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Cancers
Volume 14
Issue 15
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Cancers, Volume 14, Issue 15 (August-1 2022) – 284 articles

Cover Story (view full-size image): Myeloid-derived suppressor cells (MDSCs) create an immune-suppressive tumor microenvironment, making them an important target in cancer. Here we demonstrate, through proof-of-principle studies, the ability of near-infrared photoimmunotherapy (NIR-PIT) to visualize and selectively eliminate MDSCs that are significantly expanded in the spleen of tumor-bearing mice using an anti-Gr1 antibody conjugated to the NIR dye IR700. Anti-Gr1-IR700 conjugate retention in the spleen and lungs was respectively indicative of splenic extramedullary hematopoiesis and MDSC involvement in premetastastic niche formation during tumorigenesis. Characterization of spleen extracts, using 1H magnetic resonance spectroscopy (MRS), reveals metabolic changes indicative of MDSC elimination and spleen metabolite normalization comparable to that of the non-tumor-bearing host. View this paper
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14 pages, 2397 KiB  
Review
Cutaneous Angiosarcoma of the Head and Neck—A Retrospective Analysis of 47 Patients
by Neeraj Ramakrishnan, Ryan Mokhtari, Gregory W. Charville, Nam Bui and Kristen Ganjoo
Cancers 2022, 14(15), 3841; https://doi.org/10.3390/cancers14153841 - 08 Aug 2022
Cited by 10 | Viewed by 2439
Abstract
Cutaneous angiosarcoma (CAS) is a rare and aggressive malignant tumor with blood vessel or lymphatic-type endothelial differentiation. It has a poor prognosis with lack of standardized treatment options. This study retrospectively evaluated the clinical characteristics and treatment outcomes of 47 patients with CAS [...] Read more.
Cutaneous angiosarcoma (CAS) is a rare and aggressive malignant tumor with blood vessel or lymphatic-type endothelial differentiation. It has a poor prognosis with lack of standardized treatment options. This study retrospectively evaluated the clinical characteristics and treatment outcomes of 47 patients with CAS of the head and neck treated at an academic sarcoma center. Patient data were collected from the electronic medical records. 62% of patients were male with the scalp being the most commonly affected area (64%). The majority of patients presented with localized disease (53%). Median overall survival (OS) was 3.4 years with an OS of 36% at 5 years. There was a statistically significant increase in OS for patients who underwent surgery compared to those who did not (5.4 vs. 2.8 years). In contrast, radiotherapy (RT) or chemotherapy did not significantly increase OS. 45% of patients had recurrence of disease during their treatment course with a median time to recurrence of 22.8 months. There was not a significant difference in OS for patients who underwent immunotherapy compared to those who underwent chemotherapy, although only a few patients received immunotherapy. We found that surgery was an effective treatment modality in patients with easily resectable disease, while RT, chemotherapy, and immunotherapy did not significantly improve OS. Full article
(This article belongs to the Section Cancer Therapy)
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11 pages, 2215 KiB  
Review
Theranostics Using Indocyanine Green Lactosomes
by Masaki Kaibori, Kosuke Matsui and Mikio Hayashi
Cancers 2022, 14(15), 3840; https://doi.org/10.3390/cancers14153840 - 08 Aug 2022
Cited by 6 | Viewed by 1498
Abstract
Lactosomes™ are biocompatible nanoparticles that can be used for cancer tissue imaging and drug delivery. Lactosomes are polymeric micelles formed by the self-assembly of biodegradable amphiphilic block copolymers composed of hydrophilic polysarcosine and hydrophobic poly-L-lactic acid chains. The particle size can be controlled [...] Read more.
Lactosomes™ are biocompatible nanoparticles that can be used for cancer tissue imaging and drug delivery. Lactosomes are polymeric micelles formed by the self-assembly of biodegradable amphiphilic block copolymers composed of hydrophilic polysarcosine and hydrophobic poly-L-lactic acid chains. The particle size can be controlled in the range of 20 to 100 nm. Lactosomes can also be loaded with hydrophobic imaging probes and photosensitizers, such as indocyanine green. Indocyanine green-loaded lactosomes are stable for long-term circulation in the blood, allowing for accumulation in cancer tissues. Such lactosomes function as a photosensitizer, which simultaneously enables fluorescence diagnosis and photodynamic therapy. This review provides an overview of lactosomes with respect to molecular design, accumulation in cancer tissue, and theranostics applications. The use of lactosomes can facilitate the treatment of cancers in unresectable tissues, such as glioblastoma and head and neck cancers, which can lead to improved quality of life for patients with recurrent and unresectable cancers. We conclude by describing some outstanding questions and future directions for cancer theranostics with respect to clinical applications. Full article
(This article belongs to the Special Issue Innovative Cancer Treatments and Photodynamic Therapy)
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15 pages, 3170 KiB  
Review
CAR-NK Cells: A Chimeric Hope or a Promising Therapy?
by Mohamad Sabbah, Ludovic Jondreville, Claire Lacan, Francoise Norol, Vincent Vieillard, Damien Roos-Weil and Stéphanie Nguyen
Cancers 2022, 14(15), 3839; https://doi.org/10.3390/cancers14153839 - 08 Aug 2022
Cited by 14 | Viewed by 4064
Abstract
Immunotherapy with chimeric antigen receptor-engineered T cells (CAR-T) has revolutionized the treatment landscape of relapsed/refractory B-cell malignancies. Nonetheless, the use of autologous T cells has certain limitations, including the variable quality and quantity of collected effector T cells, extended time of cell processing, [...] Read more.
Immunotherapy with chimeric antigen receptor-engineered T cells (CAR-T) has revolutionized the treatment landscape of relapsed/refractory B-cell malignancies. Nonetheless, the use of autologous T cells has certain limitations, including the variable quality and quantity of collected effector T cells, extended time of cell processing, limited number of available CAR cells, toxicities, and a high cost. Thanks to their powerful cytotoxic capabilities, with proven antitumor effects in both haploidentical hematopoietic stem cell transplantation and adoptive cell therapy against solid tumors and hematological malignancies, Natural Killer cells could be a promising alternative. Different sources of NK cells can be used, including cellular lines, cord blood, peripheral blood, and induced pluripotent stem cells. Their biggest advantage is the possibility of using them in an allogeneic context without major toxic side effects. However, the majority of the reports on CAR-NK cells concern preclinical or early clinical trials. Indeed, NK cells might be more difficult to engineer, and the optimization and standardization of expansion and transfection protocols need to be defined. Furthermore, their short persistence after infusion is also a major setback. However, with recent advances in manufacturing engineered CAR-NK cells exploiting their cytolytic capacities, antibody-dependent cellular cytotoxicity (ADCC), and cytokine production, “off-the-shelf” allogeneic CAR-NK cells can provide a great potential in cancer treatments. Full article
(This article belongs to the Special Issue Immune Therapies for Hematologic Malignancies)
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16 pages, 2493 KiB  
Article
Detection of Microsatellite Instability in Colonoscopic Biopsies and Postal Urine Samples from Lynch Syndrome Cancer Patients Using a Multiplex PCR Assay
by Rachel Phelps, Richard Gallon, Christine Hayes, Eli Glover, Philip Gibson, Ibrahim Edidi, Tom Lee, Sarah Mills, Adam Shaw, Rakesh Heer, Angela Ralte, Ciaron McAnulty, Mauro Santibanez-Koref, John Burn and Michael S. Jackson
Cancers 2022, 14(15), 3838; https://doi.org/10.3390/cancers14153838 - 08 Aug 2022
Cited by 3 | Viewed by 2123
Abstract
Identification of mismatch repair (MMR)-deficient colorectal cancers (CRCs) is recommended for Lynch syndrome (LS) screening, and supports targeting of immune checkpoint inhibitors. Microsatellite instability (MSI) analysis is commonly used to test for MMR deficiency. Testing biopsies prior to tumour resection can inform surgical [...] Read more.
