Cancers

19 pages, 1742 KiB

Open AccessFeature PaperReview

Ultrasound Combination to Improve the Efficacy of Current Boron Neutron Capture Therapy for Head and Neck Cancer

by Yoshiaki Yura, Yusei Fujita and Masakazu Hamada

Cancers 2024, 16(15), 2770; https://doi.org/10.3390/cancers16152770 - 5 Aug 2024

Viewed by 1006

Boron neutron capture therapy (BNCT) is radiotherapy in which a nuclear reaction between boron-10 (¹⁰B) in tumor cells and neutrons produces alpha particles and recoiling ⁷Li nuclei with an extremely short range, leading to the destruction of the tumor cells. [...] Read more.

Boron neutron capture therapy (BNCT) is radiotherapy in which a nuclear reaction between boron-10 (¹⁰B) in tumor cells and neutrons produces alpha particles and recoiling ⁷Li nuclei with an extremely short range, leading to the destruction of the tumor cells. Although the neutron source has traditionally been a nuclear reactor, accelerators to generate neutron beams have been developed and commercialized. Therefore, this treatment will become more widespread. Recurrent head and neck cancer (HNC) close to the body surface is considered a candidate for BNCT using the boron compound boronophenylalanine (BPA) and has been found to be highly responsive to this treatment. However, some cases recur early after the completion of the treatment, which needs to be addressed. Ultrasound is a highly safe diagnostic method. Ultrasound with microbubbles is expected to promote the uptake of BPA into tumor cells. Ultrasound also has the ability to improve the sensitivity of tumor cells to radiotherapy. In addition, high-intensity focused ultrasound may improve the efficacy of BNCT via its thermal and mechanical effects. This review is not systematic but outlines the current status of BPA-based BNCT and proposes plans to reduce the recurrence rate of HNC after BNCT in combination with ultrasound. Full article

(This article belongs to the Special Issue Radiotherapy for Head and Neck Squamous Cell Carcinoma)

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12 pages, 1059 KiB

Open AccessPerspective

Adipose Stem Cells and Their Interplay with Cancer Cells and Mitochondrial Reservoir: A New Promising Target

by Ayesha Rehman, Martina Marigliano, Martina Torsiello, Marcella La Noce, Gianpaolo Papaccio, Virginia Tirino, Vitale Del Vecchio and Federica Papaccio

Cancers 2024, 16(15), 2769; https://doi.org/10.3390/cancers16152769 - 5 Aug 2024

Viewed by 1007

Abstract

Adipose-derived stem cells (ASCs) significantly influence tumor progression within the tumor microenvironment (TME). This review examines the pro-tumorigenic roles of ASCs, focusing on paracrine signaling, direct cell–cell interactions, and immunomodulation. ASC-mediated mitochondrial transfer through tunneling nanotubes (TNTs) and gap junctions (GJs) plays a [...] Read more.

Adipose-derived stem cells (ASCs) significantly influence tumor progression within the tumor microenvironment (TME). This review examines the pro-tumorigenic roles of ASCs, focusing on paracrine signaling, direct cell–cell interactions, and immunomodulation. ASC-mediated mitochondrial transfer through tunneling nanotubes (TNTs) and gap junctions (GJs) plays a significant role in enhancing cancer cell survival and metabolism. Cancer cells with dysfunctional mitochondria acquire mitochondria from ASCs to meet their metabolic needs and thrive in the TME. Targeting mitochondrial transfer, modulating ASC function, and influencing metabolic pathways are potential therapeutic strategies. However, challenges like TME complexity, specificity, safety concerns, and resistance mechanisms must be addressed. Disrupting the ASC–cancer cell–mitochondria axis offers a promising approach to cancer therapy. Full article

(This article belongs to the Section Cancer Therapy)

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Graphical abstract

9 pages, 674 KiB

Open AccessArticle

Real-World Survival Impact of New Treatment Strategies for Lung Cancer: A 2000–2020 French Cohort

by Clemence Basse, Matthieu Carton, Maud Milder, Romain Geiss, Pauline Du Rusquec, Catherine Daniel, Marie-Ange Massiani, Alain Livartowski and Nicolas Girard

Cancers 2024, 16(15), 2768; https://doi.org/10.3390/cancers16152768 - 5 Aug 2024

Cited by 2 | Viewed by 1438

Abstract

Over the past 20 years, several innovative therapies have been implemented in the treatment of lung cancer that have had reported survival benefits in clinical trials. Whether these improvements translate into the clinic setting has not been studied yet. We retrospectively analyzed all [...] Read more.

Over the past 20 years, several innovative therapies have been implemented in the treatment of lung cancer that have had reported survival benefits in clinical trials. Whether these improvements translate into the clinic setting has not been studied yet. We retrospectively analyzed all patients consecutively treated at Institute Curie for metastatic lung cancer. Diagnosis date was used to define three periods, based on the approvals of novel treatment strategies in the first-line setting, including targeted therapies in 2010 and immunotherapy in 2018. Endpoints included Overall survival (OS), survival rate of 2 years and 5 years, and a conditional survival rate of 2 years (if still alive at 6 months from treatment initiation). A total of 673 patients were identified for Period 1—2000 to 2009, 752 for Period 2—2010 to 2017, and 768 for Period 3—2018 to 2020. Median OS in the whole cohort was 11.1, 15.5, and 16.2 months, respectively. Median OS for patients with NSCLC or SCLC was 11.2, 17.2, and 18.2 months, or 10.9, 11.7, and 11.2 months, respectively. The two-year conditional survival was more favorable for NSCLC than SCLC patients. Outcomes were statistically higher for women as compared to men in all periods and all subgroups. Survival of patients with metastatic lung cancer has improved over the past 20 years, mostly in NSCLC, along with the implementation of novel treatment strategies. Full article

(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)

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Graphical abstract

19 pages, 4401 KiB

Open AccessArticle

Preoperative and Intraoperative Identification of Sentinel Lymph Nodes in Melanoma Surgery

by Stanley P. Leong, Mehdi Nosrati, Max C. Wu, Donald M. Torre, Ted F. Bartley, Kevin B. Kim, Christopher Soon, John Moretto and Mohammed Kashani-Sabet

Cancers 2024, 16(15), 2767; https://doi.org/10.3390/cancers16152767 - 5 Aug 2024

Viewed by 1049

Abstract

According to the American Joint Commission on Cancer (AJCC) 8th edition guidelines, SLN biopsy is recommended for primary melanomas with a Breslow thickness of at least 1 mm. Additionally, the National Comprehensive Cancer Network (NCCN) recommends that a SLN biopsy may be considered [...] Read more.

