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The Effect of Cannabis Plant Extracts on Head and Neck Squamous Cell Carcinoma and the Quest for Cannabis-Based Personalized Therapy
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CAR-Based Immunotherapy of Solid Tumours—A Survey of the Emerging Targets
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Role of Machine Learning in Precision Oncology: Applications in Gastrointestinal Cancers
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Bias and Class Imbalance in Oncologic Data—Towards Inclusive and Transferrable AI in Large Scale Oncology Data Sets
Journal Description
Cancers
Cancers
is a peer-reviewed, open access journal of oncology, published semimonthly online by MDPI. The Irish Association for Cancer Research (IACR), Signal Transduction Society (STS), Spanish Association for Cancer Research (ASEICA), Biomedical Research Centre (CIBM), British Neuro-Oncology Society (BNOS) and others are affiliated with Cancers and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Oncology) / CiteScore - Q2 (Oncology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17.4 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the second half of 2022).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 17 topical sections.
- Companion journals for Cancers include: Radiation and Onco.
Impact Factor:
6.575 (2021);
5-Year Impact Factor:
6.886 (2021)
Latest Articles
Ultrasound for Breast Cancer Screening in Resource-Limited Settings: Current Practice and Future Directions
Cancers 2023, 15(7), 2112; https://doi.org/10.3390/cancers15072112 (registering DOI) - 31 Mar 2023
Abstract
Breast cancer (BC) is the most prevalent cancer among women globally. Cancer screening can reduce mortality and improve women’s health. In developed countries, mammography (MAM) has been primarily utilized for population-based BC screening for several decades. However, it is usually unavailable in low-resource
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Breast cancer (BC) is the most prevalent cancer among women globally. Cancer screening can reduce mortality and improve women’s health. In developed countries, mammography (MAM) has been primarily utilized for population-based BC screening for several decades. However, it is usually unavailable in low-resource settings due to the lack of equipment, personnel, and time necessary to conduct and interpret the examinations. Ultrasound (US) with high detection sensitivity for women of younger ages and with dense breasts has become a supplement to MAM for breast examination. Some guidelines suggest using US as the primary screening tool in certain settings where MAM is unavailable and infeasible, but global recommendations have not yet reached a unanimous consensus. With the development of smart devices and artificial intelligence (AI) in medical imaging, clinical applications and preclinical studies have shown the potential of US combined with AI in BC screening. Nevertheless, there are few comprehensive reviews focused on the role of US in screening BC in underserved conditions, especially in technological, economical, and global perspectives. This work presents the benefits, limitations, advances, and future directions of BC screening with technology-assisted and resource-appropriate strategies, which may be helpful to implement screening initiatives in resource-limited countries.
Full article
(This article belongs to the Topic Women's Health and Aging)
Open AccessReview
The Epigenesis of Salivary Glands Carcinoma: From Field Cancerization to Carcinogenesis
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, , , , , , , , and
Cancers 2023, 15(7), 2111; https://doi.org/10.3390/cancers15072111 (registering DOI) - 31 Mar 2023
Abstract
Salivary gland carcinomas (SGCs) are a diverse collection of malignant tumors with marked differences in biological activity, clinical presentation and microscopic appearance. Although the etiology is varied, secondary radiation, oncogenic viruses as well as chromosomal rearrangements have all been linked to the formation
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Salivary gland carcinomas (SGCs) are a diverse collection of malignant tumors with marked differences in biological activity, clinical presentation and microscopic appearance. Although the etiology is varied, secondary radiation, oncogenic viruses as well as chromosomal rearrangements have all been linked to the formation of SGCs. Epigenetic modifications may also contribute to the genesis and progression of SGCs. Epigenetic modifications are any heritable changes in gene expression that are not caused by changes in DNA sequence. It is now widely accepted that epigenetics plays an important role in SGCs development. A basic epigenetic process that has been linked to a variety of pathological as well as physiological conditions including cancer formation, is DNA methylation. Transcriptional repression is caused by CpG islands hypermethylation at gene promoters, whereas hypomethylation causes overexpression of a gene. Epigenetic changes in SGCs have been identified, and they have been linked to the genesis, progression as well as prognosis of these neoplasms. Thus, we conduct a thorough evaluation of the currently known evidence on the involvement of epigenetic processes in SGCs.
