlated significantly with overall survival (p < 0.01). Conclusions: Our results highlight C5aR1’s role in HGG development and prognosis, supporting its potential as a prognostic biomarker. Our radiomics model can noninvasively and effectively predict C5aR1 expression and patient prognosis in HGG. Full article
(This article belongs to the Collection Radiomics and Cancers)
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14 pages, 1453 KiB  
Article
The Association between Lymph Node Dissection and Survival in Lymph Node-Negative Upper Urinary Tract Urothelial Cancer
by Aleksander Ślusarczyk, Piotr Zapała, Tomasz Piecha, Paweł Rajwa, Marco Moschini and Piotr Radziszewski
Cancers 2023, 15(18), 4660; https://doi.org/10.3390/cancers15184660 - 21 Sep 2023
Cited by 1 | Viewed by 750
Abstract
The benefit of lymph node dissection (LND) during radical nephroureterectomy (RNU) in lymph node (LN)-negative (cN0/pN0) UTUC remains controversial. We aimed to assess the association between LND and its extent and survival in LN-negative UTUC. The Surveillance, Epidemiology, and End Results database was [...] Read more.
The benefit of lymph node dissection (LND) during radical nephroureterectomy (RNU) in lymph node (LN)-negative (cN0/pN0) UTUC remains controversial. We aimed to assess the association between LND and its extent and survival in LN-negative UTUC. The Surveillance, Epidemiology, and End Results database was searched to identify patients with non-metastatic chemotherapy-naïve cN0/pNx or pN0 UTUC who underwent RNU +/− LND between 2004 and 2019. Overall, 4649 patients with cN0/pNx or pN0 UTUC were analyzed, including 909 (19.55%) individuals who had LND. Among them, only in 368 patients (7.92%) was LND extended to at least four LNs, and the remaining 541 patients (11.64%) have had < four LNs removed. In the whole cohort, LND contributed to better cancer-specific survival (CSS) and overall survival (OS). Furthermore, a propensity score-matched analysis adjusted for confounders confirmed that improved CSS and OS was achieved only when ≥ four LNs had been removed, especially in muscle-invasive UTUC. A multivariable analysis further confirmed an association between the extent of LND and CSS. To conclude, adequate LND during RNU was associated with improved OS and CSS in LN-negative UTUC, particularly in muscle-invasive stage. This underscores that a sufficient LN yield is required to reveal a therapeutic benefit in patients undergoing RNU. Full article
(This article belongs to the Special Issue Clinical Outcomes in Urologic Cancers)
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7 pages, 225 KiB  
Editorial
Epstein–Barr Virus Infection in Cancer
by Lucia Mundo, Lorenzo Leoncini and Rosita Accardi-Gheit
Cancers 2023, 15(18), 4659; https://doi.org/10.3390/cancers15184659 - 21 Sep 2023
Viewed by 1554
Abstract
EBV was the first human oncogenic virus identified [...] Full article
(This article belongs to the Special Issue Epstein-Barr Virus Infection in Cancer)
3 pages, 186 KiB  
Correction
Correction: Chua et al. Cost-Effectiveness Analysis of HPV Extended versus Partial Genotyping for Cervical Cancer Screening in Singapore. Cancers 2023, 15, 1812
by Brandon Chua, Li Min Lim, Joseph Soon Yau Ng, Yan Ma, Hwee Lin Wee and J. Jaime Caro
Cancers 2023, 15(18), 4658; https://doi.org/10.3390/cancers15184658 - 21 Sep 2023
Viewed by 588
Abstract
The authors wish to revise two words in Table 1 row 3, and the first paragraph of Section 2 [...] Full article
(This article belongs to the Special Issue Prevention and Screening in Gynaecological Cancers)
14 pages, 1148 KiB  
Review
MRI-Guided Radiation Therapy for Prostate Cancer: The Next Frontier in Ultrahypofractionation
by Cecil M. Benitez, Michael L. Steinberg, Minsong Cao, X. Sharon Qi, James M. Lamb, Amar U. Kishan and Luca F. Valle
Cancers 2023, 15(18), 4657; https://doi.org/10.3390/cancers15184657 - 21 Sep 2023
Cited by 1 | Viewed by 1492
Abstract
Technological advances in MRI-guided radiation therapy (MRIgRT) have improved real-time visualization of the prostate and its surrounding structures over CT-guided radiation therapy. Seminal studies have demonstrated safe dose escalation achieved through ultrahypofractionation with MRIgRT due to planning target volume (PTV) margin reduction and [...] Read more.