Identification of mismatch repair (MMR)-deficient colorectal cancers (CRCs) is recommended for Lynch syndrome (LS) screening, and supports targeting of immune checkpoint inhibitors. Microsatellite instability (MSI) analysis is commonly used to test for MMR deficiency. Testing biopsies prior to tumour resection can inform surgical and therapeutic decisions, but can be limited by DNA quantity. MSI analysis of voided urine could also provide much needed surveillance for genitourinary tract cancers in LS. Here, we reconfigure an existing molecular inversion probe-based MSI and BRAF c.1799T > A assay to a multiplex PCR (mPCR) format, and demonstrate that it can sample >140 unique molecules per marker from <1 ng of DNA and classify CRCs with 96–100% sensitivity and specificity. We also show that it can detect increased MSI within individual and composite CRC biopsies from LS patients, and within preoperative urine cell free DNA (cfDNA) from two LS patients, one with an upper tract urothelial cancer, the other an undiagnosed endometrial cancer. Approximately 60–70% of the urine cfDNAs were tumour-derived. Our results suggest that mPCR sequence-based analysis of MSI and mutation hotspots in CRC biopsies could facilitate presurgery decision making, and could enable postal-based screening for urinary tract and endometrial tumours in LS patients. Full article
(This article belongs to the Special Issue Lynch Syndrome: State of the Art)
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17 pages, 1790 KiB  
Systematic Review
Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma of the Tonsil versus Base of Tongue: A Systematic Review and Meta-Analysis
by Nicolas S. Poupore, Tiffany Chen, Shaun A. Nguyen, Cherie-Ann O. Nathan and Jason G. Newman
Cancers 2022, 14(15), 3837; https://doi.org/10.3390/cancers14153837 - 08 Aug 2022
Cited by 4 | Viewed by 2162
Abstract
Transoral Robotic Surgery (TORS) has become widely adopted for the surgical removal of oropharyngeal squamous cell carcinoma (OPSCC), with the most common locations being in the tonsil and base of tongue (BOT). However, it is currently unknown if TORS has equal efficacy and [...] Read more.
Transoral Robotic Surgery (TORS) has become widely adopted for the surgical removal of oropharyngeal squamous cell carcinoma (OPSCC), with the most common locations being in the tonsil and base of tongue (BOT). However, it is currently unknown if TORS has equal efficacy and outcomes in patients with tonsillar or BOT OPSCC. Therefore, the aim of this study was to compare the margin status and recurrence rates of tonsillar and BOT OPSCC after TORS. Per PRISMA guidelines, PubMed, Scopus, and CINAHL were systematically searched from inception to 2/28/2022. Articles including the surgical management of OPSCC with TORS that compared margin status, complications, and recurrence between tonsil and BOT were included. Meta-analyses of proportions and odds ratios were performed. A total of 28 studies were included, comprising 1769 patients with tonsillar OPSCC and 1139 patients with BOT OPSCC. HPV positivity was seen in 92.3% of tumors. BOT OPSCC had a higher rate of positive margins compared to tonsillar OPSCC (28.1% [95%CI 15.1–43.3] vs. 7.5% [95%CI 3.3–13.3]). No differences were seen in recurrence between BOT and tonsillar OPSCC (OR 1.1 [95%CI 0.8–1.5], p = 0.480). In addition, no differences in postoperative hemorrhage were seen between tonsillar and BOT OPSCC (10.7% [95%CI 6.1–16.5] vs. 8.8% [95% CI 1.5–21.3]). While a higher rate of positive margins was seen in BOT OPSCC when compared to tonsil OPSCC, this did not translate to a higher recurrence rate in the BOT group. Future research on which subset of patients with BOT is more likely to have positive margins is warranted to improve the utility of TORS further. Full article
(This article belongs to the Special Issue Epidemiology of HPV-Associated Oropharyngeal Squamous Cell Carcinoma)
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12 pages, 1483 KiB  
Article
Treatment Costs of Colorectal Cancer by Sex and Age: Population-Based Study on Health Insurance Data from Germany
by Thomas Heisser, Andreas Simon, Jana Hapfelmeier, Michael Hoffmeister and Hermann Brenner
Cancers 2022, 14(15), 3836; https://doi.org/10.3390/cancers14153836 - 08 Aug 2022
Cited by 6 | Viewed by 1898
Abstract
Objective: Evidence on the cost-effectiveness of screening for colorectal cancer (CRC) in the German general population remains scarce as key input parameters, the costs to treat CRC, are largely unknown. Here, we provide detailed estimates on CRC treatment costs over time. Methods: Using [...] Read more.
Objective: Evidence on the cost-effectiveness of screening for colorectal cancer (CRC) in the German general population remains scarce as key input parameters, the costs to treat CRC, are largely unknown. Here, we provide detailed estimates on CRC treatment costs over time. Methods: Using insurance claims data from the Vilua healthcare research database, we included subjects with newly diagnosed CRC and subjects who died of CRC between 2012 and 2016. We assessed annualized CRC-related inpatient, outpatient and medication costs for up to five years after first diagnosis and prior to death, stratified by sex and age. Findings: We identified 1748 and 1117 subjects with follow-up data for at least 1 year after diagnosis and prior to death, respectively. In those newly diagnosed, average costs were highest in the first year after diagnosis (men, EUR 16,375–16,450; women, EUR 10,071–13,250) and dropped steeply in the following years, with no consistent pattern of differences with respect to age. Costs prior to death were substantially higher as compared to the initial phase of care and consistently on a high level even several years before death, peaking in the final year of life, with strong differences by sex and age (men vs. women, <70 years, EUR 34,351 vs. EUR 31,417; ≥70 years, EUR 14,463 vs. EUR 9930). Conclusion: Once clinically manifest, CRC causes substantial treatment costs over time, particularly in the palliative care setting. Strong differences in treatment costs by sex and age warrant further investigation. Full article
(This article belongs to the Special Issue The Role of Cost-Effectiveness Analysis for Patient-Centered Cancer Care in the Era of Precision Medicine)
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27 pages, 442 KiB  
Review
Evidence from Clinical Studies Related to Dermatologic Surgeries for Skin Cancer
by Shoichiro Ishizuki and Yoshiyuki Nakamura
Cancers 2022, 14(15), 3835; https://doi.org/10.3390/cancers14153835 - 08 Aug 2022
Cited by 3 | Viewed by 1973
Abstract
Despite the significant progress made in the past several years in pharmacotherapies for skin cancer, such as BRAF/MEK inhibitors, immune checkpoint inhibitors, and Hedgehog pathway inhibitors, surgical removal of primary skin cancer is still the first choice of treatment unless distant metastases are [...] Read more.
Despite the significant progress made in the past several years in pharmacotherapies for skin cancer, such as BRAF/MEK inhibitors, immune checkpoint inhibitors, and Hedgehog pathway inhibitors, surgical removal of primary skin cancer is still the first choice of treatment unless distant metastases are evident. In cases of lymph node metastases with clinically palpable lymphadenopathy, lymph node dissection (LND) is typically performed for most skin cancers. In the surgical treatment of primary skin tumors, the surgical margin is critical not only for reducing the possibility of tumor recurrence but also for minimizing the cosmetic and functional complications associated with wide local excision. In contrast, dermatologic surgery can cause various complications. Although skin graft is frequently used for reconstruction of the surgical defect, extensive graft necrosis may develop if optimal stabilization of the graft is not obtained. LND also sometimes causes complications such as intraoperative or postoperative bleeding and postoperative lymphoceles. Moreover, as in other types of surgery, surgical site infection, intraoperative anxiety, and intraoperative and postoperative pain may also develop. These complications are frequently associated with significant morbidity and discomfort. In this review, we summarize the evidence from previous clinical studies regarding the optimal surgical margin for skin cancer and the methods for diminishing the complications associated with dermatologic surgery. Full article
(This article belongs to the Special Issue Clinical Trials in Skin Cancers)
46 pages, 3336 KiB  
Review
Hallmarks of Cancer Applied to Oral and Oropharyngeal Carcinogenesis: A Scoping Review of the Evidence Gaps Found in Published Systematic Reviews
by Miguel Ángel González-Moles, Saman Warnakulasuriya, María López-Ansio and Pablo Ramos-García
Cancers 2022, 14(15), 3834; https://doi.org/10.3390/cancers14153834 - 08 Aug 2022
Cited by 11 | Viewed by 2575
Abstract
In 2000 and 2011, Hanahan and Weinberg published two papers in which they defined the characteristics that cells must fulfil in order to be considered neoplastic cells in all types of tumours that affect humans, which the authors called “hallmarks of cancer”. These [...] Read more.
