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Overweight status predicts improved overall survival after radical nephroureterectomy for upper tract urothelial carcinoma.2 weeks agoUpper urinary tract urothelial carcinoma (UTUC) is a rare malignancy, particularly in the ureter, and is associated with high rates of recurrence and metastasis. Although body mass index (BMI) has been associated with prognosis in multiple cancer types, its role as a predictive factor in UTUC is still debated. This study aimed to investigate how BMI influences survival outcomes in patients with UTUC treated with radical nephroureterectomy (RNU).
This multi-center retrospective analysis by the Taiwan UTUC Collaboration Group involved 2503 patients who underwent treatment across 19 hospitals from 1988 to 2022. Patients were categorized into normal (18.5 ≤ BMI < 24), overweight (24 ≤ BMI < 27), and obese (BMI ≥ 27) groups. Demographic, clinical, and pathological data were analyzed. Overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and intravesical recurrence-free survival (IVRFS) were assessed using Kaplan-Meier analysis and Cox proportional hazards models.
The median follow-up period was 44.2 months. In multivariable analysis, overweight patients demonstrated significantly better OS compared with normal-weight patients (p = 0.033), and the obesity group showed a favorable, though not statistically significant, trend toward better OS. However, BMI was not an independent predictor of CSS, DFS, or IVRFS. Independent predictors of worse outcomes included older age, end-stage renal disease, ureteral tumor location, tumor size ≥3 cm, and high-grade urothelial carcinoma. Tumor stage and grade were comparable across BMI groups.
Overweight status was associated with better OS in patients with UTUC treated with RNU, while BMI had no significant impact on CSS, DFS, or IVRFS. These findings suggest a potential protective effect of higher BMI on OS, warranting further investigation in prospective studies. However, BMI alone should not guide clinical decisions and may instead reflect broader patient health characteristics.CancerAccessCare/ManagementAdvocacy -
Co-expression of CCR7 and H3K9me3 identifies aggressive B-cell lymphoma with bone marrow infiltration and poor prognosis.2 weeks agoB-cell lymphoma exhibits significant clinical heterogeneity, necessitating improved biomarkers for risk stratification. C-C chemokine receptor 7 (CCR7) and trimethylation of histone H3 lysine 9 (H3K9me3) are implicated in cellular senescence and tumor invasion. While the clinical significance of their co-expression in lymphomagenesis remains unclear. This study aims to define the expression profiles of CCR7 and H3K9me3 in B-cell lymphoma, explore their correlation with aggressive clinical indicators, and evaluate their combined prognostic value.
The expression of CCR7 and H3K9me3 in tumor tissues from B-cell lymphoma patients was analyzed by immunohistochemical (IHC) double-staining. The mechanistic association between the two was verified by co-immunoprecipitation assays and Western blot (WB) experiments detecting changes in cellular H3K9me3 levels following CCR7 ligand stimulation. The association between co-expression and patient clinical parameters, tumor burden, and progression-free survival (PFS) was evaluated through correlation analysis, Kaplan-Meier survival curves, and Cox regression analysis.
H3K9me3 expression was predominantly nuclear, whereas CCR7 was expressed on the cell membrane. Both markers were significantly upregulated in aggressive lymphomas and positively correlated with LDH, β2-microglobulin, and neutrophil percentage. An interaction between CCR7 and H3K9me3 could be demonstrated in that CCR7 ligand stimulation resulted in an upregulation of H3K9me3 expression. Enhanced H3K9me3 expression was associated with bone marrow infiltration. High expression of CCR7 was associated with poorer progression-free survival (PFS), whereas high expression of both CCR7 and H3K9me3 identified patients with the worst prognosis. Univariate and multivariate Cox regression analysis indicated that the combined expression was a potential prognostic biomarker for B-cell lymphoma.
Co-elevated CCR7 and H3K9me3 expression defines a high-risk B-cell lymphoma subgroup with high tumor burden, bone marrow infiltration, and poor prognosis, highlighting their potential as biomarkers for risk stratification and candidate therapeutic targeting.CancerAccessCare/ManagementPolicyAdvocacy -
Characterization of aberrant alternative splicing landscape in patients with metastatic renal cell carcinoma.2 weeks agoAberrant alternative splicing (AS) events have been implicated in cancer progression; however, their role in metastatic renal cell carcinoma (mRCC) remains underexplored. This study aims to identify AS events associated with clinical benefits from immune checkpoint inhibitors and targeted therapies in mRCC.