Technological advances in MRI-guided radiation therapy (MRIgRT) have improved real-time visualization of the prostate and its surrounding structures over CT-guided radiation therapy. Seminal studies have demonstrated safe dose escalation achieved through ultrahypofractionation with MRIgRT due to planning target volume (PTV) margin reduction and treatment gating. On-table adaptation with MRI-based technologies can also incorporate real-time changes in target shape and volume and can reduce high doses of radiation to sensitive surrounding structures that may move into the treatment field. Ongoing clinical trials seek to refine ultrahypofractionated radiotherapy treatments for prostate cancer using MRIgRT. Though these studies have the potential to demonstrate improved biochemical control and reduced side effects, limitations concerning patient treatment times and operational workflows may preclude wide adoption of this technology outside of centers of excellence. In this review, we discuss the advantages and limitations of MRIgRT for prostate cancer, as well as clinical trials testing the efficacy and toxicity of ultrafractionation in patients with localized or post-prostatectomy recurrent prostate cancer. Full article
(This article belongs to the Special Issue Advances in Prostate Cancer Radiotherapy)
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12 pages, 1923 KiB  
Article
Dynamic Risk Stratification Integrated with ATA Risk System for Predicting Long-Term Outcome in Papillary Thyroid Cancer
by Laura Valerio, Cristina Dalmiglio, Fabio Maino, Elisa Mattii, Andrea Trimarchi, Alessandra Cartocci and Maria Grazia Castagna
Cancers 2023, 15(18), 4656; https://doi.org/10.3390/cancers15184656 - 21 Sep 2023
Cited by 1 | Viewed by 974
Abstract
Background: In recent years, there has been a renewed interest in thyroid cancer management paradigms that use individualized risk assessments as the basis for treatment and follow-up recommendations. In this study, we assumed that the long-term follow-up of differentiated thyroid cancer patients might [...] Read more.
Background: In recent years, there has been a renewed interest in thyroid cancer management paradigms that use individualized risk assessments as the basis for treatment and follow-up recommendations. In this study, we assumed that the long-term follow-up of differentiated thyroid cancer patients might be better tailored by integrating the response to initial therapy with the America Thyroid Association (ATA) risk classes. Methods: This retrospective study included low- and intermediate-risk papillary thyroid cancer (PTC) patients followed up for a median time of 8 years and classified according to the response to initial therapy assessed 6–12 months after initial treatment. Results: After a median follow-up of 8 years, in the initial excellent response subgroup of PTC patients (n = 522), the rate of recurrent disease was significantly higher in intermediate-risk patients than in low-risk PTC patients (6.9% versus 1.2%, p = 0.0005). Similarly, in the initial biochemical incomplete response subgroup (n = 82), the rate of excellent response was significantly higher in low-risk PTC patients (58.0%) than in intermediate-risk PTC patients (33.3%) (p = 0.007). Finally, in the initial structural incomplete response subgroup (n = 66), the rate of excellent response was higher in low-risk patients (80.0%) than in intermediate-risk patients (46.4%) (p = 0.08). Moreover, all patients with initial indeterminate response had an excellent response at the last follow-up visit. ATA risk classes were independently associated with long-term outcome in each subgroup of patients classified dynamically after initial therapy and the overall prognostic performance, defined via ROC curve analysis, of response to initial therapy integrated with the ATA risk system (AUC: 0.89; 95% CI: 0.86–0.92) was significantly higher compared to the ATA risk stratification (AUC 0.69; 95% CI: 0.65–0.74, p < 0.001) or the dynamic risk stratification (DRS) systems alone (AUC: 0.86 95% CI: 0.82–0.90, p = 0.007). Conclusions: This study of a large cohort of PTC patients showed that the initial ATA risk criteria may be useful for improving the risk-adapted management of PTC patients based on the response to initial therapy. Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
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17 pages, 4795 KiB  
Article
An Interpretable Three-Dimensional Artificial Intelligence Model for Computer-Aided Diagnosis of Lung Nodules in Computed Tomography Images
by Sheng-Chieh Hung, Yao-Tung Wang and Ming-Hseng Tseng
Cancers 2023, 15(18), 4655; https://doi.org/10.3390/cancers15184655 - 21 Sep 2023
Cited by 1 | Viewed by 1039
Abstract
Lung cancer is typically classified into small-cell carcinoma and non-small-cell carcinoma. Non-small-cell carcinoma accounts for approximately 85% of all lung cancers. Low-dose chest computed tomography (CT) can quickly and non-invasively diagnose lung cancer. In the era of deep learning, an artificial intelligence (AI) [...] Read more.
