• Childhood cancer predisposition study: a prospective registry and biorepository protocol.
    1 week ago
    Cancer is the most common cause of disease-related mortality in children, highlighting the urgent need for improved care in this population. It is estimated that >15% of children diagnosed with cancer harbour a germline pathogenic variant in a cancer predisposition gene which confers an increased risk to develop cancer. There are over 100 genes associated with cancer predisposition syndromes (CPSs) and greater availability and acceptability of genetic testing in the last decade has facilitated their recognition in childhood. However, individually, each of these CPSs is rare, impeding robust research and advancement of clinical care. Once a specific CPS is diagnosed, current recommendations for clinical care are based primarily on expert consensus with a 'one size fits all' approach to management. Detailed knowledge of genotype-phenotype associations and the impact of genetic modifiers is lacking, and due to strong ascertainment bias of children already diagnosed with cancer predominantly being tested for a CPS, the true cancer risk is likely overestimated.

    The Childhood Cancer Predisposition Study (CCPS) is a multi-centre registry and biorepository for children and adolescents aged 0-21 years with a clinical or molecularly confirmed CPS and their family members (NCT04511806). The study objectives are to characterise the natural history of each CPS, correlate the natural history phenotype with CPS genotype, evaluate the efficacy of standard surveillance strategies and allow future investigation into the feasibility and effectiveness of novel surveillance strategies. The principal study question is whether adherence to recommended tumour surveillance guidelines is associated with earlier detection of tumours and/or improved survival. We will also address what barriers exist that prevent adherence to surveillance guidelines. Data collected from primary subjects includes detail about the CPS, genomic data, cancer history and family cancer history, as well as information about tumour surveillance. Required biospecimen collection includes germline DNA samples, with optional collection of serial blood and stool samples. Planned enrolment is 1050 primary subjects.

    CCPS was reviewed and approved by a central IRB (WCG IRB 2020P002450) and the Research Ethics Board at The Hospital for Sick Children in Toronto (1000072286). Written informed consent is obtained from all participants. Data and specimens are available to qualified investigators by request to address specific research questions through a standardised research application process. In addition, de-identified data are available through the Pediatric Cancer Data Commons for exploration. Analysed data will be disseminated in peer-reviewed publications and at conferences including meetings inclusive of patient and family advocacy groups.

    NCT04511806.
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  • Trajectory-Based Trauma Index and Pleural Infiltration Predict Pneumothorax After CT-Guided Lung Cryoablation.
    1 week ago
    To evaluate associations of a newly developed trajectory-based trauma index (TTI) and tumor-related pleural infiltration with pneumothorax after CT-guided lung cryoablation.

    This retrospective single-center observational cohort included procedures from May 2017 through January 2026. Eligible procedures involved transpulmonary cryoablation of primary or metastatic lung malignancy in adults. Exclusions were extrapleural access, ipsilateral pleural effusion or drainage, concomitant ipsilateral microwave ablation, and incomplete data. Ablation was indicated after multidisciplinary assessment; contraindications included uncorrectable coagulopathy, active infection, anesthesia intolerance, or no safe access. The primary endpoint was pneumothorax on immediate CT or 2-hour radiography; chest tube placement before discharge was secondary. TTI, the primary exposure, summed contributions from cryoprobes and biopsy needles based on diameter, aerated-lung traversal, and pleural entry angle. Pleural infiltration was a prespecified co-exposure and relative entry height a covariate. Associations were evaluated with logistic regression.

    Ninety procedures in 69 patients were analyzed. Across 230 pleural punctures, median diameter was 2.1 mm (IQR, 2.1-2.1), aerated-lung traversal 25.0 mm (IQR, 8.9-38.7), and entry angle 52.8° (IQR, 38.8-69.9). Pneumothorax occurred in 56/90 procedures (62%; 95% CI, 51%-72%); 34/90 (38%) required chest tubes. Higher TTI was associated with pneumothorax (OR, 21.87; 95% CI, 4.47-106.99; P<.001), whereas greater pleural infiltration was associated with lower odds (OR, 0.56; 95% CI, 0.40-0.78; P<.001). TTI was associated with chest tube placement (OR, 5.02; 95% CI, 1.60-15.78; P=.006).

