Metronomic chemotherapy with oral capecitabine + vinorelbine (Cape + VNL) provides synergistic cytostatic activity and antiangiogenic and immunomodulatory effects, potentially offering prolonged disease control with limited toxicity in HER2-negative metastatic breast cancer (MBC). However, efficacy in the real-world (RW) setting, especially in late lines, and the impact of dihydropyrimidine dehydrogenase (DPYD) polymorphisms on dose reduction and safety remain limited.

In this retrospective study, 200 patients with human epidermal growth factor receptor 2 (HER2)-negative MBC were treated at the ASST Cremona Hospital (2015-2023) with metronomic Cape (1000 mg twice daily, in normal metabolizers; 500 mg twice daily, in DPYD variant carriers) + VNL (20 mg/day, once daily, 5-days-on/2-days-off). All patients underwent pretreatment DPYD genotyping and dose adjustment. Treatment was administered in the second-to-fourth setting. The primary end point was time-to-next treatment or death (TNTD); secondary end points included overall survival (OS), disease control rate (DCR) ≥24 weeks, overall response rate (ORR), safety, and genotype-toxicity correlations.

The median age was 61 years, and DPYD variants were present in 14.5% of patients; 34%, 41%, and 25% received therapy as second-, third-, and fourth-line treatment. The median TNTD was 22.0 weeks, and the OS was 64.0 weeks. The DCR was 38.5%, and the ORR was 22.0%. Efficacy was comparable between DPYD variant carriers and normal metabolizers (all P values > .05). In later lines, Eastern Cooperative Oncology Group performance status 2 and >2 metastatic sites were independent negative prognostic factors (all values P < .05). Overall, 7.5% grade 3 toxicities occurred, especially in variant carriers without dose reduction and grade 4-5 events.

These RW data suggest that metronomic Cape + VNL may represent a clinically active and manageable option in heavily pretreated HER2-negative MBC. Our findings support prospective evaluation of DPYD-guided dose individualization as a strategy to optimize the benefit-risk balance of fluoropyrimidine-based metronomic regimens.

Ropeginterferon alfa-2b, a novel monopegylated interferon with improved pharmacokinetics, has emerged as a promising cytoreductive agent for managing polycythemia vera (PV). Despite increasing adoption, evidence synthesis of its efficacy and safety compared to standard care remains limited. The manuscript aimed to evaluate the efficacy of ropeginterferon alfa-2b in comparison to standard treatment options, including hydroxyurea and phlebotomy, in achieving complete hematologic response, partial molecular response (PMR), and reducing JAK2V617F allele burden in patients with PV.

A systematic search of 4 databases was conducted up to April 2025, following PRISMA 2020 guidelines. Randomized controlled trials (RCTs) comparing ropeginterferon alfa-2b with standard therapies in PV patients were included. Meta-analyses were performed using random-effects models to derive odds ratios for dichotomous outcomes and mean differences (MDs) for continuous outcomes. Sensitivity and subgroup analyses were conducted, and risk of bias was assessed using RoB 2.0.

Three RCTs comprising 522 patients were analyzed. Ropeginterferon alfa-2b showed no statistically significant advantage overall or over hydroxyurea for complete hematological response (CHR), PMR, or JAK2 allele burden reduction. However, subgroup analyses revealed significant benefits over phlebotomy alone in all 3 outcomes: CHR (odds ratio [OR] 3.05; 95% confidence interval [CI]: 1.36-6.80; P = .007), PMR (OR 36.34; 95% CI: 2.11-625.93; P = .01), and allele burden reduction (MD -13.70; 95% CI: -19.24 to -8.16; P < .00001).

Ropeginterferon alfa-2b demonstrates no statistically significant difference compared to hydroxyurea, but gives better outcomes over phlebotomy in short-term efficacy for PV management. Its favorable molecular and hematologic outcomes support its role as a disease-modifying therapy, particularly in low-risk patients. However, larger and longer-term trials are needed to confirm these benefits across broader populations.

Metaplastic breast cancer (MBC) is a rare and aggressive form of breast cancer. The effectiveness of chemotherapy followed by radiotherapy (CFRT) for MBC remains controversial. The present study aimed to evaluate the efficacy of CFRT on MBC patients with N0M0. A retrospective study was performed to analyze MBC from the surveillance, epidemiology, and end results database. Breast cancer-specific survival (BCSS) and overall survival (OS) rates were analyzed using the Kaplan-Meier curve. Cox proportional hazard models were used to assess BCSS and OS. CFRT might be a valid therapeutic strategy for MBC with N0M0, especially considered with surgical planning. Of the 4672 MBC patients in the surveillance, epidemiology, and end results registry, our final sample comprised 2260 patients. A total of 602 (26.6%), 292 (12.9%), 638 (28.2%), and 728 (32.2%) patients received non-therapy, only-radiotherapy, only-chemotherapy, and CFRT, respectively. Age, tumor size, tumor grade, surgery, and therapy types were independent indicators for BCSS. The Kaplan-Meier analysis showed that total mastectomy (TM) not breast-conserving surgery (BCS) improved BCSS of MBC receiving CFRT, whereas OS of MBC receving CFRT can not benefit from surgical type. Further exploration illustrated that, for BCSS, only stage T2 and T3 MBC patients underwent BCS and only stage T3 MBC patients underwent TM could benefit from CFRT. However, for OS, all stage MBC patients underwent BCS and only stage T3 MBC patients underwent TM could benefit from CFRT.