Lung cancer is typically classified into small-cell carcinoma and non-small-cell carcinoma. Non-small-cell carcinoma accounts for approximately 85% of all lung cancers. Low-dose chest computed tomography (CT) can quickly and non-invasively diagnose lung cancer. In the era of deep learning, an artificial intelligence (AI) computer-aided diagnosis system can be developed for the automatic recognition of CT images of patients, creating a new form of intelligent medical service. For many years, lung cancer has been the leading cause of cancer-related deaths in Taiwan, with smoking and air pollution increasing the likelihood of developing the disease. The incidence of lung adenocarcinoma in never-smoking women has also increased significantly in recent years, resulting in an important public health problem. Early detection of lung cancer and prompt treatment can help reduce the mortality rate of patients with lung cancer. In this study, an improved 3D interpretable hierarchical semantic convolutional neural network named HSNet was developed and validated for the automatic diagnosis of lung cancer based on a collection of lung nodule images. The interpretable AI model proposed in this study, with different training strategies and adjustment of model parameters, such as cyclic learning rate and random weight averaging, demonstrated better diagnostic performance than the previous literature, with results of a four-fold cross-validation procedure showing calcification: 0.9873 ± 0.006, margin: 0.9207 ± 0.009, subtlety: 0.9026 ± 0.014, texture: 0.9685 ± 0.006, sphericity: 0.8652 ± 0.021, and malignancy: 0.9685 ± 0.006. Full article
(This article belongs to the Special Issue Applications of Machine and Deep Learning in Thoracic Malignancies)
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17 pages, 1151 KiB  
Review
Exploring the Molecular Landscape of Myelofibrosis, with a Focus on Ras and Mitogen-Activated Protein (MAP) Kinase Signaling
by Samuel B. Reynolds, Kristen Pettit, Malathi Kandarpa, Moshe Talpaz and Qing Li
Cancers 2023, 15(18), 4654; https://doi.org/10.3390/cancers15184654 - 21 Sep 2023
Cited by 2 | Viewed by 1826
Abstract
Myelofibrosis (MF) is a clonal myeloproliferative neoplasm (MPN) characterized clinically by cytopenias, fatigue, and splenomegaly stemming from extramedullary hematopoiesis. MF commonly arises from mutations in JAK2, MPL, and CALR, which manifests as hyperactive Jak/Stat signaling. Triple-negative MF is diagnosed in [...] Read more.
Myelofibrosis (MF) is a clonal myeloproliferative neoplasm (MPN) characterized clinically by cytopenias, fatigue, and splenomegaly stemming from extramedullary hematopoiesis. MF commonly arises from mutations in JAK2, MPL, and CALR, which manifests as hyperactive Jak/Stat signaling. Triple-negative MF is diagnosed in the absence of JAK2, MPL, and CALR but when clinical, morphologic criteria are met and other mutation(s) is/are present, including ASXL1, EZH2, and SRSF2. While the clinical and classic molecular features of MF are well-established, emerging evidence indicates that additional mutations, specifically within the Ras/MAP Kinase signaling pathway, are present and may play important role in disease pathogenesis and treatment response. KRAS and NRAS mutations alone are reportedly present in up to 15 and 14% of patients with MF (respectively), and other mutations predicted to activate Ras signaling, such as CBL, NF1, BRAF, and PTPN11, collectively exist in as much as 21% of patients. Investigations into the prevalence of RAS and related pathway mutations in MF and the mechanisms by which they contribute to its pathogenesis are critical in better understanding this condition and ultimately in the identification of novel therapeutic targets. Full article
(This article belongs to the Special Issue Precision Medicine Approaches to Tackle RAS/RAF-Mutant Cancer)
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26 pages, 1882 KiB  
Review
Nuclear Estrogen Receptors in Prostate Cancer: From Genes to Function
by Silvia Belluti, Carol Imbriano and Livio Casarini
Cancers 2023, 15(18), 4653; https://doi.org/10.3390/cancers15184653 - 20 Sep 2023
Cited by 2 | Viewed by 1708
Abstract
Estrogens are almost ubiquitous steroid hormones that are essential for development, metabolism, and reproduction. They exert both genomic and non-genomic action through two nuclear receptors (ERα and ERβ), which are transcription factors with disregulated functions and/or expression in pathological processes. In the 1990s, [...] Read more.