    In this retrospective single-center cohort, higher TTI and less extensive pleural infiltration were associated with pneumothorax.
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  • Invasive Cervical Cancer Detection After Transition to Primary Human Papillomavirus Screening: Population-Based Linkage Study in Portugal.
    1 week ago
    Invasive cervical cancer (ICC) is a key outcome for evaluating cervical cancer screening (CCS) programs. Monitoring ICC trends and distinguishing cancers detected within and outside the organized screening program are essential for assessing program impact, particularly during transitions such as the introduction of human papillomavirus (HPV) based primary screening.

    We conducted a retrospective population-based study in Portugal's Central Region (2014 - 2023). Deterministic linkage was performed between the organized CCS database and hospital morbidity records. Invasive cervical cancer cases were classified as screen-detected or non-screen-detected based on prior screening history. Incidence rates were calculated using population denominators. Poisson regression models with log link and log-transformed population offsets were fitted to estimate incidence rate ratios (IRR) comparing cytology-based (2014 - 2019) and HPV-based (2020 - 2023) periods, adjusting for temporal trends.

    A total of 654 ICC cases were included. Screening participation remained broadly stable over time. The HPV-based period was associated with a significantly higher rate of screen-detected ICC (IRR = 1.94; 95% CI 1.11 - 3.40) compared with the cytology period. In contrast, ICC incidence outside the organized screening program did not differ significantly between periods (IRR = 0.94; 95% CI 0.65 - 1.35).

    The transition to HPV-based primary screening was associated with a shift in ICC detection towards the organized screening program, without evidence of a corresponding increase in incidence among women diagnosed outside the organized screening program. These findings should, however, be interpreted with caution in light of the early phase of implementation and potential external factors influencing access to diagnosis. Overall, the results support a shift in detection within the screening pathway rather than changes in underlying disease occurrence. Strengthening integration between screening, hospital, and cancer registry data remains essential for robust evaluation of cervical cancer screening policies.
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  • Symptom Tracking for Patient-Reported Outcomes in Cancer: User-Centered Design of the AthenaCompanion Web Application.
    1 week ago
    Routine monitoring of patient-reported outcomes (PROs) during cancer treatment improves symptom control and quality of life, yet real-world uptake and sustained engagement with PRO monitoring remain suboptimal. Gamification has been shown to improve engagement with digital health interventions. User-centered design approaches are needed to ensure that gamified PRO tools are acceptable, usable, and responsive to patient and clinician needs, especially for older adult users.

    This study aimed to develop a gamified symptom monitoring web application for older adult patients with cancer using a multiphase, iterative, and user-centered approach.

    The overall study design was a mixed-methods user-centered design study involving 3 phases. From 2022 to 2026, participants were recruited across online and clinical settings using multiple strategies, including ResearchMatch (Vanderbilt University Medical Center), clinician referrals, professional networks, and outreach through the electronic health record at an academic medical center. Phase 1 was a survey of older adults with chronic health conditions. They reported on symptom severity, mobile health (mHealth) preferences, and gamification preferences, which were analyzed descriptively. Phases 2 and 3 involved semistructured interviews with older adult cancer survivors and clinicians, respectively, to identify actionable feedback, followed by iterative usability testing with older adult cancer survivors.

    In Phase 1, older adults (n=216) with chronic conditions reported high frequency of mobile phone use (across 11 mobile phone behaviors, mean 6.1, SD 1.63 where 6 indicates daily use) and generally favorable attitudes toward gamification (across 18 gameful design elements, means ranged from 2.8-4.3 on a 1-5 scale and SDs ranged from 0.75-1.12), with learning elements rated most appealing (mean 4.3/5, SD 0.75). Concerns about a gamified mHealth app included data privacy and perceived trivialization of health. Phase 2 interviews (n=7) demonstrated strong interest in longitudinal symptom visualization and clinician-sharable reports; gamified content was viewed as engaging by most participants but was preferred as optional. In Phase 3, iterative clinician interviews (n=5) and patient usability testing (n=9) led to substantial refinements, including simplified navigation, enhanced visual accessibility, further guidance on score interpretation with embedded educational videos, and de-emphasis of the gamified travel learning component. Across usability testing rounds, the number of user experience problems per interview decreased from 17 to 4, indicating improved usability.

    Using a multiphase, mixed methods, user-centered design process, we developed AthenaCompanion (Northwestern University with The Ohio State University), a gamified web application for PRO monitoring tailored to older adults undergoing cancer treatment. Across surveys and interviews, patients emphasized the importance of clinical utility, clarity of symptom feedback, and low-pressure, optional gamification elements. This work demonstrates the feasibility of integrating gamification into PRO monitoring and provides a foundation for future work evaluating long-term usability, engagement, and clinical effectiveness in real-world oncology care.
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  • Perceptions of a Culturally Tailored Narrative Video for Skin Cancer Prevention Among Spanish-Speaking Hispanic Outdoor Workers: Exploratory Study.
    1 week ago
    Outdoor workers receive significantly more UV radiation exposure than indoor workers, increasing their skin cancer risk. Hispanic individuals comprise a large proportion of the outdoor workforce in the United States, but have limited access to culturally tailored prevention resources.