According to the American Joint Commission on Cancer (AJCC) 8th edition guidelines, SLN biopsy is recommended for primary melanomas with a Breslow thickness of at least 1 mm. Additionally, the National Comprehensive Cancer Network (NCCN) recommends that a SLN biopsy may be considered for melanoma patients with T1b lesions, which are 0.8–1 mm thick or less than 0.8 mm thick with ulceration. It can also be considered for T1a lesions that are less than 0.8 mm thick but have other adverse features, such as a high mitotic rate, lymphovascular invasion, or a positive deep margin. To reduce the false negative rate of melanoma SLN biopsy, we have introduced the intraoperative use of Sentinella, a gamma camera, to enhance the identification rate of SLNs beyond that of the traditional gamma hand-held probe. At the Center for Melanoma Research and Treatment at the California Pacific Medical Center, a multidisciplinary approach has been established to treat melanoma patients when the diagnosis of primary melanoma is made with a referral to our melanoma center. This comprehensive approach at the melanoma tumor board, including the efforts of pathologists, radiologists, dermatologists, surgical, medical and radiation oncologists, results in a consensus to deliver personalized and high-quality care for our melanoma patients. This multidisciplinary program for the management of melanoma can be duplicated for other types of cancer. This article consists of current knowledge to document the published methods of identification of sentinel lymph nodes. In addition, we have included new data as developed in our melanoma center as newly published materials in this article to demonstrate the utility of these methods in melanoma sentinel lymph node surgery. Informed consent has been waived by our IRB regarding the acquisition of clinical data as presented in this study. Full article

(This article belongs to the Special Issue Contemporary Surgical Management of Melanoma)

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14 pages, 1651 KiB

Open AccessReview

NRG1 Gene Fusions—What Promise Remains Behind These Rare Genetic Alterations? A Comprehensive Review of Biology, Diagnostic Approaches, and Clinical Implications

by Tomasz Kucharczyk, Marcin Nicoś, Marek Kucharczyk and Ewa Kalinka

Cancers 2024, 16(15), 2766; https://doi.org/10.3390/cancers16152766 - 5 Aug 2024

Viewed by 1244

Abstract

Non-small cell lung cancer (NSCLC) presents a variety of druggable genetic alterations that revolutionized the treatment approaches. However, identifying new alterations may broaden the group of patients benefitting from such novel treatment options. Recently, the interest focused on the neuregulin-1 gene (NRG1 [...] Read more.

Non-small cell lung cancer (NSCLC) presents a variety of druggable genetic alterations that revolutionized the treatment approaches. However, identifying new alterations may broaden the group of patients benefitting from such novel treatment options. Recently, the interest focused on the neuregulin-1 gene (NRG1), whose fusions may have become a potential predictive factor. To date, the occurrence of NRG1 fusions has been considered a negative prognostic marker in NSCLC treatment; however, many premises remain behind the targetability of signaling pathways affected by the NRG1 gene. The role of NRG1 fusions in ErbB-mediated cell proliferation especially seems to be considered as a main target of treatment. Hence, NSCLC patients harboring NRG1 fusions may benefit from targeted therapies such as pan-HER family inhibitors, which have shown efficacy in previous studies in various cancers, and anti-HER monoclonal antibodies. Considering the increased interest in the NRG1 gene as a potential clinical target, in the following review, we highlight its biology, as well as the potential clinical implications that were evaluated in clinics or remained under consideration in clinical trials. Full article

(This article belongs to the Special Issue Novel Biomarkers in Non-Small Cell Lung Cancer (NSCLC))

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13 pages, 938 KiB

Open AccessArticle

Discrimination of Lung Cancer and Benign Lung Diseases Using BALF Exosome DNA Methylation Profile

by Chinbayar Batochir, In Ae Kim, Eun Ji Jo, Eun-Bi Kim, Hee Joung Kim, Jae Young Hur, Do Won Kim, Hee Kyung Park and Kye Young Lee

Cancers 2024, 16(15), 2765; https://doi.org/10.3390/cancers16152765 - 5 Aug 2024

Cited by 1 | Viewed by 1201

Abstract

Benign lung diseases are common and often do not require specific treatment, but they pose challenges in the distinguishing of them from lung cancer during low-dose computed tomography (LDCT). This study presents a comprehensive methylation analysis using real-time PCR for minimally invasive diagnoses [...] Read more.

Benign lung diseases are common and often do not require specific treatment, but they pose challenges in the distinguishing of them from lung cancer during low-dose computed tomography (LDCT). This study presents a comprehensive methylation analysis using real-time PCR for minimally invasive diagnoses of lung cancer via employing BALF exosome DNA. A panel of seven epigenetic biomarkers was identified, exhibiting specific methylation patterns in lung cancer BALF exosome DNA. This panel achieved an area under the curve (AUC) of 0.97, with sensitivity and specificity rates of 88.24% and 97.14%, respectively. Each biomarker showed significantly higher mean methylation levels (MMLs) in both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) compared to non-cancer groups, with fold changes from 1.7 to 13.36. The MMLs of the biomarkers were found to be moderately elevated with increasing patient age and smoking history, regardless of sex. A strong correlation was found between the MMLs and NSCLC stage progression, with detection sensitivities of 79% for early stages and 92% for advanced stages. In the validation cohort, the model demonstrated an AUC of 0.95, with 94% sensitivity and specificity. Sensitivity for early-stage NSCLC detection improved from 88.00% to 92.00% when smoking history was included as an additional risk factor. Full article

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

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9 pages, 397 KiB

Open AccessArticle

Adverse In-Hospital Outcomes after Radical Prostatectomy in Leukemia History Patients

by Fabian Falkenbach, Francesco Di Bello, Natali Rodriguez Peñaranda, Mattia Longoni, Andrea Marmiroli, Quynh Chi Le, Zhe Tian, Jordan A. Goyal, Nicola Longo, Salvatore Micali, Alberto Briganti, Ottavio de Cobelli, Felix K. H. Chun, Fred Saad, Shahrokh F. Shariat, Lars Budäus, Markus Graefen and Pierre I. Karakiewicz

Cancers 2024, 16(15), 2764; https://doi.org/10.3390/cancers16152764 - 5 Aug 2024

Cited by 1 | Viewed by 941

Abstract

Introduction: Leukemia history affects some radical prostatectomy (RP) patients. Although its prevalence and effect as an adverse risk factor are well known in cardiac surgery, the number of RP patients with a leukemia history, as well as their rate of adverse in-hospital outcomes, [...] Read more.

Introduction: Leukemia history affects some radical prostatectomy (RP) patients. Although its prevalence and effect as an adverse risk factor are well known in cardiac surgery, the number of RP patients with a leukemia history, as well as their rate of adverse in-hospital outcomes, are unknown. Methods: We identified RP patients (National Inpatient Sample 2000–2019), stratified according to the presence or absence of a leukemia history. Descriptive analyses, propensity score matching (PSM, ratio 1:10), and multivariable logistic regression models were used. Results: Of 259,939 RP patients, 416 (0.2%) had a leukemia history. Their proportion increased from 0.1 to 0.2% covering the study span (p < 0.01). Leukemia history patients were older (median age, 64 vs. 62 years, p < 0.001). After PSM for age, insurance status, ethnicity, pelvic lymph node dissection, and Charlson Comorbidity Index, leukemia history RP patients exhibited higher rates of acute kidney injury (<2.6 vs. 0.9%; Odds Ratio [OR] 2.0, p = 0.02), more frequently underwent dialysis (3.6 vs. 1.9%; OR 1.9, p = 0.03), and more frequently had a length of stay exceeding one week (4.8 vs. 2.5%; OR 2.0, p = 0.006). Conclusions: Although leukemia history RP patients are rare, their numbers have increased. Renal complications and extended hospital stays are more frequent in those individuals. Full article

(This article belongs to the Special Issue Contemporary Diagnosis and Management of Prostate Cancer)

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10 pages, 1005 KiB

Open AccessArticle

A Retrospective Analysis of Breast Cancer Mortality among Jewish and Muslim Arab Women in Israel: The Role of Sociodemographic Factors

by Ronit Pinchas-Mizrachi and Dan Bouhnik

Cancers 2024, 16(15), 2763; https://doi.org/10.3390/cancers16152763 - 5 Aug 2024

Viewed by 836

Abstract

Breast cancer mortality rates vary across ethnic groups in Israel, where protective factors such as high fertility and breastfeeding rates may be moderated by socioeconomic factors and mammography rates. We aim to investigate disparities in breast cancer mortality between Jewish and Muslim Arab [...] Read more.