Estrogens are almost ubiquitous steroid hormones that are essential for development, metabolism, and reproduction. They exert both genomic and non-genomic action through two nuclear receptors (ERα and ERβ), which are transcription factors with disregulated functions and/or expression in pathological processes. In the 1990s, the discovery of an additional membrane estrogen G-protein-coupled receptor augmented the complexity of this picture. Increasing evidence elucidating the specific molecular mechanisms of action and opposing effects of ERα and Erβ was reported in the context of prostate cancer treatment, where these issues are increasingly investigated. Although new approaches improved the efficacy of clinical therapies thanks to the development of new molecules targeting specifically estrogen receptors and used in combination with immunotherapy, more efforts are needed to overcome the main drawbacks, and resistance events will be a challenge in the coming years. This review summarizes the state-of-the-art on ERα and ERβ mechanisms of action in prostate cancer and promising future therapies. Full article
(This article belongs to the Section Cancer Therapy)
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13 pages, 1026 KiB  
Article
Clinical Outcomes in AYAs (Adolescents and Young Adults) Treated with Proton Therapy for Uveal Melanoma: A Comparative Matching Study with Elder Adults
by Alessia Pica, Damien C. Weber, Claude Schweizer, Aziz Chaouch, Leonidas Zografos and Ann Schalenbourg
Cancers 2023, 15(18), 4652; https://doi.org/10.3390/cancers15184652 - 20 Sep 2023
Viewed by 766
Abstract
Objective: The aim of this study was to compare the clinical outcomes of adolescents and young adults (AYAs) with those of elder adult patients treated with proton therapy (PT) for uveal melanoma (UM). Material and Methods: A retrospective, comparative study was conducted in [...] Read more.
Objective: The aim of this study was to compare the clinical outcomes of adolescents and young adults (AYAs) with those of elder adult patients treated with proton therapy (PT) for uveal melanoma (UM). Material and Methods: A retrospective, comparative study was conducted in UM patients who underwent PT at the Ocular Oncology Unit of the Jules-Gonin Eye Hospital (University of Lausanne, Lausanne, Switzerland) and the Paul Scherrer Institute (PSI); (Villigen, Switzerland) between January 1997 and December 2007. Propensity score matching (PSM) was used to select for each AYA (between 15–39 years old) an elder adult patient (≥40 years) with similar characteristics. We assessed ocular follow-up, local tumor control, metastasis incidence, and overall and relative survival (OS and RS). Non-terminal outcomes were then compared between the two groups using competing risk survival analysis. Results: Out of a total of 2261 consecutive UM patients, after excluding 4 children (<15 years) and 6 patients who were metastatic at presentation, we identified 272 AYA patients and matched 270 of them with 270 elder adult patients. Before PSM, the AYA patients had a higher incidence of primary iris melanoma (4.0% vs. 1.4%; p = 0.005), while the elder patients were more likely to have other neoplastic diseases at presentation (9% vs. 3.7%; p = 0.004). Ocular outcomes and local tumor control were similar in both groups. Cumulative metastasis incidence for the AYA and elder adult groups was 13% and 7.9% at 5 years and 19.7% and 12.7% at 10 years, respectively, which was not significantly different between the groups (p = 0.214). The OS was similar in the two groups (p = 0.602), with estimates in the AYA and elder adult groups of 95.5% and 96.6% at 5 years and 94.6% and 91.4% at 10 years, respectively. However, the relative survival (RS) estimation was worse in the AYA group than the elder group (p = 0.036). Conclusion: While AYAs treated with PT for UM have similar ocular outcomes and present the same metastasis incidence and OS as elder adults, their RS is worse than that in elder adults, when compared with the population in general. Full article
(This article belongs to the Special Issue Current Progress in Proton Radiotherapy of Cancer)
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21 pages, 3117 KiB  
Review
Is Insulin Receptor Substrate4 (IRS4) a Platform Involved in the Activation of Several Oncogenes?
by Luis G. Guijarro, Francisco Javier Justo Bermejo, Diego Liviu Boaru, Patricia De Castro-Martinez, Diego De Leon-Oliva, Oscar Fraile-Martínez, Cielo Garcia-Montero, Melchor Alvarez-Mon, María del Val Toledo-Lobo and Miguel A. Ortega
Cancers 2023, 15(18), 4651; https://doi.org/10.3390/cancers15184651 - 20 Sep 2023
Cited by 1 | Viewed by 1397
Abstract
The IRS (insulin receptor substrate) family of scaffold proteins includes insulin receptor substrate-4 (IRS4), which is expressed only in a few cell lines, including human kidney, brain, liver, and thymus and some cell lines. Its N-terminus carries a phosphotyrosine-binding (PTB) domain and a [...] Read more.
