Cancers

40 pages, 2716 KiB

Open AccessReview

Gynotoxic Effects of Chemotherapy and Potential Protective Mechanisms

by Anna Markowska, Michał Antoszczak, Janina Markowska and Adam Huczyński

Cancers 2024, 16(12), 2288; https://doi.org/10.3390/cancers16122288 - 20 Jun 2024

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Chemotherapy is one of the leading cancer treatments. Unfortunately, its use can contribute to several side effects, including gynotoxic effects in women. Ovarian reserve suppression and estrogen deficiency result in reduced quality of life for cancer patients and are frequently the cause of [...] Read more.

Chemotherapy is one of the leading cancer treatments. Unfortunately, its use can contribute to several side effects, including gynotoxic effects in women. Ovarian reserve suppression and estrogen deficiency result in reduced quality of life for cancer patients and are frequently the cause of infertility and early menopause. Classic alkylating cytostatics are among the most toxic chemotherapeutics in this regard. They cause DNA damage in ovarian follicles and the cells they contain, and they can also induce oxidative stress or affect numerous signaling pathways. In vitro tests, animal models, and a few studies among women have investigated the effects of various agents on the protection of the ovarian reserve during classic chemotherapy. In this review article, we focused on the possible beneficial effects of selected hormones (anti-Müllerian hormone, ghrelin, luteinizing hormone, melatonin), agents affecting the activity of apoptotic pathways and modulating gene expression (C1P, S1P, microRNA), and several natural (quercetin, rapamycin, resveratrol) and synthetic compounds (bortezomib, dexrazoxane, goserelin, gonadoliberin analogs, imatinib, metformin, tamoxifen) in preventing gynotoxic effects induced by commonly used cytostatics. The presented line of research appears to provide a promising strategy for protecting and/or improving the ovarian reserve in the studied group of cancer patients. However, well-designed clinical trials are needed to unequivocally assess the effects of these agents on improving hormonal function and fertility in women treated with ovotoxic anticancer drugs. Full article

(This article belongs to the Special Issue Side Effects of Anticancer Therapy: Prevention and Management)

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14 pages, 740 KiB

Open AccessArticle

Reasonability of Frequent Laboratory Analyses during Therapy with Nivolumab and Nivolumab+Ipilimumab in Patients with Advanced or Metastatic Renal Cell Carcinoma during the Phase 2 Clinical Trial TITAN-RCC

by Klara Franke, Susan Foller, Michele Estephania Rosero Moreno, Nalyan Ali, Lutz Leistritz, Katharina Leucht and Marc-Oliver Grimm

Cancers 2024, 16(12), 2287; https://doi.org/10.3390/cancers16122287 - 20 Jun 2024

Viewed by 239

Abstract

In clinical trials, laboratory values are assessed with high frequency. This can be stressful for patients, resource intensive, and difficult to implement, for example in office-based settings. In the prospective, multicentre phase 2 TITAN-RCC trial (NCT02917772), we investigated how many relevant changes in [...] Read more.

In clinical trials, laboratory values are assessed with high frequency. This can be stressful for patients, resource intensive, and difficult to implement, for example in office-based settings. In the prospective, multicentre phase 2 TITAN-RCC trial (NCT02917772), we investigated how many relevant changes in laboratory values would have been missed if laboratory values had been assessed less frequently. Patients with metastatic renal cell carcinoma (n = 207) received a response-based approach with nivolumab and nivolumab+ipilimumab boosts for non-response. We simulated that laboratory values were obtained before every second dose instead of every dose of the study drug(s). We assessed elevated leukocyte counts, alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, amylase, lipase, and thyroid-stimulating hormone. Dose delay and discontinuation criteria were defined according to the study protocol. With the reduced frequency of laboratory analyses, dose delay criteria were rarely missed: in a maximum of <0.1% (3/4382) of assessments (1% [2/207] of patients) during nivolumab monotherapy and in a maximum of 0.2% (1/465) of assessments (1% [1/132] of patients) during nivolumab+ipilimumab boosts. An exception was lipase-related dose delay which would have been missed in 0.6% (25/4204) of assessments (7% [15/207] of patients) during nivolumab monotherapy and in 0.8% (4/480) of assessments (3% [4/134] of patients) during nivolumab+ipilimumab boosts, but would have required the presence of symptoms. Discontinuation criteria would have only been missed for amylase (<0.1% [1/3965] of assessments [0.5% (1/207) of patients] during nivolumab monotherapy, none during nivolumab+ipilimumab boosts) and lipase (0.1% [5/4204] of assessments [2% (4/207) of patients] during nivolumab monotherapy; 0.2% [1/480] of assessments [0.7% (1/134) of patients] during nivolumab+ipilimumab boosts). However, only symptomatic patients would have had to discontinue treatment due to amylase or lipase laboratory values. In conclusion, a reduced frequency of laboratory testing appears to be acceptable in asymptomatic patients with metastatic renal cell carcinoma treated with nivolumab or nivolumab+ipilimumab. Full article

(This article belongs to the Special Issue Quality of Life and Side Effects Management in Cancer Treatment (Volume II))

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11 pages, 642 KiB

Open AccessArticle

Phase II Clinical Trial of Second Course of Stereotactic Body Radiotherapy for Spinal Metastases

by Kei Ito, Yujiro Nakajima, Kentaro Taguchi, Hiroaki Ogawa, Makoto Saito and Keiko Nemoto Murofushi

Cancers 2024, 16(12), 2286; https://doi.org/10.3390/cancers16122286 - 20 Jun 2024

Viewed by 269

Abstract

Purpose: The optimal method for the second course of stereotactic body radiotherapy (SBRT) for spinal metastases remains poorly established. This single-center, single-arm, phase II trial was conducted to propose a safe and effective salvage spine SBRT. Methods: The patients initially treated with SBRT [...] Read more.

Purpose: The optimal method for the second course of stereotactic body radiotherapy (SBRT) for spinal metastases remains poorly established. This single-center, single-arm, phase II trial was conducted to propose a safe and effective salvage spine SBRT. Methods: The patients initially treated with SBRT for spine-targeted protocol treatment, or for areas adjacent to the spine, were enrolled. The second SBRT dose was 30 Gy delivered in five fractions; the spinal cord dose constraint was 15.5 Gy at the maximum point dose. The brachial or lumbosacral plexuses were dose-constrained to <30 Gy if the boundary between the nerves and tumors was detected. The primary endpoint was dose-limiting toxicity (DLT) (grade ≥ 3 severe radiation-related toxicity) within a year after the second SBRT. Results: The second SBRT was administered to the same spinal level in 12 patients and to an adjacent spinal level in 8 patients. SBRT2 was performed for 14 painful lesions, 10 MESCC, and 6 oligometastases, with some lesions having multiple indications. The median interval between SBRT sessions was 21 months (range: 6–51 months). The median follow-up duration was 14 months. No radiation myelopathy or local failure was reported during the follow-up period. DLT was confirmed in two patients (10%) within a year, both of whom developed grade 3 lumbosacral plexopathy. These two patients received SBRT twice to the S1–2 and S1–5 vertebrae, respectively, and both experienced paralysis of the tibialis anterior muscle (L5 level). Grade 3 late adverse effects (including lumbosacral plexopathy and vertebral compression fracture) were observed in 25% of the patients throughout the entire follow-up period. Conclusions: The second spine SBRT achieved good local control without causing myelopathy. However, one-quarter of the patients experienced grade 3 late adverse effects, suggesting that the treatment protocol carries a risk of toxicity. Full article

(This article belongs to the Special Issue Radiation Therapy for Modern Management of Bone Metastases)

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22 pages, 4576 KiB

Open AccessArticle

Exploring miRNA Profiles in Colon Cancer: A Focus on miR101-3p, miR106a-5p, and miR326

by Constantin-Dan Tâlvan, Elena-Teodora Tâlvan, Călin Ilie Mohor, Liviuța Budișan, Valentin Grecu, Manuela Mihalache, Oana Zănoagă, Sergiu Chira, Ioana Berindan-Neagoe, Victor Cristea and Cosmin Ioan Mohor

Cancers 2024, 16(12), 2285; https://doi.org/10.3390/cancers16122285 - 20 Jun 2024

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Abstract

Early diagnosis and prognosis of cancer progression through biomarker profiling are crucial in managing colon cancer patients. Our research aimed to investigate the expression of miR-101-3p, miR-106a-5p, and miR-326 in tumor and adjacent healthy tissues of colon cancer patients and determine their potential [...] Read more.