Full article
(This article belongs to the Special Issue Pathogenesis, Diagnostics and Prognostics in Head and Neck Cancer)
Open AccessReview
Wellbeing and Complementary Therapies in Breast Cancer Peripheral Neuropathy Care: A Scoping Review Focused on Foot Health
by
, , , , and
Cancers 2023, 15(7), 2110; https://doi.org/10.3390/cancers15072110 - 31 Mar 2023
Abstract
Background: Chemotherapy-induced peripheral neuropathy is a multidimensional health problem. Up to now, little evidence has been found concerning its impact on quality of life and foot health. Evaluation tools and prevention and treatment strategies must be reported. This study aimed to map the
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Background: Chemotherapy-induced peripheral neuropathy is a multidimensional health problem. Up to now, little evidence has been found concerning its impact on quality of life and foot health. Evaluation tools and prevention and treatment strategies must be reported. This study aimed to map the literature on the impact of this side effect on the wellbeing and foot health of people with breast cancer and to describe their main assessment strategies and complementary therapies. Methods: A scoping review was carried out while following the PRISMA-ScR and Arksey and O’Malley guidelines. Different databases (Cochrane Plus, Scopus, Web of Science, and Pubmed) were used. A total of 221 results were identified. Sixteen articles were included. Results: The thematic analysis obtained the following categories: the impact of peripheral neuropathy on quality of life and foot health, complementary therapies as a path for new strategies, and the need for clinicians and researchers to get involved in researching this side effect. Conclusions: Peripheral neuropathy has a negative impact on people’s quality of life. Implications for foot health and maintaining an active and healthy lifestyle have not been previously reported. Complementary therapies are recommended by scientific evidence, highlighting exercise. However, there is a need to develop more research that will help to incorporate them into evidence-based practice.
Full article
(This article belongs to the Special Issue Quality of Life in Cancer Rehabilitation)
Open AccessArticle
Evaluating Focal Areas of Signal Intensity (FASI) in Children with Neurofibromatosis Type-1 (NF1) Treated with Selumetinib on Pediatric Brain Tumor Consortium (PBTC)-029B
Cancers 2023, 15(7), 2109; https://doi.org/10.3390/cancers15072109 - 31 Mar 2023
Abstract
Background: Understanding the effect of selumetinib on FASI may help elucidate the biology, proliferative potential, and role in neurocognitive changes for these NF1-associated lesions. Methods: Patients with NF1-associated LGG and FASI treated with selumetinib on PBTC-029B were age-matched to untreated patients with NF1-associated
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Background: Understanding the effect of selumetinib on FASI may help elucidate the biology, proliferative potential, and role in neurocognitive changes for these NF1-associated lesions. Methods: Patients with NF1-associated LGG and FASI treated with selumetinib on PBTC-029B were age-matched to untreated patients with NF1-associated FASI at Cincinnati Children’s Hospital Medical Center. Paired bidirectional measurements were compared over time using nonparametric tests. Results: Sixteen age-matched pairs were assessed (age range: 2.8–16.9 years, 60% male). Initial FASI burden was not different between groups (median range 138.7 cm2 [88.4–182.0] for the treated subjects vs. 121.6 cm2 [79.6—181.9] for the untreated subjects; p = 0.98). Over a mean follow-up of 18.9 (±5.9) months, the LGG size consistently decreased with treatment while no consistent change among the treated or untreated FASI size was seen. At the paired time points, the median treated LGG decreased significantly more than the treated FASI (−41.3% (LGG) versus −10.7% (FASI), p = 0.006). However, there was no difference in the median size change in the treated versus untreated FASI (−10.7% (treated FASI) versus −17.9% (untreated FASI), p = 0.08). Among the treated subjects, there was no correlation between the change in LGG and FASI (r = −0.04, p = 0.88). Conclusions: Treatment with selumetinib did not affect the overall FASI size in children with NF1 treated for progressive low-grade glioma.
Full article
(This article belongs to the Special Issue Frontiers in Neurofibromatosis)
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Open AccessArticle
Cell-Free RNA from Plasma in Patients with Neuroblastoma: Exploring the Technical and Clinical Potential
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, , , , , , , , , , and
Cancers 2023, 15(7), 2108; https://doi.org/10.3390/cancers15072108 (registering DOI) - 31 Mar 2023
Abstract
Neuroblastoma affects mostly young children, bearing a high morbidity and mortality. Liquid biopsies, e.g., molecular analysis of circulating tumor-derived nucleic acids in blood, offer a minimally invasive diagnostic modality. Cell-free RNA (cfRNA) is released by all cells, especially cancer. It circulates in blood
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Neuroblastoma affects mostly young children, bearing a high morbidity and mortality. Liquid biopsies, e.g., molecular analysis of circulating tumor-derived nucleic acids in blood, offer a minimally invasive diagnostic modality. Cell-free RNA (cfRNA) is released by all cells, especially cancer. It circulates in blood packed in extracellular vesicles (EV) or attached to proteins. We studied the feasibility of analyzing cfRNA and EV, isolated by size exclusion chromatography (SEC), from platelet-poor plasma from healthy controls (n = 40) and neuroblastoma patients with localized (n = 10) and metastatic disease (n = 30). The mRNA content was determined using several multiplex droplet digital PCR (ddPCR) assays for a neuroblastoma-specific gene panel (PHOX2B, TH, CHRNA3) and a cell cycle regulation panel (E2F1, CDC6, ATAD2, H2AFZ, MCM2, DHFR). We applied corrections for the presence of platelets. We demonstrated that neuroblastoma-specific markers were present in plasma from 14/30 patients with metastatic disease and not in healthy controls and patients with localized disease. Most cell cycle markers had a higher expression in patients. The mRNA markers were mostly present in the EV-enriched SEC fractions. In conclusion, cfRNA can be isolated from plasma and EV and analyzed using multiplex ddPCR. cfRNA is an interesting novel liquid biopsy-based target to explore further.