We conducted a retrospective analysis on 101 patients with mRCC who received systemic therapy and underwent RNA sequencing. Patients were divided into subgroups based on ICIs (alone or in combination) and targeted therapies. Responders and non-responders were classified according to Response Evaluation Criteria in Solid Tumors V.1.1 criteria. Differential gene expression and splicing analyses were performed between responders and non-responders in each cohort. Novel AS events were analyzed for their potential to generate peptide neoantigens through major histocompatibility complex (MHC) class I binding predictions.
Outlier splicing analysis identified 10 aberrant splice events specific to mRCC. AS analysis revealed 461 differentially spliced events between responders and non-responders in the ICI cohort and 253 in the targeted therapy cohort, with intron retention as the predominant motif. Thirteen unique AS events were enriched in responders, including PTPN6 and ACTN1. Predictive neoantigen analysis identified high MHC class I binding potential in peptides from AS events in IFFO1 and ZNF692. High splice burden was linked to an immunogenic tumor microenvironment, characterized by enriched antigen processing and adaptive immune responses.
This study provides a comprehensive analysis of AS events in mRCC, highlighting intron retention as potential biomarkers for treatment response. Identified AS-derived neoantigens may serve as potential targets for adoptive cell therapy strategies.CancerAccessCare/ManagementAdvocacy -
Transarterial chemoembolisation-based combination therapy as a potential new standard for intermediate-stage hepatocellular carcinoma in the targeted immunotherapy era.2 weeks agoTransarterial chemoembolisation (TACE) is the standard therapy for intermediate-stage hepatocellular carcinoma (HCC); however, its efficacy is limited by significant tumour heterogeneity. Recent landmark trials (EMERALD-1 and LEAP-012) demonstrated that adding targeted immunotherapy to TACE significantly improves progression-free survival compared with TACE alone. However, the inconsistent overall survival (OS) benefit, particularly in LEAP-012, highlights the necessity for precision patient stratification. Key determinants of outcomes include tumour burden, liver function, microvascular invasion (MVI), systemic inflammation, immune status and comorbidities. For patients with low tumour burden, optimised locoregional therapies can achieve higher complete response rates. For high tumour burden, multimodal strategies are required, with increasing evidence supporting TACE plus targeted therapy with or without immunotherapy. MVI-positive HCC derives added benefit from adjuvant tyrosine kinase inhibitors (TKIs) after TACE, while dynamic liver function monitoring is crucial for safety, especially in patients with Child-Pugh B. Future directions should focus on developing and validating robust multidimensional stratification models. These models should integrate key established determinants-such as tumour burden, liver function reserve, MVI, systemic inflammatory/immune status, alpha-fetoprotein (AFP) and comorbidities-with promising emerging biomarkers (eg, circulating tumour DNA). Concurrent efforts are needed to optimise combination regimens and conduct health-economic evaluations. Global collaboration and cost-effectiveness analyses are essential to prioritise high-benefit subgroups (eg, those with high tumour burden, MVI positivity and/or mild inflammation, active immune status alongside preserved liver function and limited comorbidities) for intensive combination therapy while avoiding overtreatment in lower-benefit populations.CancerAccessCare/Management
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Comparing the Asia-Pacific Colorectal Screening and adjusted Asia-Pacific Colorectal Screening scores for risk stratification of advanced colorectal neoplasia in asymptomatic Vietnamese: a cross-sectional study.2 weeks agoThe Asia-Pacific Colorectal Screening (APCS) score is a validated tool for predicting advanced colorectal neoplasia (ACN) in the Asia-Pacific region. An adjusted APCS (A-APCS) score was recently developed by incorporating body mass index into the original score and was reported to outperform the original score but lacked external validation. This study aimed to compare the A-APCS score with the original APCS score in asymptomatic Vietnamese individuals.
A cross-sectional study.
Dai Phuoc Polyclinic, Ho Chi Minh City, Vietnam.
Asymptomatic individuals underwent colonoscopy screening.