Early diagnosis and prognosis of cancer progression through biomarker profiling are crucial in managing colon cancer patients. Our research aimed to investigate the expression of miR-101-3p, miR-106a-5p, and miR-326 in tumor and adjacent healthy tissues of colon cancer patients and determine their potential diagnostic utility. This study included 40 patients divided into four groups according to the TNM staging classification. MiRNA expression was analyzed using qRT-PCR. The results showed that miR-101-3p, miR-106a-5p, and miR-326 are overexpressed in adjacent healthy tissues but decrease in advanced cancer stages. MiR-106a-5p and miR-326 are strongly correlated with colon cancer severity. These findings suggest that miRNA profiling could be useful for early diagnosis and prognosis in colon cancer management. Full article

(This article belongs to the Special Issue Predictive Biomarkers for Colorectal Cancer)

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18 pages, 2182 KiB

Open AccessArticle

Synergistic Effect of Human Papillomavirus and Environmental Factors on Skin Squamous Cell Carcinoma, Basal Cell Carcinoma, and Melanoma: Insights from a Taiwanese Cohort

by Chun-Chia Chen, Ci-Wen Luo, Stella Chin-Shaw Tsai, Jing-Yang Huang, Shun-Fa Yang and Frank Cheu-Feng Lin

Cancers 2024, 16(12), 2284; https://doi.org/10.3390/cancers16122284 - 20 Jun 2024

Viewed by 1015

Abstract

Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated with HPV infection in Taiwan region, using data from the National Health Insurance Research Database between 2007 and 2015. [...] Read more.

Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated with HPV infection in Taiwan region, using data from the National Health Insurance Research Database between 2007 and 2015. Our analysis revealed a significant increase in skin cancer risk among those with HPV, particularly for squamous cell carcinoma (SCC), the subtype with the highest observed adjusted hazard ratio (aHR) = 5.97, 95% CI: 4.96–7.19). The overall aHR for HPV-related skin cancer was 5.22 (95% CI: 4.70–5.80), indicating a notably higher risk in the HPV-positive group. The risk of skin cancer was further stratified by type, with basal cell carcinoma (aHR = 4.88, 95% CI: 4.14–5.74), and melanoma (aHR = 4.36, 95% CI: 2.76–6.89) also showing significant associations with HPV. The study also highlighted regional variations, with increased risks in southern Taiwan and the Kaohsiung-Pingtung area. Key findings emphasize the importance of sun protection, particularly in regions of high UV exposure and among individuals in high-risk occupations. This research contributes to a better understanding of the complex interactions between HPV and skin cancer risk, reinforcing the importance of preventive strategies in public health. Full article

(This article belongs to the Special Issue Viruses in Cancer Etiology)

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18 pages, 2360 KiB

Open AccessReview

Comprehensive Insights into Chondroblastoma Metastasis: Metastatic Patterns and Therapeutic Approaches

by Ramy Samargandi, Abrar Bafail, Louis-Romée Le Nail and Julien Berhouet

Cancers 2024, 16(12), 2283; https://doi.org/10.3390/cancers16122283 - 20 Jun 2024

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Abstract

Chondroblastoma metastasis, though rare, represents a clinically significant and notably important aspect of bone tumors. Understanding its epidemiological characteristics, pathological features, and treatment modalities, despite its infrequency, is imperative for comprehensive patient management. This review aims to elucidate the epidemiology, molecular mechanisms, diagnostic [...] Read more.

Chondroblastoma metastasis, though rare, represents a clinically significant and notably important aspect of bone tumors. Understanding its epidemiological characteristics, pathological features, and treatment modalities, despite its infrequency, is imperative for comprehensive patient management. This review aims to elucidate the epidemiology, molecular mechanisms, diagnostic challenges, and therapeutic strategies associated with chondroblastoma metastasis. The patterns, prognostic factors, and treatment outcomes were explored through an analysis of case studies and clinical reports. Notably, we highlighted emerging therapeutic perspectives aimed at improving patient outcomes. To the best of our knowledge, there has been no previous review addressing these matters cumulatively, highlighting a significant gap in the existing scholarly literature. By shedding light on the nuances of chondroblastoma metastasis, this review contributes to the advancement of knowledge in this field and informs clinical decision-making for improved patient care. Full article

(This article belongs to the Special Issue Giant-Cell-Containing Tumors of Bone—New Insights into Pathobiology, the Clinical Setting and Targeted Therapies)

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15 pages, 4318 KiB

Open AccessArticle

SMARCD3 Overexpression Promotes Epithelial–Mesenchymal Transition in Gastric Cancer

by Sun Yi Park, Ji-Ho Park, Jung Wook Yang, Eun-Jung Jung, Young-Tae Ju, Chi-Young Jeong, Ju-Yeon Kim, Taejin Park, Tae-Han Kim, Miyeong Park, Young-Joon Lee and Sang-Ho Jeong

Cancers 2024, 16(12), 2282; https://doi.org/10.3390/cancers16122282 - 20 Jun 2024

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Abstract

This study investigates the role of SMARCD3 in gastric cancer by comparing its expression in signet ring cell (SRC) and well-differentiated (WD) groups within gastric cancer cell lines and tissues. We observed elevated SMARCD3 levels in the SRC group compared to the WD [...] Read more.

This study investigates the role of SMARCD3 in gastric cancer by comparing its expression in signet ring cell (SRC) and well-differentiated (WD) groups within gastric cancer cell lines and tissues. We observed elevated SMARCD3 levels in the SRC group compared to the WD group. Functional analysis was conducted through both SMARCD3 knock-in and knock-out methods. Kaplan–Meier survival analysis indicated that higher SMARCD3 expression correlates with poorer overall survival in gastric cancer patients (HR 2.16, p < 0.001). SMARCD3 knock-out cells showed decreased proliferation, migration, invasion, and expression of epithelial–mesenchymal transition (EMT) markers, contrasting with results from temporary and stable SMARCD3 overexpression experiments, which demonstrated increased cell area and irregularity (p < 0.001). Further analysis revealed that SMARCD3 overexpression in MKN-74 cells significantly enhanced p-AKT-S473 and p-ERK levels (p < 0.05), and in KATO III cells, it increased β-catenin and PI3Kp85 activities (p < 0.05). Conversely, these activities decreased in SNU 601 cells following SMARCD3 depletion. The study concludes that SMARCD3 overexpression may serve as a negative prognostic marker and a potential therapeutic target in gastric cancer treatment due to its role in promoting EMT. Full article

(This article belongs to the Special Issue Relevant Prognostic Factors in Gastric Cancer)

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32 pages, 4335 KiB

Open AccessArticle

Functional and Disability Outcomes in NSCLC Patients Post-Lobectomy Undergoing Pulmonary Rehabilitation: A Biopsychosocial Approach

by Agnieszka Zawadzka-Fabijan, Artur Fabijan, Mariusz Łochowski, Łukasz Pryt, Bartosz Polis, Krzysztof Zakrzewski, Jolanta Ewa Kujawa and Józef Kozak

Cancers 2024, 16(12), 2281; https://doi.org/10.3390/cancers16122281 - 20 Jun 2024

Viewed by 408

Abstract

Worldwide, lung cancer remains the predominant cause of cancer cases and deaths and poses significant health challenges, with surgical resection being a key treatment. Post-surgery, patients often experience functional impairments. This study aimed to develop a comprehensive ICF version for assessing the functional [...] Read more.