Patients with malignant bone and soft tissue tumors of the lower limbs frequently encounter substantial postoperative pain, delayed functional recovery, and adverse psychological reactions. Conventional nursing care may not adequately address these complex needs during the perioperative period. This study aimed to assess the efficacy of a comprehensive whole-course nursing model - encompassing preoperative education, perioperative care, postoperative rehabilitation, and psychological support - in enhancing clinical outcomes for patients undergoing limb salvage surgery. In this randomized controlled trial, 116 eligible patients were recruited and randomly allocated into either a whole-course nursing group or a routine care group. Clinical endpoints included pain intensity (VAS), lower limb function (LEFS), emotional status (HAMA), patient satisfaction (HPOI and nursing satisfaction scores), and quality of life (Karnofsky index). Data were analyzed using independent t-tests and Cox proportional hazards regression analysis. Compared with routine care, the whole-course nursing group demonstrated significantly reduced pain scores at 24 hours and 48 hours post-surgery (P = .046 and P < .001, respectively), improved lower limb functional outcomes (P < .001), diminished adverse emotions (P = .002), and enhanced quality of life scores (P = .003). Patient satisfaction regarding both pain management and overall nursing care was also markedly higher (P < .001 and P = .001). Cox regression analysis identified the nursing model (P = .017), postoperative recovery (P = .021), and quality of life (P = .028) as independent prognostic factors. The implementation of a whole-course nursing model significantly enhances pain control, emotional well-being, functional recovery, and overall quality of life in patients with malignant bone and soft tissue tumors.

Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a major clinical research focus. Patients with extensive-stage small-cell lung cancer (ES-SCLC) have been treated with different first-line ICI combinations in randomized controlled trials (RCTs), but the optimal combination strategy has not yet been determined. Our aim was to evaluate this strategy through a systematic review and meta-analysis.

Articles published from inception to October 20, 2024 were systematically searched in PubMed, Cochrane CENTRAL, Embase, and MEDLINE. Candidates were RCTs using ICI treatments as first-line treatment for ES-SCLC. According to PRISMA guidelines, 3 independent investigators extracted data. Hazard/odds ratios (HRs/ORs) with their 95% confidence intervals (CIs) and adverse event (AEs) were extracted. ICI combinations were compared for overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and AEs. A random-effects model and Bayesian network meta-analysis were used. PROSPERO: CRD42023388838.

The meta-analysis included 8 RCTs with 3910 patients. Overall, ICI-chemotherapy provided superior OS (HR, 0.78; 95% CI, 0.72 to 0.86), PFS (HR, 0.73; 95% CI, 0.64 to 0.82), ORR (OR, 1.20; 95% CI, 1.01 to 1.42) and DCR (OR, 2.64; 95% CI, 1.32 to 5.24) compared with chemotherapy alone. A higher risk of any grade irAEs (OR, 3.88; 95% CI, 2.09 to 7.18) and grade ≥ 3 irAEs (OR, 5.54; 95% CI, 2.38 to 12.88) was associated with ICI addition. ICI-chemotherapy combinations did not differ significantly in OS, PFS, ORR, DCR, or safety. In the Bayesian ranking analysis, the PD-1 inhibitor-based regimens Serplu-EP and Nivo-EP achieved the highest efficacy rankings; Serplu-EP ranked first for both OS and PFS, followed by Nivo-EP. Efficacy and safety were effectively balanced in Serplu-EP and Adebre-EP. Similar results were shown in subgroup analyses.

First-line ICI-chemotherapy combinations improved survival outcomes but increased the risk of irAEs, with no significant differences in efficacy or safety among ICI-chemotherapy combinations. Among the evaluated regimens, the PD-1 inhibitor-based Serplu-EP and Nivo-EP achieved the highest efficacy rankings, whereas Serplu-EP and Adebre-EP appeared to provide the most favorable efficacy-safety balance. Further head-to-head trials are warranted to confirm the optimal first-line ICI strategy for ES-SCLC.

