Outcome In Cancer Patients Research Articles

The Impact of Tumor Stage and Histopathology on Survival Outcomes in Esophageal Cancer Patients over the Past Decade

Background: Esophageal cancer (EC) is the sixth leading cause of cancer-related mortality worldwide, continuing to be a significant public health concern. The purpose of this study is to assess the impact of staging and histopathology of EC on associated mortality. The study also aims to further investigate clinical characteristics, prognostic factors, and survival outcomes in patients diagnosed with EC between 2010 and 2017. Furthermore, we analyzed the interaction between tumor histology and staging and the risk of mortality. Methods: A total of 24,011 patients diagnosed with EC between 2010 and 2017 in the United States were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Demographic parameters, tumor stage, and histologic subtypes were analyzed and associated overall mortality (OM) and cancer-specific mortality (CSM) were measured across all subgroups. Covariates reaching the level of statistical significance, demonstrable by a p-value equal to or less than 0.01, were incorporated into a multivariate Cox proportional hazards model. A hazard ratio greater than 1 was indicative of an increased risk of mortality in the presence of the variable under discussion. Additionally, the study explores the interaction between histology and tumor stage on outcomes. Results: The majority of patients were male (80.13%) and non-Hispanic white (77.87%), with a predominant age at diagnosis of between 60 and 79 years (59.86%). Adenocarcinoma was the most common tumor subtype (68.17%), and most patients were diagnosed at a distant stage (41.29%). Multivariate analysis revealed higher mortality risks for males, older patients, unmarried individuals, and those with advanced-stage tumors. Higher income, receiving radiation or chemotherapy, and undergoing surgery were associated with lower mortality. Tumor subtype significantly influenced mortality, with squamous cell carcinoma and neuroendocrine tumors showing higher hazard ratios compared to adenocarcinoma. Adenocarcinoma is linked to a poorer prognosis at advanced stages, whereas the opposite trend is observed for SCC. Conclusions: The study identifies significant demographic and clinicopathologic factors influencing mortality in esophageal cancer patients, highlighting the importance of early diagnosis and treatment intervention. Future research should focus on tailored treatment strategies to improve survival outcomes in high-risk groups and to understand the interaction between tumor histology and tumor stage.

Treatment adherence and effectiveness in patients treated with carfilzomib-based therapy combinations for relapsed/refractory multiple myeloma in Germany: interim results from the non-interventional CARO study

Therapy adherence can significantly influence the outcome of cancer patients. The prospective, non-interventional CARO study (NCT02970747) investigated adherence, effectiveness, and safety of carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) in the German real-world setting. In total, 359 patients were included at 69 sites. Data on carfilzomib combination regimens were evaluated for three treatment cohorts: carfilzomib with lenalidomide and dexamethasone (KRd), with dexamethasone only (Kd) or with daratumumab and dexamethasone (KdD). Encouragingly, patients maintained levels of treatment adherence ≥95% to carfilzomib across cohorts. The effectiveness outcomes of CARO were in line with previous data. Median PFS (95% CI) was 17.5 months (14.5, 24.7 [KRd]), 13.4 months (7.0, 18.1 [Kd]), and 15.6 months (9.9, NA [KdD]), respectively. Median OS was 38.9 months (31.5, 53.9 [KRd]), 24.2 months (17.3, 36.8 [Kd]), and not reached (KdD). Overall, the CARO study impressively demonstrates efficacy and safety of KRd, Kd, and KdD regimen in real-world.

Revealing Occult Malignancies in Mammograms Through GAN-Driven Breast Density Transformation

Breast cancer remains one of the primary causes of cancer-related deaths among women globally. Early detection via mammography is essential for improving prognosis and survival rates. However, mammogram diagnostic accuracy is severely hindered by dense breast tissue, which can obstruct potential malignancies, complicating early detection. To tackle this pressing issue, this study introduces an innovative approach that leverages Generative Adversarial Networks (GANs), specifically CycleGAN and GANHopper, to transform breast density in mammograms. The aim is to diminish the masking effect of dense tissue, thus enhancing the visibility of underlying malignancies. The method uses unsupervised image-to-image translation to gradually alter breast density (from high (ACR-D) to low (ACR-A)) in mammographic images, detecting obscured lesions while preserving original diagnostic features. We applied this approach to multiple mammographic datasets, demonstrating its effectiveness in diverse contexts. Experimental results exhibit substantial improvements in detecting potential malignancies concealed by dense breast tissue. The method significantly improved precision, recall, and F1-score metrics across all datasets, revealing previously obscured malignancies and image quality assessments confirmed the diagnostic relevance of transformed images. The study introduces a novel mammogram analysis method using advanced machine-learning techniques, enhancing diagnostic accuracy in dense breasts and potentially improving early breast cancer detection and patient outcomes.