Breast cancer mortality rates vary across ethnic groups in Israel, where protective factors such as high fertility and breastfeeding rates may be moderated by socioeconomic factors and mammography rates. We aim to investigate disparities in breast cancer mortality between Jewish and Muslim Arab women in Israel and examine how sociodemographic variables and number of children are associated with mortality. Our retrospective follow-up study uses data from the Israeli Central Bureau of Statistics and multivariable Cox regression models, adjusting for age, number of children, country of origin, locality size, and socioeconomic status. Compared to Jewish women, Muslim Arab women exhibited lower breast cancer mortality rates. However, after adjusting for multiple sociodemographic variables, no significant differences persisted between Jewish and Muslim Arab women. Having more than three children was associated with lower mortality among Muslim Arab women but not among Jewish women. European/American origin, larger localities, and medium socioeconomic status were associated with higher mortality. Sociodemographic factors may therefore explain the disparities in breast cancer mortality between Jewish and Muslim Arab women in Israel. Targeted intervention programs that consider the unique characteristics and risk factors of different ethnic groups are needed to reduce disparities and improve outcomes. Full article

(This article belongs to the Special Issue Socio-Demographic Factors and Cancer Research)

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12 pages, 2212 KiB

Open AccessReview

Cell Culture Models for Translational Research on Thymomas and Thymic Carcinomas: Current Status and Future Perspectives

by Denise Müller, Jürgen Loskutov, Stefan Küffer, Alexander Marx, Christian R. A. Regenbrecht, Philipp Ströbel and Manuela J. Regenbrecht

Cancers 2024, 16(15), 2762; https://doi.org/10.3390/cancers16152762 - 4 Aug 2024

Viewed by 1232

Abstract

Cell culture model systems are fundamental tools for studying cancer biology and identifying therapeutic vulnerabilities in a controlled environment. TET cells are notoriously difficult to culture, with only a few permanent cell lines available. The optimal conditions and requirements for the ex vivo [...] Read more.

Cell culture model systems are fundamental tools for studying cancer biology and identifying therapeutic vulnerabilities in a controlled environment. TET cells are notoriously difficult to culture, with only a few permanent cell lines available. The optimal conditions and requirements for the ex vivo establishment and permanent expansion of TET cells have not been systematically studied, and it is currently unknown whether different TET subtypes require different culture conditions or specific supplements. The few permanent cell lines available represent only type AB thymomas and thymic carcinomas, while attempts to propagate tumor cells derived from type B thymomas so far have been frustrated. It is conceivable that epithelial cells in type B thymomas are critically dependent on their interaction with immature T cells or their three-dimensional scaffold. Extensive studies leading to validated cell culture protocols would be highly desirable and a major advance in the field. Alternative methods such as tumor cell organoid models, patient-derived xenografts, or tissue slices have been sporadically used in TETs, but their specific contributions and advantages remain to be shown. Full article

(This article belongs to the Special Issue Thymic Tumors: New Developments and Future Directions in Molecularly Informed Therapies)

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29 pages, 1396 KiB

Open AccessSystematic Review

The Performance and Clinical Applicability of HER2 Digital Image Analysis in Breast Cancer: A Systematic Review

by Gauhar Dunenova, Zhanna Kalmataeva, Dilyara Kaidarova, Nurlan Dauletbaev, Yuliya Semenova, Madina Mansurova, Andrej Grjibovski, Fatima Kassymbekova, Aidos Sarsembayev, Daniil Semenov and Natalya Glushkova

Cancers 2024, 16(15), 2761; https://doi.org/10.3390/cancers16152761 - 3 Aug 2024

Viewed by 1738

Abstract

This systematic review aims to address the research gap in the performance of computational algorithms for the digital image analysis of HER2 images in clinical settings. While numerous studies have explored various aspects of these algorithms, there is a lack of comprehensive evaluation [...] Read more.

This systematic review aims to address the research gap in the performance of computational algorithms for the digital image analysis of HER2 images in clinical settings. While numerous studies have explored various aspects of these algorithms, there is a lack of comprehensive evaluation regarding their effectiveness in real-world clinical applications. We conducted a search of the Web of Science and PubMed databases for studies published from 31 December 2013 to 30 June 2024, focusing on performance effectiveness and components such as dataset size, diversity and source, ground truth, annotation, and validation methods. The study was registered with PROSPERO (CRD42024525404). Key questions guiding this review include the following: How effective are current computational algorithms at detecting HER2 status in digital images? What are the common validation methods and dataset characteristics used in these studies? Is there standardization of algorithm evaluations of clinical applications that can improve the clinical utility and reliability of computational tools for HER2 detection in digital image analysis? We identified 6833 publications, with 25 meeting the inclusion criteria. The accuracy rate with clinical datasets varied from 84.19% to 97.9%. The highest accuracy was achieved on the publicly available Warwick dataset at 98.8% in synthesized datasets. Only 12% of studies used separate datasets for external validation; 64% of studies used a combination of accuracy, precision, recall, and F1 as a set of performance measures. Despite the high accuracy rates reported in these studies, there is a notable absence of direct evidence supporting their clinical application. To facilitate the integration of these technologies into clinical practice, there is an urgent need to address real-world challenges and overreliance on internal validation. Standardizing study designs on real clinical datasets can enhance the reliability and clinical applicability of computational algorithms in improving the detection of HER2 cancer. Full article

(This article belongs to the Special Issue Novel Approaches to Machine Learning and Artificial Intelligence in Cancer Research and Care)

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13 pages, 706 KiB

Open AccessArticle

Prediction of PSA Response after Dexamethasone Switch during Abiraterone Acetate + Prednisolone Treatment of Metastatic Castration-Resistant Prostate Cancer Patients

by Bertalan Fekete, Krisztina Biró, Fruzsina Gyergyay, Nándor Polk, Orsolya Horváth, Lajos Géczi, Attila Patócs and Barna Budai

Cancers 2024, 16(15), 2760; https://doi.org/10.3390/cancers16152760 - 3 Aug 2024

Viewed by 939

Abstract

Background: The aim was to elaborate a predictive model to find responders for the corticosteroid switch (from prednisolone to dexamethasone) at the first prostate-specific antigen (PSA) progression (≥25% increase) during abiraterone acetate (AA) treatment of metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: If [...] Read more.

Background: The aim was to elaborate a predictive model to find responders for the corticosteroid switch (from prednisolone to dexamethasone) at the first prostate-specific antigen (PSA) progression (≥25% increase) during abiraterone acetate (AA) treatment of metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: If PSA has decreased (≥25%) after switch, patients were considered responders. Logistic regression of 19 dichotomized parameters from routine laboratory and patients’ history was used to find the best model in a cohort of 67 patients. The model was validated in another cohort of 42 patients. Results: The model provided 92.5% and 90.5% accuracy in the testing and the validation cohorts, respectively. Overall the accuracy was 91.7%. The AUC of ROC curve was 0.92 (95% CI 0.85–0.96). After a median follow-up of 27.9 (26.3–84) months, the median AA+dexamethasone treatment duration (TD) in non-responders and responders was 4.7 (3.1–6.5) and 11.1 (8.5–12.9) months and the median overall survival (OS) was 23.2 (15.6–25.8) and 33.5 (26.1–38) months, respectively. Multivariate Cox regression revealed that responsiveness was an independent marker of TD and OS. Conclusions: A high accuracy model was developed for mCRPC patients in predicting cases which might benefit from the switch. For non-responders, induction of the next systemic treatment is indicated. Full article

(This article belongs to the Special Issue Castration-Resistant Prostate Cancer: Progress and Promise)

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15 pages, 6243 KiB

Open AccessArticle

From Tumor Macroenvironment to Tumor Microenvironment: The Prognostic Role of the Immune System in Oral and Lung Squamous Cell Carcinoma

by Rosa Alessia Battista, Giacomo Maria Pini, Alex Finco, Filippo Corso, Andrea Galli, Gianluigi Arrigoni, Claudio Doglioni, Marcella Callea, Matteo Paccagnella, Luca Porcu, Federica Filipello, Marco Mazzola, Giorgia Foggetti, Vanesa Gregorc, Leone Giordano, Mario Bussi, Aurora Mirabile and Giulia Veronesi

Cancers 2024, 16(15), 2759; https://doi.org/10.3390/cancers16152759 - 3 Aug 2024

Viewed by 898

Abstract

Background: The interplay between cancer cells and the immune system is crucial in cancer progression and treatment. In this regard, the tumor immune microenvironment and macroenvironment, marked by systemic inflammation markers and TILs, could be considered key prognostic factors in tumors, including oral [...] Read more.