Full article
(This article belongs to the Collection Cancer Biomarkers in Body Fluids)
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New Perspectives on Primary Prophylaxis of Invasive Fungal Infection in Children Undergoing Hematopoietic Stem Cell Transplantation: A 10-Year Retrospective Cohort Study
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, , , , , , and
Cancers 2023, 15(7), 2107; https://doi.org/10.3390/cancers15072107 - 31 Mar 2023
Abstract
Background: Allogenic hematopoietic stem cell transplantation (a-HCT) remains a therapeutic treatment for many pediatric hematological diseases. The occurrence of invasive fungal infections (IFIs) is a complication for which ECIL-8 recommends primary antifungal prophylaxis. In this study, we evaluated the impact of our local
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Background: Allogenic hematopoietic stem cell transplantation (a-HCT) remains a therapeutic treatment for many pediatric hematological diseases. The occurrence of invasive fungal infections (IFIs) is a complication for which ECIL-8 recommends primary antifungal prophylaxis. In this study, we evaluated the impact of our local strategy of not systematically administering primary antifungal prophylaxis in children undergoing a-HCT on the occurrence and mortality of IFIs. Methods: We performed a retrospective monocentric study from 2010 to 2020. We retained all proven and probable IFIs diagnosed during the first year post a-HCT. Results: 308 patients were included. Eighteen patients developed twenty IFIs (thirteen proven, seven probable) (6.5%) among which aspergillosis (n = 10, 50%) and candidosis (n = 7, 35%) were the most frequently diagnosed infections. Only 2% of children died because of an IFI, which represents 14% of all deaths. Multivariate analysis found that age > 10 years (OR: 0.29), the use of a therapeutic antiviral treatment (OR: 2.71) and a low neutrophil count reconstitution (OR: 0.93) were significantly associated with the risk of IFI occurrence. There was also a trend of malignant underlying disease and status ≥ CR2 but it was not retained in multivariate analysis. Conclusions: IFI occurrence was not higher in our cohort than what is reported in the literature with the use of systematic antifungal prophylaxis, with a good survival rate nonetheless. Thus, a prophylaxis could be considered for children with a high risk of IFI such as those aged over 10 years.
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(This article belongs to the Topic Leukemia-Challenges and Current Treatment Options)
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Open AccessReview
Manifestations of Ovarian Cancer in Relation to Other Pelvic Diseases by MRI
Cancers 2023, 15(7), 2106; https://doi.org/10.3390/cancers15072106 (registering DOI) - 31 Mar 2023
Abstract
Imaging plays a pivotal role in the diagnostic approach of women with suspected ovarian cancer. MRI is widely used for preoperative characterization and risk stratification of adnexal masses. While epithelial ovarian cancer (EOC) has typical findings on MRI; there are several benign and
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Imaging plays a pivotal role in the diagnostic approach of women with suspected ovarian cancer. MRI is widely used for preoperative characterization and risk stratification of adnexal masses. While epithelial ovarian cancer (EOC) has typical findings on MRI; there are several benign and malignant pelvic conditions that may mimic its appearance on imaging. Knowledge of the origin and imaging characteristics of a pelvic mass will help radiologists diagnose ovarian cancer promptly and accurately. Finally, in special subgroups, including adolescents and gravid population, the prevalence of various ovarian tumors differs from that of the general population and there are conditions which uniquely manifest during these periods of life.
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(This article belongs to the Special Issue Updates on Imaging of Common Urogenital Neoplasms)
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Open AccessReview
Precision Oncology Targets in Biliary Tract Cancer
Cancers 2023, 15(7), 2105; https://doi.org/10.3390/cancers15072105 - 31 Mar 2023
Abstract
Targeted therapies in biliary tract cancer (BTC) are emerging as options for patients not who do not respond to first-line treatment. Agents acting on tumor-specific oncogenes in BTC may target fibroblast growth factor receptor 2 (FGFR2), isocitrate dehydrogenase (IDH), B-raf kinase (BRAF), and
[...] Read more.