In 2000 and 2011, Hanahan and Weinberg published two papers in which they defined the characteristics that cells must fulfil in order to be considered neoplastic cells in all types of tumours that affect humans, which the authors called “hallmarks of cancer”. These papers have represented a milestone in our understanding of the biology of many types of cancers and have made it possible to reach high levels of scientific evidence in relation to the prognostic impact that these hallmarks have on different tumour types. However, to date, there is no study that globally analyses evidence-based knowledge on the importance of these hallmarks in oral and oropharyngeal squamous cell carcinomas. For this reason, we set out to conduct this scoping review of systematic reviews with the aim of detecting evidence gaps in relation to the relevance of the cancer hallmarks proposed by Hanahan and Weinberg in oral and oropharyngeal cancer, and oral potentially malignant disorders, and to point out future lines of research in this field. Full article
(This article belongs to the Section Cancer Biomarkers)
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25 pages, 2411 KiB  
Review
The Role of Pathology-Based Methods in Qualitative and Quantitative Approaches to Cancer Immunotherapy
by Olga Kuczkiewicz-Siemion, Kamil Sokół, Beata Puton, Aneta Borkowska and Anna Szumera-Ciećkiewicz
Cancers 2022, 14(15), 3833; https://doi.org/10.3390/cancers14153833 - 08 Aug 2022
Cited by 4 | Viewed by 2416
Abstract
Immune checkpoint inhibitors, including those concerning programmed cell death 1 (PD-1) and its ligand (PD-L1), have revolutionised the cancer therapy approach in the past decade. However, not all patients benefit from immunotherapy equally. The prediction of patient response to this type of therapy [...] Read more.
Immune checkpoint inhibitors, including those concerning programmed cell death 1 (PD-1) and its ligand (PD-L1), have revolutionised the cancer therapy approach in the past decade. However, not all patients benefit from immunotherapy equally. The prediction of patient response to this type of therapy is mainly based on conventional immunohistochemistry, which is limited by intraobserver variability, semiquantitative assessment, or single-marker-per-slide evaluation. Multiplex imaging techniques and digital image analysis are powerful tools that could overcome some issues concerning tumour-microenvironment studies. This novel approach to biomarker assessment offers a better understanding of the complicated interactions between tumour cells and their environment. Multiplex labelling enables the detection of multiple markers simultaneously and the exploration of their spatial organisation. Evaluating a variety of immune cell phenotypes and differentiating their subpopulations is possible while preserving tissue histology in most cases. Multiplexing supported by digital pathology could allow pathologists to visualise and understand every cell in a single tissue slide and provide meaning in a complex tumour-microenvironment contexture. This review aims to provide an overview of the different multiplex imaging methods and their application in PD-L1 biomarker assessment. Moreover, we discuss digital imaging techniques, with a focus on slide scanners and software. Full article
(This article belongs to the Special Issue Quantitative Approaches to Cancer Immunotherapy)
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21 pages, 3886 KiB  
Review
Microbiota and the Immune System—Actors in the Gastric Cancer Story
by Marek Majewski, Paulina Mertowska, Sebastian Mertowski, Konrad Smolak, Ewelina Grywalska and Kamil Torres
Cancers 2022, 14(15), 3832; https://doi.org/10.3390/cancers14153832 - 08 Aug 2022
Cited by 7 | Viewed by 3080
Abstract
Gastric cancer remains one of the most commonly diagnosed cancers in the world, with a relatively high mortality rate. Due to the heterogeneous course of the disease, its diagnosis and treatment are limited and difficult, and it is associated with a reduced prognosis [...] Read more.
Gastric cancer remains one of the most commonly diagnosed cancers in the world, with a relatively high mortality rate. Due to the heterogeneous course of the disease, its diagnosis and treatment are limited and difficult, and it is associated with a reduced prognosis for patients. That is why it is so important to understand the mechanisms underlying the development and progression of this cancer, with particular emphasis on the role of risk factors. According to the literature data, risk factors include: changes in the composition of the stomach and intestinal microbiota (microbiological dysbiosis and the participation of Helicobacter pylori), improper diet, environmental and genetic factors, and disorders of the body’s immune homeostasis. Therefore, the aim of this review is to systematize the knowledge on the influence of human microbiota dysbiosis on the development and progression of gastric cancer, with particular emphasis on the role of the immune system in this process. Full article
(This article belongs to the Special Issue Microbiome in Cancer: When the Poison Is the Cure)
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15 pages, 3158 KiB  
Review
The Challenging Management of Craniopharyngiomas in Adults: Time for a Reappraisal?
by Thomas Cuny, Michael Buchfelder, Henry Dufour, Ashley Grossman, Blandine Gatta-Cherifi, Emmanuel Jouanneau, Gerald Raverot, Alexandre Vasiljevic and Frederic Castinetti
Cancers 2022, 14(15), 3831; https://doi.org/10.3390/cancers14153831 - 07 Aug 2022
Cited by 5 | Viewed by 2516
Abstract
Craniopharyngiomas (CPs) are rare tumors of the skull base, developing near the pituitary gland and hypothalamus and responsible for severe hormonal deficiencies and an overall increase in mortality rate. While surgery and radiotherapy represent the recommended first-line therapies for CPs, a new paradigm [...] Read more.
Craniopharyngiomas (CPs) are rare tumors of the skull base, developing near the pituitary gland and hypothalamus and responsible for severe hormonal deficiencies and an overall increase in mortality rate. While surgery and radiotherapy represent the recommended first-line therapies for CPs, a new paradigm for treatment is currently emerging, as a consequence of accumulated knowledge concerning the molecular mechanisms involved in tumor growth, paving the way for anticipated use of targeted therapies. Significant clinical and basic research conducted in the field of CPs will undoubtedly constitute a real step forward for a better understanding of the behavior of these tumors and prevent associated complications. In this review, our aim is to summarize the multiple steps in the management of CPs in adults and emphasize the most recent studies that will contribute to advancing the diagnostic and therapeutic algorithms. Full article
(This article belongs to the Special Issue Rare Primary Brain Tumors in Adults)
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14 pages, 1320 KiB  
Article
The Association between a Decrease in On-Treatment Neutrophil-to-Eosinophil Ratio (NER) at Week 6 after Ipilimumab Plus Nivolumab Initiation and Improved Clinical Outcomes in Metastatic Renal Cell Carcinoma
by Yu-Wei Chen, Matthew D. Tucker, Landon C. Brown, Hesham A. Yasin, Kristin K. Ancell, Andrew J. Armstrong, Kathryn E. Beckermann, Nancy B. Davis, Michael R. Harrison, Elizabeth G. Kaiser, Renee K. McAlister, Kerry R. Schaffer, Deborah E. Wallace, Daniel J. George, W. Kimryn Rathmell, Brian I. Rini and Tian Zhang
Cancers 2022, 14(15), 3830; https://doi.org/10.3390/cancers14153830 - 07 Aug 2022
Cited by 4 | Viewed by 2833
Abstract
A lower baseline neutrophil-to-eosinophil ratio (NER) has been associated with improved responses to immune checkpoint inhibitors (ICI)-treated metastatic renal cell carcinoma (mRCC). This study investigated the decrease in NER at week 6 after ipilimumab/nivolumab (ipi/nivo) initiation and treatment responses in mRCC. A retrospective [...] Read more.