Development and validation of a nomogram for predicting outcomes in ovarian cancer patients with liver metastases

PurposeTo develop and validate a nomogram for predicting the overall survival (OS) of ovarian cancer patients with liver metastases (OCLM).MethodsThis study identified 821 patients in the Surveillance, Epidemiology, and End Results (SEER) database. All patients were randomly divided in a ratio of 7:3 into a training cohort (n = 574) and a validation cohort (n = 247). Clinical factors associated with OS were assessed using univariate and multivariate Cox regression analyses, and backward stepwise regression was applied using the Akaike information criterion (AIC) to select the optimal predictor variables. The nomogram for predicting the OS of the OCLM patients was constructed based on the identified prognostic factors. Their prediction ability was evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curves analysis (DCA) in both the training and validation cohorts.ResultsWe identified factors that predict OS for OCLM patients and constructed a nomogram based on the data. The ROC, C-index, and calibration analyses indicated that the nomogram performed well over the 1, 2, and 3-year OS in both the training and validation cohorts. Additionally, in contrast to the External model from multiple perspectives, our model shows higher stability and accuracy in predictive power. DCA curves, NRI, and IDI index demonstrated that the nomogram was clinically valuable and superior to the External model.ConclusionWe established and validated a nomogram to predict 1,2- and 3-year OS of OCLM patients, and our results may also be helpful in clinical decision-making.

Co-developing a theory of change for a personalised multimodal cancer prehabilitation programme in South Wales

BackgroundEvidence suggests that prehabilitation interventions, which optimise physical and mental health prior to treatment, can improve outcomes for surgical cancer patients and save costs to the health system through faster recovery and fewer complications. However, robust, theory-based evaluations of these programmes are needed. Using a theory of change (ToC) approach can guide evaluation plans by describing how and why a programme is expected to work. Theories of Change have not been developed for cancer prehabilitation programmes in the literature to date. This paper aims to provide an overview of the methodological steps we used to retrospectively construct a ToC for Prehab2Rehab (P2R), a cancer prehabilitation programme being implemented by the Cardiff and Vale University Health Board.MethodsWe used an iterative, participatory approach to develop the ToC. Following a literature review and document analysis, we facilitated a workshop with fourteen stakeholders from across the programme using a ‘backwards mapping’ approach. After the workshop, stakeholders had three additional opportunities to refine and validate a final working version of the ToC.ResultsOur process resulted in the effective and timely development of a ToC. The ToC captures how P2R’s interventions or activities are expected to bring about short, medium and long-term outcomes that, collectively, should result in the overarching desired impacts of the programme, which were improved patient flow and reduced costs to the health system. The process of developing a ToC also enabled us to have a better understanding of the programme and build rapport with key stakeholders.ConclusionsThe ToC has guided the design of an evaluation that covers the complexity of P2R and will generate lessons for policy and clinical practice on supporting surgical cancer patients in Wales and beyond. We recommend that evaluators apply a ToC development process at the outset of evaluations to bring together stakeholders and enhance the utilisation of the findings. This paper details a pragmatic, efficient and replicable process that evaluators could adopt to develop a ToC. Theory-informed evaluations may provide better evidence to develop and refine cancer prehabilitation interventions and other complex public health interventions.

The cardio-oncologic burden of breast cancer: molecular mechanisms and importance of preclinical models.

Breast cancer, the most prevalent cancer affecting women worldwide, poses a significant cardio-oncological burden. Despite advancements in novel therapeutic strategies, anthracyclines, HER2 antagonists, and radiation remain the cornerstones of oncological treatment. However, each carries a risk of cardiotoxicity, though the molecular mechanisms underlying these adverse effects differ. Common mechanisms include DNA damage response, increased reactive oxygen species, and mitochondrial dysfunction, which are key areas of ongoing research for potential cardioprotective strategies. Since these mechanisms are also essential for effective tumor cytotoxicity, we explore tumor-specific effects, particularly in hereditary breast cancer linked to BRCA1 and BRCA2 mutations. These genetic variants impair DNA repair mechanisms, increase the risk of tumorigenesis and possibly for cardiotoxicity from treatments such as anthracyclines and HER2 antagonists. Novel therapies, including immune checkpoint inhibitors, are used in the clinic for triple-negative breast cancer and improve the oncological outcomes of breast cancer patients. This review discusses the molecular mechanisms underlying BRCA dysfunction and the associated pathological pathways. It gives an overview of preclinical models of breast cancer, such as genetically engineered mouse models, syngeneic murine models, humanized mouse models, and various in vitro and ex vivo systems and models to study cardiovascular side effects of breast cancer therapies. Understanding the underlying mechanism of cardiotoxicity and developing cardioprotective strategies in preclinical models are essential for improving treatment outcomes and reducing long-term cardiovascular risks in breast cancer patients.