Targeted therapies in biliary tract cancer (BTC) are emerging as options for patients not who do not respond to first-line treatment. Agents acting on tumor-specific oncogenes in BTC may target fibroblast growth factor receptor 2 (FGFR2), isocitrate dehydrogenase (IDH), B-raf kinase (BRAF), and human epidermal growth factor receptor 2 (HER-2). Additionally, given the heterogeneous genetic landscape of advanced BTCs, many harbor genetic aberrations that are common among solid tumors, including RET fusions, tropomyosin receptor kinase (TRK) fusions, and high tumor mutational burden (TMB). This review aims to provide updates on the evolving array of therapeutics available, and to summarize promising works on the horizon.
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(This article belongs to the Special Issue Oncology: State-of-the-Art Research in the USA)
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Open AccessArticle
Sodium-Glucose Cotransporter-2 Inhibitor versus Beta-Blocker Use for Hepatocellular Carcinoma Risk among People with Hepatitis B or C Virus Infection and Diabetes Mellitus
by
and
Cancers 2023, 15(7), 2104; https://doi.org/10.3390/cancers15072104 - 31 Mar 2023
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Objective: The current study detects the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2I) versus beta-blocker (BB) in diabetes mellitus (DM) with chronic hepatitis B or C on hepatocellular carcinoma (HCC) outcomes. Methods: The multivariate logistic regression model, including all baseline characteristics and index year,
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Objective: The current study detects the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2I) versus beta-blocker (BB) in diabetes mellitus (DM) with chronic hepatitis B or C on hepatocellular carcinoma (HCC) outcomes. Methods: The multivariate logistic regression model, including all baseline characteristics and index year, was used to calculate the propensity scores, and we performed the greedy algorithm on propensity scores to create matched pairs of SGLT2I and BB users. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of HCC were estimated by Cox proportional hazards regression models, and we adjusted for confounding factors by including the baseline characteristics in the regression models. Results: After matching in a ratio of 1:1, 7023 SGLT2I users and 7023 BB users were included in the following statistical analyses. The overall HRs showed a significantly lower risk of HCC in SGLT2I users in comparison to a reference group of BB users with an adjusted HR of 0.27 (0.21, 0.34). Conclusions: Compared to BB use, SGLT2I was associated with a significant risk reduction in HCC occurrence.
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Open AccessArticle
Phase IIa Clinical Biomarker Trial of Dietary Arginine Restriction and Aspirin in Colorectal Cancer Patients
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, , , , , and
Cancers 2023, 15(7), 2103; https://doi.org/10.3390/cancers15072103 - 31 Mar 2023
Abstract
After potentially curative treatment, colorectal cancer (CRC) patients remain at high risk for recurrence, second primary CRC, and high-risk adenomas. In combination with existing data, our previous findings provide a rationale for reducing tissue polyamines as tertiary prevention in non-metastatic CRC patients. The
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After potentially curative treatment, colorectal cancer (CRC) patients remain at high risk for recurrence, second primary CRC, and high-risk adenomas. In combination with existing data, our previous findings provide a rationale for reducing tissue polyamines as tertiary prevention in non-metastatic CRC patients. The goal of this study was to demonstrate rectal tissue polyamine reduction in optimally treated stage I-III CRC patients after intervention with daily oral aspirin + dietary arginine restriction. A single-institution phase IIa clinical trial was conducted. Patients were treated with aspirin 325 mg/day and an individualized dietary regimen designed to reduce arginine intake by ≥30% over a 12-week study period. Dietary intake, endoscopy with rectal biopsies, and phlebotomy were performed pre- and post-intervention. The primary endpoint was to demonstrate ≥50% decrease in rectal tissue putrescine levels from baseline as a measure of polyamine reduction in the target tissue. Twenty eligible patients completed the study. After study intervention, mean dietary arginine intake decreased from 3.7 g/day ± 1.3 SD to 2.6 g/day ± 1.2 SD (29.7% decrease, p < 0.02 by Sign test). Mean plasma arginine levels decreased from 46.0 ng/mL ± 31.5 SD at baseline to 35 ng/mL ± 21.7 SD (p < 0.001). Rectal tissue putrescine levels were 0.90 nMol/mg-protein pre-intervention and 0.99 nMol/mg-protein post-intervention (p < 0.64, NS). No significant differences were observed for the other tissue polyamines investigated: spermidine (p < 0.13), spermine (p < 0.21), spermidine:spermine ratio (p < 0.71). Among CRC survivors, treatment with daily oral aspirin and an individualized dietary arginine restriction intervention resulted in lower calculated dietary arginine intake and plasma arginine levels but did not affect rectal tissue polyamine levels.