A lower baseline neutrophil-to-eosinophil ratio (NER) has been associated with improved responses to immune checkpoint inhibitors (ICI)-treated metastatic renal cell carcinoma (mRCC). This study investigated the decrease in NER at week 6 after ipilimumab/nivolumab (ipi/nivo) initiation and treatment responses in mRCC. A retrospective study of ipi/nivo-treated mRCC at two US academic cancer centers was conducted. A landmark analysis at week 6 was performed to assess the association between the change in NER and clinical responses (progression-free survival (PFS)/overall survival (OS)). Week 6 NER was modeled as a continuous variable, after log transformation (Ln NER), and a categorical variable by percent change. There were 150 mRCC patients included: 78% had clear cell histology, and 78% were IMDC intermediate/poor risk. In multivariable regression analysis, every decrease of 1 unit of Ln NER at week 6 was associated with improved PFS (adjusted hazard ratio (AHR): 0.78, p-value:0.005) and OS (AHR: 0.67, p-value: 0.002). When NER was modeled by percent change, decreased NER > 50% was associated with improved PFS (AHR: 0.55, p-value: 0.03) and OS (AHR: 0.37, p-value: 0.02). The decrease in week 6 NER was associated with improved PFS/OS in ipi/nivo-treated mRCC. Prospective studies are warranted to validate NER change as a biomarker to predict ICI responses. Full article
(This article belongs to the Special Issue Advances in Immunotherapy for Genitourinary Malignancies)
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21 pages, 3949 KiB  
Article
Over-Detection of Melanoma-Suspect Lesions by a CE-Certified Smartphone App: Performance in Comparison to Dermatologists, 2D and 3D Convolutional Neural Networks in a Prospective Data Set of 1204 Pigmented Skin Lesions Involving Patients’ Perception
by Anna Sophie Jahn, Alexander Andreas Navarini, Sara Elisa Cerminara, Lisa Kostner, Stephanie Marie Huber, Michael Kunz, Julia-Tatjana Maul, Reinhard Dummer, Seraina Sommer, Anja Dominique Neuner, Mitchell Paul Levesque, Phil Fang Cheng and Lara Valeska Maul
Cancers 2022, 14(15), 3829; https://doi.org/10.3390/cancers14153829 - 07 Aug 2022
Cited by 19 | Viewed by 3335
Abstract
The exponential increase in algorithm-based mobile health (mHealth) applications (apps) for melanoma screening is a reaction to a growing market. However, the performance of available apps remains to be investigated. In this prospective study, we investigated the diagnostic accuracy of a class 1 [...] Read more.
The exponential increase in algorithm-based mobile health (mHealth) applications (apps) for melanoma screening is a reaction to a growing market. However, the performance of available apps remains to be investigated. In this prospective study, we investigated the diagnostic accuracy of a class 1 CE-certified smartphone app in melanoma risk stratification and its patient and dermatologist satisfaction. Pigmented skin lesions ≥ 3 mm and any suspicious smaller lesions were assessed by the smartphone app SkinVision® (SkinVision® B.V., Amsterdam, the Netherlands, App-Version 6.8.1), 2D FotoFinder ATBM® master (FotoFinder ATBM® Systems GmbH, Bad Birnbach, Germany, Version 3.3.1.0), 3D Vectra® WB360 (Canfield Scientific, Parsippany, NJ, USA, Version 4.7.1) total body photography (TBP) devices, and dermatologists. The high-risk score of the smartphone app was compared with the two gold standards: histological diagnosis, or if not available, the combination of dermatologists’, 2D and 3D risk assessments. A total of 1204 lesions among 114 patients (mean age 59 years; 51% females (55 patients at high-risk for developing a melanoma, 59 melanoma patients)) were included. The smartphone app’s sensitivity, specificity, and area under the receiver operating characteristics (AUROC) varied between 41.3–83.3%, 60.0–82.9%, and 0.62–0.72% according to two study-defined reference standards. Additionally, all patients and dermatologists completed a newly created questionnaire for preference and trust of screening type. The smartphone app was rated as trustworthy by 36% (20/55) of patients at high-risk for melanoma, 49% (29/59) of melanoma patients, and 8.8% (10/114) of dermatologists. Most of the patients rated the 2D TBP imaging (93% (51/55) resp. 88% (52/59)) and the 3D TBP imaging (91% (50/55) resp. 90% (53/59)) as trustworthy. A skin cancer screening by combination of dermatologist and smartphone app was favored by only 1.8% (1/55) resp. 3.4% (2/59) of the patients; no patient preferred an assessment by a smartphone app alone. The diagnostic accuracy in clinical practice was not as reliable as previously advertised and the satisfaction with smartphone apps for melanoma risk stratification was scarce. MHealth apps might be a potential medium to increase awareness for melanoma screening in the lay population, but healthcare professionals and users should be alerted to the potential harm of over-detection and poor performance. In conclusion, we suggest further robust evidence-based evaluation before including market-approved apps in self-examination for public health benefits. Full article
(This article belongs to the Special Issue Recent Progress in the Diagnosis and Treatment of Melanoma and Other Skin Cancers)
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13 pages, 1888 KiB  
Article
Human Leucocyte Antigens as Prognostic Markers in Head and Neck Squamous Cell Carcinoma
by Gerhard Dyckhoff, Christel Herold-Mende, Sabine Scherer, Peter K. Plinkert and Rolf Warta
Cancers 2022, 14(15), 3828; https://doi.org/10.3390/cancers14153828 - 07 Aug 2022
Cited by 4 | Viewed by 1566
Abstract
Background: The induction and regulation of immune responses depend on human leucocyte antigen (HLA) molecules that present peptides derived from mutated neoantigens or tumor-associated antigens to cytotoxic T cells. The natural variation of HLA molecules might differ between tumor patients and the normal [...] Read more.
Background: The induction and regulation of immune responses depend on human leucocyte antigen (HLA) molecules that present peptides derived from mutated neoantigens or tumor-associated antigens to cytotoxic T cells. The natural variation of HLA molecules might differ between tumor patients and the normal population. Thus, there might be associations between the frequencies of HLA alleles and the survival of tumor patients. Methods: This issue was studied in a cohort of 84 patients with head and neck squamous cell carcinomas (HNSCCs) of different localizations. The cohort was followed up for more than 10 years. HLA-A/B/C CTS-PCR-SSP typing at 1 field level from blood samples was performed, and the results were correlated with survival. Results: HLA-A*02 was the most prevalent allele in our cohort and was present in 51.1% of patients. The HLA-A*25 and HLA-C*06 alleles exhibited a significantly higher frequency in cancer patients than in the normal population of 174 blood and kidney donors (p = 0.02 and p = 0.01, respectively, Fisher’s exact test). For HLA-C*04, a negative impact on overall survival in univariate analysis (p = 0.045) and a negative, but statistically insignificant effect on survival toward poorer survival in multivariate analysis (HR: 1.82; 95% CI: 0.99–3.34, p = 0.053) were observed. In addition, HLA-A*02 was also beneficial for overall survival and progression-free survival in multivariate analysis (HR 0.54; 95% CI: 0.31–0.92; p = 0.023). Conclusion: HLA-A*02 allele expression might not only predict better survival but might also indicate superior tumor antigen presentation and, thus, help to select patients who could benefit from T-cell-dependent immunotherapies. Full article
(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)
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12 pages, 761 KiB  
Article
A New Clinical Instrument for Estimating the Ambulatory Status after Irradiation for Malignant Spinal Cord Compression
by Dirk Rades, Ahmed Al-Salool, Christian Staackmann, Florian Cremers, Jon Cacicedo, Darejan Lomidze, Barbara Segedin, Blaz Groselj, Natalia Jankarashvili, Antonio J. Conde-Moreno, Raquel Ciervide, Charlotte Kristiansen and Steven E. Schild
Cancers 2022, 14(15), 3827; https://doi.org/10.3390/cancers14153827 - 07 Aug 2022
Cited by 3 | Viewed by 1498
Abstract
Estimating post-treatment ambulatory status can improve treatment personalization of patients irradiated for malignant spinal cord compression (MSCC). A new clinical score was developed from data of 283 patients treated with radiotherapy alone in prospective trials. Radiotherapy regimen, age, gender, tumor type, interval from [...] Read more.