The IRS (insulin receptor substrate) family of scaffold proteins includes insulin receptor substrate-4 (IRS4), which is expressed only in a few cell lines, including human kidney, brain, liver, and thymus and some cell lines. Its N-terminus carries a phosphotyrosine-binding (PTB) domain and a pleckstrin homology domain (PH), which distinguishes it as a member of this family. In this paper, we collected data about the molecular mechanisms that explain the relevance of IRS4 in the development of cancer and identify IRS4 differences that distinguish it from IRS1 and IRS2. Search engines and different databases, such as PubMed, UniProt, ENSEMBL and SCANSITE 4.0, were used. We used the name of the protein that it encodes “(IRS-4 or IRS4)”, or the combination of these terms with the word “(cancer)” or “(human)”, for searches. Terms related to specific tumor pathologies (“breast”, “ovary”, “colon”, “lung”, “lymphoma”, etc.) were also used. Despite the lack of knowledge on IRS4, it has been reported that some cancers and benign tumors are characterized by high levels of IRS-4 expression. Specifically, the role of IRS-4 in different types of digestive tract neoplasms, gynecological tumors, lung cancers, melanomas, hematological tumors, and other less common types of cancers has been shown. IRS4 differs from IRS1 and IRS2 in that can activate several oncogenes that regulate the PI3K/Akt cascade, such as BRK and FER, which are characterized by tyrosine kinase-like activity without regulation via extracellular ligands. In addition, IRS4 can activate the CRKL oncogene, which is an adapter protein that regulates the MAP kinase cascade. Knowledge of the role played by IRS4 in cancers at the molecular level, specifically as a platform for oncogenes, may enable the identification and validation of new therapeutic targets. Full article
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16 pages, 775 KiB  
Article
Radiomic Assessment of Radiation-Induced Alterations of Skeletal Muscle Composition in Head and Neck Squamous Cell Carcinoma within the Currently Clinically Defined Optimal Time Window for Salvage Surgery—A Pilot Study
by Matthias Santer, Herbert Riechelmann, Benedikt Hofauer, Joachim Schmutzhard, Wolfgang Freysinger, Annette Runge, Timo Maria Gottfried, Philipp Zelger, Gerlig Widmann, Hanna Kranebitter, Stephanie Mangesius, Julian Mangesius, Florian Kocher and Daniel Dejaco
Cancers 2023, 15(18), 4650; https://doi.org/10.3390/cancers15184650 - 20 Sep 2023
Viewed by 866
Abstract
Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) frequently require primary radiochemotherapy (RCT). Despite intensity modulation, the desired radiation-induced effects observed in HNSCC may also be observed as side effects in healthy tissue, e.g., the sternocleidomastoid muscle (SCM). These side [...] Read more.
Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) frequently require primary radiochemotherapy (RCT). Despite intensity modulation, the desired radiation-induced effects observed in HNSCC may also be observed as side effects in healthy tissue, e.g., the sternocleidomastoid muscle (SCM). These side effects (e.g., tissue fibrosis) depend on the interval between the completion of RCT and restaging CT. For salvage surgery, the optimal time window for surgery is currently clinically postulated at between 6 and 12 weeks after completion of RCT. Thus, no extensive tissue fibrosis is to be expected. This interval is based on clinical studies exploring surgical complications. Studies directly exploring radiation-induced changes of the SCM in HNSCC patients are sparse. The present study quantified tissue alterations in the SCM and paravertebral musculature (PVM) after RCT, applying radiomics to determine the optimal time window for salvage surgery. Three radiomic key parameters, (1) volume, (2) mean positivity of pixels (MPP), and (3) uniformity, were extracted with mint LesionTM in the staging CTs and restaging CTs of 98 HNSCC patients. Of these, 25 were female, the mean age was 62 (±9.6) years, and 80.9% were UICC Stage IV. The mean restaging interval was 55 (±28; range 29–229) days. Only the mean volume significantly decreased after RCT, from 9.0 to 8.4 and 96.5 to 91.9 mL for the SCM and PVM, respectively (both p = 0.007, both Cohen’s d = 0.28). In addition, the mean body mass index (BMI) decreased from 23.9 (±4.2) to 21.0 (±3.6) kg/m² (p < 0.001; Cohen’s d = 0.9). The mean BMI decreased significantly and was correlated with the volume decrease for the SCM (r = 0.27; p = 0.007) and PVM (r = 0.41; p < 0.001). If t-test p-values were adjusted for the BMI decrease, no significant change in volumes for the SCM and PVM was observed (both p > 0.05). The present data support the clinically postulated optimal interval for salvage surgery of 6 to 12 weeks. Full article
(This article belongs to the Special Issue Advances in Diagnostics and Treatment of Head and Neck Cancer)
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19 pages, 1560 KiB  
Article
Comparative Analysis of Three Predictive Models of Performance Indicators with Results-Based Management: Cancer Data Statistics in a National Institute of Health
by Joel Martínez-Salazar and Filiberto Toledano-Toledano
Cancers 2023, 15(18), 4649; https://doi.org/10.3390/cancers15184649 - 20 Sep 2023
Cited by 3 | Viewed by 1045
Abstract
Predictive models play a crucial role in RBMs to analyze performance indicator results to manage unexpected events and make timely decisions to resolve them. Their use in Mexico is deficient, and monitoring and evaluation are among the weakest pillars of the model. In [...] Read more.
Predictive models play a crucial role in RBMs to analyze performance indicator results to manage unexpected events and make timely decisions to resolve them. Their use in Mexico is deficient, and monitoring and evaluation are among the weakest pillars of the model. In response to these needs, the aim of this study was to perform a comparative analysis of three predictive models to analyze 10 medical performance indicators and cancer data related to children with cancer. To accomplish these purposes, a comparative and retrospective study with nonprobabilistic convenience sampling was conducted. The predictive models were exponential smoothing, autoregressive integrated moving average, and linear regression. The lowest mean absolute error was used to identify the best model. Linear regression performed best regarding nine of the ten indicators, with seven showing p < 0.05. Three of their assumptions were checked using the Shapiro–Wilk, Cook’s distance, and Breusch–Pagan tests. Predictive models with RBM are a valid and relevant instrument for monitoring and evaluating performance indicator results to support forecasting and decision-making based on evidence and must be promoted for use with cancer data statistics. The place numbers obtained by cancer disease inside the main causes of death, morbidity and hospital outpatients in a National Institute of Health were presented as evidence of the importance of implementing performance indicators associated with children with cancer. Full article
(This article belongs to the Special Issue Advances in Cancer Data and Statistics)
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16 pages, 1131 KiB  
Review
Angiogenesis in Lung Cancer: Understanding the Roles of Growth Factors
by Tchawe Yvan Sinclair Ngaha, Angelina V. Zhilenkova, Freddy Elad Essogmo, Ikenna K. Uchendu, Moses Owoicho Abah, Lionel Tabola Fossa, Zaiana D. Sangadzhieva, Varvara D. Sanikovich, Alexander S. Rusanov, Yuliya N. Pirogova, Alexander Boroda, Alexander Rozhkov, Jean D. Kemfang Ngowa, Leonid N. Bagmet and Marina I. Sekacheva
Cancers 2023, 15(18), 4648; https://doi.org/10.3390/cancers15184648 - 20 Sep 2023
Cited by 4 | Viewed by 1339
Abstract
Research has shown the role of growth factors in lung cancer angiogenesis. Angiogenesis promotes lung cancer progression by stimulating tumor growth, enhancing tumor invasion, contributing to metastasis, and modifying immune system responses within the tumor microenvironment. As a result, new treatment techniques based [...] Read more.