Worldwide, lung cancer remains the predominant cause of cancer cases and deaths and poses significant health challenges, with surgical resection being a key treatment. Post-surgery, patients often experience functional impairments. This study aimed to develop a comprehensive ICF version for assessing the functional profile and disability in lung cancer patients post-thoracic surgery undergoing pulmonary rehabilitation using the ICF and WHODAS 2.0 tool. We analyzed the correlation between the ICF Core Set and WHODAS 2.0 data to understand the impact on daily functioning. This study included 50 patients (23 F, 27 M) from the Clinic of Thoracic Surgery and Respiratory Rehabilitation in Lodz. Essential ICF codes were determined using the Delphi method, and assessments were conducted on the third day post-operation. Statistical analyses included various tests with α = 0.05. The results showed no impairments in voice functions (b310), respiration rates (b4400), and diaphragm functions (b4451), but there were significant issues with chest pain (b28011), respiratory muscle functions (b445), exercise tolerance (b455), and muscle endurance (b740). In Activities and Participation and Environmental Factors, most codes were not problematic, except for employment (d845, d850) and atmospheric pressure (e2252). Significant correlations were found between mobility limitations (d410, d460) and self-care (d510, d540) with the WHODAS 2.0 results. The comprehensive ICF Core Set effectively described the functional profile of post-surgery patients, confirming its utility and highlighting the impact of disability on daily functioning. Full article

(This article belongs to the Special Issue Prevention and Quality of Life of Lung Cancer)

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28 pages, 1286 KiB

Open AccessReview

Circulating Tumor DNA in Genitourinary Cancers: Detection, Prognostics, and Therapeutic Implications

by Margo B. Gerke, Caroline S. Jansen and Mehmet A. Bilen

Cancers 2024, 16(12), 2280; https://doi.org/10.3390/cancers16122280 - 20 Jun 2024

Viewed by 485

Abstract

CtDNA is emerging as a non-invasive clinical detection method for several cancers, including genitourinary (GU) cancers such as prostate cancer, bladder cancer, and renal cell carcinoma (RCC). CtDNA assays have shown promise in early detection of GU cancers, providing prognostic information, assessing real-time [...] Read more.

CtDNA is emerging as a non-invasive clinical detection method for several cancers, including genitourinary (GU) cancers such as prostate cancer, bladder cancer, and renal cell carcinoma (RCC). CtDNA assays have shown promise in early detection of GU cancers, providing prognostic information, assessing real-time treatment response, and detecting residual disease and relapse. The ease of obtaining a “liquid biopsy” from blood or urine in GU cancers enhances its potential to be used as a biomarker. Interrogating these “liquid biopsies” for ctDNA can then be used to detect common cancer mutations, novel genomic alterations, or epigenetic modifications. CtDNA has undergone investigation in numerous clinical trials, which could address clinical needs in GU cancers, for instance, earlier detection in RCC, therapeutic response prediction in castration-resistant prostate cancer, and monitoring for recurrence in bladder cancers. The utilization of liquid biopsy for ctDNA analysis provides a promising method of advancing precision medicine within the field of GU cancers. Full article

(This article belongs to the Special Issue Biomarkers for the Early Detection and Treatment of Cancers)

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9 pages, 502 KiB

Open AccessArticle

Musculoskeletal Disorders Related to Upper Limb Disability after One-Year Lung Cancer Resection

by Javier Martín Núñez, Julia Raya Benítez, Florencio Quero Valenzuela, Andrés Calvache Mateo, Alba Navas Otero, Alejandro Heredia Ciuró and Marie Carmen Valenza

Cancers 2024, 16(12), 2279; https://doi.org/10.3390/cancers16122279 - 19 Jun 2024

Viewed by 291

Abstract

Lung resection represents the main curative treatment in lung cancer; however, this surgical process leads to several disorders in tissues and organs. Previous studies have reported cardiovascular, pulmonary, and muscular disturbances that affect the functional capacity of these patients in the short, mid, [...] Read more.

Lung resection represents the main curative treatment in lung cancer; however, this surgical process leads to several disorders in tissues and organs. Previous studies have reported cardiovascular, pulmonary, and muscular disturbances that affect the functional capacity of these patients in the short, mid, and long term. However, upper limb impairment has been scarcely explored in the long term, despite the relevance in the independence of the patients. The aim of this study was to characterize the upper limb impairment in survivors of lung cancer one year after pulmonary resection. In this observational trial, patients who underwent lung cancer surgery were compared to control, healthy subjects matched by age and gender. Upper limb musculoskeletal disorders (shoulder range of motion, pain pressure threshold, nerve-related symptoms) and functional capacity (upper limb exercise capacity) were evaluated one-year post-surgery. A total of 76 survivors of lung cancer and 74 healthy subjects were included in the study. Significant differences between groups were found for active shoulder mobility (p < 0.05), widespread hypersensitivity to mechanical pain (p < 0.001), mechanosensitivity of the neural tissue (p < 0.001), and upper limb exercise capacity (p < 0.001). Patients who undergo lung cancer surgery show upper limb musculoskeletal disorders and upper limb functional impairment after a one-year lung resection. This clinical condition could limit the functionality and quality of life of patients with lung cancer. Full article

(This article belongs to the Special Issue Advancements in Lung Cancer Surgical Treatment and Prognosis)

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22 pages, 7938 KiB

Open AccessArticle

The Histogenetic Origin of Malignant Cells Predicts Their Susceptibility towards Synthetic Lethality Utilizing the TK.007 System

by Fabian Bernhard Pallasch, Vera Freytag, Malte Kriegs, Dennis Gatzemeier, Thomas Mair, Hannah Voss, Kristoffer Riecken, Mona Dawood, Boris Fehse, Thomas Efferth, Hartmut Schlüter and Udo Schumacher

Cancers 2024, 16(12), 2278; https://doi.org/10.3390/cancers16122278 - 19 Jun 2024

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Abstract

Background: Remarkable differences exist in the outcome of systemic cancer therapies. Lymphomas and leukemias generally respond well to systemic chemotherapies, while solid cancers often fail. We engineered different human cancer cells lines to uniformly express a modified herpes simplex virus thymidine kinase TK.007 [...] Read more.