Estimating post-treatment ambulatory status can improve treatment personalization of patients irradiated for malignant spinal cord compression (MSCC). A new clinical score was developed from data of 283 patients treated with radiotherapy alone in prospective trials. Radiotherapy regimen, age, gender, tumor type, interval from tumor diagnosis to MSCC, number of affected vertebrae, other bone metastases, visceral metastases, time developing motor deficits, ambulatory status, performance score, sensory deficits, and sphincter dysfunction were evaluated. For factors with prognostic relevance in the multivariable logistic regression model after backward stepwise variable selection, scoring points were calculated (post-radiotherapy ambulatory rate in % divided by 10) and added for each patient. Four factors (primary tumor type, sensory deficits, sphincter dysfunction, ambulatory status) were used for the instrument that includes three prognostic groups (17–21, 22–31, and 32–37 points). Post-radiotherapy ambulatory rates were 10%, 65%, and 97%, respectively, and 2-year local control rates were 100%, 75%, and 88%, respectively. Positive predictive values to predict ambulatory and non-ambulatory status were 97% and 90% using the new score, and 98% and 79% using the previous instrument. The new score appeared more precise in predicting non-ambulatory status. Since patients with 32–37 points had high post-radiotherapy ambulatory and local control rates, they may not require surgery. Full article
(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)
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20 pages, 1941 KiB  
Article
Chemokine Receptor Expression on T Cells Is Modulated by CAFs and Chemokines Affect the Spatial Distribution of T Cells in Pancreatic Tumors
by Laia Gorchs, Marlies Oosthoek, Tülay Yucel-Lindberg, Carlos Fernández Moro and Helen Kaipe
Cancers 2022, 14(15), 3826; https://doi.org/10.3390/cancers14153826 - 06 Aug 2022
Cited by 8 | Viewed by 2450
Abstract
The accumulation of T cells is associated with a better prognosis in pancreatic cancer. However, the immunosuppressive tumor microenvironment, largely composed by cancer-associated fibroblasts (CAFs), can prevent T cells from reaching the tumor nests. We examined how human CAFs modulated chemokine receptors known [...] Read more.
The accumulation of T cells is associated with a better prognosis in pancreatic cancer. However, the immunosuppressive tumor microenvironment, largely composed by cancer-associated fibroblasts (CAFs), can prevent T cells from reaching the tumor nests. We examined how human CAFs modulated chemokine receptors known to be associated with T cell trafficking, CXCR3 and CCR5, and T cell exclusion, CXCR4. CAFs decreased the expression of CXCR3 and CCR5 but increased CXCR4 expression in both 2D and 3D cultures, affecting the migratory capacity of T cells towards CXCL10. An immunohistochemistry analysis showed that very few T cells were found in the tumor nests. Within the stroma, CD8+ T cells were localized more distantly from the malignant cells whereas CD4+ T cells were more equally distributed. Tumor tissues with a high production of chemokines were associated with less T cell infiltration when the whole tissue was analyzed. However, when the spatial localization of CD8+ T cells within the tissue was taken into account, levels of CXCR3 ligands and the CCR5 ligand CCL8 showed a positive association with a high relative T cell infiltration in tumor-rich areas. Thus, CXCR3 ligands could mediate T cell trafficking but CAFs could prevent T cells from reaching the malignant cells. Full article
(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)
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9 pages, 901 KiB  
Article
The Spectrum of Co-Diagnoses in Patients with Colorectal Cancer: A Retrospective Cohort Study of 17,824 Outpatients in Germany
by Sven H. Loosen, David Schöler, Simon Labuhn, Alexander Mertens, Markus S Jördens, Mark Luedde, Karel Kostev, Tom Luedde and Christoph Roderburg
Cancers 2022, 14(15), 3825; https://doi.org/10.3390/cancers14153825 - 06 Aug 2022
Viewed by 1717
Abstract
Background: The prognosis of colorectal cancer (CRC) patients is determined to a decisive extent by comorbidities. On the other hand, anti-cancer treatments for CRC are associated with relevant toxicities and may therefore cause additional comorbidities. Methods: This retrospective cohort study assessed the prevalence [...] Read more.
Background: The prognosis of colorectal cancer (CRC) patients is determined to a decisive extent by comorbidities. On the other hand, anti-cancer treatments for CRC are associated with relevant toxicities and may therefore cause additional comorbidities. Methods: This retrospective cohort study assessed the prevalence of various diseases in patients 12 months before and 12 months after an initial diagnosis of colorectal cancer (ICD-10: C18, C20) in 1274 general practices in Germany between January 2000 and December 2018. The study is based on the Disease Analyzer database (IQVIA), which contains drug prescriptions, diagnoses, and basic medical and demographic data. Patients with and without CRC were matched by sex, age, and index year. Results: We identified several diagnoses with a significantly higher prevalence among CRC patients 12 months prior to the index date compared to controls. These diagnoses included gastrointestinal hemorrhage, hemorrhoids, perianal venous thrombosis, and abdominal and pelvic pain, as well as functional intestinal disorders. In contrast, the prevalence of lipid metabolism disorder, depression, hypertension, coronary heart disease, or acute bronchitis was significantly lower in CRC cases. After diagnosis of CRC, we found a significantly higher prevalence of anemia, polyneuropathies, functional intestinal disorders, and chronic kidney disease among CRC patients compared to the control group, while the prevalence of acute upper respiratory infections of multiple and unspecified sites and acute bronchitis was significantly lower in CRC patients compared to non-CRC patients. Conclusions: In the present study, we identified a variety of diseases occurring at higher or lower frequencies in CRC patients compared to matched controls without CRC. This might help to select patients for early CRC screening and improve the clinical management of CRC patients. Full article
(This article belongs to the Special Issue Colorectal Cancer Early Detection, Diagnosis, and Staging)
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20 pages, 350 KiB  
Review
HER2 Inhibition in Gastric Cancer—Novel Therapeutic Approaches for an Established Target
by Caroline Fong and Ian Chau
Cancers 2022, 14(15), 3824; https://doi.org/10.3390/cancers14153824 - 06 Aug 2022
Cited by 7 | Viewed by 2640
Abstract
Gastric cancer is a leading cause of cancer-related deaths globally. Human epidermal growth receptor 2 (HER2) overexpression of HER2 gene amplification is present in 20% of gastric cancers and defines a subset amenable to HER2-directed therapeutics. The seminal ToGA study led to routine [...] Read more.