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(This article belongs to the Special Issue Gastrointestinal Tract Cancers, an Increasing Burden of the Modern Era: Epidemiology and Prevention)
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p53 and p63 Proteoforms Derived from Alternative Splicing Possess Differential Seroreactivity in Colorectal Cancer with Distinct Diagnostic Ability from the Canonical Proteins
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, , , , , , , , , , and
Cancers 2023, 15(7), 2102; https://doi.org/10.3390/cancers15072102 - 31 Mar 2023
Abstract
Colorectal cancer (CRC) is the third most common cancer and the second most frequent cause of cancer-related death worldwide. The detection in plasma samples of autoantibodies against specific tumor-associated antigens has been demonstrated to be useful for the early diagnosis of CRC by
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Colorectal cancer (CRC) is the third most common cancer and the second most frequent cause of cancer-related death worldwide. The detection in plasma samples of autoantibodies against specific tumor-associated antigens has been demonstrated to be useful for the early diagnosis of CRC by liquid biopsy. However, new studies related to the humoral immune response in cancer are needed to enable blood-based diagnosis of the disease. Here, our aim was to characterize the humoral immune response associated with the different p53 and p63 proteoforms derived from alternative splicing and previously described as aberrantly expressed in CRC. Thus, here we investigated the diagnostic ability of the twelve p53 proteoforms and the eight p63 proteoforms described to date, and their specific N-terminal and C-terminal end peptides, by means of luminescence HaloTag beads immunoassays. Full-length proteoforms or specific peptides were cloned as HaloTag fusion proteins and their seroreactivity analyzed using plasma from CRC patients at stages I-IV (n = 31), individuals with premalignant lesions (n = 31), and healthy individuals (n = 48). p53γ, Δ40p53β, Δ40p53γ, Δ133p53γ, Δ160p53γ, TAp63α, TAp63δ, ΔNp63α, and ΔNp63δ, together with the specific C-terminal end α and δ p63 peptides, were found to be more seroreactive against plasma from CRC patients and/or individuals with premalignant lesions than from healthy individuals. In addition, ROC (receiver operating characteristic) curves revealed a high diagnostic ability of those p53 and p63 proteoforms to detect CRC and premalignant individuals (AUC higher than 85%). Finally, electrochemical biosensing platforms were employed in POC-like devices to investigate their usefulness for CRC detection using selected p53 and p63 proteoforms. Our results demonstrate not only the potential of these biosensors for the simultaneous analysis of proteoforms’ seroreactivity, but also their convenience and versatility for the clinical detection of CRC by liquid biopsy. In conclusion, we here show that p53 and p63 proteoforms possess differential seroreactivity in CRC patients in comparison to controls, distinctive from canonical proteins, which should improve the diagnostic panels for obtaining a blood-based biomarker signature for CRC detection.
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(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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Open AccessReview
The Role of the Gut Microbiome in Cancer Immunotherapy: Current Knowledge and Future Directions
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, , , , , and
Cancers 2023, 15(7), 2101; https://doi.org/10.3390/cancers15072101 - 31 Mar 2023
Abstract
Cancer immunotherapy is a treatment modality that aims to stimulate the anti-tumor immunity of the host to elicit favorable clinical outcomes. Immune checkpoint inhibitors (ICIs) gained traction due to the lasting effects and better tolerance in patients carrying solid tumors in comparison to
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Cancer immunotherapy is a treatment modality that aims to stimulate the anti-tumor immunity of the host to elicit favorable clinical outcomes. Immune checkpoint inhibitors (ICIs) gained traction due to the lasting effects and better tolerance in patients carrying solid tumors in comparison to conventional treatment. However, a significant portion of patients may present primary or acquired resistance (non-responders), and thus, they may have limited therapeutic outcomes. Resistance to ICIs can be derived from host-related, tumor-intrinsic, or environmental factors. Recent studies suggest a correlation of gut microbiota with resistance and response to immunotherapy as well as with the incidence of adverse events. Currently, preclinical and clinical studies aim to elucidate the unique microbial signatures related to ICI response and anti-tumor immunity, employing metagenomics and/or multi-omics. Decoding this complex relationship can provide the basis for manipulating the malleable structure of the gut microbiota to enhance therapeutic success. Here, we delve into the factors affecting resistance to ICIs, focusing on the intricate gut microbiome–immunity interplay. Additionally, we review clinical studies and discuss future trends and directions in this promising field.
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(This article belongs to the Special Issue The Microbiome-Immunity-Cancer Axis in Cancers)
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Impact of Sex-Specific Preoperative Fat Mass Assessment on Long-Term Prognosis after Gastrectomy for Gastric Cancer
Cancers 2023, 15(7), 2100; https://doi.org/10.3390/cancers15072100 - 31 Mar 2023
Abstract
We investigated the impact of the difference in fat distribution between men and women on long-term prognosis after gastrectomy in patients with advanced gastric cancer. Patients with advanced gastric cancer deeper than p-T2 who underwent gastrectomy between April 2008 and June 2018 were
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We investigated the impact of the difference in fat distribution between men and women on long-term prognosis after gastrectomy in patients with advanced gastric cancer. Patients with advanced gastric cancer deeper than p-T2 who underwent gastrectomy between April 2008 and June 2018 were included. Visceral fat mass index (VFI) and subcutaneous fat mass index (SFI) were calculated by dividing the cross-sectional area at the umbilical level by the height squared. The medians of VFI and SFI by sex were defined as cut-off values, below which values were defined as low VFI and low SFI. Of the 485 patients, 323 (66.6%) were men and 162 (33.4%) were women. Men with a low VFI had a significantly worse overall survival (OS) (p = 0.004) and women with a low SFI had a significantly worse OS (p = 0.007). Patients with a low VFI and low SFI had the worst prognosis. Multivariate analysis showed that a low VFI was an independent poor prognostic factor in men, while a low SFI was an independent poor prognostic factor in women. In conclusion, a low visceral fat mass in men and a low subcutaneous fat mass in women were independent poor prognostic factors after radical gastrectomy for advanced gastric cancer.