Background: Remarkable differences exist in the outcome of systemic cancer therapies. Lymphomas and leukemias generally respond well to systemic chemotherapies, while solid cancers often fail. We engineered different human cancer cells lines to uniformly express a modified herpes simplex virus thymidine kinase TK.007 as a suicide gene when ganciclovir (GCV) is applied, thus in theory achieving a similar response in all cell lines. Methods: Fifteen different cell lines were engineered to express the TK.007 gene. XTT-cell proliferation assays were performed and the IC₅₀-values were calculated. Functional kinome profiling, mRNA sequencing, and bottom-up proteomics analysis with Ingenuity pathway analysis were performed. Results: GCV potency varied among cell lines, with lymphoma and leukemia cells showing higher susceptibility than solid cancer cells. Functional kinome profiling implies a contribution of the SRC family kinases and decreased overall kinase activity. mRNA sequencing highlighted alterations in the MAPK pathways and bottom-up proteomics showed differences in apoptotic and epithelial junction signaling proteins. Conclusions: The histogenetic origin of cells influenced the susceptibility of human malignant cells towards cytotoxic agents with leukemias and lymphomas being more sensitive than solid cancer cells. Full article

(This article belongs to the Section Molecular Cancer Biology)

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13 pages, 2920 KiB

Open AccessArticle

Does a “Western Lifestyle” Confer a Higher Burden of Colorectal Cancer? A Comparison of EU15+ Countries versus Global Trends between 1990 and 2019

by Bradley Walker, Chinmay T. Jani, Weitao Liu, Shoheera Punjwani, Samuel Kareff, Peter Ceglowski, Harpreet Singh, Melissa Mariano, Justin D. Salciccioli, Lawrence Borges and Gilberto Lopes

Cancers 2024, 16(12), 2277; https://doi.org/10.3390/cancers16122277 - 19 Jun 2024

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Abstract

The incidence of colorectal cancer (CRC) in the U.S. is declining in adults 50 years and older; however, recent studies suggest an increasing disease burden among adults under age 50. This study aims to compare the incidence, mortality, and mortality-to-incidence ratios (MIRs) of [...] Read more.

The incidence of colorectal cancer (CRC) in the U.S. is declining in adults 50 years and older; however, recent studies suggest an increasing disease burden among adults under age 50. This study aims to compare the incidence, mortality, and mortality-to-incidence ratios (MIRs) of CRC in EU15+ countries to determine if similar age-stratified occurrences are observed across these countries with similar “Western lifestyle”-related risk factors. Incidence and mortality rates for CRC between 1990 and 2019 were extracted using the Global Burden of Disease database. The data were age-stratified into groups between ages 25–49, 50–69, and greater than 69 years. We observed that the incidence of CRC increased globally for all age groups, with the highest increase observed for males (75.9%) and females (27.7%) aged 25–49. A similar trend was observed in 15 of the 19 EU15+ countries for males and 16 of the 19 EU15+ countries for females aged 25–49. Global mortality rates decreased for all age groups in females but increased for males in all age groups. This raises concerns regarding potentially modifiable risk factors contributing to increased CRC development and underscores the importance of implementing standardized screening at an earlier stage to ensure adequate detection in the younger population. Full article

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

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12 pages, 861 KiB

Open AccessArticle

Baseline Cell-Free DNA Can Predict Malignancy of Nodules Observed in the ITALUNG Screening Trial

by Simonetta Bisanzi, Donella Puliti, Giulia Picozzi, Chiara Romei, Francesco Pistelli, Annalisa Deliperi, Giulia Carreras, Giovanna Masala, Giuseppe Gorini, Marco Zappa, Cristina Sani, Laura Carrozzi, Eugenio Paci, Rudolf Kaaks, Francesca Maria Carozzi and Mario Mascalchi

Cancers 2024, 16(12), 2276; https://doi.org/10.3390/cancers16122276 - 19 Jun 2024

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Abstract

The role of total plasma cell-free DNA (cfDNA) in lung cancer (LC) screening with low-dose computed tomography (LDCT) is uncertain. We hypothesized that cfDNA could support differentiation between malignant and benign nodules observed in LDCT. The baseline cfDNA was measured in 137 subjects [...] Read more.

The role of total plasma cell-free DNA (cfDNA) in lung cancer (LC) screening with low-dose computed tomography (LDCT) is uncertain. We hypothesized that cfDNA could support differentiation between malignant and benign nodules observed in LDCT. The baseline cfDNA was measured in 137 subjects of the ITALUNG trial, including 29 subjects with screen-detected LC (17 prevalent and 12 incident) and 108 subjects with benign nodules. The predictive capability of baseline cfDNA to differentiate malignant and benign nodules was compared to that of Lung-RADS classification and Brock score at initial LDCT (iLDCT). Subjects with prevalent LC showed both well-discriminating radiological characteristics of the malignant nodule (16 of 17 were classified as Lung-RADS 4) and markedly increased cfDNA (mean 18.8 ng/mL). The mean diameters and Brock scores of malignant nodules at iLDCT in subjects who were diagnosed with incident LC were not different from those of benign nodules. However, 75% (9/12) of subjects with incident LC showed a baseline cfDNA ≥ 3.15 ng/mL, compared to 34% (37/108) of subjects with benign nodules (p = 0.006). Moreover, baseline cfDNA was correlated (p = 0.001) with tumor growth, measured with volume doubling time. In conclusion, increased baseline cfDNA may help to differentiate subjects with malignant and benign nodules at LDCT. Full article

(This article belongs to the Special Issue Predictive Biomarkers for Lung Cancer)

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13 pages, 2400 KiB

Open AccessArticle

Prediction of Efficacy for Atezolizumab/Bevacizumab in Unresectable Hepatocellular Carcinoma with Hepatobiliary-Phase Gadolinium Ethoxybenzyl-Diethylenetriaminepentaacetic Acid MRI

by Hideki Kunichika, Kiyoyuki Minamiguchi, Tetsuya Tachiiri, Kozo Shimizu, Ryosuke Taiji, Aya Yamada, Ryota Nakano, Mariko Irizato, Satoshi Yamauchi, Aki Marugami, Nagaaki Marugami, Hayato Kishida, Hiroyuki Nakagawa, Megumi Takewa, Ken Kageyama, Akira Yamamoto, Eisuke Ueshima, Keitaro Sofue, Ryuichi Kita, Hiroyuki Kurakami and Toshihiro Tanaka Show full author list Hide full author list

Cancers 2024, 16(12), 2275; https://doi.org/10.3390/cancers16122275 - 19 Jun 2024

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Abstract

Background: This study aimed to examine whether the coefficient of variation (CV) in the hepatobiliary-phase (HBP) of Gd-EOB-DTPA-MRI could be an independent predictive factor for tumor progression. Methods: Patients who underwent Gd-EOB-DTPA-MRI before Atezolizumab/bevacizumab therapy at six affiliated institutions between 2018 and 2022 [...] Read more.

Background: This study aimed to examine whether the coefficient of variation (CV) in the hepatobiliary-phase (HBP) of Gd-EOB-DTPA-MRI could be an independent predictive factor for tumor progression. Methods: Patients who underwent Gd-EOB-DTPA-MRI before Atezolizumab/bevacizumab therapy at six affiliated institutions between 2018 and 2022 were included. CV for each patient was calculated as the mean value for up to five tumors larger than 10 mm, and CV of the whole tumor was calculated using LIFEx software. The tumor response was evaluated within 6–10 weeks. The primary endpoint was to investigate the predictive factors, including CV, related to tumor progression using logistic regression analysis. The secondary endpoints were tumor response rate and progression-free survival (PFS) based on CV. Results: Of the 46 enrolled patients, 13 (28.3%) underwent early progressive disease. Multivariate analysis revealed that a high CV (≥0.22) was an independent predictive factor for tumor progression (p = 0.043). Patients with a high CV had significantly frequent PD than those with a low CV (43.5 vs. 13.0%, p = 0.047). Patients with a high CV tended to have shorter PFS than those with a low CV (3.5 vs. 6.7 months, p = 0.071). Conclusion: Quantitative analysis using CV in the HBP of Gd-EOB-DTPA-MRI may be useful for predicting tumor progression for atezolizumab/bevacizumab therapy. Full article

(This article belongs to the Special Issue Chemotherapy for Primary Liver Cancer: Recent Updates and Future Perspectives)