Gastric cancer is a leading cause of cancer-related deaths globally. Human epidermal growth receptor 2 (HER2) overexpression of HER2 gene amplification is present in 20% of gastric cancers and defines a subset amenable to HER2-directed therapeutics. The seminal ToGA study led to routine use of the monoclonal antibody trastuzumab in conjunction to platinum-fluoropyridimine first-line chemotherapy for HER2-positive gastric cancers as standard-of-care. Although limited progress was made in the decade following ToGA, there is now an abundance of novel therapeutic approaches undergoing investigation in parallel. Additionally, new data from randomised trials have indicated efficacy of the antibody-drug conjugate trastuzumab deruxtecan in chemorefractory patients and increased responses with the addition of first-line immune checkpoint blockade to trastuzumab and chemotherapy. This review will outline the data supporting HER2 targeting in gastric cancers, discuss mechanisms of response and resistance to HER2-directed therapies and summarise the emerging therapies under clinical evaluation that may evolve the way we manage this subset of gastric cancers in the future. Full article
(This article belongs to the Special Issue Contemporary Perspectives and Emerging Trends in the Management of Gastric Cancer)
14 pages, 627 KiB  
Article
Can National Registries Contribute to Predict the Risk of Cancer? The Cancer Risk Assessment Model (CRAM)
by Dorte E. Jarbøl, Nana Hyldig, Sören Möller, Sonja Wehberg, Sanne Rasmussen, Kirubakaran Balasubramaniam, Peter F. Haastrup, Jens Søndergaard and Katrine H. Rubin
Cancers 2022, 14(15), 3823; https://doi.org/10.3390/cancers14153823 - 06 Aug 2022
Cited by 3 | Viewed by 1551
Abstract
Purpose: To develop a predictive model based on Danish administrative registers to facilitate automated identification of individuals at risk of any type of cancer. Methods: A nationwide register-based cohort study covering all individuals in Denmark aged +20 years. The outcome was all-type cancer [...] Read more.
Purpose: To develop a predictive model based on Danish administrative registers to facilitate automated identification of individuals at risk of any type of cancer. Methods: A nationwide register-based cohort study covering all individuals in Denmark aged +20 years. The outcome was all-type cancer during 2017 excluding nonmelanoma skin cancer. Diagnoses, medication, and contact with general practitioners in the exposure period (2007–2016) were considered for the predictive model. We applied backward selection to all variables by logistic regression to develop a risk model for cancer. We applied the models to the validation cohort, calculated the receiver operating characteristic curves, and estimated the corresponding areas under the curve (AUC). Results: The study population consisted of 4.2 million persons; 32,447 (0.76%) were diagnosed with cancer in 2017. We identified 39 predictive risk factors in women and 42 in men, with age above 30 as the strongest predictor for cancer. Testing the model for cancer risk showed modest accuracy, with an AUC of 0.82 (95% CI 0.81–0.82) for men and 0.75 (95% CI 0.74–0.75) for women. Conclusion: We have developed and tested a model for identifying the individual risk of cancer through the use of administrative data. The models need to be further investigated before being applied to clinical practice. Full article
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15 pages, 2003 KiB  
Article
Far-Red Fluorescent Murine Glioma Model for Accurate Assessment of Brain Tumor Progression
by Tatiana A. Mishchenko, Irina V. Balalaeva, Maria O. Klimenko, Anna A. Brilkina, Nina N. Peskova, Evgenii L. Guryev, Dmitri V. Krysko and Maria V. Vedunova
Cancers 2022, 14(15), 3822; https://doi.org/10.3390/cancers14153822 - 06 Aug 2022
Cited by 1 | Viewed by 1882
Abstract
Glioma is the most common brain tumor, for which no significant improvement in life expectancy and quality of life is yet possible. The creation of stable fluorescent glioma cell lines is a promising tool for in-depth studies of the molecular mechanisms of glioma [...] Read more.
Glioma is the most common brain tumor, for which no significant improvement in life expectancy and quality of life is yet possible. The creation of stable fluorescent glioma cell lines is a promising tool for in-depth studies of the molecular mechanisms of glioma initialization and pathogenesis, as well as for the development of new anti-cancer strategies. Herein, a new fluorescent glioma GL261-kat cell line stably expressing a far-red fluorescent protein (TurboFP635; Katushka) was generated and characterized, and then validated in a mouse orthotopic glioma model. By using epi-fluorescence imaging, we detect the fluorescent glioma GL261-kat cells in mice starting from day 14 after the inoculation of glioma cells, and the fluorescence signal intensity increases as the glioma progresses. Tumor growth is confirmed by magnetic resonance imaging and histology. A gradual development of neurological deficit and behavioral alterations in mice is observed during glioma progression. In conclusion, our results demonstrate the significance and feasibility of using the novel glioma GL261-kat cell line as a model of glioma biology, which can be used to study the initialization of glioma and monitor its growth by lifetime non-invasive tracking of glioma cells, with the prospect of monitoring the response to anti-cancer therapy. Full article
(This article belongs to the Special Issue Discovering Glioblastoma: From Diagnosis to Treatment)
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17 pages, 1140 KiB  
Review
How Gut Microbiota Are Shaped by Pattern Recognition Receptors in Colitis and Colorectal Cancer
by Furong Qing, Tao Xie, Lu Xie, Tianfu Guo and Zhiping Liu
Cancers 2022, 14(15), 3821; https://doi.org/10.3390/cancers14153821 - 06 Aug 2022
Cited by 5 | Viewed by 2242
Abstract
Disorders of gut microbiota have been closely linked to the occurrence of various intestinal diseases including colitis and colorectal cancer (CRC). Specifically, the production of beneficial bacteria and intestinal metabolites may slow the development of some intestinal diseases. Recently, it has been proposed [...] Read more.
Disorders of gut microbiota have been closely linked to the occurrence of various intestinal diseases including colitis and colorectal cancer (CRC). Specifically, the production of beneficial bacteria and intestinal metabolites may slow the development of some intestinal diseases. Recently, it has been proposed that pattern recognition receptors (PRRs) not only recognize pathogens and initiate inflammatory signal transduction to induce immune responses but also influence the composition of intestinal microorganisms. However, the mechanisms through which PRRs regulate gut microbiota in the setting of colitis and CRC have rarely been systematically reviewed. Therefore, in this paper, we summarize recent advances in our understanding of how PRRs shape gut microbiota and how this influences the development of colitis and CRC. Full article
(This article belongs to the Special Issue Signaling Pathway in Gastrointestinal Cancer)
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26 pages, 1250 KiB  
Review
DEAD-Box RNA Helicases DDX3X and DDX5 as Oncogenes or Oncosuppressors: A Network Perspective
by Massimiliano Secchi, Camilla Lodola, Anna Garbelli, Silvia Bione and Giovanni Maga
Cancers 2022, 14(15), 3820; https://doi.org/10.3390/cancers14153820 - 06 Aug 2022
Cited by 7 | Viewed by 3064
Abstract
RNA helicases of the DEAD-box family are involved in several metabolic pathways, from transcription and translation to cell proliferation, innate immunity and stress response. Given their multiple roles, it is not surprising that their deregulation or mutation is linked to different pathological conditions, [...] Read more.
RNA helicases of the DEAD-box family are involved in several metabolic pathways, from transcription and translation to cell proliferation, innate immunity and stress response. Given their multiple roles, it is not surprising that their deregulation or mutation is linked to different pathological conditions, including cancer. However, while in some cases the loss of function of a given DEAD-box helicase promotes tumor transformation, indicating an oncosuppressive role, in other contexts the overexpression of the same enzyme favors cancer progression, thus acting as a typical oncogene. The roles of two well-characterized members of this family, DDX3X and DDX5, as both oncogenes and oncosuppressors have been documented in several cancer types. Understanding the interplay of the different cellular contexts, as defined by the molecular interaction networks of DDX3X and DDX5 in different tumors, with the cancer-specific roles played by these proteins could help to explain their apparently conflicting roles as cancer drivers or suppressors. Full article
(This article belongs to the Section Cancer Therapy)
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17 pages, 620 KiB  
Review
Lung Cancer in the Course of COPD-Emerging Problems Today
by Robert Uliński, Iwona Kwiecień and Joanna Domagała-Kulawik
Cancers 2022, 14(15), 3819; https://doi.org/10.3390/cancers14153819 - 06 Aug 2022
Cited by 5 | Viewed by 2557
Abstract
Tobacco smoking remains the main cause of tobacco-dependent diseases like lung cancer, chronic obstructive pulmonary disease (COPD), in addition to cardiovascular diseases and other cancers. Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, [...] Read more.
