Cancers

17 pages, 3531 KiB

Open AccessArticle

Role of Machine Learning (ML)-Based Classification Using Conventional ¹⁸F-FDG PET Parameters in Predicting Postsurgical Features of Endometrial Cancer Aggressiveness

by Carolina Bezzi, Alice Bergamini, Gregory Mathoux, Samuele Ghezzo, Lavinia Monaco, Giorgio Candotti, Federico Fallanca, Ana Maria Samanes Gajate, Emanuela Rabaiotti, Raffaella Cioffi, Luca Bocciolone, Luigi Gianolli, GianLuca Taccagni, Massimo Candiani, Giorgia Mangili, Paola Mapelli and Maria Picchio

Cancers 2023, 15(1), 325; https://doi.org/10.3390/cancers15010325 - 3 Jan 2023

Cited by 3 | Viewed by 2902

Abstract

Purpose: to investigate the preoperative role of ML-based classification using conventional ¹⁸F-FDG PET parameters and clinical data in predicting features of EC aggressiveness. Methods: retrospective study, including 123 EC patients who underwent ¹⁸F-FDG PET (2009–2021) for preoperative staging. Maximum standardized uptake [...] Read more.

Purpose: to investigate the preoperative role of ML-based classification using conventional ¹⁸F-FDG PET parameters and clinical data in predicting features of EC aggressiveness. Methods: retrospective study, including 123 EC patients who underwent ¹⁸F-FDG PET (2009–2021) for preoperative staging. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were computed on the primary tumour. Age and BMI were collected. Histotype, myometrial invasion (MI), risk group, lymph-nodal involvement (LN), and p53 expression were retrieved from histology. The population was split into a train and a validation set (80–20%). The train set was used to select relevant parameters (Mann-Whitney U test; ROC analysis) and implement ML models, while the validation set was used to test prediction abilities. Results: on the validation set, the best accuracies obtained with individual parameters and ML were: 61% (TLG) and 87% (ML) for MI; 71% (SUVmax) and 79% (ML) for risk groups; 72% (TLG) and 83% (ML) for LN; 45% (SUVmax; SUVmean) and 73% (ML) for p53 expression. Conclusions: ML-based classification using conventional ¹⁸F-FDG PET parameters and clinical data demonstrated ability to characterize the investigated features of EC aggressiveness, providing a non-invasive way to support preoperative stratification of EC patients. Full article

(This article belongs to the Special Issue The Role of PET Imaging in Oncology: New Advancements in Clinical and Research Setting)

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25 pages, 3043 KiB

Open AccessEditor’s ChoiceReview

Physical Exercise and the Hallmarks of Breast Cancer: A Narrative Review

by Celia García-Chico, Susana López-Ortiz, Saúl Peñín-Grandes, José Pinto-Fraga, Pedro L. Valenzuela, Enzo Emanuele, Claudia Ceci, Grazia Graziani, Carmen Fiuza-Luces, Simone Lista, Alejandro Lucia and Alejandro Santos-Lozano

Cancers 2023, 15(1), 324; https://doi.org/10.3390/cancers15010324 - 3 Jan 2023

Cited by 18 | Viewed by 9482

Abstract

Growing evidence suggests that, among the different molecular/cellular pathophysiological mechanisms associated with cancer, there are 14 hallmarks that play a major role, including: (i) sustaining proliferative signaling, (ii) evading growth suppressors, (iii) activating invasion and metastasis, (iv) enabling replicative immortality, (v) inducing angiogenesis, [...] Read more.

Growing evidence suggests that, among the different molecular/cellular pathophysiological mechanisms associated with cancer, there are 14 hallmarks that play a major role, including: (i) sustaining proliferative signaling, (ii) evading growth suppressors, (iii) activating invasion and metastasis, (iv) enabling replicative immortality, (v) inducing angiogenesis, (vi) resisting cell death, (vii) reprogramming energy metabolism, (viii) evading immune destruction, (ix) genome instability and mutations, (x) tumor-promoting inflammation, (xi) unlocking phenotypic plasticity, (xii) nonmutational epigenetic reprogramming, (xiii) polymorphic microbiomes, and (xiv) senescent cells. These hallmarks are also associated with the development of breast cancer, which represents the most prevalent tumor type in the world. The present narrative review aims to describe, for the first time, the effects of physical activity/exercise on these hallmarks. In summary, an active lifestyle, and particularly regular physical exercise, provides beneficial effects on all major hallmarks associated with breast cancer, and might therefore help to counteract the progression of the disease or its associated burden. Full article

(This article belongs to the Special Issue Breast Cancer: Tailored Rehabilitation Strategies to Address the Challenge of Survivorship Issues)

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12 pages, 881 KiB

Open AccessArticle

Oligometastatic Prostate Cancer Treated with Metastasis-Directed Therapy Guided by Positron Emission Tomography: Does the Tracer Matter?

by Francesco Lanfranchi, Liliana Belgioia, Michela Marcenaro, Elisa Zanardi, Giorgia Timon, Mattia Riondato, Veronica Giasotto, Jeries Paolo Zawaideh, Laura Tomasello, Guglielmo Mantica, Nataniele Piol, Marco Borghesi, Paolo Traverso, Camilla Satragno, Daniele Panarello, Claudio Scaffidi, Andrea Romagnoli, Sara Elena Rebuzzi, Angela Coco, Bruno Spina, Silvia Morbelli, Gianmario Sambuceti, Carlo Terrone, Salvina Barra, Giuseppe Fornarini and Matteo Bauckneht Show full author list Hide full author list

Cancers 2023, 15(1), 323; https://doi.org/10.3390/cancers15010323 - 3 Jan 2023

Cited by 3 | Viewed by 3814

Abstract

The superior diagnostic accuracy of [68Ga]Ga-prostate-specific membrane antigen-11 (PSMA) ([68Ga]Ga-PSMA-11) compared to [18F]F-Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT) in Prostate Cancer (PCa) is established. However, it is currently unclear if the added diagnostic accuracy actually translates into improved clinical outcomes in oligometastatic PCa [...] Read more.

The superior diagnostic accuracy of [68Ga]Ga-prostate-specific membrane antigen-11 (PSMA) ([68Ga]Ga-PSMA-11) compared to [18F]F-Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT) in Prostate Cancer (PCa) is established. However, it is currently unclear if the added diagnostic accuracy actually translates into improved clinical outcomes in oligometastatic PCa patients treated with [68Ga]Ga-PSMA-11 PET-guided metastasis-directed therapy (MDT). The present study aimed to assess the impact of these two imaging techniques on Progression-Free Survival (PFS) in a real-world sample of oligometastatic PCa patients submitted to PET-guided MDT. Thirty-seven oligometastatic PCa patients treated with PET-guided MDT were retrospectively enrolled. MDT was guided by [18F]F-Fluorocholine PET/CT in eleven patients and by [68Ga]Ga-PSMA-11 PET/CT in twenty-six. Progression was defined as biochemical recurrence (BR), radiological progression at subsequent PET/CT imaging, clinical progression, androgen deprivation therapy initiation, or death. Clinical and imaging parameters were assessed as predictors of PFS. [18F]F-Fluorocholine PET-guided MDT was associated with significantly lower PFS compared to the [68Ga]Ga-PSMA-11 group (median PFS, mPFS 15.47 months, 95% CI: 4.13–38.00 vs. 40.93 months, 95% CI: 40.93–40.93, respectively; p < 0.05). Coherently, the radiotracer used for PET-guided MDT resulted in predictive PFS at the univariate analysis, as well as the castration-resistant status at the time of MDT and the PSA nadir after MDT. However, in the multivariate analysis, castration resistance and PSA nadir after MDT remained the sole independent predictors of PFS. In conclusion, in the present proof-of-concept study, [68Ga]Ga-PSMA-11 provided higher PFS rates than [18F]F-Fluorocholine imaging in oligometastatic PCa patients receiving PET-guided MDT. Although preliminary, this finding suggests that enlarging the “tip of the iceberg”, by detecting a major proportion of the submerged disease thanks to next-generation imaging may favourably impact the oncological outcome of oligometastatic PCa treated with MDT. Full article

(This article belongs to the Special Issue PET/CT in Prostate Cancer)

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12 pages, 748 KiB

Open AccessArticle

Discovering the Clinical and Prognostic Role of Pan-Immune-Inflammation Values on Oral Cavity Squamous Cell Carcinoma

by Chia-Chi Yeh, Huang-Kai Kao, Yenlin Huang, Tsung-You Tsai, Chi-Kuang Young, Shao-Yu Hung, Chuieng-Yi Lu and Kai-Ping Chang

Cancers 2023, 15(1), 322; https://doi.org/10.3390/cancers15010322 - 3 Jan 2023

Cited by 17 | Viewed by 2725

Abstract

A newly introduced pan-immune-inflammation value (PIV) was not evaluated for its role in oral cavity squamous cell carcinoma (OSCC). In this study, the PIV was calculated with the following equation (neutrophil count × platelet count × monocyte count)/lymphocyte count from the results of [...] Read more.