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(This article belongs to the Special Issue The Progressive Skeletal Muscle and Body Weight Loss in Cancer Patients)
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Targeting the Molecular and Immunologic Features of Leiomyosarcoma
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Cancers 2023, 15(7), 2099; https://doi.org/10.3390/cancers15072099 - 31 Mar 2023
Abstract
Leiomyosarcoma (LMS) is a rare, aggressive mesenchymal tumor with smooth muscle differentiation. LMS is one of the most common histologic subtypes of soft tissue sarcoma; it most frequently occurs in the extremities, retroperitoneum, or uterus. LMS often demonstrates aggressive tumor biology, with a
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Leiomyosarcoma (LMS) is a rare, aggressive mesenchymal tumor with smooth muscle differentiation. LMS is one of the most common histologic subtypes of soft tissue sarcoma; it most frequently occurs in the extremities, retroperitoneum, or uterus. LMS often demonstrates aggressive tumor biology, with a higher risk of developing distant metastatic disease than most sarcoma histologic types. The prognosis is poor, particularly in patients with uterine disease, and there is a need for the development of more effective therapies. Genetically, LMS is karyotypically complex and characterized by a low tumor mutational burden, with frequent alterations in TP53, RB1, PTEN, and DNA damage response pathways that may contribute to resistance against immune-checkpoint blockade monotherapy. The LMS immune microenvironment is highly infiltrated with tumor-associated macrophages and tumor-infiltrating lymphocytes, which may represent promising biomarkers. This review provides an overview of the clinical and pathologic behavior of both soft tissue and uterine LMS and summarizes the genomic and immune characteristics of these tumors and how they may provide opportunities for the development of biomarker-based immune therapies.
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(This article belongs to the Special Issue Innovations in Soft Tissue Sarcoma Diagnosis and Treatment)
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Diagnostic Performance of Afirma and Interpace Diagnostics Genetic Testing in Indeterminate Thyroid Nodules: A Single Center Study
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, , , , , , , , , and
Cancers 2023, 15(7), 2098; https://doi.org/10.3390/cancers15072098 - 31 Mar 2023
Abstract
Indeterminate thyroid nodules (ITN) represent 20–30% of biopsied nodules, with a 10–60% risk of malignancy. Molecular testing can stratify the risk of malignancy among ITNs, and subsequently reduce the need for unnecessary diagnostic surgery. We aimed to assess the performance of these molecular
[...] Read more.
Indeterminate thyroid nodules (ITN) represent 20–30% of biopsied nodules, with a 10–60% risk of malignancy. Molecular testing can stratify the risk of malignancy among ITNs, and subsequently reduce the need for unnecessary diagnostic surgery. We aimed to assess the performance of these molecular tests at a single institution. Patients with Bethesda III, IV, and V nodules with Afirma and Interpace Diagnostics genetic testing data from November 2013 to November 2021 were included. Three cohorts were formed, including GSC + XA, ThyGeNEXT + ThyraMIR, and GSC + GEC. Statistical analysis determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic odds ratio (DOR), and accuracy of each type of testing. The PPV of nodules undergoing genetic testing by ThyGeNEXT + ThyraMIR (45.00%, 95%CI: 28.28–62.93%, p = 0.032) and GSC + XA (57.14%, 95%CI: 29.32–81.08%, p < 0.001) were superior to that of GEC + GSC (30.72%, 95%CI: 26.83–34.90%). The NPV was above 85% in all cohorts, suggesting overall suitable rule-out tests. The Afirma platform (GSC + XA) had the highest NPV at 96.97%. The overall accuracy for nodules undergoing ThyGeNEXT + ThyraMIR was 81.42% (95%CI: 73.01–88.11%, p < 0.001). A total of 230 patients underwent thyroidectomy, including less than 60% of each of the ThyGeNEXT + ThyraMIR and GSC + XA cohorts. Specifically, only 25% of patients in the GSC + XA cohort underwent surgery, considerably decreasing the rate of unnecessary surgical intervention. Sub-group analysis, including only patients with surgical pathology, found that PPV tended to be higher in the GSC + XA cohort, at 66.67% (95%CI: 37.28–87.06%), as compared to the ThyGeNEXT + ThyraMIR cohort, at 52.94% (95%CI: 35.25–69.92%). The Afirma genetic testing platform GSC + XA outperformed the other platforms with regards to both PPV and NPV and decreased the rate of surgery in patients with ITNs by 75%, significantly preventing unnecessary surgical intervention.