    This exploratory study assessed the perceptions of a culturally tailored narrative video to promote skin cancer prevention among Spanish-speaking Hispanic outdoor workers.

    A qualitative study was conducted using two focus groups with Hispanic outdoor workers. Prior to viewing the video, participants completed surveys assessing sociodemographic factors, sun exposure, and protective behaviors. Focus group discussions explored video comprehension, cultural relevance, emotional engagement, and dissemination strategies. Quantitative data were summarized descriptively, and qualitative data were analyzed using rapid qualitative analysis.

    Among 19 participants, the mean age was 46.5 (SD 15.5) years, and 94.7% (18/19) identified as male. While 47.4% (9/19) reported 6-9 hours of outdoor work per day, more than half (10/19, 52.6%) reported not engaging in sun protection. Participants described the video as culturally resonant, realistic, and engaging. Identification with characters and family-centered themes increased perceived relevance and message credibility. Many participants reported increased awareness of skin cancer risk and greater confidence in adopting sun-protective behaviors. Dissemination recommendations included workplaces, social media, schools, daycares, clinics, and other community settings.

    Our video shows promise in improving skin cancer awareness and prevention, reflecting strong acceptability among participants. Future randomized controlled studies are needed to assess its effectiveness in enhancing long-term sun-protective behaviors.
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  • Clinical Significance of SOX2 Promoter Methylation in Breast Cancer Prognosis.
    1 week ago
    IntroductionSOX2, a key pluripotency gene, plays a central role in breast cancer stem cell (BCSC) biology, driving tumor aggressiveness. Although SOX2 dysregulation has been widely studied across various cancers, its specific regulatory mechanisms in breast cancer (BC) remain incompletely elucidated. This study examined the regulatory axis of the SOX2 gene and associated molecular mechanisms underlying BCSC maintenance and prognosis.MethodsThis retrospective cross-sectional study analyzed breast tumor tissues and adjacent normal controls collected consecutively from two tertiary hospitals. SOX2 promoter methylation was assessed using methylation-Specific PCR, and expression of SOX2, DNMT3b, TET3, miR-200b-3p, and TGFβ1 was quantified by qPCR.ResultsAberrant methylation of the SOX2 promoter, linked to increased expression, was observed in the BC cohort. Notably, several samples exhibited a poised promoter state, reflecting an epigenetic configuration associated with stemness. Upregulation of DNMT3b in miR-200b-reduced cells was significantly associated with SOX2 promoter methylation, suggesting a feedback loop modulating methylation dynamics. Additionally, a positive association between deregulated TET3 and TGFβ1 highlights a positive feedback loop in the dynamic tumor microenvironment. SOX2 methylation emerged as a strong prognostic marker, characterized by a low hazard ratio and high diagnostic sensitivity. Its combination with DNMT3b improved specificity (SE = 90%, SP = 79%). Reduced TET3 and miR200b expression correlated with poor outcomes, and their integration with SOX2 formed a tri-gene signature that enhanced patient stratification. Correlation analyses revealed coordinated expression among SOX2, TET3, and TGFβ1, supporting their role in methylome regulation.ConclusionThe findings underscore the clinical significance of this axis and its embedded feedback circuits in shaping BC progression and therapeutic response.
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  • Assessing the Impact of Patient Selection and Analytical Methods on mRNA Biomarker Identification in Ovarian Cancer Using TCGA Data.
    1 week ago
    IntroductionThe Cancer Genome Atlas (TCGA) data has been extensively used for differentially expressed genes (DEGs) discovery and validation in high-grade serous ovarian cancer (HGSOC), however platinum-sensitivity biomarkers have not yet reached clinical application. We aimed to propose a robust analytical framework for TCGA platinum sensitivity studies and systematically demonstrate how patient characteristics influence DEG analyses between platinum-sensitive and resistant groups, while also considering experimental platforms and analysis pipelines, as their impact is recognized but not comprehensively evaluated.MethodsThis retrospective TCGA cohort study used publicly available microarray and RNA-seq gene expression data. TCGA-derived datasets were identified through a literature review, including only studies enabling unambiguous patient identification. Three TCGA-based cohorts were assembled-two directly from published studies and one curated through own selection-differing in patient numbers (230, 201 and 142 patients, respectively) and stage distribution. Data were analyzed using DESeq2, edgeR, limma-voom, and Wilcoxon rank-sum test to compare the impact of patient selection and pipeline choice on DEGs outcome. Genes with an adjusted p-value < 0.05 and an |log2 fold change| > 2 were considered differentially expressed.ResultsThe three cohorts showed partial overlap of DEGs across platforms and pipelines. Both patient selection and analytical workflow influenced which genes were identified, highlighting findings variability even when using the same TCGA dataset. We establish a robust analytical framework for TCGA HGSOC biomarker studies, including the provision of patient barcodes and openly shared workflows that enable straightforward replication of our analyses from data download to DEG analysis.ConclusionsReproducibility of TCGA studies is limited by variability in patient selection, platinum sensitivity definitions, data sources, and analysis pipelines. We addressed these factors by providing a robust framework that can serve as a template for data analysis and transparent reporting when identifying and validating predictive signatures of platinum sensitivity in HGSOC patients.
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  • Percutaneous Hepatic Perfusion: Continuum of Nursing Care and Safety Implications for Managing Patients With Metastatic Uveal Melanoma.
    1 week ago
    Uveal melanoma is a rare cancer that can metastasize to the liver. Percutaneous hepatic perfusion (PHP) is a minimally invasive technique that delivers melphalan directly to the liver to treat metastatic uveal melanoma.