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2 pages, 159 KiB

Open AccessCorrection

Correction: Ishikawa et al. Systematic Review of Beta-Lactam vs. Beta-Lactam plus Aminoglycoside Combination Therapy in Neutropenic Cancer Patients. Cancers 2024, 16, 1934

by Kazuhiro Ishikawa, Tomoaki Nakamura, Fujimi Kawai, Erika Ota and Nobuyoshi Mori

Cancers 2024, 16(12), 2274; https://doi.org/10.3390/cancers16122274 - 19 Jun 2024

Viewed by 187

Abstract

There was an error in the original publication [...] Full article

11 pages, 1250 KiB

Open AccessArticle

Clinical Outcomes of Online Adaptive Magnetic Resonance-Guided Stereotactic Body Radiotherapy of Adrenal Metastases from a Single Institution

by Philipp Hoegen-Saßmannshausen, Inga Jessen, Carolin Buchele, Fabian Schlüter, Carolin Rippke, Claudia Katharina Renkamp, Fabian Weykamp, Sebastian Regnery, Jakob Liermann, Eva Meixner, Line Hoeltgen, Tanja Eichkorn, Laila König, Jürgen Debus, Sebastian Klüter and Juliane Hörner-Rieber

Cancers 2024, 16(12), 2273; https://doi.org/10.3390/cancers16122273 - 19 Jun 2024

Viewed by 301

Abstract

(1) Background: Recent publications foster stereotactic body radiotherapy (SBRT) in patients with adrenal oligometastases or oligoprogression. However, local control (LC) after non-adaptive SBRT shows the potential for improvement. Online adaptive MR-guided SBRT (MRgSBRT) improves tumor coverage and organ-at-risk (OAR) sparing. Long-term results of [...] Read more.

(1) Background: Recent publications foster stereotactic body radiotherapy (SBRT) in patients with adrenal oligometastases or oligoprogression. However, local control (LC) after non-adaptive SBRT shows the potential for improvement. Online adaptive MR-guided SBRT (MRgSBRT) improves tumor coverage and organ-at-risk (OAR) sparing. Long-term results of adaptive MRgSBRT are still sparse. (2) Methods: Adaptive MRgSBRT was performed on a 0.35 T MR-Linac. LC, overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity were assessed. (3) Results: 35 patients with 40 adrenal metastases were analyzed. The median gross tumor volume was 30.6 cc. The most common regimen was 10 fractions at 5 Gy. The median biologically effective dose (BED₁₀) was 75.0 Gy. Plan adaptation was performed in 98% of all fractions. The median follow-up was 7.9 months. One local failure occurred after 16.6 months, resulting in estimated LC rates of 100% at one year and 90% at two years. ORR was 67.5%. The median OS was 22.4 months, and the median PFS was 5.1 months. No toxicity > CTCAE grade 2 occurred. (4) Conclusions: LC and ORR after adrenal adaptive MRgSBRT were excellent, even in a cohort with comparably large metastases. A BED₁₀ of 75 Gy seems sufficient for improved LC in comparison to non-adaptive SBRT. Full article

(This article belongs to the Special Issue New Approaches in Radiotherapy for Cancer)

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14 pages, 1460 KiB

Open AccessArticle

Predictive and Prognostic Factors in Melanoma Central Nervous System Metastases—A Cohort Study

by Estefania Serra, Álvaro Abarzua-Araya, Ana Arance, Roberto Martin-Huertas, Francisco Aya, María Lourdes Olondo, Daniel Rizo-Potau, Josep Malvehy, Susana Puig, Cristina Carrera and Sebastian Podlipnik

Cancers 2024, 16(12), 2272; https://doi.org/10.3390/cancers16122272 - 19 Jun 2024

Viewed by 365

Abstract

Background: Melanoma is the cancer with the highest risk of dissemination to the central nervous system (CNS), one of the leading causes of mortality from this cancer. Objective: To identify patients at higher risk of developing CNS metastases and to evaluate associated prognostic [...] Read more.

Background: Melanoma is the cancer with the highest risk of dissemination to the central nervous system (CNS), one of the leading causes of mortality from this cancer. Objective: To identify patients at higher risk of developing CNS metastases and to evaluate associated prognostic factors. Methods: A cohort study (1998–2023) assessed patients who developed CNS melanoma metastases. Multivariate logistic regression was used to identify predictive factors at melanoma diagnosis for CNS metastasis. Cox regression analysis evaluated the CNS-independent metastasis-related variables impacting survival. Results: Out of 4718 patients, 380 (8.05%) developed CNS metastases. Multivariate logistic regression showed that a higher Breslow index, mitotic rate ≥ 1 mm², ulceration, and microscopic satellitosis were significant risk factors for CNS metastasis development. Higher patient age and the location of the primary tumor in the upper or lower extremities were protective factors. In survival analysis, post-CNS metastasis, symptomatic disease, prior non-CNS metastases, CNS debut with multiple metastases, elevated LDH levels, and leptomeningeal involvement correlated with poorer survival. Conclusion: Predictive factors in the primary tumor independently associated with brain metastases include microscopic satellitosis, ulceration, higher Breslow index, and trunk location. Prognostic factors for lower survival in CNS disease include symptomatic disease, multiple CNS metastases, and previous metastases from different sites. Full article

(This article belongs to the Section Cancer Metastasis)

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11 pages, 1219 KiB

Open AccessArticle

Assessment of Arterial Involvement in Pancreatic Cancer: Utility of Reconstructed CT Images Perpendicular to Artery

by Yoshifumi Noda, Kazuhiro Kobayashi, Masaya Kawaguchi, Tomohiro Ando, Yukiko Takai, Taketo Suto, Yukako Iritani, Takuma Ishihara, Masahiro Fukada, Katsutoshi Murase, Nobuyuki Kawai, Tetsuro Kaga, Toshiharu Miyoshi, Fuminori Hyodo, Hiroki Kato, Tatsuhiko Miyazaki, Nobuhisa Matsuhashi, Kazuhiro Yoshida and Masayuki Matsuo

Cancers 2024, 16(12), 2271; https://doi.org/10.3390/cancers16122271 - 19 Jun 2024

Viewed by 256

Abstract

The purpose of this study was to investigate the utility of reconstructed CT images perpendicular to the artery for assessing arterial involvement from pancreatic cancer and compare the interobserver variability between it and the current diagnostic imaging method. This retrospective study included patients [...] Read more.

The purpose of this study was to investigate the utility of reconstructed CT images perpendicular to the artery for assessing arterial involvement from pancreatic cancer and compare the interobserver variability between it and the current diagnostic imaging method. This retrospective study included patients with pancreatic cancer in the pancreatic body or tail who underwent preoperative pancreatic protocol CT and distal pancreatectomy. Five radiologists used axial and coronal CT images (current method) and perpendicular reconstructed CT images (proposed method) to determine if the degree of solid soft-tissue contact with the splenic artery was ≤180° or >180°. The generalized estimating equations were used to compare the diagnostic performance of solid soft-tissue contact >180° between the current and proposed methods. Fleiss’ ĸ statistics were used to assess interobserver variability. The sensitivity and negative predictive value for diagnosing solid soft-tissue contact >180° were higher (p < 0.001 for each) and the specificity (p = 0.003) and positive predictive value (p = 0.003) were lower in the proposed method than the current method. Interobserver variability was improved in the proposed method compared with the current method (ĸ = 0.87 vs. 0.67). Reconstructed CT images perpendicular to the artery showed higher sensitivity and negative predictive value for diagnosing solid soft-tissue contact >180° than the current method and demonstrated improved interobserver variability. Full article

(This article belongs to the Section Methods and Technologies Development)

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40 pages, 3503 KiB

Open AccessReview

Contemporary Approaches to Immunotherapy of Solid Tumors

by Alla V. Kuznetsova, Xenia A. Glukhova, Olga P. Popova, Igor P. Beletsky and Alexey A. Ivanov

Cancers 2024, 16(12), 2270; https://doi.org/10.3390/cancers16122270 - 19 Jun 2024

Viewed by 618

Abstract

In recent years, the arrival of the immunotherapy industry has introduced the possibility of providing transformative, durable, and potentially curative outcomes for various forms of malignancies. However, further research has shown that there are a number of issues that significantly reduce the effectiveness [...] Read more.