Background: The interplay between cancer cells and the immune system is crucial in cancer progression and treatment. In this regard, the tumor immune microenvironment and macroenvironment, marked by systemic inflammation markers and TILs, could be considered key prognostic factors in tumors, including oral and lung squamous cell carcinoma. Methods: We conducted a retrospective clinical study on patients with Oral Squamous Cell Carcinoma (OSCC) and Lung Squamous Cell Carcinoma (LUSCC), examining stages, comorbidities, treatments, and outcomes. We evaluated the prognostic significance of pre-surgical systemic inflammation markers and tumor microenvironment composition. Results: Associations were found between systemic inflammation markers—NLR, MLR, and PLR—and tumor microenvironment factors, such as TILs and CD8+ cell prevalence—elevated inflammation markers correlated with advanced stages. Specifically, NLR was prognostic in OSCC, whereas PLR was prognostic in LUSCC. Using a cutoff value, we divided our tumor samples into two prognostic groups. Moreover, TILs levels >15% of tumor stroma correlated with prolonged overall survival in both OSCC and LUSCC, while increased CD8+ expression was linked to extended disease-free survival in LUSCC. Discussion: Systemic inflammation markers and TILs can be valuable prognostic factors of survival, highlighting the immune response’s role in OSCC and LUSCC. Despite limited clinical integration of the presented cohorts due to a lack of standardization, we concluded that analyzing tumor immune profiles may offer novel prognostic insights. Conclusions: Future integration into cancer classification could improve risk stratification and treatment guidance. Full article

(This article belongs to the Special Issue The Tumor Microenvironment and Its Role in Tumor Growth and Angiogenesis)

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13 pages, 2231 KiB

Open AccessReview

Emerging Role of Hippo-YAP (Yes-Associated Protein)/TAZ (Transcriptional Coactivator with PDZ-Binding Motif) Pathway Dysregulation in Renal Cell Carcinoma Progression

by Varsha Mondal, Paul J. Higgins and Rohan Samarakoon

Cancers 2024, 16(15), 2758; https://doi.org/10.3390/cancers16152758 - 3 Aug 2024

Viewed by 1204

Abstract

Although Hippo-YAP/TAZ pathway involvement has been extensively studied in the development of certain cancers, the involvement of this cascade in kidney cancer progression is not well-established and, therefore, will be the focus of this review. Renal cell carcinoma (RCC), the most prevalent kidney [...] Read more.

Although Hippo-YAP/TAZ pathway involvement has been extensively studied in the development of certain cancers, the involvement of this cascade in kidney cancer progression is not well-established and, therefore, will be the focus of this review. Renal cell carcinoma (RCC), the most prevalent kidney tumor subtype, has a poor prognosis and a high mortality rate. Core Hippo signaling inactivation (e.g., LATS kinases) leads to the nuclear translocation of YAP/TAZ where they bind to co-transcriptional factors such as TEAD promoting transcription of genes which initiates various fibrotic and neoplastic diseases. Loss of expression of LATS1/2 kinase and activation of YAP/TAZ correlates with poor survival in RCC patients. Renal-specific ablation of LATS1 in mice leads to the spontaneous development of several subtypes of RCC in a YAP/TAZ-dependent manner. Genetic and pharmacological inactivation of YAP/TAZ reverses the oncogenic potential in LATS1-deficient mice, highlighting the therapeutic benefit of network targeting in RCC. Here, we explore the unique upstream controls and downstream consequences of the Hippo-YAP/TAZ pathway deregulation in renal cancer. This review critically evaluates the current literature on the role of the Hippo pathway in RCC progression and highlights the recent scientific evidence designating YAP/TAZ as novel therapeutic targets against kidney cancer. Full article

(This article belongs to the Section Cancer Pathophysiology)

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10 pages, 253 KiB

Open AccessReview

Assessing Health-Related Quality of Life in Mycosis Fungoides and Sézary Syndrome: Unmet Needs

by Danielle Brazel, Cecilia Larocca and Michi M. Shinohara

Cancers 2024, 16(15), 2757; https://doi.org/10.3390/cancers16152757 - 3 Aug 2024

Viewed by 862

Abstract

Mycosis fungoides (MF) and Sézary syndrome (SS) can impair multiple dimensions of health-related quality of life (HRQoL). Currently, there is no standardized assessment tool for measuring HRQoL in patients with MF/SS. Here, we describe the existing literature on multiple dimensions of HRQoL in [...] Read more.

Mycosis fungoides (MF) and Sézary syndrome (SS) can impair multiple dimensions of health-related quality of life (HRQoL). Currently, there is no standardized assessment tool for measuring HRQoL in patients with MF/SS. Here, we describe the existing literature on multiple dimensions of HRQoL in MF/SS with a special focus on the gaps in the current knowledge and identify future directions necessary to assess the HRQoL of patients with this disease. Full article

(This article belongs to the Special Issue Cutaneous Lymphoma)

12 pages, 1115 KiB

Open AccessArticle

Prognostic Significance of EGFR, HER2, and c-Met Overexpression in Surgically Treated Patients with Adenocarcinoma of the Ampulla of Vater

by Se Jun Park, Kabsoo Shin, Tae Ho Hong, Sung Hak Lee, In-Ho Kim, Younghoon Kim and MyungAh Lee

Cancers 2024, 16(15), 2756; https://doi.org/10.3390/cancers16152756 - 3 Aug 2024

Viewed by 884

Abstract

Adenocarcinoma of the ampulla of Vater (AAC) is a rare malignancy with heterogeneous tumors arising from various histologic subtypes, necessitating new therapeutic strategies. This study examines epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and c-Met expression in AAC, [...] Read more.

Adenocarcinoma of the ampulla of Vater (AAC) is a rare malignancy with heterogeneous tumors arising from various histologic subtypes, necessitating new therapeutic strategies. This study examines epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and c-Met expression in AAC, given their potential as druggable targets. Among 87 patients who underwent curative resection, EGFR overexpression was found in 87.4%, HER2 in 11.5%, and c-Met in 50%. EGFR overexpression was more common in the pancreatobiliary subtype (p = 0.018) and associated with a higher histologic grade (p = 0.008). HER2 did not correlate with clinicopathological features, while c-Met was more common in node-negative groups (p = 0.004) and often co-expressed with EGFR (p = 0.049). EGFR-positive patients had worse disease-free (HR = 2.89; 95% CI, 1.35–6.20; p = 0.061) and overall survival (HR = 6.89; 95% CI, 2.94–16.2; p = 0.026) than EGFR-negative patients. HER2-positive AAC showed a trend towards shorter survival, although not statistically significant, and c-Met had no impact on survival outcomes. In the context of systemic disease, survival outcomes did not vary according to EGFR, HER2, and c-Met expression, but the HER2-positive group showed a trend towards inferior progression-free survival (HR = 1.90; 95% CI, 0.56–6.41; p = 0.166). This study underscores the potential of EGFR, HER2, and c-Met as targets for personalized therapy in AAC, warranting further research to evaluate targeted treatments. Full article

(This article belongs to the Special Issue Current Clinical Studies of Pancreatic Ductal Adenocarcinoma)

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8 pages, 1055 KiB

Open AccessArticle

Three-Year Analysis of Adjuvant Therapy in Postoperative Melanoma including Acral and Mucosal Subtypes

by Yusuke Muto, Yumi Kambayashi, Hiroshi Kato, Satoru Mizuhashi, Takamichi Ito, Takeo Maekawa, Shoichiro Ishizuki, Hiroshi Uchi, Shigeto Matsushita, Yuki Yamamoto, Koji Yoshino, Yasuhiro Fujisawa, Ryo Amagai, Kentaro Ohuchi, Akira Hashimoto, Satoshi Fukushima, Yoshihide Asano and Taku Fujimura

Cancers 2024, 16(15), 2755; https://doi.org/10.3390/cancers16152755 - 2 Aug 2024

Viewed by 1299

Abstract

Background: Adjuvant therapy has improved the clinical prognosis for postoperative melanoma patients. However, the long-term efficacy of this therapy on the melanoma acral and mucosal subtypes has not been fully evaluated in previous trials. This study assessed the 3-year recurrence-free survival and overall [...] Read more.