    This article presents nursing care and safety recommendations across all phases of the PHP procedure for patients with metastatic uveal melanoma.

    A multidisciplinary team of subject matter expert nurses, along with a clinic-based physician assistant, reviewed current literature, clinical guidelines, and trial protocols. The team identified best practices for nursing care during clinic visits, preprocedure preparation, intraprocedure monitoring, hazardous drug safe handling, postprocedure care, critical care and recovery, and follow-up.

    Collaborative nursing care across specialties is essential for the safe and effective delivery of melphalan via PHP. These recommendations provide guidance on patient assessment, monitoring, management of adverse events, and patient education. As PHP becomes more widely used nationally, nurses unfamiliar with this specialized procedure will benefit from structured, evidence-informed care protocols.
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  • Enhancing the Delivery of Educational Content for Patients Starting Cancer Treatment.
    1 week ago
    Oncology nurses educate patients and caregivers about treatment. At one cancer center, treatment education was previously delivered via an in-person group class offered twice weekly to adults. This educational approach strained available resources, prompting the team to identify a new method for educating patients.

    This quality improvement initiative aimed to implement a longer interval between patient education and first treatment to enhance patients' retention of educational content and maintain resource-neutral workflows.

    Educational videos were developed and made available in the patient portal, via email, or for in-clinic viewing by the patient or caregiver. Scripting was developed for nurses to conduct teach-back during follow-up calls, which standardized content and teach-back delivery. The time from patient education to treatment initiation was compared for different educational methods.

    This quality improvement project increased the length of time between patient education delivery and cancer treatment initiation. Patients and nurses reported satisfaction with the new process, and patients appreciated the opportunity to directly ask a nurse questions.
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  • Perspectives on Palliative Care Among Patients With Pancreatic Cancer: A Pilot Study.
    1 week ago
    Palliative care (PC) is specialized health care that can improve quality of life for patients with cancer. However, PC tends to be underutilized or relegated to end-of-life care, limiting patients' ability to benefit from patient-centered, goal-concordant care. Patients with pancreatic cancer, who are often diagnosed at an advanced stage and with high symptom burdens, could benefit from PC. A chart review conducted in 2022 at a southern New Jersey academic medical center and cancer center found that among 77 patients diagnosed with cancer, only 26 were referred to palliative care services. Of those referred, just 6 received referrals for goal-concordant care discussions; the remaining 20 were referred primarily for cancer-related pain and symptom management or hospice care.

    This pilot observational quality improvement study sought to increase PC referrals for patients with pancreatic cancer, and to determine whether the PC received was goal concordant.

    Patients (N = 19) received referrals to PC and completed pre- and postvisit surveys.

    All patients who completed the postvisit survey (N = 9) expressed satisfaction with care received from the PC team. However, there were significant delays from diagnosis to the PC visit. Nurses support oncology care and tend to be aware of patients' needs; including nurses in discussions about PC may be a mechanism to increase referrals for this patient population.
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