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(This article belongs to the Special Issue Innovations in Endocrine Cancer—Technology, Techniques and Therapy)
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Open AccessEditorial
Iron and Cancer: A Special Issue
by
and
Cancers 2023, 15(7), 2097; https://doi.org/10.3390/cancers15072097 - 31 Mar 2023
Abstract
Iron is an essential element for all organisms, and iron-containing proteins play critical roles in cellular functions [...]
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(This article belongs to the Special Issue Iron and Cancer)
Open AccessArticle
Disparity and Diversity in NSCLC Imaging and Genomics: Evaluation of a Mature, Multicenter Database
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Cancers 2023, 15(7), 2096; https://doi.org/10.3390/cancers15072096 - 31 Mar 2023
Abstract
Lung cancer remains the leading cancer-related death across North America. Imaging is fundamental. Recently, healthcare disparities came into research focus. Our aim was to explore disparity from an imaging, genetic, and outcome perspective. We utilized the AACR Project GENIE Biopharma Consortium (BPC) dataset
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Lung cancer remains the leading cancer-related death across North America. Imaging is fundamental. Recently, healthcare disparities came into research focus. Our aim was to explore disparity from an imaging, genetic, and outcome perspective. We utilized the AACR Project GENIE Biopharma Consortium (BPC) dataset v 1.1 to build a collated NSCLC dataset. Descriptive and analytical statistics were applied according to data characteristics. From 1849 patients, mean age was 64.4 y (±10.5), 58% (n = 1065) were female, 23% (n = 419) never smoked, 84% (n = 1545) were of white race, and 57% (n = 1052) were < stage III. No difference (p > 0.05) was found for baseline imaging by race. White race showed higher 3-month surveillance imaging (p = 0.048) and a baseline stage < IV (OR 0.61). KRAS (33.3 vs. 17.9%), STK11 (14.8 vs. 7.3%), and KEAP1 (13.3 vs. 5.3%) mutations were predominant among white patients while EGFR mutation (19.2 vs. 44.1%) was less predominant. Mutations in TP53 or KEAP1 had worse PFS and OS. The latter was also reduced in STK11, KRAS + STK11, and KRAS + KEAP1 mutations. Meanwhile, EGFR mutation had increased OS. Multivariate analysis showed that progression on imaging at 3 or 6 months (HR 1.69 and 1.43, respectively), TP53 (HR 1.37) and KRAS (HR 1.26) had lower OS while EGFR and LRP1B (HR 0.69 and 0.39, respectively) had higher OS. No racial disparity at baseline imaging was observed. Higher initial stages among non-white patients might reflect inequalities in accessing healthcare. However, race wasn’t associated to OS. Finally, progression in imaging at 3 or 6 months showed the higher hazard ratios for death.
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(This article belongs to the Section Cancer Informatics and Big Data)
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Open AccessArticle
The Effect of Risk-Reducing Salpingo-Oophorectomy on Breast Cancer Incidence and Histopathological Features in Women with a BRCA1 or BRCA2 Germline Pathogenic Variant
by
, , , , and
Cancers 2023, 15(7), 2095; https://doi.org/10.3390/cancers15072095 - 31 Mar 2023
Abstract
Background: Risk-reducing salpingo-oophorectomy (RRSO) is advised for female BRCA1/2 germline pathogenic variant (GPV) carriers to reduce tubal/ovarian cancer risk. RRSO may also affect breast cancer (BC) incidence. The aim was to investigate the effect of RRSO on BC incidence and histopathological features in
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Background: Risk-reducing salpingo-oophorectomy (RRSO) is advised for female BRCA1/2 germline pathogenic variant (GPV) carriers to reduce tubal/ovarian cancer risk. RRSO may also affect breast cancer (BC) incidence. The aim was to investigate the effect of RRSO on BC incidence and histopathological features in female BRCA1/2 GPV carriers. Methods: Prospectively collected clinical data from BRCA1/2 GPV carriers in our hospital-based data/biobank were linked to the Dutch Nationwide Pathology Databank (PALGA) in January 2022. Multivariable Cox-proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (95% CIs), where the pre-RRSO group was considered the reference group and the primary endpoint was the first primary BC. Histopathological features of BCs pre- and post-RRSO were compared using descriptive statistics. Results: In 1312 women, 164 incident primary BCs were observed. RRSO did not decrease BC risk for BRCA1 GPV (HR: 1.48, 95% CI: 0.91–2.39) or BRCA2 GPV (HR: 0.95, 95% CI: 0.43–2.07) carriers. BCs tended to be smaller post-RRSO (median: 12 mm) than pre-RRSO (15 mm, p: 0.08). There were no statistically significant differences in histopathological features. Conclusions: RRSO did not decrease BC risk or affect BC features in BRCA1/2 GPV in this study, although BCs diagnosed post-RRSO tended to be smaller.