VIM-AS1, which is regulated by CpG methylation, cooperates with IGF2BP1 to inhibit tumor aggressiveness via EPHA3 degradation in hepatocellular carcinoma.

Early tumor recurrence in hepatocellular carcinoma (HCC) remains a challenging area, as the mechanisms involved are not fully understood. While microvascular invasion is linked to early recurrence, established biomarkers for diagnosis and prognostication are lacking. In this study, our objective was to identify DNA methylation sites that can predict the outcomes of liver cancer patients and elucidate the molecular mechanisms driving HCC aggressiveness. Using DNA methylome data from HCC patient samples from the CGRC and TCGA databases, we pinpointed hypermethylated CpG sites in HCC. Our analysis revealed that cg02746869 acts as a crucial regulatory site for VIM-AS1 (vimentin antisense RNA1), a 1.8 kb long noncoding RNA. RNA sequencing of HCC cells with manipulated VIM-AS1 expression revealed EPHA3 as a pathogenic target of VIM-AS1, which performs an oncogenic function in HCC. Hypermethylation-induced suppression of VIM-AS1 significantly impacted HCC cell dynamics, particularly impairing motility and invasiveness. Mechanistically, reduced VIM-AS1 expression stabilized EPHA3 mRNA by enhancing the binding of IGF2BP1 to EPHA3 mRNA, leading to increased expression of EPHA3 mRNA and the promotion of HCC progression. In vivo experiments further confirmed that the VIM-AS1‒EPHA3 axis controlled tumor growth and the tumor microenvironment in HCC. These findings suggest that the downregulation of VIM-AS1 due to hypermethylation at cg02746869 increased EPHA3 mRNA expression via a m6A-dependent mechanism to increase HCC aggressiveness.

Electrochemical immunosensor for the predictive cancer biomarker SLFN11 using reduced graphene oxide/MIL-101(Cr)-NH2 composite

SLFN11 is a predictive cancer biomarker essential for identifying tumors that are sensitive to DNA-damaging agents, facilitating more personalized and effective treatment approaches. Detecting this biomarker can guide therapeutic decisions and improve outcomes for cancer patients. However, existing detection methods for SLFN11 are complex and require advanced techniques. In this study, we introduce the first immunosensor designed for on-site detection of SLFN11. An advanced electrochemical immunosensor platform utilizing a composite of graphene oxide (GO) and chromium-based metal organic framework (MIL-101 (Cr)-NH2) was developed. The integration of GO and MIL-101(Cr)-NH2 was characterized through FT-IR, XRD, SEM, and XPS, affirming the formation of the composite. The subsequent electrochemical reduction to rGO/MIL-101(Cr)-NH2 significantly improved the electrochemical performance and stability. A glutaraldehyde cross-linker was then utilized to attach the SLFN11-specific antibody to the amine groups of the MOF-modified electrodes. This led to the development of rapid, sensitive, portable, and cost-effective immunosensor for SLFN11 at concentrations as low as 8.9 pg/mL which holds promise for early cancer diagnosis. High specificity was achieved, with minimal cross-reactivity observed with other cancer biomarkers such as pepsinogen I, claudin 18.2 and Programmed cell death protein 1. Demonstrating practical applicability, the electrochemical immunosensor validated by commercial ELISA kit showed successful detection in serum samples with high recovery rates and reproducibility. This research highlights the potential of rGO/MOFs composites in electrochemical biosensors developments for early cancer diagnostics and personalized medicine.

Association of the Inflammatory Burden Index With Increased Mortality Among Cancer Patients: Insights From the NHANES Study.