Participants were categorised into three risk groups based on the sum of the APCS and A-APCS scores: average risk (AR), moderate risk (MR) and high risk (HR). The performance of the two scores was compared via receiver operating characteristic (ROC) analysis and McNemar tests.
A total of 714 participants (median age 51 years, range: 18-79; female-to-male ratio: 1:1.46) were included, with an ACN prevalence of 9.0%. Both scores indicated effective predictive ability for ACN in the HR group compared with the AR group, with OR=3.878 (95% CI 1.777 to 8.068) and 3.266 (95% CI 1.617 to 6.595), respectively. The A-APCS score was more effective than the APCS score in predicting ACN in the MR group than in the AR group. However, no significant differences in area under the ROC curve were observed between the two scores for ACN prediction.
Compared with the APCS score, the A-APCS score may not provide improved ACN risk stratification in asymptomatic Vietnamese individuals. Both scores are suboptimal and should be used to prioritise, rather than exclude, candidates for colonoscopy.CancerAccessCare/ManagementAdvocacyEducation -
Factors influencing adherence to intravesical instillation therapies for non-muscle-invasive bladder cancer: a scoping review protocol.2 weeks agoNon-muscle-invasive bladder cancer is often treated with repeated weekly intravesical instillations of chemotherapy or immunotherapy. The number of instillations received influences the risk of recurrence and progression; thus, treatment completion is crucial. However, previous research indicates that nearly half of patients do not adhere to treatment for various reasons. This scoping review aims to define the concept of treatment adherence to intravesical instillation therapies and identify and map the factors that influence treatment adherence in intravesical instillation therapies.
This scoping review will adhere to the Joanna Briggs Institute's Manual for Evidence Synthesis and will be reported in accordance with the PRISMA Extension for Scoping Reviews. A comprehensive search strategy will be employed to guide the literature search across databases, including MEDLINE, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Central Register of Controlled Trials.We will include studies on intravesical instillation therapies with BCG or Mitomycin C for non-muscle-invasive bladder cancer, as well as studies that describe factors influencing patients' adherence to treatment. Screening of abstracts and full texts, as well as data charting, will be performed independently by two researchers using the Covidence software. We will collect and chart data concerning characteristics of the source and setting, treatment specifics, reasons for non-adherence and any factors that affect adherence.We will summarise each included source and present the identified factors in a narrative synthesis. Furthermore, we will describe how the results inform the review objective.
Ethical approval is not required for this scoping review, as all data have been published. The findings of the scoping review will be disseminated in a scientific publication and widely presented to researchers, healthcare professionals and patients.CancerAccessCare/Management -
Association between comorbidities and differences in treatment decisions and outcomes in patients with colon or rectal cancer: a systematic review.2 weeks agoTo systematically evaluate associations between comorbidities and differences in treatment decisions, outcomes, health-related quality of life (HRQoL), healthcare resource utilisation and costs, in patients with colon or rectal cancer.
Systematic review.
PubMed (Medline) and Embase databases were searched for studies published from January 2000 until January 2024.
We included articles that compared the presence and absence of comorbidities, evaluated multiple comorbid conditions or used the Charlson Comorbidity Index, or variations such as the Charlson-Deyo Index. Primary and secondary outcome measures included cancer treatments, outcomes (including complications from treatments, survival and mortality rates), HRQoL, healthcare resource use and costs.
Two independent reviewers used standardised methods to search, screen and code included studies. Risk of bias was assessed using the Joanna Briggs Institute checklists to ensure the quality of data. Findings were summarised narratively.
After duplicates were removed, 15 394 hits were screened and 31 studies were selected for inclusion in this systematic review. Comorbidities were associated with a lower likelihood of receiving treatment and lower survival rates and HRQoL, alongside a higher likelihood of complications following treatment, higher mortality rates and higher healthcare resource use. There were very limited studies that reported on HRQoL and resource use, and none reporting data directly relating to the impact of comorbidities on costs. These results were consistent across North America, Europe, Australia and New Zealand.