Tobacco smoking remains the main cause of tobacco-dependent diseases like lung cancer, chronic obstructive pulmonary disease (COPD), in addition to cardiovascular diseases and other cancers. Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, occurring as co-morbidities at a higher rate than if they were independently triggered by smoking. A patient with COPD has a four- to six-fold greater risk of developing lung cancer independent of smoking exposure, when compared to matched smokers with normal lung function. The 10 year risk is about 8.8% in the COPD group and only 2% in patients with normal lung function. COPD is not a uniform disorder: there are different phenotypes. One of them is manifested by the prevalence of emphysema and this is complicated by malignant processes most often. Here, we present and discuss the clinical problems of COPD in patients with lung cancer and against lung cancer in the course of COPD. There are common pathological pathways in both diseases. These are inflammation with participation of macrophages and neutrophils and proteases. It is known that anticancer immune regulation is distorted towards immunosuppression, while in COPD the elements of autoimmunity are described. Cytotoxic T cells, lymphocytes B and regulatory T cells with the important role of check point molecules are involved in both processes. A growing number of lung cancer patients are treated with immune check point inhibitors (ICIs), and it was found that COPD patients may have benefits from this treatment. Altogether, the data point to the necessity for deeper analysis and intensive research studies to limit the burden of these serious diseases by prevention and by elaboration of specific therapeutic options. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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22 pages, 727 KiB  
Review
miRacle of microRNA-Driven Cancer Nanotherapeutics
by Goknur Kara, Banu Arun, George A. Calin and Bulent Ozpolat
Cancers 2022, 14(15), 3818; https://doi.org/10.3390/cancers14153818 - 06 Aug 2022
Cited by 17 | Viewed by 3173
Abstract
MicroRNAs (miRNAs) are non-protein-coding RNA molecules 20–25 nucleotides in length that can suppress the expression of genes involved in numerous physiological processes in cells. Accumulating evidence has shown that dysregulation of miRNA expression is related to the pathogenesis of various human diseases and [...] Read more.
MicroRNAs (miRNAs) are non-protein-coding RNA molecules 20–25 nucleotides in length that can suppress the expression of genes involved in numerous physiological processes in cells. Accumulating evidence has shown that dysregulation of miRNA expression is related to the pathogenesis of various human diseases and cancers. Thus, stragegies involving either restoring the expression of tumor suppressor miRNAs or inhibiting overexpressed oncogenic miRNAs hold potential for targeted cancer therapies. However, delivery of miRNAs to tumor tissues is a challenging task. Recent advances in nanotechnology have enabled successful tumor-targeted delivery of miRNA therapeutics through newly designed nanoparticle-based carrier systems. As a result, miRNA therapeutics have entered human clinical trials with promising results, and they are expected to accelerate the transition of miRNAs from the bench to the bedside in the next decade. Here, we present recent perspectives and the newest developments, describing several engineered natural and synthetic novel miRNA nanocarrier formulations and their key in vivo applications and clinical trials. Full article
(This article belongs to the Special Issue Understanding New Therapeutic Options and Promising Predictive Biomarkers for Lung Cancer Patients. A Selection of Papers from the Third Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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11 pages, 851 KiB  
Article
Retrospective Cohort Analysis of the Effect of Age on Lymph Node Harvest, Positivity, and Ratio in Colorectal Cancer
by Samara L. Lewis, Kenneth E. Stewart, Tabitha Garwe, Zoona Sarwar and Katherine T. Morris
Cancers 2022, 14(15), 3817; https://doi.org/10.3390/cancers14153817 - 06 Aug 2022
Cited by 3 | Viewed by 1301
Abstract
Introduction: Colon cancer among young patients has increased in incidence and mortality over the past decade. Our objective was to determine if age-related differences exist for total positive nodes (TPN), total lymph node harvest (TLH), and lymph node ratio (LNR). Material and Methods: [...] Read more.
Introduction: Colon cancer among young patients has increased in incidence and mortality over the past decade. Our objective was to determine if age-related differences exist for total positive nodes (TPN), total lymph node harvest (TLH), and lymph node ratio (LNR). Material and Methods: A retrospective review of stage III surgically resected colorectal cancer patient data in the National Cancer Database (2004–2016) was performed, reviewing TPN, TLH, and LNR (TPN/TLH). Results: Unadjusted analyses suggested significantly higher levels of TLH and TPN (p < 0.0001) in younger patients, while LNR did not differ by age group. On adjusted analysis, TLH remained higher in younger patients (<35 years 1.56 (CI 95 1.54, 1.59)). The age-related effect was less pronounced for LNR (<35 years 1.16 (CI 95 1.13, 1.2)). Conclusion: Younger patients have increased TLH, even after adjusting for known confounders, while age does not have a strong independent impact on LNR. Full article
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24 pages, 639 KiB  
Systematic Review
mHealth Interventions to Promote a Healthy Diet and Physical Activity among Cancer Survivors: A Systematic Review of Randomized Controlled Trials
by Lufan Wang, Crystal S. Langlais, Stacey A. Kenfield, June M. Chan, Rebecca E. Graff, Isabel E. Allen, Chloe E. Atreya and Erin L. Van Blarigan
Cancers 2022, 14(15), 3816; https://doi.org/10.3390/cancers14153816 - 06 Aug 2022
Cited by 10 | Viewed by 3067
Abstract
Background: Technology-based interventions are increasingly used to improve physical activity (PA) and diet. Methods: We conducted a systematic review of randomized controlled trials (RCTs) published up to August 2021 that tested mobile health (mHealth) PA and/or dietary interventions among cancer survivors [...] Read more.
Background: Technology-based interventions are increasingly used to improve physical activity (PA) and diet. Methods: We conducted a systematic review of randomized controlled trials (RCTs) published up to August 2021 that tested mobile health (mHealth) PA and/or dietary interventions among cancer survivors and reported on the feasibility, satisfaction, behavioral change, and/or quality of life (QOL) outcomes. Results: In total, 61 articles were identified on PubMed, and 23 of those met the inclusion criteria. The most common cancers were breast (n = 1000), prostate (n = 713), and colorectal (n = 650). Participants were predominantly White (median: 84%, interquartile range (IQR): 20%) and college-educated (58%). The interventions varied, but the most common combination of components (six studies) was a website/mobile app with an activity tracker and coaching. In terms of duration, 70% (n = 16) of the interventions lasted 12 weeks. The median total tracker wear was 87% of the study days (IQR: 6%) and the median text-message reply rate was 73% (IQR 4%). Most participants (median: 87%; IQR: 16%) were satisfied with at least one intervention component. Eleven out of 18 studies examining behavioral change reported significant between-group differences and six out of 11 studies examining QoL reported significant improvements. Conclusions: mHealth interventions are a promising approach to improving the PA and diets of cancer survivors. Research in racially/ethnically and socioeconomically diverse populations is needed. Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
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12 pages, 1769 KiB  
Systematic Review
Relationship between Dose Prescription Methods and Local Control Rate in Stereotactic Body Radiotherapy for Early Stage Non-Small-Cell Lung Cancer: Systematic Review and Meta-Analysis
by Takahisa Eriguchi, Atsuya Takeda, Takafumi Nemoto, Yuichiro Tsurugai, Naoko Sanuki, Yudai Tateishi, Yuichi Kibe, Takeshi Akiba, Mari Inoue, Kengo Nagashima and Nobuyuki Horita
Cancers 2022, 14(15), 3815; https://doi.org/10.3390/cancers14153815 - 05 Aug 2022
Cited by 7 | Viewed by 1989
Abstract
Variations in dose prescription methods in stereotactic body radiotherapy (SBRT) for early stage non-small-cell lung cancer (ES-NSCLC) make it difficult to properly compare the outcomes of published studies. We conducted a comprehensive search of the published literature to summarize the outcomes by discerning [...] Read more.