Research has shown the role of growth factors in lung cancer angiogenesis. Angiogenesis promotes lung cancer progression by stimulating tumor growth, enhancing tumor invasion, contributing to metastasis, and modifying immune system responses within the tumor microenvironment. As a result, new treatment techniques based on the anti-angiogenic characteristics of compounds have been developed. These compounds selectively block the growth factors themselves, their receptors, or the downstream signaling pathways activated by these growth factors. The EGF and VEGF families are the primary targets in this approach, and several studies are being conducted to propose anti-angiogenic drugs that are increasingly suitable for the treatment of lung cancer, either as monotherapy or as combined therapy. The efficacy of the results are encouraging, but caution must be placed on the higher risk of toxicity, outlining the importance of personalized follow-up in the management of these patients. Full article
(This article belongs to the Section Cancer Therapy)
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17 pages, 844 KiB  
Article
Simultaneous Integrated Boost for Dose Escalation in Node-Positive Cervical Cancer: 5-Year Experience in a Single Institution
by Elki Sze-Nga Cheung, Frederick Chun-Him Law, Nelson Tsz-Cheong Fung, Inda Sung Soong, Rico Hing-Ming Hung, Teddy Ka-Ho Tse, Ken Ka-Shing Wong and Philip Yuguang Wu
Cancers 2023, 15(18), 4647; https://doi.org/10.3390/cancers15184647 - 20 Sep 2023
Cited by 1 | Viewed by 832
Abstract
This study retrospectively evaluates clinical outcomes of dose escalation to involved nodes using volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) for node-positive locally advanced cervical cancer (LACC) at a single institution. Consecutive patients with node-positive LACC (FIGO2018 IIIC1-IVA) who [...] Read more.
This study retrospectively evaluates clinical outcomes of dose escalation to involved nodes using volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) for node-positive locally advanced cervical cancer (LACC) at a single institution. Consecutive patients with node-positive LACC (FIGO2018 IIIC1-IVA) who received definitive chemoradiotherapy by VMAT 45 Gy in 25 fractions with SIB to 55–57.5 Gy, followed by magnetic resonance image-guided adaptive brachytherapy (IGABT) between 2018 and 2022 were identified. A standardized strategy regarding nodal boost delivery and elective para-aortic (PAO) irradiation was employed. Primary endpoints were involved nodal control (INC) and regional nodal control (RNC). Secondary endpoints were pelvic control (PC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), failure pattern, and radiotherapy-related toxicities. A total of 234 involved nodes (182 pelvic and 52 PAO) in 54 patients, with a median of 3 involved nodes per patient (range 1–16), were analyzed. After a median follow-up of 19.6 months, excellent INC was achieved, with four (2%) boost-volume failures occurring in three patients. The 2-year actuarial RNC, PC, LRC, DFS, and OS were 93%, 87%, 87%, 78%, and 85%, respectively. Adenocarcinoma histology was associated with worse RNC (p = 0.02) and OS (p = 0.04), whereas the primary tumor maximum standardized uptake value (SUVmax) was associated with worse PC (p = 0.04) and LRC (p = 0.046) on univariate analysis. The incidence of grade ≥3 acute and late radiotherapy-related toxicity were 2% and 4%, respectively. Treatment of node-positive LACC with VMAT with SIB allows safe and effective dose escalation. The 5-year local experience demonstrated excellent treatment outcomes without additional toxicity. Full article
(This article belongs to the Section Cancer Therapy)
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16 pages, 8878 KiB  
Article
Inhibition of EphA3 Expression in Tumour Stromal Cells Suppresses Tumour Growth and Progression
by Mary E. Vail, Rae H. Farnsworth, Linda Hii, Stacey Allen, Sakshi Arora, Robin L. Anderson, Ross A. Dickins, Akira Orimo, Sunny Z. Wu, Alexander Swarbrick, Andrew M. Scott and Peter W. Janes
Cancers 2023, 15(18), 4646; https://doi.org/10.3390/cancers15184646 - 20 Sep 2023
Cited by 2 | Viewed by 1704
Abstract
Tumour progression relies on interactions with untransformed cells in the tumour microenvironment (TME), including cancer-associated fibroblasts (CAFs), which promote blood supply, tumour progression, and immune evasion. Eph receptor tyrosine kinases are cell guidance receptors that are most active during development but re-emerge in [...] Read more.