For patients with colon and rectal cancer, comorbidities are associated with a lower likelihood of receiving treatments and poorer health outcomes. With global populations ageing, there is likely to be an increase in patients with colon and rectal cancer with comorbidities. Therefore, further research is necessary, especially to inform decisions regarding patient management and treatment, and to understand the implications on healthcare resource allocation, costs and HRQoL.CancerAccessCare/ManagementAdvocacy -
Closing the Gap to Interventions for Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders (TAND): Protocol for a Longitudinal Study of TAND Severity, Predictors, and Caregiver Well-Being (TANDem-2).2 weeks agoTuberous sclerosis complex (TSC) is a rare genetic disorder caused by pathogenic variants in the TSC1 or TSC2 genes. Apart from multisystem physical manifestations, most individuals with TSC experience TSC-associated neuropsychiatric disorders (TAND). Little is known about how TAND severity changes over time and what factors may predict these changes. Preliminary data suggest the presence of differential TAND severity trajectories. Caregiver well-being may act as a mediator of TAND severity, and a well-being intervention designed for caregivers of children with developmental disabilities may improve caregiver well-being.
The study aims are to (1) examine longitudinal trajectories of TAND severity in a large sample of individuals with TSC and to examine potential predictors of differential trajectories, (2) evaluate the association between caregiver well-being characteristics, TAND severity, and severity trajectories, and (3) adapt and evaluate the feasibility, acceptability, and potential efficacy of a brief, online group-based well-being intervention for family caregivers.
For the first 2 aims, 500 individuals with TSC or their caregivers will be recruited in an accelerated longitudinal design to document TAND severity at 5 time points over 12 months via a web-based app. At each time point, participants will complete demographic, TSC characteristics, intervention, and well-being questionnaires. Data will be analyzed using latent class mixed and multinomial regression modeling (aim 1) and structural equation and mediation modeling (aim 2). Participatory methods will be used to adapt an existing caregiver well-being intervention for the TSC community (aim 3). Thirty caregivers will be invited to participate in the adapted group-based online well-being intervention.
This study was funded from July 2024 (HT94252410790 and HT94252410791), and ethics approvals were obtained from the University of Cape Town (July 2024), Vrije Universiteit Brussel (November 2024), and the Department of Defense Office of Human Research Oversight (December 2024). The TAND Toolkit app was adapted for longitudinal data collection (aims 1 and 2). Recruitment started in December 2025 and will continue until 500 participants are enrolled (anticipated December 2026). Primary outputs are expected by July 2028. For aim 3, experiential and adaptation workshops were completed in June 2025, the pilot intervention was delivered in November 2025, and data collection will continue till May 2026. Outputs are expected by December 2026.
Identification of differential longitudinal TAND trajectories and their correlates will stimulate research in TSC and generate evidence for the self-report quantified TAND checklist as a clinical outcome measure. Understanding the association between caregiver well-being and TAND severity will provide support for targeted well-being interventions. A successful pilot trial will provide preliminary data for larger-scale clinical trials, with the potential to support caregivers and improve TAND outcomes. Together, the findings from the study will help close the gap in interventions for TAND.
ClinicalTrials.gov NCT06879665; https://clinicaltrials.gov/study/NCT06879665.
DERR1-10.2196/91726.CancerMental HealthAccessCare/ManagementAdvocacy -
Sarcopenia in Patients With Cancer and Its Association With Chemotherapy-Induced Peripheral Neurotoxicity.2 weeks agoChemotherapy-induced peripheral neurotoxicity (CIPN) is the most common neurologic complication of cancer treatment. Sarcopenia, characterized by muscle mass loss, has been associated with treatment-related toxicity, but its association with CIPN remains unclear. We aimed to assess the association of pretreatment sarcopenia with the development of CIPN.
A single-center, prospective observational study at the Hospital Universitari de Bellvitge-Institut Català d'Oncologia was conducted on patients with cancer scheduled to receive brentuximab vedotin (BV), oxaliplatin (OXA), or paclitaxel (PTX). A pretreatment CT or PET-CT (≤30 days) was required. Sarcopenia was assessed using the skeletal muscle index at the third lumbar vertebra. Patients were evaluated before (T0) and after (T1) chemotherapy treatment. All patients were assessed using the Total Neuropathy Score-clinical version (TNSc) and Common Terminology Criteria for Adverse Events (CTCAE) at T0 and T1. Nerve conduction studies (NCS) and blood measurements (neurofilament [NfL], myostatin, and albumin) were conducted at the same time points. Clinically relevant (CR) CIPN was defined as CTCAE grade ≥2. Associations were analyzed using multivariate logistic regression.