The systemic inflammatory response significantly influences the progression and prognosis of various cancers. The novel Inflammatory Burden Index (IBI) was recently introduced as a biomarker to gauge systemic inflammation and evaluate cancer patient prognosis. However, studies investigating the relationship between IBI and mortality rates in cancer patients remain limited. This study analyzed data from 2748 cancer patients enrolled in the National Health and Nutrition Examination Surveys between 1999 and 2018. We used weighted Cox regression analysis and restricted cubic spline models to examine the relationship between the IBI and mortality due to all causes, cardiovascular disease (CVD), and cancer. Furthermore, we employed Kaplan-Meier survival curves, subgroup analyses, and receiver operating characteristic curves to elaborate on these associations. Over a median follow-up period of 112 months, the cohort experienced 1067 deaths, including 320 from cancer, 239 attributable to heart disease, and 508 from various other causes. The Kaplan-Meier curve indicated that individuals in the higher quartiles of the IBI faced significantly increased mortality risks compared to those in lower quartiles. Analyses using weighted Cox proportional hazards models demonstrated that subjects in the top IBI quartile were at a substantially higher risk for all-cause mortality (Hazard Ratio [HR] 2.09, 95% Confidence Interval [CI] 1.67-2.62, p < 0.001), CVD mortality (HR = 1.95, 95% CI= 1.18-3.23, p = 0.010), and cancer mortality (HR = 2.06, 95% CI = 1.31-3.26, p = 0.002). Furthermore, stratification and interaction analyses affirmed the uniformity of these initial findings. The areas under the curve for the 3-, 5-, and 10-year survival predictions for all-cause mortality were 0.62, 0.62, and 0.67, respectively; for cardiovascular mortality, they were 0.64, 0.64, and 0.70; and for cancer mortality, they were 0.62, 0.77, and 0.70. In cancer patients, higher IBI levels significantly correlate with increased mortality from all causes, CVD, and cancer-specific deaths. This index could possess considerable diagnostic and prognostic importance, possibly acting as a new biomarker for evaluating outcomes in cancer patients.

Mammography Among Women Residing in Urban Versus Rural Utah: Breast Cancer Survival.

Annual or biennial breast cancer screenings are recommended for women 40 and older. Women residing in rural areas have worse breast cancer survival rates than urban women, but no study has focused on rural versus urban residence in Utah regarding breast cancer screening and mortality. Cases (n = 14,516) were women aged > 39 diagnosed with a first primary invasive breast cancer between 1998 and 2017 in Utah. Controls (n = 63,117) without a history of breast cancer were matched to cases by birth year and birth state. Mammography screening status was identified by Current Procedural Terminology (CPT) codes. Logistic regression was used to assess the odds of breast cancer diagnosis. The Cox proportional hazards model was used to assess survival outcomes for rural and urban breast cancer patients based on screening status. Screening mammography usage among rural patients diagnosed with breast cancer was lower (17.7%) than urban usage (20.7%). Usage of screening mammograms resulted in higher odds of breast cancer diagnosis at localized stage rather than at a regional and distant stage. Rural breast cancer cases had a higher proportion of deaths, and a lower proportion screened, than urban breast cancer cases. Hazard ratios showed that screening mammography usage was associated with better survival among both rural (HR = 0.50, 95% CI = 0.44-0.57) and urban (HR = 0.56, 95% CI = 0.39-0.82) breast cancer cases. Screening mammography usage was associated with better overall survival regardless of place of residence. Removing barriers and improving information regarding breast cancer screenings are needed in both rural and urban settings in Utah to increase mammography usage, with the overall goal of increasing early detection and outcomes of breast cancer.

Perioperative Anemia Is an Independent Prognostic Factor for Gastric Cancer Patients Who Receive Curative Treatment.

This study evaluated the clinical impact of anemia during the perioperative period on both short- and long-term oncological outcomes in resectable gastric cancer (GC) patients who received curative treatment. We conducted a retrospective review of medical records and collected data from consecutive patients with gastric cancer who underwent curative resection at Yokohama City University between 2015 and 2022. A total of 330 patients were evaluated in this study. In the present study, we set the cutoff value of preoperative hemoglobin at 11.0 g/dl. The 1-, 3-, and 5-year overall survival rates were 88.6%, 59.8%, and 47.0%, respectively, in patients with hemoglobin levels <11 g/dl, and 96.8%, 86.0%, and 80.0% in those with hemoglobin levels ≥11 g/dl. Based on univariate and multivariate analyses, the preoperative hemoglobin status was identified as an independent prognostic factor for both overall survival (hazard ratio=1.772, 95% confidence interval=1.109-2.831, p=0.017) and recurrence-free survival (hazard ratio=1.782; 95% confidence interval=1.166-2.723, p=0.008). In addition, perioperative anemia was also found to affect the clinical course of postoperative surgical complications and postoperative adjuvant chemotherapy. Perioperative anemia was identified as an independent prognostic factor in GC patients who received curative treatment. To improve the survival of patients with GC, it is necessary to provide care and management for perioperative anemia before curative treatment.