A newly introduced pan-immune-inflammation value (PIV) was not evaluated for its role in oral cavity squamous cell carcinoma (OSCC). In this study, the PIV was calculated with the following equation (neutrophil count × platelet count × monocyte count)/lymphocyte count from the results of the automated hematology analyzers in 853 OSCC patients from 2005 to 2017. The optimal cutoff for the preoperative PIV was 268, as determined by a receiver operating characteristic curve. Significant differences were observed for alcohol consumption, smoking, pT status, pN status, overall pathological status, extranodal extension, cell differentiation, depth of invasion, and perineural invasion between higher and lower PIV patients (all p values < 0.05). Kaplan-Meier and univariate regression analyses indicated that higher PIV was associated with worse overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival (all p values < 0.001). Multivariate analyses adjusted by various factors further demonstrated that PIV was an independent prognostic factor for overall and distant metastasis-free survival (p = 0.027, HR: 1.281 and p = 0.031, HR: 1.274, respectively). In conclusion, a higher PIV level was associated with poor clinicopathological factors in OSCC patients and could be used to predict poor posttreatment outcomes, especially for overall and distant metastasis-free survival. Full article

(This article belongs to the Special Issue Evolution of Treatment and Predictive Factors in SCCHN)

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28 pages, 1054 KiB

Open AccessEditor’s ChoiceReview

Immunotherapy for Triple-Negative Breast Cancer: Combination Strategies to Improve Outcome

by Liying Li, Fan Zhang, Zhenyu Liu and Zhimin Fan

Cancers 2023, 15(1), 321; https://doi.org/10.3390/cancers15010321 - 3 Jan 2023

Cited by 40 | Viewed by 8004

Abstract

Due to the absence of hormone receptor (both estrogen receptors and progesterone receptors) along with human epidermal growth factor receptor 2 (HER-2) amplification, the treatment of triple-negative breast cancer (TNBC) cannot benefit from endocrine or anti-HER-2 therapy. For a long time, [...] Read more.

Due to the absence of hormone receptor (both estrogen receptors and progesterone receptors) along with human epidermal growth factor receptor 2 (HER-2) amplification, the treatment of triple-negative breast cancer (TNBC) cannot benefit from endocrine or anti-HER-2 therapy. For a long time, chemotherapy was the only systemic treatment for TNBC. Due to the lack of effective treatment options, the prognosis for TNBC is extremely poor. The successful application of immune checkpoint inhibitors (ICIs) launched the era of immunotherapy in TNBC. However, the current findings show modest efficacy of programmed cell death- (ligand) 1 (PD-(L)1) inhibitors monotherapy and only a small proportion of patients can benefit from this approach. Based on the basic principles of immunotherapy and the characteristics of the tumor immune microenvironment (TIME) in TNBC, immune combination therapy is expected to further enhance the efficacy and expand the beneficiary population of patients. Given the diversity of drugs that can be combined, it is important to select effective biomarkers to identify the target population. Moreover, the side effects associated with the combination of multiple drugs should also be considered. Full article

(This article belongs to the Special Issue Immunotherapy of Triple-Negative Breast Cancer)

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13 pages, 1587 KiB

Open AccessArticle

Novel Adaption of the SARC-F Score to Classify Pediatric Hemato-Oncology Patients with Functional Sarcopenia

by Emma J. Verwaaijen, Patrick van der Torre, Josef Vormoor, Rob Pieters, Marta Fiocco, Annelies Hartman and Marry M. van den Heuvel-Eibrink

Cancers 2023, 15(1), 320; https://doi.org/10.3390/cancers15010320 - 3 Jan 2023

Cited by 2 | Viewed by 2316

Abstract

Sarcopenia in pediatric hemato-oncology patients is undesirable because of the consequences it may have for treatment continuation and outcome, physical abilities and participation in daily life. An easy-to-use screening tool for sarcopenia will facilitate the identification of children at risk who need interventions [...] Read more.

Sarcopenia in pediatric hemato-oncology patients is undesirable because of the consequences it may have for treatment continuation and outcome, physical abilities and participation in daily life. An easy-to-use screening tool for sarcopenia will facilitate the identification of children at risk who need interventions to prevent serious physical deterioration. In the elderly, the use of the SARC-F score as a case-finding tool for sarcopenia is recommended. The aim of this cross-sectional study was to investigate the accuracy of the pediatric SARC-F (PED-SARC-F) for identifying sarcopenia in pediatric hemato-oncology patients, including the determination of a cut-off point for clinical use. Patients 3–20 years of age, under active treatment or within 12 months after treatment cessation were eligible. Patients had a physiotherapy assessment including a PED-SARC-F (0–10) and measurements of muscle strength (handheld dynamometry), physical performance (various tests) and/or muscle mass (bio-impedance analysis), as part of the standard of care. Spearman’s correlation coefficient (r_s) between the PED-SARC-F and physiotherapy outcomes were calculated. Structural sarcopenia was defined as low appendicular skeletal muscle mass (ASMM) in combination with low muscle strength and/or low physical performance. Functional sarcopenia indicated low muscle strength combined with low physical performance. Multiple logistic regression models were estimated to study the associations between the PED-SARC-F and structural/functional sarcopenia. To evaluate which cut-off point provides the most accurate classification, the area under the receiver operating characteristic curve (AUCs), sensitivity and specificity per point were calculated. In total, 215 assessments were included, 62% were performed in boys and the median age was 12.9 years (interquartile range: 8.5–15.8). The PED-SARC-F scores correlated moderately with the measurements of muscle strength (r_s = −0.37 to −0.47, p < 0.001) and physical performance (r_s = −0.45 to −0.66, p < 0.001), and weakly with ASMM (r_s = −0.27, p < 0.001). The PED-SARC-F had an AUC of 0.90 (95% confidence interval (CI) = 0.84–0.95) for functional sarcopenia and 0.79 (95% CI = 0.68–0.90) for structural sarcopenia. A cut-off point of ≥5 had the highest specificity of 96% and a sensitivity of 74%. In conclusion, we adapted the SARC-F to a pediatric version, confirmed its excellent diagnostic accuracy for identifying functional sarcopenia and defined a clinically useful cut-off point in pediatric hemato-oncology patients. Full article

(This article belongs to the Section Pediatric Oncology)

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17 pages, 3254 KiB

Open AccessArticle

Pancreatic Cancer Cells Undergo Immunogenic Cell Death upon Exposure to Gas Plasma-Oxidized Ringers Lactate

by Lea Miebach, Hager Mohamed, Kristian Wende, Vandana Miller and Sander Bekeschus

Cancers 2023, 15(1), 319; https://doi.org/10.3390/cancers15010319 - 3 Jan 2023

Cited by 7 | Viewed by 2841

Abstract

Survival rates among patients with pancreatic cancer, the most lethal gastrointestinal cancer, have not improved compared to other malignancies. Early tumor dissemination and a supportive, cancer-promoting tumor microenvironment (TME) limit therapeutic options and consequently impede tumor remission, outlining an acute need for effective [...] Read more.