A total of 105 patients (47.6% female; median age 55 years) were studied. Before treatment (T0), 47.6% of patients had sarcopenia. CIPN occurred in 84.7% of patients, with CR-CIPN observed in 39% (33.3% grade 2; 5.7% grade 3). At T1, NfL and TNSc scores increased significantly, while distal sensory and motor NCS amplitudes decreased. Sarcopenia was more common in patients developing CR-CIPN (61.9% vs 38.1%; p = 0.028). Multivariate analysis identified sarcopenia as an independent risk factor of CR-CIPN (odds ratio [OR] 2.5; 95% CI 1.07-5.83; p = 0.033), and patients receiving microtubule-based agents-PTX (OR 0.17, 95% CI 0.03-0.92, p = 0.04) or BV (OR 0.37, 95% CI 0.15-0.90, p = 0.027)-had lower odds of CR-CIPN compared with those receiving OXA.
Pretreatment sarcopenia is associated with 2.5-fold higher odds of moderate-to-severe CIPN. Assessing sarcopenia using routine prechemotherapy imaging techniques can help identify individuals at higher risk of CR-CIPN.CancerAccessCare/ManagementAdvocacy -
Attitudes and Willingness to Participate in Drug Clinical Trials Among Patients With Cancer: Multistage Qualitative Study.2 weeks agoCancer clinical trials are essential for advancing therapeutic innovations; however, patient enrollment remains a persistent challenge globally. Understanding the attitudes and willingness of patients with cancer to participate in clinical trials is critical for improving recruitment strategies. While previous studies have explored barriers and facilitators, few have integrated multiple data sources or used emerging analytical approaches, such as large language models (LLMs), to capture the multidimensional nature of patient decision-making. Furthermore, limited research has examined these perspectives within the Chinese health care context, where cultural, economic, and systemic factors may uniquely influence participation decisions.
This study aimed to examine the attitudes and willingness of patients with cancer to participate in drug clinical trials in China by (1) identifying key themes influencing patients' decision-making processes, (2) comparing thematic findings derived from investigator-led qualitative analysis with those generated by 2 LLMs (Gemini Pro 2.5 and DeepSeek R1), and (3) evaluating the complementary value of hybrid analytical approaches in qualitative health research.
A multistage qualitative study was conducted using 2 data sources: semistructured face-to-face interviews with patients with cancer (n=11) from a tertiary hospital in Shanghai and publicly available comments from 2 Chinese online health communities (Zhihu and Yuaigongwu). Of the 3148 initial comments, 219 met the inclusion criteria after systematic screening. Three parallel analytical approaches were used: investigator-led thematic analysis, Gemini Pro 2.5-assisted analysis, and DeepSeek R1-assisted analysis. Both LLMs received identical, structured prompts. Thematic outputs were systematically compared to identify convergent and divergent findings.
The 3 analytical methods jointly identified 7 core themes: treatment selection, financial burden relief, uncertain therapeutic efficacy, uncertainty regarding control groups, lack of cognition, misconceptions, and physician trust. Substantial thematic overlap was observed between investigator-led and DeepSeek R1 analyses (8 shared themes, including family-involved decisions and service-related factors) and between investigator-led and Gemini Pro 2.5 analyses (3 shared themes, including regional disparities and autonomous decision-making). Method-specific themes included recognition of medical value (investigator only), insufficient clinical data (DeepSeek R1 only), and lack of information resource (Gemini Pro 2.5 only). These findings highlight the multidimensional nature of trial participation decisions, encompassing treatment expectations, economic considerations, risk perceptions, cognitive factors, trust relationships, and structural barriers to accessibility.
The willingness of patients with cancer to participate in clinical trials is shaped by a complex interplay of treatment expectations, economic considerations, risk perceptions, cognitive factors, and relational dynamics. The hybrid analytical framework demonstrated complementary strengths: human analysis provided contextual depth and cultural sensitivity, while LLMs offered efficiency and identified additional thematic dimensions. These findings underscore the need for patient-centered communication strategies, transparent trial information, and culturally tailored recruitment approaches. Future research should expand sample diversity and further validate the use of LLMs in qualitative health research.CancerAccessCare/ManagementAdvocacy