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(This article belongs to the Special Issue BRCA-Associated Breast Cancer)
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Stereotactic Radiation Therapy for Brain Metastases: Factors Affecting Outcomes and Radiation Necrosis
by
, , , , , , , , , , and
Cancers 2023, 15(7), 2094; https://doi.org/10.3390/cancers15072094 - 31 Mar 2023
Abstract
Stereotactic radiation therapy (SRT) is a proven effective treatment for brain metastases (BM); however, symptomatic radiation necrosis (RN) is a late effect that may impact on patient’s quality of life. The aim of our study was to retrospectively evaluate survival outcomes and characterize
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Stereotactic radiation therapy (SRT) is a proven effective treatment for brain metastases (BM); however, symptomatic radiation necrosis (RN) is a late effect that may impact on patient’s quality of life. The aim of our study was to retrospectively evaluate survival outcomes and characterize the occurrence of RN in a cohort of BM patients treated with ablative SRT at Federico II University Hospital. Clinical and dosimetric factors of 87 patients bearing a total of 220 BMs treated with SRT from 2016 to 2022 were analyzed. Among them, 46 patients with 127 BMs having clinical and MRI follow-up (FUP) ≥ 6 months were selected for RN evaluation. Dosimetric parameters of the uninvolved brain (brain without GTV) were extracted. The crude local control was 91% with neither clinical factors nor prescription dose correlating with local failure (LF). At a median FUP of 9 (1–68) months, the estimated median overall survival (OS), progression-free survival (PFS), and brain progression-free survival (bPFS) were 16, 6, and 9 months, respectively. The estimated OS rates at 1 and 3 years were 59.8% and 18.3%, respectively; bPFS at 1 and 3 years was 29.9% and 13.5%, respectively; PFS at 1 and 3 years was 15.7% and 0%, respectively; and local failure-free survival (LFFS) at 1 and 3 years was 87.2% and 83.8%, respectively. Extracranial disease status was an independent factor related to OS. Fourteen (30%) patients manifested RN. At multivariate analysis, adenocarcinoma histology, left location, and absence of chemotherapy were confirmed as independent risk factors for any-grade RN. Nine (20%) patients developed symptomatic (G2) RN, which improved or stabilized after 1–16 months of steroid therapy. With prompt recognition and, when necessary, medical therapy, RN radiological and clinical amelioration can be obtained.
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(This article belongs to the Special Issue Advances in Stereotactic Radiotherapy of Brain Metastases)
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Open AccessArticle
Proton or Carbon Ion Therapy for Skull Base Chordoma: Rationale and First Analysis of a Mono-Institutional Experience
by
, , , , , , , , , and
Cancers 2023, 15(7), 2093; https://doi.org/10.3390/cancers15072093 - 31 Mar 2023
Abstract
Background: Skull base chordomas are radio-resistant tumors that require high-dose, high-precision radiotherapy, as can be delivered by particle therapy (protons and carbon ions). We performed a first clinical outcome analysis of particle therapy based on the initial 4-years of operation. Methods: Between August
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Background: Skull base chordomas are radio-resistant tumors that require high-dose, high-precision radiotherapy, as can be delivered by particle therapy (protons and carbon ions). We performed a first clinical outcome analysis of particle therapy based on the initial 4-years of operation. Methods: Between August 2017 and October 2021, 44 patients were treated with proton (89%) or carbon ion therapy (11%). Prior gross total resection had been performed in 21% of lesions, subtotal resection in 57%, biopsy in 12% and decompression in 10%. The average prescription dose was 75.2 Gy RBE in 37 fractions for protons and 66 Gy RBE in 22 fractions for carbon ions. Results: At a median follow-up of 34.3 months (range: 1–55), 2-, and 3-year actuarial local control rates were 95.5% and 90.9%, respectively. The 2-, and 3-year overall and progression-free survival rates were 97.7%, 93.2%, 95.5% and 90.9%, respectively. The tumor volume at the time of particle therapy was highly predictive of local failure (p < 0.01), and currently, there is 100% local control in patients with tumors < 49 cc. No grade ≥3 toxicities were observed. There was no significant difference in outcome or side effect profile seen for proton versus carbon ion therapy. Five patients (11.4%) experienced transient grade ≤2 radiation-induced brain changes. Conclusions: The first analysis suggests the safety and efficacy of proton and carbon ion therapy at our center. The excellent control of small to mid-size chordomas underlines the effectiveness of particle therapy and importance of upfront maximum debulking of large lesions.
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(This article belongs to the Special Issue Skull Base Tumors)
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