Background: Adjuvant therapy has improved the clinical prognosis for postoperative melanoma patients. However, the long-term efficacy of this therapy on the melanoma acral and mucosal subtypes has not been fully evaluated in previous trials. This study assessed the 3-year recurrence-free survival and overall survival of patients with melanoma, including the acral and mucosal subtypes, treated with anti-PD-1 antibody (Ab) or with the combination of the BRAF and MEK inhibitors dabrafenib and trametinib. Methods: We retrospectively analyzed both the 3-year time to relapse (TTR) and overall survival (OS) of 120 patients treated with anti-PD-1 antibody (Ab), or with the combination of dabrafenib and trametinib. Results: The overall median TTR was 18.4 months, with a range of 0.69 to 36 months. The 3-year TTR of the acral and mucosal types was 28.1% and 38.5%, respectively. Baseline tumor thickness (TT) and acral type were associated with the TTR in subgroup analysis. Moreover, we classified 104 acral and non-acral cutaneous patients into the anti-PD-1 Abs or dabrafenib plus trametinib combined therapies cohort in multiple analyses. The acral subtype and TT were detected as important prognostic factors. In the 3-year OS, only tumor ulceration was associated with the OS in both univariate and multiple analyses. There was no significant difference in baseline or treatment-related factors of the mucosal type (p > 0.05). Conclusion: This study suggests that adjuvant therapy is more effective with non-acral cutaneous melanoma than either the acral or mucosal types at the 3-year TTR endpoint. Full article

(This article belongs to the Special Issue Advances in Skin Cancer: Diagnosis, Treatment and Prognosis)

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35 pages, 3486 KiB

Open AccessReview

Non-Receptor Tyrosine Kinases: Their Structure and Mechanistic Role in Tumor Progression and Resistance

by Abdulaziz M. Eshaq, Thomas W. Flanagan, Sofie-Yasmin Hassan, Sara A. Al Asheikh, Waleed A. Al-Amoudi, Simeon Santourlidis, Sarah-Lilly Hassan, Maryam O. Alamodi, Marcelo L. Bendhack, Mohammed O. Alamodi, Youssef Haikel, Mossad Megahed and Mohamed Hassan

Cancers 2024, 16(15), 2754; https://doi.org/10.3390/cancers16152754 - 2 Aug 2024

Cited by 1 | Viewed by 1190

Abstract

Protein tyrosine kinases (PTKs) function as key molecules in the signaling pathways in addition to their impact as a therapeutic target for the treatment of many human diseases, including cancer. PTKs are characterized by their ability to phosphorylate serine, threonine, or tyrosine residues [...] Read more.

Protein tyrosine kinases (PTKs) function as key molecules in the signaling pathways in addition to their impact as a therapeutic target for the treatment of many human diseases, including cancer. PTKs are characterized by their ability to phosphorylate serine, threonine, or tyrosine residues and can thereby rapidly and reversibly alter the function of their protein substrates in the form of significant changes in protein confirmation and affinity for their interaction with protein partners to drive cellular functions under normal and pathological conditions. PTKs are classified into two groups: one of which represents tyrosine kinases, while the other one includes the members of the serine/threonine kinases. The group of tyrosine kinases is subdivided into subgroups: one of them includes the member of receptor tyrosine kinases (RTKs), while the other subgroup includes the member of non-receptor tyrosine kinases (NRTKs). Both these kinase groups function as an “on” or "off" switch in many cellular functions. NRTKs are enzymes which are overexpressed and activated in many cancer types and regulate variable cellular functions in response to extracellular signaling-dependent mechanisms. NRTK-mediated different cellular functions are regulated by kinase-dependent and kinase-independent mechanisms either in the cytoplasm or in the nucleus. Thus, targeting NRTKs is of great interest to improve the treatment strategy of different tumor types. This review deals with the structure and mechanistic role of NRTKs in tumor progression and resistance and their importance as therapeutic targets in tumor therapy. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Treatment Resistance)

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24 pages, 3685 KiB

Open AccessReview

FUCA1: An Underexplored p53 Target Gene Linking Glycosylation and Cancer Progression

by Die Hu, Naoya Kobayashi and Rieko Ohki

Cancers 2024, 16(15), 2753; https://doi.org/10.3390/cancers16152753 - 2 Aug 2024

Viewed by 1296

Abstract

Cancer is a difficult-to-cure disease with high worldwide incidence and mortality, in large part due to drug resistance and disease relapse. Glycosylation, which is a common modification of cellular biomolecules, was discovered decades ago and has been of interest in cancer research due [...] Read more.

Cancer is a difficult-to-cure disease with high worldwide incidence and mortality, in large part due to drug resistance and disease relapse. Glycosylation, which is a common modification of cellular biomolecules, was discovered decades ago and has been of interest in cancer research due to its ability to influence cellular function and to promote carcinogenesis. A variety of glycosylation types and structures regulate the function of biomolecules and are potential targets for investigating and treating cancer. The link between glycosylation and carcinogenesis has been more recently revealed by the role of p53 in energy metabolism, including the p53 target gene alpha-L-fucosidase 1 (FUCA1), which plays an essential role in fucosylation. In this review, we summarize roles of glycan structures and glycosylation-related enzymes to cancer development. The interplay between glycosylation and tumor microenvironmental factors is also discussed, together with involvement of glycosylation in well-characterized cancer-promoting mechanisms, such as the epidermal growth factor receptor (EGFR), phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and p53-mediated pathways. Glycan structures also modulate cell–matrix interactions, cell–cell adhesion as well as cell migration and settlement, dysfunction of which can contribute to cancer. Thus, further investigation of the mechanistic relationships among glycosylation, related enzymes and cancer progression may provide insights into potential novel cancer treatments. Full article

(This article belongs to the Section Molecular Cancer Biology)

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Graphical abstract

22 pages, 2434 KiB

Open AccessReview

Targeting Isocitrate Dehydrogenase (IDH) in Solid Tumors: Current Evidence and Future Perspectives

by Francesca Carosi, Elisabetta Broseghini, Laura Fabbri, Giacomo Corradi, Riccardo Gili, Valentina Forte, Roberta Roncarati, Daria Maria Filippini and Manuela Ferracin

Cancers 2024, 16(15), 2752; https://doi.org/10.3390/cancers16152752 - 2 Aug 2024

Cited by 2 | Viewed by 1729

Abstract

The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response. IDH mutations have been associated with tumor development and progression in various solid tumors such as glioma, [...] Read more.