Healthcare professionals’ promotion of physical activity to people living with and beyond head and neck cancer: a cross-sectional survey

PurposePhysical activity (PA) can improve health-related outcomes for head and neck cancer (HaNC) patients, and PA guidance from healthcare professionals’ can increase patients’ PA levels. However, less than 9% of HaNC patients are physically active. This study explored healthcare professionals’ promotion of PA across the National Health Service (NHS) in North West England and North Wales, to HaNC patients.MethodsA cross-sectional online survey exploring healthcare professionals’ promotion of PA in HaNC. The International Physical Activity Questionnaire–Short Form was used to estimate healthcare professionals’ PA levels. Quantitative data were analyzed using descriptive or inferential statistics and qualitative data were analyzed using reflexive thematic analysis. Data were synthesized drawing on the capability-opportunity-motivation-behavior model and theoretical domains framework.ResultsEighty-one professionals participated. Fifty-three percent self-reported high levels of PA. Seventy-five percent considered PA promotion as part of their role; however, only 39% discussed PA with their patients (reflective motivation and social/professional role and identity). Only 38% felt confident initiating PA discussions and 76% reported needing further training. Training on the benefits of PA for HaNC patients and how to encourage health-related behavior change were identified as beneficial (psychological capability and knowledge).ConclusionHealthcare professionals are influential in enabling patients to adopt health-related behavior change; however, PA promotion was not routine practice for professionals involved in the care of HaNC patients. Training should be provided to professionals on PA promotion, with a focus on behavior change techniques. Future research should explore how behavior change techniques can be implemented into clinical practice to improve health-related outcomes in HaNC.

Addition of Bevacizumab to Chemotherapy and Its Impact on Clinical Efficacy in Cervical Cancer: A Systematic Review and Meta-Analysis

Background and Objectives: Cervical cancer is the third leading cause of cancer-related mortality in females. One of the most successful therapeutic modalities to date is suppressing vascular endothelial growth factor (VEGF)-mediated angiogenesis. Bevacizumab is a monoclonal antibody that targets VEGF-A. The outcomes for cervical cancer patients treated with bevacizumab in combination with platinum-based chemotherapy have been explored in several studies. This study aimed to assess the impact of bevacizumab on progression-free survival (PFS) and overall survival (OS) in patients with metastatic cervical cancer. Materials and Methods: This systematic review was registered in PROSPERO (CRD42023456755). Following PRISMA guidelines, a comprehensive literature search on PubMed and Google Scholar identified 28 studies meeting the inclusion criteria. The outcomes of interest were PFS and OS. The statistical analysis computed hazard ratios (HRs) with 95% confidence intervals (CIs). The study also included a subgroup analysis by cervical cancer stage. Results: The pooled analysis revealed that bevacizumab-based therapy significantly improved both PFS with HR 0.77 (95% CI: 0.58–0.96; p &lt; 0.01; I2 = 58%) and OS with HR 0.63 (95% CI: 0.45–0.89; p &lt; 0.01; I2 = 41%) in cervical cancer patients. Subgroup analysis by stage of cervical cancer demonstrated better efficacy of bevacizumab in metastatic stage IVB cervical cancer patients indicated by HR for PFS (0.69, 95% CI: 0.54–0.79; p &lt; 0.01) and HR for OS (0.57, 95% CI: 0.46–0.73; p &lt; 0.01). Conclusions: Bevacizumab exhibits a significant increase in PFS and OS, underscoring the efficacy of anti-angiogenesis therapy in cervical cancer, particularly in stage IVB metastatic cervical cancer patients.

Exploring the Potential Role of Phytopharmaceuticals in Alleviating Toxicities of Chemotherapeutic Agents.

Chemotherapy is the mainstay of cancer treatment, bringing patients optimism about recurrence and survival. However, the clinical effectiveness of chemotherapeutic drugs is frequently jeopardized by their intrinsic toxicity, resulting in side effects affecting the quality of life of cancer patients. This analysis explores the ethnopharmacological impact of phytopharmaceuticals, highlighting their traditional use in many cultures. The present study, which takes its cues from indigenous knowledge, aims to close the knowledge gap between traditional medicine and modern medicine in reducing the toxicities of chemotherapy treatments. The present in-depth study aims to highlight the current research and upcoming developments in phytopharmaceuticals for reducing the toxicity of chemotherapeutic drugs. Further, we address the mechanisms through which phytopharmaceuticals may reduce chemotherapy-induced side effects that include nausea, vomiting, myelosuppression, nephropathy, neuropathy, and cardiotoxicity using data from a variety of preclinical and clinical investigations. The literature search was carried out by employing search engines such as PubMed and Google Scholar with keywords such as cancer, chemotherapy, CNS toxicity, hematopoietic toxicity, renal toxicity, GI toxicity, CNS toxicity, and phytopharmaceuticals. Bioactive chemicals found in plants, such as fruits, vegetables, herbs, and spices, are being studied for their capacity to improve the safety and acceptability of chemotherapy regimens. The current review also dives into the investigation of phytopharmaceuticals as adjuvant medicines in cancer treatment, which is a viable path for addressing the pressing need to lessen chemotherapy-induced toxicities. The present review revealed that the potential of phytopharmaceuticals in alleviating chemotherapeutic drug toxicities would pave the way for better cancer treatment and patient outcomes, harmonizing with the larger trend towards personalized and holistic approaches to chemotherapy.