In recent years, the arrival of the immunotherapy industry has introduced the possibility of providing transformative, durable, and potentially curative outcomes for various forms of malignancies. However, further research has shown that there are a number of issues that significantly reduce the effectiveness of immunotherapy, especially in solid tumors. First of all, these problems are related to the protective mechanisms of the tumor and its microenvironment. Currently, major efforts are focused on overcoming protective mechanisms by using different adoptive cell therapy variants and modifications of genetically engineered constructs. In addition, a complex workforce is required to develop and implement these treatments. To overcome these significant challenges, innovative strategies and approaches are necessary to engineer more powerful variations of immunotherapy with improved antitumor activity and decreased toxicity. In this review, we discuss recent innovations in immunotherapy aimed at improving clinical efficacy in solid tumors, as well as strategies to overcome the limitations of various immunotherapies. Full article

(This article belongs to the Special Issue Immunotherapy for Cancers)

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13 pages, 235 KiB

Open AccessReview

Imaging in Vulval Cancer

by Minah Ha and Lois Eva

Cancers 2024, 16(12), 2269; https://doi.org/10.3390/cancers16122269 - 19 Jun 2024

Viewed by 286

Abstract

Vulval cancer is a rare gynaecological cancer, accounting for 3% of all gynaecological malignancies, with 47,000 cases in 2022 globally. Various imaging modalities are widely used in conjunction with clinical assessment in the diagnosis and staging of vulval cancers; however, there is significant [...] Read more.

Vulval cancer is a rare gynaecological cancer, accounting for 3% of all gynaecological malignancies, with 47,000 cases in 2022 globally. Various imaging modalities are widely used in conjunction with clinical assessment in the diagnosis and staging of vulval cancers; however, there is significant heterogeneity in which modalities are recommended in international guidelines, reflecting the paucity of evidence in this area. We reviewed the current evidence for the role of imaging in vulval cancer. A systematic search of the literature was performed on the PubMed database using the MeSH terms ‘vulval neoplasm’ and ‘diagnostic imaging’. We found that there is insufficient evidence to support the routine use of imaging for primary vulval tumours. For nodal assessment, there is no ideal imaging modality with sensitivity or specificity that is superior to other modalities. For distant metastases, CT CAP and FDG-PET/CT have the most evidence to support their use. In conclusion, the evidence for role of imaging in vulval cancer is limited by the heterogeneity of the study design and diagnostic criteria used in each study and the small sample size and retrospective nature of most studies. Full article

(This article belongs to the Special Issue The Role of Medical Imaging in Gynecological Cancer)

11 pages, 1059 KiB

Open AccessArticle

Distance of Biopsy-Confirmed High-Risk Breast Lesion from Concurrently Identified Breast Malignancy Associated with Risk of Carcinoma at the High-Risk Lesion Site

by Julie Le, Thomas J. O’Keefe, Sohini Khan, Sara M. Grossi, Hye Young Choi, Haydee Ojeda-Fournier, Ava Armani, Anne M. Wallace and Sarah L. Blair

Cancers 2024, 16(12), 2268; https://doi.org/10.3390/cancers16122268 - 19 Jun 2024

Viewed by 235

Abstract

High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are not routinely excised due to low upgrade rates to carcinoma. We aim to identify features of these lesions [...] Read more.

High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are not routinely excised due to low upgrade rates to carcinoma. We aim to identify features of these lesions predictive of upgrade when identified concurrently with invasive disease. Methods: A single-center retrospective cohort study was performed for patients who underwent multi-site lumpectomies with invasive disease at one site and a high-risk lesion at another site between 2006 and 2021. A multinomial logistic regression was performed. Results: Sixty-five patients met the inclusion criteria. Four patients (6.2%) had an upgrade to in situ disease (DCIS) and one (1.5%) to invasive carcinoma. Three upgraded high-risk lesions were ipsilateral to the concurrent carcinoma and two were contralateral. In the multivariate model, a high-risk lesion within 5 cm of an ipsilateral malignancy was associated with increased risk of upgrade. The 3.8% upgrade rate for high-risk lesions located greater than 5 cm from ipsilateral malignancy or in the contralateral breast suggests that omission of excisional biopsy may be considered. Excisional biopsy of lesions within 5 cm of ipsilateral malignancy is recommended given the 25% upgrade risk in our series. Full article

(This article belongs to the Special Issue Cancer Causes and Control)

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13 pages, 1344 KiB

Open AccessSystematic Review

Topographic Patterns of Intracranial Meningioma Recurrences—Systematic Review with Clinical Implication

by Sergio Corvino, Roberto Altieri, Giuseppe La Rocca, Amedeo Piazza, Giuseppe Corazzelli, Carmela Palmiero, Giuseppe Mariniello, Francesco Maiuri, Andrea Elefante and Oreste de Divitiis

Cancers 2024, 16(12), 2267; https://doi.org/10.3390/cancers16122267 - 19 Jun 2024

Viewed by 299

Abstract

Background: While several risk factors for recurrences have been defined, the topographic pattern of meningioma recurrences after surgical resection has been scarcely investigated. The possibility of theoretically predicting the site of recurrence not only allows us to better understand the pathogenetic bases of [...] Read more.

Background: While several risk factors for recurrences have been defined, the topographic pattern of meningioma recurrences after surgical resection has been scarcely investigated. The possibility of theoretically predicting the site of recurrence not only allows us to better understand the pathogenetic bases of the disease and consequently to drive the development of new targeted therapies, but also guides the decision-making process for treatment strategies and tailored follow-ups to decrease/prevent recurrence. Methods: The authors performed a comprehensive and detailed systematic literature review of the EMBASE and MEDLINE electronic online databases regarding the topographic pattern of recurrence after surgical treatment for intracranial meningiomas. Demographics and histopathological, neuroradiological and treatment data, pertinent to the topography of recurrences, as well as time to recurrences, were extracted and analyzed. Results: Four studies, including 164 cases of recurrences according to the inclusion criteria, were identified. All studies consider the possibility of recurrence at the previous dural site; three out of four, which are the most recent, consider 1 cm outside the previous dural margin to be the main limit to distinguish recurrences closer to the previous site from those more distant. Recurrences mainly occur within or close to the surgical bed; higher values of proliferation index are associated with recurrences close to the original site rather than within it. Conclusions: Further studies, including genomic characterization of different patterns of recurrence, will better clarify the main features affecting the topography of recurrences. A comparison between topographic classifications of intracranial meningioma recurrences after surgery and after radiation treatment could provide further interesting information. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and the Management of Intracranial Tumors)

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13 pages, 2798 KiB

Open AccessSystematic Review

A 22-G or a 25-G Needle: Which One to Use in the Diagnostics of Solid Pancreatic Lesions? A Systematic Review and Meta-Analysis

by Łukasz Nawacki, Iwona Gorczyca-Głowacka, Paweł Zieliński, Przemysław Znamirowski, Monika Kozłowska-Geller, Agnieszka Ciba-Stemplewska and Magdalena Kołomańska

Cancers 2024, 16(12), 2266; https://doi.org/10.3390/cancers16122266 - 19 Jun 2024

Viewed by 287

Abstract

With the 12th highest incidence and a common late diagnostic at advanced stages, neoadjuvant therapies for pancreatic cancer are important, but they require a confirmed diagnosis. Being a diagnostic standard, the clarification of the clinical relevance of needle gauges is needed, as larger [...] Read more.