The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response. IDH mutations have been associated with tumor development and progression in various solid tumors such as glioma, cholangiocarcinoma, chondrosarcoma, and other tumor types and have become crucial markers in molecular classification and prognostic assessment. The intratumoral and serum levels of D-2-hydroxyglutarate (D-2-HG) could serve as diagnostic biomarkers for identifying IDH mutant (IDHmut) tumors. As a result, an increasing number of clinical trials are evaluating targeted treatments for IDH1/IDH2 mutations. Recent studies have shown that the focus of these new therapeutic strategies is not only the neomorphic activity of the IDHmut enzymes but also the epigenetic shift induced by IDH mutations and the potential role of combination treatments. Here, we provide an overview of the current knowledge about IDH mutations in solid tumors, with a particular focus on available IDH-targeted treatments and emerging results from clinical trials aiming to explore IDHmut tumor-specific features and to identify the clinical benefit of IDH-targeted therapies and their combination strategies. An insight into future perspectives and the emerging roles of circulating biomarkers and radiomic features is also included. Full article

(This article belongs to the Special Issue Cancer Cell Metabolism and Drug Targets)

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31 pages, 20539 KiB

Open AccessArticle

Imaging Biomarkers of Oral Dysplasia and Carcinoma Measured with In Vivo Endoscopic Optical Coherence Tomography

by Jeanie Malone, Chloe Hill, Adrian Tanskanen, Kelly Liu, Samson Ng, Calum MacAulay, Catherine F. Poh and Pierre M. Lane

Cancers 2024, 16(15), 2751; https://doi.org/10.3390/cancers16152751 - 2 Aug 2024

Viewed by 1126

Abstract

Optical coherence tomography is a noninvasive imaging technique that provides three-dimensional visualization of subsurface tissue structures. OCT has been proposed and explored in the literature as a tool to assess oral cancer status, select biopsy sites, or identify surgical margins. Our endoscopic OCT [...] Read more.

Optical coherence tomography is a noninvasive imaging technique that provides three-dimensional visualization of subsurface tissue structures. OCT has been proposed and explored in the literature as a tool to assess oral cancer status, select biopsy sites, or identify surgical margins. Our endoscopic OCT device can generate widefield (centimeters long) imaging of lesions at any location in the oral cavity—but it is challenging for raters to quantitatively assess and score large volumes of data. Leveraging a previously developed epithelial segmentation network, this work develops quantifiable biomarkers that provide direct measurements of tissue properties in three dimensions. We hypothesize that features related to morphology, tissue attenuation, and contrast between tissue layers will be able to provide a quantitative assessment of disease status (dysplasia through carcinoma). This work retrospectively assesses seven biomarkers on a lesion-contralateral matched OCT dataset of the lateral and ventral tongue (40 patients, 70 sites). Epithelial depth and loss of epithelial–stromal boundary visualization provide the strongest discrimination between disease states. The stroma optical attenuation coefficient provides a distinction between benign lesions from dysplasia and carcinoma. The stratification biomarkers visualize subsurface changes, which provides potential for future utility in biopsy site selection or treatment margin delineation. Full article

(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection)

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13 pages, 1027 KiB

Open AccessArticle

Retrospective Cohort Study on the Impact of Travel Distance on Late-Stage Oral Cancer Treatment and Outcomes: An NCDB Analysis

by Courtney S. Harris, Adrienne Groman, S. Lynn Sigurdson, William J. Magner, Anurag K. Singh and Vishal Gupta

Cancers 2024, 16(15), 2750; https://doi.org/10.3390/cancers16152750 - 2 Aug 2024

Viewed by 665

Abstract

The National Comprehensive Cancer Network guidelines provide evidence-based consensus for optimal individual site- and stage-specific treatments. This is a cohort study of 11,121 late-stage oral cancer patients in the National Cancer Database from 2010 to 2016. We hypothesized that patient travel distance may [...] Read more.

The National Comprehensive Cancer Network guidelines provide evidence-based consensus for optimal individual site- and stage-specific treatments. This is a cohort study of 11,121 late-stage oral cancer patients in the National Cancer Database from 2010 to 2016. We hypothesized that patient travel distance may affect treatment choices and impact outcome. We split travel distance (miles) into quartiles (D1–4) and assessed treatment choices, type of facility, and survival outcome in relation to distance traveled. Univariate and multivariate analyses addressed contributions of specific variables. White patients were most likely to travel farthest (D4) for treatment compared to Black patients (D1). Urban area patients traveled shorter distances than those from rural areas. Greater travel distance was associated with patients undergoing surgical-based therapies and treatment at academic centers. Patients in D1 had the lowest median survival of all distance quartiles. Surgery-based multimodality treatment (surgery and radiation) had a median survival significantly greater than for non-surgical therapy. Several factors including travel distance and treatment facility were associated with survival outcomes for late-stage oral cavity cancers. Consideration of these factors may help improve the outcome for this patient population. Full article

(This article belongs to the Section Cancer Survivorship and Quality of Life)

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16 pages, 834 KiB

Open AccessArticle

Observation and Management of Juvenile Myelomonocytic Leukemia and Noonan Syndrome-Associated Myeloproliferative Disorder: A Real-World Experience

by Bryony J. Lucas, Jeremy S. Connors, Heping Wang, Shannon Conneely, Branko Cuglievan, Miriam B. Garcia and Rachel E. Rau

Cancers 2024, 16(15), 2749; https://doi.org/10.3390/cancers16152749 - 2 Aug 2024

Cited by 1 | Viewed by 1053

Abstract

Juvenile Myelomonocytic Leukemia (JMML) is a rare and clonal hematopoietic disorder of infancy and early childhood with myeloproliferative/myelodysplastic features resulting from germline or somatic mutations in the RAS pathway. Treatment is not uniform, with management varying from observation to stem cell transplant. The [...] Read more.

Juvenile Myelomonocytic Leukemia (JMML) is a rare and clonal hematopoietic disorder of infancy and early childhood with myeloproliferative/myelodysplastic features resulting from germline or somatic mutations in the RAS pathway. Treatment is not uniform, with management varying from observation to stem cell transplant. The aim of our retrospective review is to describe the treatment and outcomes of a cohort of patients with JMML or Noonan Syndrome-associated Myeloproliferative Disorder (NS-MPD) to provide management guidance for this rare and heterogeneous disease. We report on 22 patients with JMML or NS-MPD managed at three institutions in the Texas Medical Center. Of patients with known genetic mutations and cytogenetics, 6 harbored germline mutations, 12 had somatic mutations, and 9 showed cytogenetic abnormalities. Overall, 14/22 patients are alive. Spontaneous clinical remission occurred in one patient with somatic NRAS mutation, as well as two with germline PTPN11 mutations with NS-MPD, and two others with germline PTPN11 mutations and NS-MPD remain under surveillance. Patients with NS-MPD were excluded from treatment analysis as none required chemotherapeutic intervention. All patients (5/5) treated with 5-azacitidine alone and one of the four treated with 6-mercaptopurine monotherapy had a reduction in mutant variant allele frequency. Transformation to acute myeloid leukemia was seen in two patients who both died. Among patients who received transplants, 7/13 are alive, and relapse post-transplant occurred in 3/13 with a median time to relapse of 3.55 months. This report provides insight into therapy responses and long-term outcomes across different genetic subsets of JMML and lends insight into the expected time to spontaneous resolution in patients with NS-MPD with germline PTPN11 mutations. Full article

(This article belongs to the Special Issue Molecular and Genetic Diagnosis and Targeted Therapy of Myeloproliferative Neoplasms)

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17 pages, 4146 KiB

Open AccessArticle

Definition of a Multi-Omics Signature for Esophageal Adenocarcinoma Prognosis Prediction

by Luca Lambroia, Carola Maria Conca Dioguardi, Simone Puccio, Andrea Pansa, Giorgia Alvisi, Gianluca Basso, Javier Cibella, Federico Simone Colombo, Salvatore Marano, Silvia Basato, Rita Alfieri, Simone Giudici, Carlo Castoro and Clelia Peano

Cancers 2024, 16(15), 2748; https://doi.org/10.3390/cancers16152748 - 1 Aug 2024

Viewed by 1576

Abstract

Esophageal cancer is a highly lethal malignancy, representing 5% of all cancer-related deaths. The two main subtypes are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). While most research has focused on ESCC, few studies have analyzed EAC for transcriptional signatures linked [...] Read more.