Survival rates among patients with pancreatic cancer, the most lethal gastrointestinal cancer, have not improved compared to other malignancies. Early tumor dissemination and a supportive, cancer-promoting tumor microenvironment (TME) limit therapeutic options and consequently impede tumor remission, outlining an acute need for effective treatments. Gas plasma-oxidized liquid treatment showed promising preclinical results in other gastrointestinal and gynecological tumors by targeting the tumor redox state. Here, carrier solutions are enriched with reactive oxygen (ROS) and nitrogen (RNS) species that can cause oxidative distress in tumor cells, leading to a broad range of anti-tumor effects. Unfortunately, clinical relevance is often limited, as many studies have forgone the use of medical-grade solutions. This study investigated the efficacy of gas plasma-oxidized Ringer’s lactate (oxRilac), a physiological solution often used in clinical practice, on two pancreatic cancer cell lines to induce tumor toxicity and provoke immunogenicity. Tumor toxicity of the oxRilac solutions was further confirmed in three-dimensional tumor spheroids monitored over 72 h and in ovo using stereomicroscope imaging of excised GFP-expressing tumors. We demonstrated that cell death signaling was induced in a dose-dependent fashion in both cell lines and was paralleled by the increased surface expression of key markers of immunogenic cell death (ICD). Nuclear magnetic resonance (NMR) spectroscopy analysis suggested putative reaction pathways that may cause the non-ROS related effects. In summary, our study suggests gas plasma-deposited ROS in clinically relevant liquids as an additive option for treating pancreatic cancers via immune-stimulating and cytotoxic effects. Full article

(This article belongs to the Special Issue Plasma Oncology)

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25 pages, 1551 KiB

Open AccessReview

Modulating Effects of Cancer-Derived Exosomal miRNAs and Exosomal Processing by Natural Products

by Ya-Ting Chuang, Jen-Yang Tang, Jun-Ping Shiau, Ching-Yu Yen, Fang-Rong Chang, Kun-Han Yang, Ming-Feng Hou, Ammad Ahmad Farooqi and Hsueh-Wei Chang

Cancers 2023, 15(1), 318; https://doi.org/10.3390/cancers15010318 - 3 Jan 2023

Cited by 6 | Viewed by 2819

Abstract

Cancer-derived exosomes exhibit sophisticated functions, such as proliferation, apoptosis, migration, resistance, and tumor microenvironment changes. Several clinical drugs modulate these exosome functions, but the impacts of natural products are not well understood. Exosome functions are regulated by exosome processing, such as secretion and [...] Read more.

Cancer-derived exosomes exhibit sophisticated functions, such as proliferation, apoptosis, migration, resistance, and tumor microenvironment changes. Several clinical drugs modulate these exosome functions, but the impacts of natural products are not well understood. Exosome functions are regulated by exosome processing, such as secretion and assembly. The modulation of these exosome-processing genes can exert the anticancer and precancer effects of cancer-derived exosomes. This review focuses on the cancer-derived exosomal miRNAs that regulate exosome processing, acting on the natural-product-modulating cell functions of cancer cells. However, the role of exosomal processing has been overlooked in several studies of exosomal miRNAs and natural products. In this study, utilizing the bioinformatics database (miRDB), the exosome-processing genes of natural-product-modulated exosomal miRNAs were predicted. Consequently, several natural drugs that modulate exosome processing and exosomal miRNAs and regulate cancer cell functions are described here. This review sheds light on and improves our understanding of the modulating effects of exosomal miRNAs and their potential exosomal processing targets on anticancer treatments based on the use of natural products. Full article

(This article belongs to the Special Issue Non-coding RNAs and Extracellular Vesicles in Cancer Crosstalk: Diagnostic and Therapeutic Implications)

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13 pages, 290 KiB

Open AccessArticle

Epidemiology and Characteristics of Gastric Carcinoma in Childhood—An Analysis of Data from Population-Based and Clinical Cancer Registries

by Michael Abele, Lisa Grabner, Tabea Blessing, Andreas Block, Abbas Agaimy, Christian Kratz, Thorsten Simon, Gabriele Calaminus, Sabine Heine, Selim Corbacioglu, Holger Christiansen, Dominik T. Schneider and Ines B. Brecht

Cancers 2023, 15(1), 317; https://doi.org/10.3390/cancers15010317 - 3 Jan 2023

Cited by 2 | Viewed by 2226

Abstract

(1) Background: Gastric carcinoma is an exceptionally rare tumor in childhood. Little is known about the etiology, epidemiology, and clinical features of pediatric gastric carcinomas. This analysis aimed to fill this gap by increasing knowledge about the occurrence of gastric carcinoma in childhood. [...] Read more.

(1) Background: Gastric carcinoma is an exceptionally rare tumor in childhood. Little is known about the etiology, epidemiology, and clinical features of pediatric gastric carcinomas. This analysis aimed to fill this gap by increasing knowledge about the occurrence of gastric carcinoma in childhood. (2) Material and methods: Data from gastric carcinoma cases diagnosed between 2000 and 2017/2018 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) and the German Center for Cancer Registry Data. Data from patients <20 years of age were analyzed for patient- and tumor-related characteristics. In addition, clinical data from patients with gastric carcinoma registered in the German Registry for Rare Pediatric Tumors (STEP) were analyzed for diagnostics, therapy, and outcome. (3) Results: Ninety-one cases of gastric carcinoma, mainly in adolescents, were identified in the epidemiologic cancer registries. Among patients with recorded staging data, advanced tumor stages were common (66.7%). Within the follow-up period covered, 63.7% of patients with clinical follow-up data died. Eight pediatric patients with gastric carcinoma were enrolled in the STEP registry, among whom two were patients with hereditary CDH1 mutations and another was a patient with Peutz–Jeghers syndrome. Three patients were found to have distinctly decreased immunoglobulin concentrations. All four patients in whom complete resection was achieved remained in remission. Three of the other four patients died despite multimodal therapy. (4) Conclusions: A combination of Helicobacter pylori infection and tumor predisposition and/or immunodeficiency appears to promote the development of gastric carcinoma in childhood. While patients with localized disease stages have a good chance of achieving durable remission through complete resection, patients with stage IV carcinomas face a dismal prognosis, highlighting the need to develop new strategies such as mutation-guided treatments. Full article

(This article belongs to the Section Pediatric Oncology)

19 pages, 2329 KiB

Open AccessArticle

Adherence to the CDK 4/6 Inhibitor Palbociclib and Omission of Dose Management Supported by Pharmacometric Modelling as Part of the OpTAT Study

by Carole Bandiera, Isabella Locatelli, Perrine Courlet, Evelina Cardoso, Khalil Zaman, Athina Stravodimou, Ana Dolcan, Apostolos Sarivalasis, Jean-Philippe Zurcher, Veronica Aedo-Lopez, Jennifer Dotta-Celio, Solange Peters, Monia Guidi, Anna Dorothea Wagner, Chantal Csajka and Marie P. Schneider

Cancers 2023, 15(1), 316; https://doi.org/10.3390/cancers15010316 - 3 Jan 2023

Cited by 5 | Viewed by 2811

Abstract

The cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib is administered orally and cyclically, causing medication adherence challenges. We evaluated components of adherence to palbociclib, its relationship with pharmacokinetics (PK), and drug-induced neutropenia. Patients with metastatic breast cancer (MBC) receiving palbociclib, delivered in electronic monitors [...] Read more.

The cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib is administered orally and cyclically, causing medication adherence challenges. We evaluated components of adherence to palbociclib, its relationship with pharmacokinetics (PK), and drug-induced neutropenia. Patients with metastatic breast cancer (MBC) receiving palbociclib, delivered in electronic monitors (EM), were randomized 1:1 to an intervention and a control group. The intervention was a 12-month interprofessional medication adherence program (IMAP) along with monthly motivational interviews by a pharmacist. Implementation adherence was compared between groups using generalized estimating equation models, in which covariates were included. Model-based palbociclib PK and neutrophil profiles were simulated under real-life implementation scenarios: (1) optimal, (2) 2 doses omitted and caught up at cycle end. At 6 months, implementation was slightly higher and more stable in the intervention (n = 19) than in the control (n = 19) group, 99.2% and 97.3% (Δ1.95%, 95% CI 1.1–2.9%), respectively. The impact of the intervention was larger in patients diagnosed with MBC for >2 years (Δ3.6%, 95% CI 2.1–5.4%), patients who received >4 cycles before inclusion (Δ3.1%, 95% CI 1.7–4.8%) and patients >65 (Δ2.3%, 95% CI 0.8–3.6%). Simulations showed that 25% of patients had neutropenia grade ≥3 during the next cycle in scenario 1 versus 30% in scenario 2. Education and monitoring of patient CDK4/6i cycle management and adherence along with therapeutic drug monitoring can help clinicians improve prescription and decrease toxicity. Full article

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9 pages, 268 KiB

Open AccessReview

Predictors of Symptomatic Venous Thromboembolism in Patients with Soft Tissue Sarcoma in the Lower Extremity

by Pramod N. Kamalapathy, Adam Kline, Hannah Hollow, Kevin Raskin, Joseph H. Schwab and Santiago Lozano-Calderón

Cancers 2023, 15(1), 315; https://doi.org/10.3390/cancers15010315 - 3 Jan 2023

Cited by 1 | Viewed by 1986

Abstract

Orthopedic surgery and soft-tissue sarcoma (STS) both independently increase the risk of developing symptomatic venous thromboembolic events (SVTE), but there are no established risk factors or guidelines for how to prophylactically treat patients with STS undergoing surgery. The objectives of this study were [...] Read more.