Advances in Cardio-Oncology: The Emerging Role of Sglt2 Inhibitors in Cardioprotection

&amp;lt;i&amp;gt;Background: &amp;lt;/i&amp;gt;The cardiotoxic effects of anti-tumor therapies represent a critical concern in oncology, as they compromise patient survival and quality of life by inducing cardiovascular diseases. With an increasing number of cancer patients undergoing treatments such as chemotherapy and radiation, the incidence of cardiotoxicity has surged. These adverse effects underscore the necessity of early detection, risk stratification, and preventive strategies tailored to mitigate cardiotoxicity and improve patient outcomes. &amp;lt;i&amp;gt;Objective: &amp;lt;/i&amp;gt;This meta-analysis aims to systematically evaluate the effectiveness of various interventions designed to prevent or reduce cardiotoxicity associated with anti-tumor therapies. By synthesizing evidence from existing studies, we seek to identify the most effective measures, providing a comprehensive overview of the current landscape in cardioprotective strategies. &amp;lt;i&amp;gt;Methods: &amp;lt;/i&amp;gt;We conducted a comprehensive literature search, including peer-reviewed studies that investigated preventive strategies for cardiotoxicity in patients undergoing anti-tumor therapy. Inclusion criteria were studies evaluating pharmacological and non-pharmacological interventions and their effects on cardiac function and patient outcomes. Data were extracted and analyzed to assess the impact of interventions on cardiotoxicity incidence, cardiac biomarkers, and clinical endpoints. &amp;lt;i&amp;gt;Main Findings: &amp;lt;/i&amp;gt;Our analysis demonstrates a range of effective cardioprotective interventions, particularly focusing on beta-blockers, ACE inhibitors, and lifestyle modifications. Beta-blockers were found to reduce the incidence of left ventricular dysfunction, while ACE inhibitors showed promise in improving cardiac biomarkers. Additionally, lifestyle interventions, including exercise and dietary modifications, contributed to overall cardiovascular health, though further research is needed to define optimal protocols. &amp;lt;i&amp;gt;Conclusion: &amp;lt;/i&amp;gt;Preventive strategies play a pivotal role in managing cardiotoxicity in cancer patients undergoing anti-tumor therapies. Pharmacological interventions, especially beta-blockers and ACE inhibitors, show significant potential in mitigating cardiac damage, while lifestyle interventions offer supplementary benefits. Our findings underscore the importance of an integrative approach, combining pharmacological and lifestyle modifications to protect cardiac function. Future research should focus on personalized cardioprotective protocols to optimize outcomes for cancer patients, ensuring that cardiovascular health is maintained alongside effective anti-tumor treatment.

Stability of Feature Selection in Multi-Omics Data Analysis

In the rapidly evolving field of multi-omics data analysis, understanding the stability of feature selection is critical for reliable biomarker discovery and clinical applications. This study investigates the stability of feature-selection methods across various cancer types by utilizing 15 datasets from The Cancer Genome Atlas (TCGA). We employed classifiers with embedded feature selection, including Support Vector Machines (SVM), Logistic Regression (LR), and Lasso regression, each incorporating L1 regularization. Through a comprehensive evaluation using five-fold cross-validation, we measured feature-selection stability and assessed the accuracy of predictions regarding TP53 mutations, a known indicator of poor clinical outcomes in cancer patients. All three classifiers demonstrated optimal feature-selection stability, measured by the Nogueira metric, with higher regularization (fewer selected features), while lower regularization generally resulted in decreased stability across all omics layers. Our findings indicate differences in feature stability across the various omics layers; mirna consistently exhibited the highest stability across classifiers, while the mutation and rna layers were generally less stable, particularly with lower regularization. This work highlights the importance of careful feature selection and validation in high-dimensional datasets to enhance the robustness and reliability of multi-omics analyses.

Association of hTERT MNS16A polymorphism with clinical outcomes of North Indian lung cancer patients undergoing platinum-based doublet chemotherapy.