Tumour progression relies on interactions with untransformed cells in the tumour microenvironment (TME), including cancer-associated fibroblasts (CAFs), which promote blood supply, tumour progression, and immune evasion. Eph receptor tyrosine kinases are cell guidance receptors that are most active during development but re-emerge in cancer and are recognised drug targets. EphA3 is overexpressed in a wide range of tumour types, and we previously found expression particularly in stromal and vascular tissues of the TME. To investigate its role in the TME, we generated transgenic mice with inducible shRNA-mediated knockdown of EphA3 expression. EphA3 knockdown was confirmed in aortic mesenchymal stem cells (MSCs), which displayed reduced angiogenic capacity. In mice with syngeneic lung tumours, EphA3 knockdown reduced vasculature and CAF/MSC-like cells in tumours, and inhibited tumour growth, which was confirmed also in a melanoma model. Single cell RNA sequencing analysis of multiple human tumour types confirmed EphA3 expression in CAFs, including in breast cancer, where EphA3 was particularly prominent in perivascular- and myofibroblast-like CAFs. Our results thus indicate expression of the cell guidance receptor EphA3 in distinct CAF subpopulations is important in supporting tumour angiogenesis and tumour growth, highlighting its potential as a therapeutic target. Full article
(This article belongs to the Section Tumor Microenvironment)
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28 pages, 4967 KiB  
Review
Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells
by Farjana Afrin, Sameena Mateen, Jordan Oman, James C. K. Lai, Jared J. Barrott and Srinath Pashikanti
Cancers 2023, 15(18), 4645; https://doi.org/10.3390/cancers15184645 - 20 Sep 2023
Cited by 1 | Viewed by 1171
Abstract
Molecular targeting strategies have been used for years in order to control cancer progression and are often based on targeting various enzymes involved in metabolic pathways. Keeping this in mind, it is essential to determine the role of each enzyme in a particular [...] Read more.
Molecular targeting strategies have been used for years in order to control cancer progression and are often based on targeting various enzymes involved in metabolic pathways. Keeping this in mind, it is essential to determine the role of each enzyme in a particular metabolic pathway. In this review, we provide in-depth information on various enzymes such as ceramidase, sphingosine kinase, sphingomyelin synthase, dihydroceramide desaturase, and ceramide synthase which are associated with various types of cancers. We also discuss the physicochemical properties of well-studied inhibitors with natural product origins and their related structures in terms of these enzymes. Targeting ceramide metabolism exhibited promising mono- and combination therapies at preclinical stages in preventing cancer progression and cemented the significance of sphingolipid metabolism in cancer treatments. Targeting ceramide-metabolizing enzymes will help medicinal chemists design potent and selective small molecules for treating cancer progression at various levels. Full article
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4 pages, 196 KiB  
Editorial
Multifaceted Insights into Innovative Approaches to Treating Colorectal Cancer Metastasis: From Emerging Biological Factors to Radiomics
by Alessandro Ottaiano, Luisa Circelli, Mariachiara Santorsola and Michele Caraglia
Cancers 2023, 15(18), 4644; https://doi.org/10.3390/cancers15184644 - 20 Sep 2023
Cited by 1 | Viewed by 579
Abstract
We extend our appreciation to the authors who have made substantial contributions to the Special Issue focusing on “Colorectal Cancer Metastasis” [...] Full article
(This article belongs to the Special Issue Colorectal Cancer Metastasis)
16 pages, 1287 KiB  
Article
Using Single-Case Experimental Design and Patient-Reported Outcome Measures to Evaluate the Treatment of Cancer-Related Cognitive Impairment in Clinical Practice
by Robert J. Ferguson, Lauren Terhorst, Benjamin Gibbons, Donna M. Posluszny, Hsuan Chang, Dana H. Bovbjerg and Brenna C. McDonald
Cancers 2023, 15(18), 4643; https://doi.org/10.3390/cancers15184643 - 20 Sep 2023
Viewed by 992
Abstract
Cancer-related cognitive impairment (CRCI) affects a large proportion of cancer survivors and has significant negative effects on survivor function and quality of life (QOL). Treatments for CRCI are being developed and evaluated. Memory and attention adaptation training (MAAT) is a cognitive-behavioral therapy (CBT) [...] Read more.
Cancer-related cognitive impairment (CRCI) affects a large proportion of cancer survivors and has significant negative effects on survivor function and quality of life (QOL). Treatments for CRCI are being developed and evaluated. Memory and attention adaptation training (MAAT) is a cognitive-behavioral therapy (CBT) demonstrated to improve CRCI symptoms and QOL in previous research. The aim of this article is to describe a single-case experimental design (SCED) approach to evaluate interventions for CRCI in clinical practice with patient-reported outcome measures (PROs). We illustrate the use of contemporary SCED methods as a means of evaluating MAAT, or any CRCI treatment, once clinically deployed. With the anticipated growth of cancer survivorship and concurrent growth in the number of survivors with CRCI, the treatment implementation and evaluation methods described here can be one way to assess and continually improve CRCI rehabilitative services. Full article
(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)
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