Orthopedic surgery and soft-tissue sarcoma (STS) both independently increase the risk of developing symptomatic venous thromboembolic events (SVTE), but there are no established risk factors or guidelines for how to prophylactically treat patients with STS undergoing surgery. The objectives of this study were to (1) identify the prevalence of SVTE in patients undergoing STS surgery, (2) identify risk factors for SVTE, and (3) determine the risk of wound complications associated with VTE prophylaxis. This retrospective study was conducted in a tertiary level, academic hospital. A total of 642 patients were treated for soft-tissue sarcoma in the lower extremity with follow up for at least 90 days for the development of SVTE such as deep venous thrombosis and pulmonary embolism. Multivariate logistic regression was used to identify predictors for these events by controlling for patient characteristics, surgical characteristics, and treatment variables, with significance held at p < 0.05. Twenty eight patients (4.36%) were diagnosed with SVTE. Multivariate analysis found six significant predictors ordered based on standardized coefficients: pre-operative (PTT) partial thromboplastin time (p < 0.001), post-operative PTT (p = 0.010), post-op chemotherapy (p = 0.013), metastasis at diagnosis (p = 0.025), additional surgery for metastasis or local recurrence (p = 0.004), and tumor size larger than 10 cm (p < 0.001). The risk of wound complications (p = 0.04) and infection (p = 0.017) increased significantly in patients who received chemical prophylaxis. Our study identifies risk factors for patients at increased risk of developing VTE. Further prospective research is necessary to identify which protocols would be beneficial in preventing SVTE in high-risk patients with a low profile of wound complications. Full article

(This article belongs to the Special Issue Advances in Soft Tissue and Bone Sarcoma)

16 pages, 2476 KiB

Open AccessArticle

An Explainable AI-Enabled Framework for Interpreting Pulmonary Diseases from Chest Radiographs

by Zubaira Naz, Muhammad Usman Ghani Khan, Tanzila Saba, Amjad Rehman, Haitham Nobanee and Saeed Ali Bahaj

Cancers 2023, 15(1), 314; https://doi.org/10.3390/cancers15010314 - 3 Jan 2023

Cited by 20 | Viewed by 4517

Abstract

Explainable Artificial Intelligence is a key component of artificially intelligent systems that aim to explain the classification results. The classification results explanation is essential for automatic disease diagnosis in healthcare. The human respiration system is badly affected by different chest pulmonary diseases. Automatic [...] Read more.

Explainable Artificial Intelligence is a key component of artificially intelligent systems that aim to explain the classification results. The classification results explanation is essential for automatic disease diagnosis in healthcare. The human respiration system is badly affected by different chest pulmonary diseases. Automatic classification and explanation can be used to detect these lung diseases. In this paper, we introduced a CNN-based transfer learning-based approach for automatically explaining pulmonary diseases, i.e., edema, tuberculosis, nodules, and pneumonia from chest radiographs. Among these pulmonary diseases, pneumonia, which COVID-19 causes, is deadly; therefore, radiographs of COVID-19 are used for the explanation task. We used the ResNet50 neural network and trained the network on extensive training with the COVID-CT dataset and the COVIDNet dataset. The interpretable model LIME is used for the explanation of classification results. Lime highlights the input image’s important features for generating the classification result. We evaluated the explanation using radiologists’ highlighted images and identified that our model highlights and explains the same regions. We achieved improved classification results with our fine-tuned model with an accuracy of 93% and 97%, respectively. The analysis of our results indicates that this research not only improves the classification results but also provides an explanation of pulmonary diseases with advanced deep-learning methods. This research would assist radiologists with automatic disease detection and explanations, which are used to make clinical decisions and assist in diagnosing and treating pulmonary diseases in the early stage. Full article

(This article belongs to the Special Issue Recent Advances in Deep Learning and Medical Imaging for Cancer Treatment)

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16 pages, 507 KiB

Open AccessReview

Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors in the Treatment of Advanced Renal Cancer

by Florent Puisset, Mourad Mseddi, Loïc Mourey, Damien Pouessel, Benoit Blanchet, Etienne Chatelut and Christine Chevreau

Cancers 2023, 15(1), 313; https://doi.org/10.3390/cancers15010313 - 3 Jan 2023

Cited by 6 | Viewed by 2865

Abstract

Seven tyrosine kinase inhibitor compounds with anti-angiogenic properties remain key drugs to treat advanced renal cell carcinoma. There is a strong rationale to develop therapeutic drug monitoring for these drugs. General considerations of such monitoring of the several groups of anticancer drugs are [...] Read more.

Seven tyrosine kinase inhibitor compounds with anti-angiogenic properties remain key drugs to treat advanced renal cell carcinoma. There is a strong rationale to develop therapeutic drug monitoring for these drugs. General considerations of such monitoring of the several groups of anticancer drugs are given, with a focus on oral therapy. Pharmacokinetics and the factors of inter- and intraindividual variabilities of these tyrosine kinase inhibitors are described together with an exhaustive presentation of their pharmacokinetic/pharmacodynamic relationships. The latter was observed in studies where every patient was treated with the same dose, and the results of several prospective studies based on dose individualization support the practice of increasing individual dosage in case of low observed plasma drug concentrations. Finally, the benefits and limits of therapeutic drug monitoring as a routine practice are discussed. Full article

(This article belongs to the Special Issue High Unmet Medical Needs in the Treatment of Renal Cell Carcinoma)

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31 pages, 1197 KiB

Open AccessReview

Neprilysin Inhibition in the Prevention of Anthracycline-Induced Cardiotoxicity

by Aleksandra M. Sobiborowicz-Sadowska, Katarzyna Kamińska and Agnieszka Cudnoch-Jędrzejewska

Cancers 2023, 15(1), 312; https://doi.org/10.3390/cancers15010312 - 3 Jan 2023

Cited by 13 | Viewed by 3053

Abstract

Anthracycline-induced cardiotoxicity (AIC) poses a clinical challenge in the management of cancer patients. AIC is characterized by myocardial systolic dysfunction and remodeling, caused by cardiomyocyte DNA damage, oxidative stress, mitochondrial dysfunction, or renin-angiotensin-aldosterone system (RAAS) dysregulation. In the past decade, after positive results [...] Read more.

Anthracycline-induced cardiotoxicity (AIC) poses a clinical challenge in the management of cancer patients. AIC is characterized by myocardial systolic dysfunction and remodeling, caused by cardiomyocyte DNA damage, oxidative stress, mitochondrial dysfunction, or renin-angiotensin-aldosterone system (RAAS) dysregulation. In the past decade, after positive results of a PARADIGM-HF trial, a new class of drugs, namely angiotensin receptor/neprilysin inhibitors (ARNi), was incorporated into the management of patients with heart failure with reduced ejection fraction. As demonstrated in a variety of preclinical studies of cardiovascular diseases, the cardioprotective effects of ARNi administration are associated with decreased oxidative stress levels, the inhibition of myocardial inflammatory response, protection against mitochondrial damage and endothelial dysfunction, and improvement in the RAAS imbalance. However, data on ARNi’s effectiveness in the prevention of AIC remains limited. Several reports of ARNi administration in animal models of AIC have shown promising results, as ARNi prevented ventricular systolic dysfunction and electrocardiographic changes and ameliorated oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and the inflammatory response associated with anthracyclines. There is currently an ongoing PRADAII trial aimed to assess the efficacy of ARNi in patients receiving breast cancer treatment, which is expected to be completed by late 2025. Full article

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14 pages, 303 KiB

Open AccessReview

Laparoscopic Function-Preserving Gastrectomy for Proximal Gastric Cancer or Esophagogastric Junction Cancer: A Narrative Review

by Yosuke Kano, Manabu Ohashi and Souya Nunobe

Cancers 2023, 15(1), 311; https://doi.org/10.3390/cancers15010311 - 3 Jan 2023

Cited by 3 | Viewed by 2371

Abstract

Function-preserving procedures to maintain postoperative quality of life are an important aspect of treatment for early gastric cancer. Laparoscopic proximal gastrectomy (LPG) and laparoscopic distal gastrectomy with a small remnant stomach, namely laparoscopic subtotal gastrectomy (LsTG), are alternative function-preserving procedures for laparoscopic total [...] Read more.