Esophageal cancer is a highly lethal malignancy, representing 5% of all cancer-related deaths. The two main subtypes are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). While most research has focused on ESCC, few studies have analyzed EAC for transcriptional signatures linked to diagnosis or prognosis. In this study, we utilized single-cell RNA sequencing and bulk RNA sequencing to identify specific immune cell types that contribute to anti-tumor responses, as well as differentially expressed genes (DEGs). We have characterized transcriptional signatures, validated against a wide cohort of TCGA patients, that are capable of predicting clinical outcomes and the prognosis of EAC post-surgery with efficacy comparable to the currently accepted prognostic factors. In conclusion, our findings provide insights into the immune landscape and therapeutic targets of EAC, proposing novel immunological biomarkers for predicting prognosis, aiding in patient stratification for post-surgical outcomes, follow-up, and personalized adjuvant therapy decisions. Full article

(This article belongs to the Special Issue Combination Immunotherapy for Cancer Treatment)

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16 pages, 1677 KiB

Open AccessArticle

Five-Year Relative Survival Rates of Women Diagnosed with Uterine Cancer by County-Level Socioeconomic Status Overall and across Histology and Race/Ethnicity

by Akemi T. Wijayabahu, Jennifer K. McGee-Avila, Meredith S. Shiels, Alfonsus Adrian H. Harsono, Rebecca C. Arend and Megan A. Clarke

Cancers 2024, 16(15), 2747; https://doi.org/10.3390/cancers16152747 - 1 Aug 2024

Viewed by 956

Abstract

Understanding socioeconomic factors contributing to uterine cancer survival disparities is crucial, especially given the increasing incidence of uterine cancer, which disproportionately impacts racial/ethnic groups. We investigated the impact of county-level socioeconomic factors on five-year survival rates of uterine cancer overall and by histology [...] Read more.

Understanding socioeconomic factors contributing to uterine cancer survival disparities is crucial, especially given the increasing incidence of uterine cancer, which disproportionately impacts racial/ethnic groups. We investigated the impact of county-level socioeconomic factors on five-year survival rates of uterine cancer overall and by histology across race/ethnicity. We included 333,013 women aged ≥ 30 years with microscopically confirmed uterine cancers (2000–2018) from the Surveillance, Epidemiology, and End Results 22 database followed through 2019. Age-standardized five-year relative survival rates were compared within race/ethnicity and histology, examining the differences across tertiles of county-level percent (%) <high-school education, %<150 percent poverty, %unemployment, median household income, and %urbanicity. Overall age-adjusted five-year relative survival was 77.7%. Rates were lowest among those residing in the least advantaged counties (tertile 3) and highest among the most advantaged (tertile 1): education (74.7% vs. 80.2%), poverty (72.9% vs. 79.8%), unemployment (75.7% vs. 80.5%), and income (73.3% tertile 1 vs. 78.1% tertile 3). Impact of county-level socioeconomic characteristics on survival across histology was minimal. We observed considerable survival disparities among NH-Black and NH-Native American/Alaskan Native women, regardless of tumor and socioeconomic characteristics. These findings add to our understanding of how county-level socioeconomic characteristics affect uterine cancer survival inequalities among racial/ethnic groups. Full article

(This article belongs to the Special Issue Gynecologic Cancer: Risk Factors, Interception and Prevention)

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22 pages, 652 KiB

Open AccessReview

Screening and Surveillance of Colorectal Cancer: A Review of the Literature

by Marcello Maida, Dushyant Singh Dahiya, Yash R. Shah, Angad Tiwari, Harishankar Gopakumar, Ishaan Vohra, Aqsa Khan, Fouad Jaber, Daryl Ramai and Antonio Facciorusso

Cancers 2024, 16(15), 2746; https://doi.org/10.3390/cancers16152746 - 1 Aug 2024

Viewed by 2514

Abstract

Colorectal cancer (CRC) has the highest mortality rate among men and is the second highest among women under fifty, with incidence and mortality rates rising in younger populations. Studies indicate that up to one-third of patients diagnosed before fifty have a family history [...] Read more.

Colorectal cancer (CRC) has the highest mortality rate among men and is the second highest among women under fifty, with incidence and mortality rates rising in younger populations. Studies indicate that up to one-third of patients diagnosed before fifty have a family history or genetic factors, highlighting the need for earlier screening. Contrariwise, diagnosis in healthy subjects through screening strategies enables early-stage detection of the tumor and better clinical outcomes. In recent years, mortality rates of CRC in Western countries have been on a steady decline, which is largely attributed to widespread screening programs and advancements in treatment modalities. Indeed, early detection through screening significantly improves prognosis, with stark differences in survival rates between localized and metastatic disease. This article aims to provide a comprehensive review of the existing literature, delving into the performance and efficacy of various CRC screening strategies. It navigates through available screening tools, evaluating their efficacy and cost-effectiveness. The discussion extends to delineating target populations for screening, emphasizing the importance of tailored approaches for individuals at heightened risk. Full article

(This article belongs to the Special Issue Novel Strategies in the Prevention/Treatment of Colorectal Cancer)

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14 pages, 1613 KiB

Open AccessArticle

Improving Hepatocellular Carcinoma Surveillance Outcomes in Patients with Cirrhosis after Hepatitis C Cure: A Modelling Study

by Jacob Cumming, Nick Scott, Jessica Howell, Joan Ericka Flores, Damian Pavlyshyn, Margaret E. Hellard, Leon Shin-han Winata, Marno Ryan, Tom Sutherland, Alexander J. Thompson, Joseph S. Doyle and Rachel Sacks-Davis

Cancers 2024, 16(15), 2745; https://doi.org/10.3390/cancers16152745 - 1 Aug 2024

Viewed by 967

Abstract

Background & Aims: Hepatocellular carcinoma (HCC) presents a significant global health challenge, particularly among individuals with liver cirrhosis, with hepatitis C (HCV) a major cause. In people with HCV-related cirrhosis, an increased risk of HCC remains after cure. HCC surveillance with six monthly [...] Read more.

Background & Aims: Hepatocellular carcinoma (HCC) presents a significant global health challenge, particularly among individuals with liver cirrhosis, with hepatitis C (HCV) a major cause. In people with HCV-related cirrhosis, an increased risk of HCC remains after cure. HCC surveillance with six monthly ultrasounds has been shown to improve survival. However, adherence to biannual screening is currently suboptimal. This study aimed to evaluate the effect of increased HCC surveillance uptake and improved ultrasound sensitivity on mortality among people with HCV-related cirrhosis post HCV cure. Methods: This study utilized mathematical modelling to assess HCC progression, surveillance, diagnosis, and treatment among individuals with cirrhosis who had successfully been treated for HCV. The deterministic compartmental model incorporated Barcelona Clinic Liver Cancer (BCLC) stages to simulate disease progression and diagnosis probabilities in 100 people with cirrhosis who had successfully been treated for hepatitis C over 10 years. Four interventions were modelled to assess their potential for improving life expectancy: realistic improvements to surveillance adherence, optimistic improvements to surveillance adherence, diagnosis sensitivity enhancements, and improved treatment efficacy Results: Realistic adherence improvements resulted in 9.8 (95% CI 7.9, 11.6) life years gained per cohort of 100 over a 10-year intervention period; 17.2 (13.9, 20.3) life years were achieved in optimistic adherence improvements. Diagnosis sensitivity improvements led to a 7.0 (3.6, 13.8) year gain in life years, and treatment improvements improved life years by 9.0 (7.5, 10.3) years. Conclusions: Regular HCC ultrasound surveillance remains crucial to reduce mortality among people with cured hepatitis C and cirrhosis. Our study highlights that even minor enhancements to adherence to ultrasound surveillance can significantly boost life expectancy across populations more effectively than strategies that increase surveillance sensitivity or treatment efficacy. Full article