With the 12th highest incidence and a common late diagnostic at advanced stages, neoadjuvant therapies for pancreatic cancer are important, but they require a confirmed diagnosis. Being a diagnostic standard, the clarification of the clinical relevance of needle gauges is needed, as larger ones may retrieve more tissue for diagnostics, but may also increase the risk of complications. We performed a meta-analysis to compare the efficiency of the most commonly used 22-G and 25-G needles for EUS guided biopsy in solid pancreatic lesions. The MEDLINE (via PubMed), Embase, Cochrane (CENTRAL), and Scopus databases were searched with “EUS”, “needle”, “FNA”, “pancreas”, “prospective”, “22G”, and “25G” keywords. Mixed effects were assessed in the model, with a mean of 86% and a 95% confidence interval. Fourteen prospective studies that compared the efficiency of 22-G and 25-G biopsy needles in 508 and 524 lesions, respectively, were analyzed, along with 332 specimens biopsied using both needle sizes. The groups did not significantly differ in the outcomes. A low degree of heterogeneity was observed overall, except for specimen adequacy. Moreover, 22-G and 25-G needles have comparable safety and efficacy for focal pancreatic lesion biopsies without a high risk of complications. Full article

(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)

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13 pages, 2599 KiB

Open AccessArticle

Limited Additional Value of a Chest CT in Whole-Body Staging with PET-MRI: A Retrospective Cohort Study

by Tineke van de Weijer, Wilhelmina L. van der Meer, Rik P. M. Moonen, Thiemo J. A. van Nijnatten, Hester A. Gietema, Cristina Mitea, Jochem A. J. van der Pol, Joachim E. Wildberger and Felix M. Mottaghy

Cancers 2024, 16(12), 2265; https://doi.org/10.3390/cancers16122265 - 19 Jun 2024

Viewed by 381

Abstract

Hybrid PET-MRI systems are being used more frequently. One of the drawbacks of PET-MRI imaging is its inferiority in detecting lung nodules, so it is often combined with a computed tomography (CT) of the chest. However, chest CT often detects additional, indeterminate lung [...] Read more.

Hybrid PET-MRI systems are being used more frequently. One of the drawbacks of PET-MRI imaging is its inferiority in detecting lung nodules, so it is often combined with a computed tomography (CT) of the chest. However, chest CT often detects additional, indeterminate lung nodules. The objective of this study was to assess the sensitivity of detecting metastatic versus indeterminate nodules with PET-MRI compared to chest CT. A total of 328 patients were included. All patients had a PET/MRI whole-body scan for (re)staging of cancer combined with an unenhanced chest CT performed at our center between 2014 and 2020. Patients had at least a two-year follow-up. Six percent of the patients had lung metastases at initial staging. The sensitivity and specificity of PET-MRI for detecting lung metastases were 85% and 100%, respectively. The incidence of indeterminate lung nodules on chest CT was 30%. The sensitivity of PET-MRI to detect indeterminate lung nodules was poor (23.0%). The average size of the indeterminate lung nodules detected on PET-MRI was 7 ± 4 mm, and the missed indeterminate nodules on PET-MRI were 4 ± 1 mm (p < 0.001). The detection of metastatic lung nodules is fairly good with PET-MRI, whereas the sensitivity of PET-MRI for detecting indeterminate lung nodules is size-dependent. This may be an advantage, limiting unnecessary follow-up of small, indeterminate lung nodules while adequately detecting metastases. Full article

(This article belongs to the Special Issue PET/CT and Conventional Imaging in Cancers)

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10 pages, 1068 KiB

Open AccessArticle

Breast Cancer Screening Using Inverse Modeling of Surface Temperatures and Steady-State Thermal Imaging

by Nithya Sritharan, Carlos Gutierrez, Isaac Perez-Raya, Jose-Luis Gonzalez-Hernandez, Alyssa Owens, Donnette Dabydeen, Lori Medeiros, Satish Kandlikar and Pradyumna Phatak

Cancers 2024, 16(12), 2264; https://doi.org/10.3390/cancers16122264 - 19 Jun 2024

Viewed by 420

Abstract

Cancer is characterized by increased metabolic activity and vascularity, leading to temperature changes in cancerous tissues compared to normal cells. This study focused on patients with abnormal mammogram findings or a clinical suspicion of breast cancer, exclusively those confirmed by biopsy. Utilizing an [...] Read more.

Cancer is characterized by increased metabolic activity and vascularity, leading to temperature changes in cancerous tissues compared to normal cells. This study focused on patients with abnormal mammogram findings or a clinical suspicion of breast cancer, exclusively those confirmed by biopsy. Utilizing an ultra-high sensitivity thermal camera and prone patient positioning, we measured surface temperatures integrated with an inverse modeling technique based on heat transfer principles to predict malignant breast lesions. Involving 25 breast tumors, our technique accurately predicted all tumors, with maximum errors below 5 mm in size and less than 1 cm in tumor location. Predictive efficacy was unaffected by tumor size, location, or breast density, with no aberrant predictions in the contralateral normal breast. Infrared temperature profiles and inverse modeling using both techniques successfully predicted breast cancer, highlighting its potential in breast cancer screening. Full article

(This article belongs to the Topic AI in Medical Imaging and Image Processing)

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18 pages, 357 KiB

Open AccessReview

The Challenging Approach to Multiple Myeloma: From Disease Diagnosis and Monitoring to Complications Management

by Sonia Morè, Laura Corvatta, Valentina Maria Manieri, Erika Morsia and Massimo Offidani

Cancers 2024, 16(12), 2263; https://doi.org/10.3390/cancers16122263 - 19 Jun 2024

Viewed by 727

Abstract

The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better stratify disease risk, development of more effective therapies and better management of side effects related to them. [...] Read more.

The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better stratify disease risk, development of more effective therapies and better management of side effects related to them. However, handling all these aspects requires an interdisciplinary approach involving multiple knowledge and collaboration of different specialists. The hematologist, faced with a patient with MM, must not only choose a treatment according to patient and disease characteristics but must also know when therapy needs to be started and how to monitor it during and after treatment. Moreover, he must deal not only with organ issues related to MM such as bone disease, renal failure or neurological disease but also with adverse events, often very serious, related to novel therapies, particularly new generation immunotherapies such as CAR T cell therapy and bispecific antibodies. In this review, we provide an overview on the newer MM diagnostic and monitoring strategies and on the main side effects of MM therapies, focusing on adverse events occurring during treatment with CAR T cells and bispecific antibodies. Full article

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

61 pages, 8029 KiB

Open AccessReview

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

by Radomir M. Slominski, Tae-Kang Kim, Zorica Janjetovic, Anna A. Brożyna, Ewa Podgorska, Katie M. Dixon, Rebecca S. Mason, Robert C. Tuckey, Rahul Sharma, David K. Crossman, Craig Elmets, Chander Raman, Anton M. Jetten, Arup K. Indra and Andrzej T. Slominski

Cancers 2024, 16(12), 2262; https://doi.org/10.3390/cancers16122262 - 18 Jun 2024

Viewed by 930

Abstract

Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and a high mortality rate. This review discusses etiologic and risk factors for melanoma, diagnostic and prognostic tools, including recent advances [...] Read more.

Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and a high mortality rate. This review discusses etiologic and risk factors for melanoma, diagnostic and prognostic tools, including recent advances in molecular biology, omics, and bioinformatics, and provides an overview of its therapy. Since the incidence of melanoma is rising and mortality remains unacceptably high, we discuss its inherent properties, including melanogenesis, that make this disease resilient to treatment and propose to use AI to solve the above complex and multidimensional problems. We provide an overview on vitamin D and its anticancerogenic properties, and report recent advances in this field that can provide solutions for the prevention and/or therapy of melanoma. Experimental papers and clinicopathological studies on the role of vitamin D status and signaling pathways initiated by its active metabolites in melanoma prognosis and therapy are reviewed. We conclude that vitamin D signaling, defined by specific nuclear receptors and selective activation by specific vitamin D hydroxyderivatives, can provide a benefit for new or existing therapeutic approaches. We propose to target vitamin D signaling with the use of computational biology and AI tools to provide a solution to the melanoma problem. Full article

(This article belongs to the Special Issue Latest Development in Melanoma Research)

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10 pages, 1870 KiB

Open AccessArticle

Identification of Alcohol Use Prior to Major Cancer Surgery: Timeline Follow Back Interview Compared to Four Other Markers

by Johanna Nicklasson, Moa Sjödell, Hanne Tønnesen, Susanne Vahr Lauridsen and Mette Rasmussen

Cancers 2024, 16(12), 2261; https://doi.org/10.3390/cancers16122261 - 18 Jun 2024

Viewed by 392

Abstract

Background: The postoperative complication rate is 30–64% among patients undergoing muscle-invasive and recurrent high-risk non-muscle-invasive bladder cancer surgery. Preoperative risky alcohol use increases the risk. The aim was to evaluate the accuracy of markers for identifying preoperative risky alcohol. Methods: Diagnostic test sub-study [...] Read more.

Background: The postoperative complication rate is 30–64% among patients undergoing muscle-invasive and recurrent high-risk non-muscle-invasive bladder cancer surgery. Preoperative risky alcohol use increases the risk. The aim was to evaluate the accuracy of markers for identifying preoperative risky alcohol. Methods: Diagnostic test sub-study of a randomized controlled trial (STOP-OP trial), based on a cohort of 94 patients scheduled for major bladder cancer surgery. Identification of risky alcohol use using Timeline Follow Back interviews (TLFB) were compared to the AUDIT–C questionnaire and three biomarkers: carbohydrate-deficient transferrin in plasma (P–CDT), phosphatidyl-ethanol in blood (B–PEth), and ethyl glucuronide in urine (U–EtG). Results: The correlation between TLFB and AUDIT–C was strong (ρ = 0.75), while it was moderate between TLFB and the biomarkers (ρ = 0.55–0.65). Overall, sensitivity ranged from 56 to 82% and specificity from 38 to 100%. B–PEth showed the lowest sensitivity at 56%, but the highest specificity of 100%. All tests had high positive predictive values (79–100%), but low negative predictive values (42–55%). Conclusions: Despite high positive predictive values, negative predictive values were weak compared to TLFB. For now, TLFB interviews seem preferable for preoperative identification of risky alcohol use. Full article

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

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13 pages, 2179 KiB

Open AccessArticle

Transcript-Level Biomarkers of Early Lung Carcinogenesis in Bronchial Lesions

by Mikhail A. Pyatnitskiy and Ekaterina V. Poverennaya

Cancers 2024, 16(12), 2260; https://doi.org/10.3390/cancers16122260 - 18 Jun 2024

Viewed by 235

Abstract

Premalignant lesions within the bronchial epithelium signify the initial phases of squamous cell lung carcinoma, posing challenges for detection via conventional methods. Instead of focusing solely on gene expression, in this study, we explore transcriptomic alterations linked to lesion progression, with an emphasis [...] Read more.

Premalignant lesions within the bronchial epithelium signify the initial phases of squamous cell lung carcinoma, posing challenges for detection via conventional methods. Instead of focusing solely on gene expression, in this study, we explore transcriptomic alterations linked to lesion progression, with an emphasis on protein-coding transcripts. We reanalyzed a publicly available RNA-Seq dataset on airway epithelial cells from 82 smokers with and without premalignant lesions. Transcript and gene abundance were quantified using kallisto, while differential expression and transcript usage analysis was performed utilizing sleuth and RATs packages. Functional characterization involved overrepresentation analysis via clusterProfiler, weighted coexpression network analysis (WGCNA), and network analysis via Enrichr-KG. We detected 5906 differentially expressed transcripts and 4626 genes, exhibiting significant enrichment within pathways associated with oxidative phosphorylation and mitochondrial function. Remarkably, transcript-level WGCNA revealed a single module correlated with dysplasia status, notably enriched in cilium-related biological processes. Notable hub transcripts included RABL2B (ENST00000395590), DNAH1 (ENST00000420323), EFHC1 (ENST00000635996), and VWA3A (ENST00000563389) along with transcription factors such as FOXJ1 and ZNF474 as potential regulators. Our findings underscore the value of transcript-level analysis in uncovering novel insights into premalignant bronchial lesion biology, including identification of potential biomarkers associated with early lung carcinogenesis. Full article

(This article belongs to the Special Issue Feature Papers in Section "Cancer Biomarkers" in 2023–2024)

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18 pages, 1834 KiB

Open AccessReview

Resistance to Targeted Inhibitors of the PI3K/AKT/mTOR Pathway in Advanced Oestrogen-Receptor-Positive Breast Cancer

by Iseult M. Browne and Alicia F. C. Okines

Cancers 2024, 16(12), 2259; https://doi.org/10.3390/cancers16122259 - 18 Jun 2024

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Abstract

The PI3K/AKT/mTOR signalling pathway is one of the most frequently activated pathways in breast cancer and also plays a central role in the regulation of several physiologic functions. There are major efforts ongoing to exploit precision medicine by developing inhibitors that target the [...] Read more.

The PI3K/AKT/mTOR signalling pathway is one of the most frequently activated pathways in breast cancer and also plays a central role in the regulation of several physiologic functions. There are major efforts ongoing to exploit precision medicine by developing inhibitors that target the three kinases (PI3K, AKT, and mTOR). Although multiple compounds have been developed, at present, there are just three inhibitors approved to target this pathway in patients with advanced ER-positive, HER2-negative breast cancer: everolimus (mTOR inhibitor), alpelisib (PIK3CA inhibitor), and capivasertib (AKT inhibitor). Like most targeted cancer drugs, resistance poses a major problem in the clinical setting and is a factor that has frequently limited the overall efficacy of these agents. Drug resistance can be categorised into intrinsic or acquired resistance depending on the timeframe it has developed within. Whereas intrinsic resistance exists prior to a specific treatment, acquired resistance is induced by a therapy. The majority of patients with ER-positive, HER2-negative advanced breast cancer will likely be offered an inhibitor of the PI3K/AKT/mTOR pathway at some point in their cancer journey, with the options available depending on the approval criteria in place and the cancer’s mutation status. Within this large cohort of patients, it is likely that most will develop resistance at some point, which makes this an area of interest and an unmet need at present. Herein, we review the common mechanisms of resistance to agents that target the PI3K/AKT/mTOR signalling pathway, elaborate on current management approaches, and discuss ongoing clinical trials attempting to mitigate this significant issue. We highlight the need for additional studies into AKT1 inhibitor resistance in particular. Full article

(This article belongs to the Special Issue Molecular Insights into Drug Resistance in Cancer)

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