Function-preserving procedures to maintain postoperative quality of life are an important aspect of treatment for early gastric cancer. Laparoscopic proximal gastrectomy (LPG) and laparoscopic distal gastrectomy with a small remnant stomach, namely laparoscopic subtotal gastrectomy (LsTG), are alternative function-preserving procedures for laparoscopic total gastrectomy of early proximal gastric cancer. In LPG, esophagogastrostomy with techniques to prevent reflux and double-tract and jejunal interposition including esophagojejunostomy is usually chosen for reconstruction. The double-flap technique is currently a preferred reconstruction technique in Japan as an esophagogastrostomy approach to prevent reflux esophagitis. However, standardized reconstruction methods after LPG have not yet been established. In LsTG, preservation of the esophagogastric junction and the fundus prevents reflux and malnutrition, which may maintain quality of life. However, whether LsTG is an oncologically and nutritionally acceptable procedure compared with laparoscopic total gastrectomy or LPG is a concern. In this review, we summarize the status of reconstruction in LPG and the oncological and nutritional aspects of LsTG as a function-preserving gastrectomy for early proximal gastric or esophagogastric junction cancer. Full article

(This article belongs to the Section Cancer Therapy)

19 pages, 3104 KiB

Open AccessArticle

BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression

by Annika C. Betzler, Hannah Strobel, Tsima Abou Kors, Jasmin Ezić, Kristina Lesakova, Ronja Pscheid, Ninel Azoitei, Johanna Sporleder, Anna-Rebekka Staufenberg, Robert Drees, Stephanie E. Weissinger, Jens Greve, Johannes Doescher, Marie-Nicole Theodoraki, Patrick J. Schuler, Simon Laban, Toshiro Kibe, Michiko Kishida, Shosei Kishida, Christian Idel, Thomas K. Hoffmann, Marialuisa Lavitrano, Emanuela Grassilli and Cornelia Brunner Show full author list Hide full author list

Cancers 2023, 15(1), 310; https://doi.org/10.3390/cancers15010310 - 3 Jan 2023

Cited by 3 | Viewed by 3116

Abstract

Here, we describe the expression of Bruton’s Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart [...] Read more.

Here, we describe the expression of Bruton’s Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, particularly in B cells, we identified the 80 kDa and 65 kDa BTK isoforms in HNSCC, recently described as oncogenic. Importantly, we revealed that both isoforms are products of the same mRNA. By investigating the mechanism regulating oncogenic BTK-p80/p65 expression in HNSSC versus healthy or benign tissues, our data suggests that the epigenetic process of methylation might be responsible for the initiation of BTK-p80/p65 expression in HNSCC. Our findings demonstrate that chemical or genetic abrogation of BTK activity leads to inhibition of tumor progression in terms of proliferation and vascularization in vitro and in vivo. These observations were associated with cell cycle arrest and increased apoptosis and autophagy. Together, these data indicate BTK-p80 and BTK-p65 as novel HNSCC-associated oncogenes. Owing to the fact that abundant BTK expression is a characteristic feature of primary and metastatic HNSCC, targeting BTK activity appears as a promising therapeutic option for HNSCC patients. Full article

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3 pages, 196 KiB

Open AccessComment

Comment on Billant et al. p53, A Victim of the Prion Fashion. Cancers 2021, 13, 269

by Susan W. Liebman, Irina L. Derkatch, Sangeun Park and Sei-Kyoung Park

Cancers 2023, 15(1), 309; https://doi.org/10.3390/cancers15010309 - 3 Jan 2023

Viewed by 1219

Abstract

The p53 tumor suppressor is a central protein in the fight against cancer [...] Full article

18 pages, 13914 KiB

Open AccessEditor’s ChoiceReview

Emerging Indications for Interventional Oncology: Expert Discussion on New Locoregional Treatments

by Roberto Iezzi, Afshin Gangi, Alessandro Posa, Uei Pua, Ping Liang, Ernesto Santos, Anil N. Kurup, Alessandro Tanzilli, Lorenzo Tenore, Davide De Leoni, Dimitrios Filippiadis, Felice Giuliante, Vincenzo Valentini, Antonio Gasbarrini, Shraga N. Goldberg, Martijn Meijerink, Riccardo Manfredi, Alexis Kelekis, Cesare Colosimo and David C. Madoff

Cancers 2023, 15(1), 308; https://doi.org/10.3390/cancers15010308 - 2 Jan 2023

Cited by 4 | Viewed by 4639

Abstract

Interventional oncology (IO) employs image-guided techniques to perform minimally invasive procedures, providing lower-risk alternatives to many traditional medical and surgical therapies for cancer patients. Since its advent, due to rapidly evolving research development, its role has expanded to encompass the diagnosis and treatment [...] Read more.

Interventional oncology (IO) employs image-guided techniques to perform minimally invasive procedures, providing lower-risk alternatives to many traditional medical and surgical therapies for cancer patients. Since its advent, due to rapidly evolving research development, its role has expanded to encompass the diagnosis and treatment of diseases across multiple body systems. In detail, interventional oncology is expanding its role across a wide spectrum of disease sites, offering a potential cure, control, or palliative care for many types of cancer patients. Due to its widespread use, a comprehensive review of the new indications for locoregional procedures is mandatory. This article summarizes the expert discussion and report from the “MIOLive Meet SIO” (Society of Interventional Oncology) session during the last MIOLive 2022 (Mediterranean Interventional Oncology Live) congress held in Rome, Italy, integrating evidence-reported literature and experience-based perceptions. The aim of this paper is to provide an updated review of the new techniques and devices available for innovative indications not only to residents and fellows but also to colleagues approaching locoregional treatments. Full article

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10 pages, 1782 KiB

Open AccessArticle

A “Seed-and-Soil” Radiomics Model Predicts Brain Metastasis Development in Lung Cancer: Implications for Risk-Stratified Prophylactic Cranial Irradiation

by Xiao Chu, Jing Gong, Xi Yang, Jianjiao Ni, Yajia Gu and Zhengfei Zhu

Cancers 2023, 15(1), 307; https://doi.org/10.3390/cancers15010307 - 2 Jan 2023

Cited by 9 | Viewed by 3121

Abstract

Introduction: Brain is a major site of metastasis for lung cancer, and effective therapy for developed brain metastasis (BM) is limited. Prophylactic cranial irradiation (PCI) has been shown to reduce BM rate and improve survival in small cell lung cancer, but this result [...] Read more.

Introduction: Brain is a major site of metastasis for lung cancer, and effective therapy for developed brain metastasis (BM) is limited. Prophylactic cranial irradiation (PCI) has been shown to reduce BM rate and improve survival in small cell lung cancer, but this result was not replicated in unselected non-small cell lung cancer (NSCLC) and had the risk of inducing neurocognitive dysfunctions. We aimed to develop a radiomics BM prediction model for BM risk stratification in NSCLC patients. Methods: 256 NSCLC patients with no BM at baseline brain magnetic resonance imaging (MRI) were selected; 128 patients developed BM within three years after diagnosis and 128 remained BM-free. For radiomics analysis, both the BM and non-BM groups were randomly distributed into training and testing datasets at an 70%:30% ratio. Both brain MRI (representing the soil) and chest computed tomography (CT, representing the seed) radiomic features were extracted to develop the BM prediction models. We first developed the radiomic models using the training dataset (89 non-BM and 90 BM cases) and subsequently validated the models in the testing dataset (39 non-BM and 38 BM cases). A radiomics BM score (RadBM score) was generated, and BM-free survival were compared between RadBM score-high and RadBM score-low groups. Results: The radiomics model developed from baseline brain MRI features alone can predict BM development in NSCLC patients. A fusion model integrating brain MRI features with primary tumor CT features (seed-and-soil model) provided synergetic effect and was more efficient in predicting BM (areas under the receiver operating characteristic curve 0.84 (95% confidence interval: 0.80–0.89) and 0.80 (95% confidence interval: 0.71–0.88) in the training and testing datasets, respectively). BM-free survival was significantly shorter in the RadBM score-high group versus the RadBM score-low group (Log-rank, p < 0.001). Hazard ratios for BM were 1.056 (95% confidence interval: 1.044–1.068) per 0.01 increment in RadBM score. Cumulative BM rates at three years were 75.8% and 24.2% for the RadBM score-high and RadBM score-low groups, respectively. Only 1.2% (7/565) of the BM lesions were located within the hippocampal avoidance region. Conclusion: The results demonstrated that intrinsic features of a non-metastatic brain exert a significant impact on BM development, which is first-in-class in metastasis prediction studies. A radiomics BM prediction model utilizing both primary tumor and pre-metastatic brain features might provide a useful tool for individualized PCI administration in NSCLC patients more prone to develop BM. Full article