Variations in dose prescription methods in stereotactic body radiotherapy (SBRT) for early stage non-small-cell lung cancer (ES-NSCLC) make it difficult to properly compare the outcomes of published studies. We conducted a comprehensive search of the published literature to summarize the outcomes by discerning the relationship between local control (LC) and dose prescription sites. We systematically searched PubMed to identify observational studies reporting LC after SBRT for peripheral ES-NSCLC. The correlations between LC and four types of biologically effective doses (BED) were evaluated, which were calculated from nominal, central, and peripheral prescription points and, from those, the average BED. To evaluate information on SBRT for peripheral ES-NSCLC, 188 studies were analyzed. The number of relevant articles increased over time. The use of an inhomogeneity correction was mentioned in less than half of the articles, even among the most recent. To evaluate the relationship between the four BEDs and LC, 33 studies were analyzed. Univariate meta-regression revealed that only the central BED significantly correlated with the 3-year LC of SBRT for ES-NSCLC (p = 0.03). As a limitation, tumor volume, which might affect the results of this study, could not be considered due to a lack of data. In conclusion, the central dose prescription is appropriate for evaluating the correlation between the dose and LC of SBRT for ES-NSCLC. The standardization of SBRT dose prescriptions is desirable. Full article
(This article belongs to the Special Issue Stereotactic Body Radiotherapy for Various Cancers: Recent Advances and Future)
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12 pages, 593 KiB  
Systematic Review
The Role of [68Ga]Ga-Pentixafor PET/CT or PET/MRI in Lymphoma: A Systematic Review
by Domenico Albano, Francesco Dondi, Francesco Bertagna and Giorgio Treglia
Cancers 2022, 14(15), 3814; https://doi.org/10.3390/cancers14153814 - 05 Aug 2022
Cited by 10 | Viewed by 2449
Abstract
The aim of this systematic review was to investigate published data about the role of gallium-68 Pentixafor positron emission tomography/computed tomography ([68Ga]Ga-Pentixafor PET/CT) or PET/magnetic resonance imaging (PET/MRI) in patients affected by lymphoma. A comprehensive computer literature search of the Scopus, [...] Read more.
The aim of this systematic review was to investigate published data about the role of gallium-68 Pentixafor positron emission tomography/computed tomography ([68Ga]Ga-Pentixafor PET/CT) or PET/magnetic resonance imaging (PET/MRI) in patients affected by lymphoma. A comprehensive computer literature search of the Scopus, PubMed/MEDLINE, and Embase databases was conducted including articles indexed up to June 2022. In total, 14 studies or subsets in studies were eligible for inclusion. From the analyses of the selected studies, the following main findings have been found: (1) lymphomas can be considered [68Ga]Ga-Pentixafor avid diseases, also in cases of fluorine-18 fluorodeoxyglucose [18F]FDG-not avid forms such as lymphoplasmacytic lymphoma (LPL), chronic lymphocytic leukemia (CLL), marginal zone lymphoma (MZL) and central nervous system lymphoma (CNSL); (2) among lymphomas, mantle cell lymphoma (MCL) and MZL are those with highest [68Ga]Ga-Pentixafor uptake; (3) [68Ga]Ga-Pentixafor PET/CT or PET/MRI is a useful tool for the staging and treatment response evaluation; (4) [68Ga]Ga-Pentixafor PET seems to have a better diagnostic performance than [18F]FDG PET in evaluating lymphomas. Despite several limitations affecting this analysis, especially related to the heterogeneity of the included studies, [68Ga]Ga-Pentixafor PET may be considered a useful imaging method for staging and treatment response evaluation of several lymphomas, especially MZL, CNSL and LPL. Full article
(This article belongs to the Topic Lymphoma: Update on the Role of Imaging in the Understanding, Diagnosis, Treatment and Management)
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18 pages, 814 KiB  
Article
An Examination of the Anti-Cancer Properties of Plant Cannabinoids in Preclinical Models of Mesothelioma
by Emily K. Colvin, Amanda L. Hudson, Lyndsey L. Anderson, Ramyashree Prasanna Kumar, Iain S. McGregor, Viive M. Howell and Jonathon C. Arnold
Cancers 2022, 14(15), 3813; https://doi.org/10.3390/cancers14153813 - 05 Aug 2022
Cited by 6 | Viewed by 6496
Abstract
Mesothelioma is an aggressive cancer with limited treatment options and a poor prognosis. Phytocannabinoids possess anti-tumour and palliative properties in multiple cancers, however their effects in mesothelioma are unknown. We investigated the anti-cancer effects and potential mechanisms of action for several phytocannabinoids in [...] Read more.
Mesothelioma is an aggressive cancer with limited treatment options and a poor prognosis. Phytocannabinoids possess anti-tumour and palliative properties in multiple cancers, however their effects in mesothelioma are unknown. We investigated the anti-cancer effects and potential mechanisms of action for several phytocannabinoids in mesothelioma cell lines. A panel of 13 phytocannabinoids inhibited growth of human (MSTO and H2452) and rat (II-45) mesothelioma cells in vitro, and cannabidiol (CBD) and cannabigerol (CBG) were the most potent compounds. Treatment with CBD or CBG resulted in G0/G1 arrest, delayed entry into S phase and induced apoptosis. CBD and CBG also significantly reduced mesothelioma cell migration and invasion. These effects were supported by changes in the expression of genes associated with the cell cycle, proliferation, and cell movement following CBD or CBG treatment. Gene expression levels of CNR1, GPR55, and 5HT1A also increased with CBD or CBG treatment. However, treatment with CBD or CBG in a syngeneic orthotopic rat mesothelioma model was unable to increase survival. Our data show that cannabinoids have anti-cancer effects on mesothelioma cells in vitro and alternatives of drug delivery may be needed to enhance their effects in vivo. Full article
(This article belongs to the Special Issue Recent Research on Mesothelioma)
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13 pages, 1076 KiB  
Review
Pathogenic Roles of RNA-Binding Proteins in Sarcomas
by Yu Hai, Asuka Kawachi, Xiaodong He and Akihide Yoshimi
Cancers 2022, 14(15), 3812; https://doi.org/10.3390/cancers14153812 - 05 Aug 2022
Cited by 3 | Viewed by 2479
Abstract
RNA-binding proteins (RBPs) are proteins that physically and functionally bind to RNA to regulate the RNA metabolism such as alternative splicing, polyadenylation, transport, maintenance of stability, localization, and translation. There is accumulating evidence that dysregulated RBPs play an essential role in the pathogenesis [...] Read more.
RNA-binding proteins (RBPs) are proteins that physically and functionally bind to RNA to regulate the RNA metabolism such as alternative splicing, polyadenylation, transport, maintenance of stability, localization, and translation. There is accumulating evidence that dysregulated RBPs play an essential role in the pathogenesis of malignant tumors including a variety of types of sarcomas. On the other hand, prognosis of patients with sarcoma, especially with sarcoma in advanced stages, is very poor, and almost no effective standard treatment has been established for most of types of sarcomas so far, highlighting the urgent need for identifying novel therapeutic targets based on the deep understanding of pathogenesis. Therefore, defining the network of interactions between RBPs and disease-related RNA targets will contribute to a better understanding of sarcomagenesis and identification of a novel therapeutic target for sarcomas. Full article
(This article belongs to the Special Issue The Role and Therapeutic Target Potential of RBPs in Cancer)
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