Telomerase has been linked to aging and cancer. The MNS16A polymorphism in the hTERT gene plays a significant role in modulating telomerase activity and highlights the complexity of telomere-related genetics in cancer research. We genotyped 401 lung-cancer samples treated with platinum-based chemotherapy to identify the MNS16A polymorphism. We assessed overall survival using the Kaplan-Meier method and Cox regression analysis for adjusted hazard ratios. Stratified analyses evaluated risks for subgroups based on clinicopathologic parameters, outcomes, and toxicity calculated. Our findings show no significant link between MNS16A polymorphism and lung-cancer survival. However, in squamous cell carcinoma (SQCC) patients, the SS genotype was associated with poorer survival (p = 0.004). Patients with LS + SS genotypes responded better to gemcitabine in univariate (p = 0.003) and multivariate analyses (p = 0.014). The LS genotype was linked to a lower risk of progression to stage 4 (p = 0.011) and metastasis (p = 0.015) but an increased risk of T4 tumor size (p = 0.026). No significant correlations were found between MNS16A polymorphism and treatment-related toxicities. The MNS16A polymorphism does not significantly impact overall lung-cancer survival but affects specific subgroups, influencing certain lung-cancer subtypes and treatment responses while having limited predictive value for overall outcomes or toxicity risks.

Identification of tumor-antigen signatures and immune subtypes for mRNA vaccine selection in muscle-invasive bladder cancer

BackgroundMuscle-invasive bladder cancer continues to lack reliable diagnostic and prognostic biomarkers. Recently, tumor vaccines targeting specific molecules have emerged as a promising treatment in inhibiting tumor progression, which was rekindled under the background of coronavirus disease-2019 pandemic. However, the application of mRNA vaccine targeting muscle-invasive bladder cancer–specific antigens remains limited, and there has been a lack of comprehensive studies or validations to identify suitable patient subgroups for vaccination. This study aims to explore novel muscle-invasive bladder cancer antigen signatures to identify patients most likely to benefit from vaccination. MethodsGene expression profiles of muscle-invasive bladder cancer samples, along with corresponding clinical data, were retrieved from the Cancer Genome Atlas Program. The least absolute shrinkage and selection operator model was applied to develop signatures for stratifying muscle-invasive bladder cancer patients. Prognostic accuracy of each factor was assessed using receiver operating characteristic analysis. Tumor Immune Estimation Resource was employed to visualize the relationship between the proportion of antigen-presenting cells and the expression of selected genes. The CIBERSORT and WGCNA R packages were used to identify differences in immune infiltration levels across muscle-invasive bladder cancer subgroups. Additionally, the STRING database and Cytoscape were used to construct the protein-protein interaction network. CCK-8 and colony formation assays were employed in invitro experiments. ResultsA total of 49 potential tumor antigens were identified. Using least absolute shrinkage and selection operator Cox regression, 14 tumor antigens were selected to develop a risk evaluation signature. The risk score signature can serve as a valuable tool for predicting the outcomes of muscle-invasive bladder cancer patients. Based on differential clinical, molecular, and immune-related gene profiles, muscle-invasive bladder cancer patients were classified into 2 subtypes: the immune “cold” subtype (immune score 1) and the immune “hot” subtype (immune score 2). The immune score signature, developed using a logistic score model, effectively distinguishes between patients more likely to belong to immune score 1 or 2. Notably, patients with a high risk score exhibited a higher proportion of immune score 2 compared to those with a low risk score. Additionally, the prognostic accuracy was significantly enhanced when the risk score and immune score were combined. Different tumor subtypes displayed distinct immune landscapes and signaling pathways. Moreover, novel tumor antigens associated with oxidative stress were identified. ConclusionThe risk score and immune score signatures based on tumor antigens have identified potential effective neo-antigens for the development of mRNA vaccines targeting muscle-invasive bladder cancer. Patients with low risk score and immune score 1 subtype are more likely to benefit from mRNA vaccination. Additionally, this study highlights the critical role of oxidative stress in modulating the efficacy of the mRNA vaccine.

Artificial intelligence measured 3D lumbosacral body composition and clinical outcomes in rectal cancer patients.