(This article belongs to the Special Issue Radiotherapy for Thoracic Malignancies: New Advances and Challenges)

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11 pages, 2317 KiB

Open AccessSystematic Review

Prevalence of Germline BRCA1/2 Variants in Ashkenazi and Non-Ashkenazi Prostate Cancer Populations: A Systematic Review and Meta-Analysis

by Antonio Cioffi, Ottavio De Cobelli, Paolo Veronesi, Carlo La Vecchia, Patrick Maisonneuve and Giovanni Corso

Cancers 2023, 15(1), 306; https://doi.org/10.3390/cancers15010306 - 2 Jan 2023

Cited by 2 | Viewed by 2224

Abstract

Background and aims: International guidelines recommend testing BRCA2 in men with prostate cancer, due to the presence of a strong association with this gene. Some ethnicities present disparities in genetic distribution for the relation with specific founder variants. Ashkenazi Jewish people are, importantly, [...] Read more.

Background and aims: International guidelines recommend testing BRCA2 in men with prostate cancer, due to the presence of a strong association with this gene. Some ethnicities present disparities in genetic distribution for the relation with specific founder variants. Ashkenazi Jewish people are, importantly, at high risk of breast cancer for their inherited cluster with germline BRCA1/2 variants. However, in Ashkenazi men with prostate cancer, the prevalence of BRCA1 and/or BRCA2 is not well defined. We assessed the frequency of these variants in Ashkenazi vs. non-Ashkenazi men with prostate cancer. Materials and Methods: In accord with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, we revised all germline BRCA variants reported in MEDLINE from 1996 to 2021 in Ashkenazi and non-Ashkenazi men with prostate cancer. Results: Thirty-five original studies were selected for the analysis. Among populations from Israel and North America, Ashkenazi Jewish men presented higher prevalence of BRCA1 variants [0.9% (0.4–1.5) vs. 0.5% (0.2–1.1), p = 0.09] and a lower prevalence of BRCA2 variants [1.5% (1.1–2.0) vs. 3.5% (1.7–5.9), p = 0.08] in comparison to the non-Ashkenazi population. Conclusions: Since germline BRCA1 variants are more prevalent and BRCA2 variants are less prevalent in PCa patients of Ashkenazi Jewish ethnicity in comparison to non-Ashkenazi patients, prostate cancer genetic screening in Ashkenazi men should not be restricted to the BRCA2 gene. Full article

(This article belongs to the Special Issue Genes in Cancer)

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10 pages, 1515 KiB

Open AccessArticle

Comparison of the Basal Cell Carcinoma (BCC) Tumour Microenvironment to Other Solid Malignancies

by Eliana-Ruobing Zhang, Sarah Ghezelbash, Pingxing Xie, Misha Fotovati, Ivan V. Litvinov and Philippe Lefrançois

Cancers 2023, 15(1), 305; https://doi.org/10.3390/cancers15010305 - 2 Jan 2023

Cited by 4 | Viewed by 2650

Abstract

Basal cell carcinoma (BCC) is the most common form of skin cancer, contributing to nearly a third of new cancer cases in Western countries. Most BCCs are considered low risk “routine” lesions that can either be excised through surgery or treated with chemotherapeutic [...] Read more.

Basal cell carcinoma (BCC) is the most common form of skin cancer, contributing to nearly a third of new cancer cases in Western countries. Most BCCs are considered low risk “routine” lesions that can either be excised through surgery or treated with chemotherapeutic agents. However, around 1–2% of BCC cases are locally aggressive, present a high risk of metastasis, and often develop chemoresistance, termed advanced BCC. There currently exists no animal model or cell line that can recapitulate advanced BCC, let alone intermediate-risk and high-risk early BCC. We previously found that aggressive BCC tumours presented a Th2 cytokine inflammation profile, mesenchymal stem cell properties, and macrophage-induced tumoral inflammation. In this study, we aimed to identify potential BCC “relatives” among solid-organ malignancies who present similar immune cell proportions in their microenvironment compositions. Using immune cell type deconvolution by CIBERSORTx, and cell type enrichment by xCell, we determined three cancers with the most similar tumour microenvironments as compared to BCC. Specifically, chromophobe renal cell carcinoma, sarcoma, and skin cutaneous melanoma presented significance in multiple cell types, namely in CD4+ T lymphocytes, gammadelta T lymphocytes, and NK cell populations. Consequently, further literature analysis was conducted to understand similarities between BCC and its “relatives”, as well as investigating novel treatment targets. By identifying cancers most like BCC, we hope to propose prospective druggable pathways, as well as to gain insight on developing a reliable animal or cell line model to represent advanced BCC. Full article

(This article belongs to the Section Tumor Microenvironment)

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13 pages, 4056 KiB

Open AccessArticle

Protoporphyrin IX (PpIX) Fluorescence during Meningioma Surgery: Correlations with Histological Findings and Expression of Heme Pathway Molecules

by Dorothee C. Spille, Eva C. Bunk, Christian Thomas, Zeynep Özdemir, Andrea Wagner, Burak H. Akkurt, Manoj Mannil, Werner Paulus, Oliver M. Grauer, Walter Stummer, Volker Senner and Benjamin Brokinkel

Cancers 2023, 15(1), 304; https://doi.org/10.3390/cancers15010304 - 2 Jan 2023

Cited by 2 | Viewed by 1981

Abstract

Background: The usefulness of 5-ALA-mediated fluorescence-guided resection (FGR) in meningiomas is controversial, and information on the molecular background of fluorescence is sparse. Methods: Specimens obtained during 44 FGRs of intracranial meningiomas were analyzed for the presence of tumor tissue and fluorescence. Protein/mRNA expression [...] Read more.

Background: The usefulness of 5-ALA-mediated fluorescence-guided resection (FGR) in meningiomas is controversial, and information on the molecular background of fluorescence is sparse. Methods: Specimens obtained during 44 FGRs of intracranial meningiomas were analyzed for the presence of tumor tissue and fluorescence. Protein/mRNA expression of key transmembrane transporters/enzymes involved in PpIX metabolism (ABCB6, ABCG2, FECH, CPOX) were investigated using immunohistochemistry/qPCR. Results: Intraoperative fluorescence was observed in 70 of 111 specimens (63%). No correlation was found between fluorescence and the WHO grade (p = 0.403). FGR enabled the identification of neoplastic tissue (sensitivity 84%, specificity 67%, positive and negative predictive value of 86% and 63%, respectively, AUC: 0.75, p < 0.001), and was improved in subgroup analyses excluding dura specimens (86%, 88%, 96%, 63% and 0.87, respectively; p < 0.001). No correlation was found between cortical fluorescence and tumor invasion (p = 0.351). Protein expression of ABCB6, ABCG2, FECH and CPOX was found in meningioma tissue and was correlated with fluorescence (p < 0.05, each), whereas this was not confirmed for mRNA expression. Aberrant expression was observed in the CNS. Conclusion: FGR enables the intraoperative identification of meningioma tissue with limitations concerning dura invasion and due to ectopic expression in the CNS. ABCB6, ABCG2, FECH and CPOX are expressed in meningioma tissue and are related to fluorescence. Full article

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16 pages, 3271 KiB

Open AccessArticle

Long Non-Coding RNAs Associated with Mitogen-Activated Protein Kinase in Human Pancreatic Cancer

by Tomohiko Ishikawa, Shinichi Fukushige, Yuriko Saiki, Katsuya Hirose, Takako Hiyoshi, Takenori Ogawa, Yukio Katori and Toru Furukawa

Cancers 2023, 15(1), 303; https://doi.org/10.3390/cancers15010303 - 2 Jan 2023

Cited by 3 | Viewed by 2424

Abstract

Long non-coding RNAs (lncRNAs) have emerged as a significant player in various cancers, including pancreatic cancer. However, how lncRNAs are aberrantly expressed in cancers is largely unknown. We hypothesized that lncRNAs would be regulated by signaling pathways and contribute to malignant phenotypes of [...] Read more.