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

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6 pages, 1820 KiB

Open AccessCorrection

Correction: Tasci et al. RadWise: A Rank-Based Hybrid Feature Weighting and Selection Method for Proteomic Categorization of Chemoirradiation in Patients with Glioblastoma. Cancers 2023, 15, 2672

by Erdal Tasci, Sarisha Jagasia, Ying Zhuge, Mary Sproull, Theresa Cooley Zgela, Megan Mackey, Kevin Camphausen and Andra Valentina Krauze

Cancers 2024, 16(15), 2744; https://doi.org/10.3390/cancers16152744 - 1 Aug 2024

Viewed by 581

Abstract

In the original publication [...] Full article

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10 pages, 1093 KiB

Open AccessArticle

Assessing the Adequacy of Traditional Vertebral Landmarks as Upper Border of Whole Pelvic Radiotherapy Field for Stage IB2-IIB Cervical Cancer

by Ji Hwan Jo, Jeong Won Lee and Ki Ho Seol

Cancers 2024, 16(15), 2743; https://doi.org/10.3390/cancers16152743 - 1 Aug 2024

Viewed by 771

Abstract

This study investigates the impact of insufficient common iliac lymph node (CIN) irradiation on treatment outcomes in patients with stage IB2-IIB cervical cancer receiving concurrent chemoradiotherapy (CCRT). We retrospectively analyzed 68 patients with Federation of Gynecology and Obstetrics stage IB2-IIB, treated with weekly [...] Read more.

This study investigates the impact of insufficient common iliac lymph node (CIN) irradiation on treatment outcomes in patients with stage IB2-IIB cervical cancer receiving concurrent chemoradiotherapy (CCRT). We retrospectively analyzed 68 patients with Federation of Gynecology and Obstetrics stage IB2-IIB, treated with weekly cisplatin-based CCRT from 2008 to 2018. Patients received external-beam whole pelvic radiotherapy (WPRT) and concurrent cisplatin chemotherapy, followed by high-dose-rate brachytherapy. The WPRT upper border was at L4-5 in 61 patients and L3-4 in 7 patients. Thirty-seven patients had the CIN area fully included (full-CIN group), while 31 had partial inclusion (partial-CIN group). Recurrence rates and survival outcomes were analyzed over a median follow-up of 111 months. Patient characteristics and the irradiated dose were comparable. Treatment failure occurred in three patients (8.1%) in the full-CIN group and in six patients (19.4%) in the partial-CIN group, with CIN and para-aortic lymph node recurrence in two and one patients, respectively. The 5-year cumulative recurrence rate was 0% for the full-CIN group and 11.4% for the partial-CIN group (p = 0.04). Cause-specific survival was 100% vs. 87.1% (p = 0.025), and the overall survival was 94.3% vs. 87.1% (p = 0.44). Fully including the CIN area in WPRT is crucial for stage IB2-IIB cervical cancer. Vascular anatomical margins should be considered over vertebral landmarks. Full article

(This article belongs to the Special Issue Radiotherapy in Gynecological Cancer: State of the Art)

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12 pages, 1211 KiB

Open AccessArticle

High-Dose-Rate Brachytherapy for Treatment of Facial Skin Cancers: Local Control, Toxicity, and Quality of Life in 67 Patients

by Jeanne Monge-Cadet, Benjamin Vairel, Mathilde Morisseau, Elizabeth Moyal, Anne Ducassou, Ciprian Chira, Cécile Pagès, Vincent Sibaud, Thomas Brun and Anouchka Modesto

Cancers 2024, 16(15), 2742; https://doi.org/10.3390/cancers16152742 - 1 Aug 2024

Viewed by 778

Abstract

While treatment of localized cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) is based on surgery, brachytherapy, which delivers a high dose of radiation to tumor tissue while sparing healthy tissue, is an alternative. Since the withdrawal of iridium wires from [...] Read more.

While treatment of localized cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) is based on surgery, brachytherapy, which delivers a high dose of radiation to tumor tissue while sparing healthy tissue, is an alternative. Since the withdrawal of iridium wires from the market, brachytherapy has mainly been performed with high-dose-rate iridium-192 (HDR). This study evaluated the efficacy of HDR brachytherapy in terms of local control, survival, toxicity, and quality of life in patients with facial periorificial cutaneous SCC or BCC treated in our center between 2015 and 2021. Sixty-seven patients were treated for SCC (n = 49) or BCC (n = 18), on the nose (n = 29), lip (n = 28), eyelid (n = 7), or ear (n = 3). The majority had Tis or T1 tumors (73.1%). After a median follow-up of 28 months, 8 patients had a local recurrence. The local control rate at 3 years was 87.05% (95% CI 74.6–93.7). All patients developed grade 1–2 acute radio-mucositis or radiodermatitis and one experienced reversible grade 3 acute radio-mucositis. Of the 27 patients who completed the quality-of-life questionnaire, 77.8% recommended the treatment. This study confirms that HDR brachytherapy for facial cutaneous carcinomas provides good local control, good tolerance, and satisfactory functional outcome. Full article

(This article belongs to the Special Issue Novel Developments on Skin Cancer Diagnostics and Treatment)

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11 pages, 239 KiB

Open AccessArticle

Predictors of Clavien–Dindo Grade III–IV or Grade V Complications after Metastatic Spinal Tumor Surgery: An Analysis of Sociodemographic, Socioeconomic, Clinical, Oncologic, and Operative Parameters

by Rafael De la Garza Ramos, Jessica Ryvlin, Ali Haider Bangash, Mousa K. Hamad, Mitchell S. Fourman, John H. Shin, Yaroslav Gelfand, Saikiran Murthy and Reza Yassari

Cancers 2024, 16(15), 2741; https://doi.org/10.3390/cancers16152741 - 1 Aug 2024

Viewed by 728

Abstract

The rate of major complications and 30-day mortality after surgery for metastatic spinal tumors is relatively high. While most studies have focused on baseline comorbid conditions and operative parameters as risk factors, there is limited data on the influence of other parameters such [...] Read more.

The rate of major complications and 30-day mortality after surgery for metastatic spinal tumors is relatively high. While most studies have focused on baseline comorbid conditions and operative parameters as risk factors, there is limited data on the influence of other parameters such as sociodemographic or socioeconomic data on outcomes. We retrospectively analyzed data from 165 patients who underwent surgery for spinal metastases between 2012–2023. The primary outcome was development of major complications (i.e., Clavien–Dindo Grade III–IV complications), and the secondary outcome was 30-day mortality (i.e., Clavien–Dindo Grade V complications). An exploratory data analysis that included sociodemographic, socioeconomic, clinical, oncologic, and operative parameters was performed. Following multivariable analysis, independent predictors of Clavien–Dindo Grade III–IV complications were Frankel Grade A–C, lower modified Bauer score, and lower Prognostic Nutritional Index. Independent predictors of Clavien–Dindo Grade V complications) were lung primary cancer, lower modified Bauer score, lower Prognostic Nutritional Index, and use of internal fixation. No sociodemographic or socioeconomic factor was associated with either outcome. Sociodemographic and socioeconomic factors did not impact short-term surgical outcomes for metastatic spinal tumor patients in this study. Optimization of modifiable factors like nutritional status may be more important in improving outcomes in this complex patient population. Full article

(This article belongs to the Special Issue Socio-Demographic Factors and Cancer Research)

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