Patient body composition (BC) has been shown to help predict clinical outcomes in rectal cancer patients. Artificial intelligence algorithms have allowed for easier acquisition of BC measurements, creating a comprehensive BC profile in patients using data from an entire three-dimensional (3D) region of the body. This study has utilized AI technology to measure BC from the entire lumbosacral (L1-S5) region and assessed the associations between BC and clinical outcomes in rectal cancer patients who have undergone neoadjuvant therapy followed by surgery. A retrospective, cross sectional analysis was performed on locally advanced rectal cancer (LARC) patients treated with neoadjuvant long-course chemoradiotherapy followed by curative resection with total mesorectal excision at a tertiary referral centre, Western Health, Melbourne, Australia. A pre-trained and validated in-house AI segmentation model was used to automatically segment and measure intramuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and skeletal muscle (SM) from CT slices across the entire L1-S5 level of each patient. Multivariate analysis between patient BC and clinical outcomes was performed. Two hundred and fourteen patients were included in the study. One hundred and fifty-one (70.6%) patients were male and 63 (29.4%) patients were female. The average age at diagnosis was 62.4 (±12.7) years. SM density, but not volume, was associated with better overall survival (OS) (HR 0.24, P = 0.029), recurrence-free survival (RFS) (HR 0.45, P = 0.048) and decreased length of stay (LoS) (HR 1.58, P = 0.036). Both IMAT volume (HR 0.13, P = 0.008) and density (HR 0.26, P = 0.006) were associated with better OS. This study measured 3D BC from the entire lumbosacral region of rectal cancer patients. SM density was the most significant BC parameter, and was associated with improved OS, RFS and LoS. This adds to growing evidence that SM is a key component of BC in cancer patients and should be optimized prior to treatment. IMAT was also a prognostic factor, giving rise to avenues of future research into the role of adiposity on nutrition and tumour immunology.

Clinical pharmacist interventions on pain management in cancer patients (PharmaCAP) in low resource settings: a multicenter feasibility-pilot randomized controlled trial.

Cancer pain management is frequently insufficient worldwide, especially in low- and middle-income countries where significant challenges related to workforce resources persist. Clinical pharmacists could potentially enhance outcomes in this context, yet their role remains largely unexplored. This study aimed to assess the feasibility and acceptability of integrating clinical pharmacists into the multidisciplinary team (MDT) to manage cancer pain and assess preliminary outcomes in cancerpatients receiving pain treatment. This pilot study was undertaken to inform a future definitive randomized controlled trial (RCT). The protocol was registered with ClinicalTrials.gov (NCT05021393). The PharmaCAP trial was conducted in two oncology centers in Nepal, where patients were randomly enrolled into usual care (UC) or an intervention group (PharmaCAP). The latter received a clinical pharmacist-led medication review, which involved a comprehensive assessment of the patient's current medications, identification of potential drug-related problems, and personalized recommendations for optimizing pain management. This was accompanied by pain assessment, educationand counseling on pain management strategies. Baseline and 4-weeks post-intervention assessments measured primary outcomes, i.e., feasibility metrics (recruitment of the patients, retention of patients, patient satisfaction). Secondary outcomes included pain intensity, health-related QoL, anxiety, depression, barriers to pain management, and medication adherence at 4weeks. Out of 140 screened patients, 108 were evaluated for eligibility, with 16 opting out primarily due to lack of interest (n = 11) and communication barriers (n = 5). A total of ninety-two participants with cancer pain were randomized into two groups, with 91 patients successfully recruited and 85 (93.4%) completing 4weeks post-intervention assessment). Completion rates for the UC and PharmaCAP groups were 91.3% and 93.4%, respectively. The primary feasibility outcomes were positive: 100% of patients found random allocation acceptable. Retention rates were high, with 91.3% in the UC group and 93.4% in the PharmaCAP group, despite a few dropouts due to being unreachable, COVID-related issues, and changes in treatment centers. No evidence of contamination between groups was found, as participants did not discuss interventions or influence each other's attitudes, ensuring effective isolation of interventions The PharmaCAP intervention showed significant improvement in QoL (P < 0.001), physical functioning (P < 0.001), and financial difficulties (P < 0.001). There was also clinical benefit observed in anxiety and depression (P < 0.001) and enhancements in medication adherence (P < 0.001). While pain intensity decreased in both groups, the difference was not statistically significant. Satisfaction with the PharmaCAP intervention was high, with 93.0% of participants expressing satisfaction and 88.3% acknowledging that the clinical pharmacists effectively addressed their drug-related queries. Findings of this RCT demonstrate that integrating clinical pharmacists into the MDT team in low low-resource setting is feasible and shows promise in improving QoL, reducing anxiety and depression, and enhancing medication adherence among cancer patients. These findings support the feasibility of conducting a full-scale RCT. Enabling clinical pharmacists to assist with cancer pain management in low-resource settings can benefit patients, healthcare teams, and health systems. ClinicalTrials.gov NCT05021393. Registered on 25th August 2022.