Long non-coding RNAs (lncRNAs) have emerged as a significant player in various cancers, including pancreatic cancer. However, how lncRNAs are aberrantly expressed in cancers is largely unknown. We hypothesized that lncRNAs would be regulated by signaling pathways and contribute to malignant phenotypes of cancer. In this study, to understand the significance of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), which is a major aberrant signaling pathway in pancreatic cancer, for the expression of lncRNAs, we performed comparative transcriptome analyses between pancreatic cancer cell lines with or without activation of MAPK. We identified 45 lncRNAs presumably associated with MAPK in pancreatic cancer cells; among these, LINC00941 was consistently upregulated by MAPK. The immediate genomic upstream region flanking LINC00941 was identified as a promoter region, the activity of which was found to be preferentially associated with MAPK activity via ETS-1 binding site. LINC00941 promoted cell proliferation in vitro. Moreover, TCGA data analysis indicated that high expression of LINC00941 was associated with poor prognosis of patients with pancreatic cancer. Transcriptomes comparing transcriptions between cells with and without LINC00941 knockdown revealed 3229 differentially expressed genes involved in 44 biological processes, including the glycoprotein biosynthetic process, beta-catenin-TCF complex assembly, and histone modification. These results indicate that MAPK mediates the aberrant expression of lncRNAs. LINC00941 is the lncRNA by MAPK most consistently promoted, and is implicated in the dismal prognosis of pancreatic cancer. MAPK-associated lncRNAs may play pivotal roles in malignant phenotypes of pancreatic cancer, and as such might represent both potentially valid therapeutic targets and diagnostic biomarkers. Full article

(This article belongs to the Topic Non-coding RNAs in Cancer: Markers in Disease Progression and Therapy)

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15 pages, 1674 KiB

Open AccessArticle

Longitudinal Plasma Proteomics-Derived Biomarkers Predict Response to MET Inhibitors for MET-Dysregulated NSCLC

by Guang-Ling Jie, Lun-Xi Peng, Mei-Mei Zheng, Hao Sun, Song-Rong Wang, Si-Yang Maggie Liu, Kai Yin, Zhi-Hong Chen, Hong-Xia Tian, Jin-Ji Yang, Xu-Chao Zhang, Hai-Yan Tu, Qing Zhou, Catherine C. L. Wong and Yi-Long Wu

Cancers 2023, 15(1), 302; https://doi.org/10.3390/cancers15010302 - 1 Jan 2023

Cited by 2 | Viewed by 3248

Abstract

MET inhibitors have shown promising efficacy for MET-dysregulated non-small cell lung cancer (NSCLC). However, quite a few patients cannot benefit from it due to the lack of powerful biomarkers. This study aims to explore the potential role of plasma proteomics-derived biomarkers for patients [...] Read more.

MET inhibitors have shown promising efficacy for MET-dysregulated non-small cell lung cancer (NSCLC). However, quite a few patients cannot benefit from it due to the lack of powerful biomarkers. This study aims to explore the potential role of plasma proteomics-derived biomarkers for patients treated with MET inhibitors using mass spectrometry. We analyzed the plasma proteomics from patients with MET dysregulation (including MET amplification and MET overexpression) treated with MET inhibitors. Thirty-three MET-dysregulated NSCLC patients with longitudinal 89 plasma samples were included. We classified patients into the PD group and non-PD group based on clinical response. The baseline proteomic profiles of patients in the PD group were distinct from those in the non-PD group. Through protein screening, we found that a four-protein signature (MYH9, GNB1, ALOX12B, HSD17B4) could predict the efficacy of patients treated with MET inhibitors, with an area under the curve (AUC) of 0.93, better than conventional fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) tests. In addition, combining the four-protein signature with FISH or IHC test could also reach higher predictive performance. Further, the combined signature could predict progression-free survival for MET-dysregulated NSCLC (p < 0.001). We also validated the performance of the four-protein signature in another cohort of plasma using an enzyme-linked immunosorbent assay. In conclusion, the four plasma protein signature (MYH9, GNB1, ALOX12B, and HSD17B4 proteins) might play a substitutable or complementary role to conventional MET FISH or IHC tests. This exploration will help select patients who may benefit from MET inhibitors. Full article

(This article belongs to the Special Issue Roles of MET in Cancer Development and Treatment)

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13 pages, 1974 KiB

Open AccessReview

The Diagnostic Approach towards Combined Hepatocellular-Cholangiocarcinoma—State of the Art and Future Perspectives

by Johannes Eschrich, Zuzanna Kobus, Dominik Geisel, Sebastian Halskov, Florian Roßner, Christoph Roderburg, Raphael Mohr and Frank Tacke

Cancers 2023, 15(1), 301; https://doi.org/10.3390/cancers15010301 - 1 Jan 2023

Cited by 9 | Viewed by 3288

Abstract

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer which displays clinicopathologic features of both hepatocellular (HCC) and cholangiocellular carcinoma (CCA). The similarity to HCC and CCA makes the diagnostic workup particularly challenging. Alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) are blood [...] Read more.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer which displays clinicopathologic features of both hepatocellular (HCC) and cholangiocellular carcinoma (CCA). The similarity to HCC and CCA makes the diagnostic workup particularly challenging. Alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) are blood tumour markers related with HCC and CCA, respectively. They can be used as diagnostic markers in cHCC-CCA as well, albeit with low sensitivity. The imaging features of cHCC-CCA overlap with those of HCC and CCA, dependent on the predominant histopathological component. Using the Liver Imaging and Reporting Data System (LI-RADS), as many as half of cHCC-CCAs may be falsely categorised as HCC. This is especially relevant since the diagnosis of HCC may be made without histopathological confirmation in certain cases. Thus, in instances of diagnostic uncertainty (e.g., simultaneous radiological HCC and CCA features, elevation of CA 19-9 and AFP, HCC imaging features and elevated CA 19-9, and vice versa) multiple image-guided core needle biopsies should be performed and analysed by an experienced pathologist. Recent advances in the molecular characterisation of cHCC-CCA, innovative diagnostic approaches (e.g., liquid biopsies) and methods to analyse multiple data points (e.g., clinical, radiological, laboratory, molecular, histopathological features) in an all-encompassing way (e.g., by using artificial intelligence) might help to address some of the existing diagnostic challenges. Full article

(This article belongs to the Special Issue Combined Hepatocellular-Cholangiocarcinoma: An Update on Epidemiology, Classification, Diagnosis and Management)

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27 pages, 2053 KiB

Open AccessReview

The Research Advances of Aptamers in Hematologic Malignancies

by Yongkang Liao, Shijun Xiong, Zaid Ur Rehman, Xiaoli He, Hongling Peng, Jing Liu and Shuming Sun

Cancers 2023, 15(1), 300; https://doi.org/10.3390/cancers15010300 - 1 Jan 2023

Cited by 2 | Viewed by 3263

Abstract

Currently, research for hematological malignancies is very intensive, with many breakthroughs. Among them, aptamer-based targeted therapies could be counted. Aptamer is a targeting tool with many unique advantages (easy synthesis, low toxicity, easy modification, low immunogenicity, nano size, long stability, etc.), therefore many [...] Read more.

Currently, research for hematological malignancies is very intensive, with many breakthroughs. Among them, aptamer-based targeted therapies could be counted. Aptamer is a targeting tool with many unique advantages (easy synthesis, low toxicity, easy modification, low immunogenicity, nano size, long stability, etc.), therefore many experts screened corresponding aptamers in various hematological malignancies for diagnosis and treatment. In this review, we try to summarize and provide the recent progress of aptamer research in the diagnosis and treatment of hematologic malignancies. Until now, 29 aptamer studies were reported in hematologic malignancies, of which 12 aptamers were tested in vivo and the remaining 17 aptamers were only tested in vitro. In this case, 11 aptamers were combined with chemotherapeutic drugs for the treatment of hematologic malignancies, 4 aptamers were used in combination with nanomaterials for the diagnosis and treatment of hematologic malignancies, and some studies used aptamers for the targeted transportation of siRNA and miRNA for targeted therapeutic effects. Their research provides multiple approaches to achieve more targeted goals. These findings show promising and encouraging future for both hematological malignancies basic and clinical trials research. Full article

(This article belongs to the Special Issue Aptamers and Cancer)

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10 pages, 520 KiB

Open AccessArticle

Ovarian Cancer in a Northern Italian Province and the Multidisciplinary Team

by Lucia Mangone, Francesco Marinelli, Isabella Bisceglia, Maria Barbara Braghiroli, Valentina Mastrofilippo, Loredana Cerullo, Carlotta Pellegri, Alessandro Zambelli, Lorenzo Aguzzoli and Vincenzo Dario Mandato

Cancers 2023, 15(1), 299; https://doi.org/10.3390/cancers15010299 - 31 Dec 2022

Cited by 11 | Viewed by 2262

Abstract

Ovarian cancer represents one of the most aggressive female cancers in the world, remaining a tumor with high lethality. This study aims to present how a multidisciplinary team (MDT) approach can improve the prognosis in terms of recurrence and death of patients. In [...] Read more.

Ovarian cancer represents one of the most aggressive female cancers in the world, remaining a tumor with high lethality. This study aims to present how a multidisciplinary team (MDT) approach can improve the prognosis in terms of recurrence and death of patients. In total, 448 ovarian cancer cases registered in an Italian Cancer Registry between 2012 and 2020 were included. Information on age, morphology, stage, and treatment was collected. Recurrence and death rates were reported 1 and 2 years after diagnosis, comparing MDT vs. non-MDT approaches. Ninety-three percent had microscopic confirmation, and most showed cystic-mucinous morphology. In total, 50% were older than 65 years old. The distribution by stage was 17.6%, 4%, 44.9%, and 32.6% for stages I, II, III, and IV, respectively. The women followed by the MDT were 24.1%. Disease-free survival 1-year post-diagnosis, recurrences, recurrences-deaths, and deaths were 67.5%, 14.5%, 8.4%, and 9.6%, respectively, better than the non-MDT group (46.2%, 13.2%, 20.8 %, and 19.8%, respectively) (p < 0.01). The same positive results were confirmed two years after diagnosis, particularly for stages III and IV. Albeit small numbers, the study confirms a better prognosis for women managed by MDT with fewer recurrences and deaths, especially within the first 24 months of diagnosis. Full article

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

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17 pages, 1384 KiB

Open AccessReview

Special Techniques of Adjuvant Breast Carcinoma Radiotherapy

by Iveta Kolářová, Bohuslav Melichar, Jaroslav Vaňásek, Igor Sirák, Jiří Petera, Kateřina Horáčková, Denisa Pohanková, Zuzana Šinkorová, Oldřich Hošek and Milan Vošmik

Cancers 2023, 15(1), 298; https://doi.org/10.3390/cancers15010298 - 31 Dec 2022

Cited by 3 | Viewed by 2140

Abstract

Modern radiotherapy techniques are designed to permit reduced irradiation of healthy tissue, resulting in a diminished risk of adverse effects and shortened recovery times. Several randomized studies have demonstrated the benefits of increased dosage to the tumor bed area in combination with whole [...] Read more.

Modern radiotherapy techniques are designed to permit reduced irradiation of healthy tissue, resulting in a diminished risk of adverse effects and shortened recovery times. Several randomized studies have demonstrated the benefits of increased dosage to the tumor bed area in combination with whole breast irradiation (WBI). Conventional WBI treatment following breast-conserving procedures, which required 5–7 weeks of daily treatments, has been reduced to 3–4 weeks when using hyperfractionated regimens. The dosage administration improves local control, albeit with poorer cosmesis. The method of accelerated partial breast irradiation (APBI) shortens the treatment period whilst reducing the irradiated volume. APBI can be delivered using intraoperative radiation, brachytherapy, or external beam radiotherapy. Currently available data support the use of external beam partial breast irradiation in selected patients. Modern radiotherapy techniques make it possible to achieve favorable cosmesis in most patients undergoing immediate breast reconstruction surgery, and studies confirm that current methods of external beam radiation allow an acceptable coverage of target volumes both in the reconstructed breast and in the regional lymphatic nodes. Full article

(This article belongs to the Collection Breast Cancer: From Pathophysiology to Prevention and Treatment)

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11 pages, 1216 KiB

Open AccessArticle

PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Study

by Amina Banda, Bastiaan M. Privé, Youssra Allach, Maike J. M. Uijen, Steffie M. B. Peters, Cato C. Loeff, Martin Gotthardt, Constantijn H. J. Muselaers, J. Alfred Witjes, Inge M. van Oort, J. P. Michiel Sedelaar, Harm Westdorp, Niven Mehra, Fadi Khreish, Samer Ezziddin, Amir Sabet, Michael C. Kreissl, Thomas Winkens, Philipp Seifert, Marcel J. R. Janssen, Willemijn A. M. van Gemert and James Nagarajah Show full author list Hide full author list

Cancers 2023, 15(1), 297; https://doi.org/10.3390/cancers15010297 - 31 Dec 2022

Cited by 11 | Viewed by 3480

Abstract

Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [ [...] Read more.

Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [¹⁷⁷Lu]Lu-PSMA- (¹⁷⁷Lu-PSMA) or [²²⁵Ac]Ac-PSMA-radioligand treatment (²²⁵Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMA-RLT in early-stage and hormone-sensitive metastatic prostate cancer patients. Methods: A retrospective study was performed in patients who received ¹⁷⁷Lu-PSMA and/or ²²⁵Ac-PSMA with early-stage metastatic prostate cancer. The primary outcome parameter evaluated in this study was the progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcome parameters were prostate-specific antigen (PSA) response and the date of onset of CRPC state. Results: In total, 20 patients were included of which 18 patients received ¹⁷⁷Lu-PSMA radioligand and two patients received tandem treatment with both ¹⁷⁷Lu-PSMA and ²²⁵Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1–6) and a median activity of 6.2 GBq ¹⁷⁷Lu-PSMA per cycle (interquartile range (IQR) 5.2–7.4 GBq). PSMA-RLT was overall well-tolerated. The most common grade 1–2 side effects were xerostomia (n = 6) and fatigue (n = 8), which were only temporarily reported. One patient that received ²²⁵Ac-PSMA developed grade 3–4 bone marrow toxicity. The median PFS was 12 months (95% confidence interval (CI), 4.09–19.9 months). Seventeen (85%) patients had a ≥50% PSA response following PSMA-RLT. One patient developed CRPC 9 months following PSMA-RLT. Conclusions: In this small cohort study, PSMA-RLT appeared safe and showed encouraging efficacy for (metastasized) early-stage and hormone-sensitive prostate cancer patients. Prospective studies are awaited and should include long-term follow-up. Full article

(This article belongs to the Special Issue Current Use of PSMA in Prostate Cancer Treatment)

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Open AccessArticle

High ME1 Expression Is a Molecular Predictor of Post-Transplant Survival of Patients with Acute Myeloid Leukemia

by César Alexander Ortiz Rojas, Abel Costa-Neto, Diego A. Pereira-Martins, Duy Minh Le, Dominique Sternadt, Isabel Weinhäuser, Gerwin Huls, Jan Jacob Schuringa and Eduardo Magalhães Rego

Cancers 2023, 15(1), 296; https://doi.org/10.3390/cancers15010296 - 31 Dec 2022

Cited by 1 | Viewed by 2994

Abstract

Several laboratory and clinical variables have been reported to be associated with the outcome of intensive chemotherapy for acute myeloid leukemia (AML), but only a few have been tested in the context of hematopoietic stem cell transplant (HSCT). This study aimed to identify [...] Read more.

Several laboratory and clinical variables have been reported to be associated with the outcome of intensive chemotherapy for acute myeloid leukemia (AML), but only a few have been tested in the context of hematopoietic stem cell transplant (HSCT). This study aimed to identify genes whose expression of AML at diagnosis were associated with survival after HSCT. For this purpose, three publicly available adult AML cohorts (TCGA, BeatAML, and HOVON), whose patients were treated with intensive chemotherapy and then subjected to allogeneic or autologous HSCT, were included in this study. After whole transcriptome analysis, we identified ME1 as the only gene whose high expression was associated with shorter survival in patients subjected to HSCT. In addition, the inclusion of ME1 expression was able to improve the European LeukemiaNet risk stratification. Pathways related to lipid biosynthesis, mainly fatty acids, and cholesterol were positively correlated with ME1 expression. Furthermore, ME1 expression was associated with an M2 macrophage-enriched microenvironment, mature AML blasts hierarchy, and oxidative phosphorylation metabolism. Therefore, ME1 expression can be used as biomarker of poor response to HSCT in AML. Full article

(This article belongs to the Section Cancer Biomarkers)

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Cancers, Volume 15, Issue 1 (January-1 2023) – 325 articles

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