This study aimed to investigate the effects of demographic factors, diet, sleep patterns, and physical exercise on the incidence of colorectal cancer (CRC) in Hunan, China. This study consecutively recruited patients newly diagnosed with CRC between July 30, 2020, and October 27, 2021. Each case was individually matched in a 1:1 ratio with one of the patient's family members' data control based on gender and age (±2 years). Additionally, efforts were made to ensure that matches were closely aligned with respect to educational level, place of residence, and occupation. The results showed that participants with primary school education or below were more likely to develop CRC compared with those with college education or above (OR = 5.693, 95% confidence interval [CI] = 0.789-41.076, P = .085). A balanced diet appears to be a risk factor for CRC compared with a plant-preference diet (PPD) (OR = 1.726, 95%CI = 0.980-3.040, P = .059). The risk of CRC was 1.542 times higher in participants who drank carbonated beverages than in those who did not (OR = 1.542, 95%CI = 0.989-2.405, P = .056). Participants with a walking habit exhibited a protective factor relative to those without a walking habit (OR = 0.533, 95%CI = 0.392-0.725, P < .001). After adjusting for gender and age, our case-control study found that the following factors were associated with an increased risk of CRC: consumption of carbonated soft drinks, lack of exercise, having a balanced diet compared with a PPD, and educational attainment at primary school level or below compared with college or higher. It should be noted that people with higher education level, regular exercise routines, and walking habits can reduce their risk of CRC. However, this paired study failed to prove the influence of alcohol consumption (AC) and smoking on the incidence of CRC. Since the incidence of CRC is the result of complex effects of multiple factors, further research is needed to discover its mechanism.

The association between diet-exercise patterns and self-reported prostate cancer remains unclear, which was explored based on the National Health and Nutrition Examination Survey (NHANES) database in this study. A cross-sectional study design was adopted using data from the NHANES 2007-2010. The diet-exercise components (37 food variables and 6 exercise variables) were derived through multiple factor analysis, and diet-exercise patterns were derived by K-means clustering analysis. Given the complex sampling design of NHANES, this study accounted for stratification (SDMVSTRA), cluster sampling (SDMVPSU), and sample weights. We applied the Mobile Examination Center examination weights (WTMEC2YR) and adjusted them for the pooled survey cycles. Weighted multivariate logistic regression analysis, weighted subgroup analysis and weighted sensitivity analysis were applied to explore the association between different diet-exercise clusters and prostate cancer. This study enrolled 2825 participants: prostate cancer group (N = 105) and non-prostate cancer group (N = 2720). A total of 43 principal components were extracted via multiple factor analysis. The k-means clustering algorithm identified 2 distinct clusters with divergent diet and physical activity profiles. Weighted logistic regression models revealed no significant association between Cluster 2 and lower odds of prevalent self-reported prostate cancer relative to Cluster 1 (Model 1: odds ratio [OR] = 0.61, 95% CI: 0.37-1.00, P = .057; Model 2: OR = 1.34, 95% CI: 0.70-2.57, P = .379; Model 3: OR = 1.46, 95% CI: 0.73-2.92, P = .300). A significant interaction by age was observed (P for interaction < .001). Compared with Cluster 1, Cluster 2 was associated with lower prevalent self-reported prostate cancer among participants younger than 65 years (OR = 0.20, 95% CI: 0.04-0.86, P = .044), whereas this pattern associated with higher prevalent self-reported prostate cancer among older adults aged ≥65 years (OR = 2.61, 95% CI: 1.37-4.99, P = .009). Sensitivity analyses yielded consistent primary findings. No significant association between diet-exercise patterns and the prevalent self-reported prostate cancer was detected in the overall population, whereas age exerted a statistically significant effect modification on this relationship. Among participants younger than 65 years, Cluster 2, characterized by high physical activity combined with an unhealthy diet, was correlated with reduced prevalence of prostate cancer; conversely, Cluster 2 was significantly associated with elevated prevalence in individuals aged 65 years and older.

This study aimed to evaluate the prognostic significance of hemoglobin, albumin, lymphocyte, and platelet (HALP) levels at diagnosis in patients with multiple myeloma (MM). We retrospectively analyzed 450 patients diagnosed with MM between 2008 and 2023. The HALP score was calculated using pretreatment laboratory values of hemoglobin, albumin, lymphocytes, and platelets. Patients were categorized into the high and low HALP groups. Survival outcomes were analyzed using the Kaplan-Meier and Cox regression methods. Patients with HALP ≤ 27.68 had a significantly lower overall survival (OS) (median 50 vs 79 months, P < .001). Patients with low HALP scores had significantly shorter median OS and progression-free survival than those with high HALP scores (P < .001). In the multivariate analysis, HALP ≤ 27.68 was independently associated with increased mortality risk (hazard ratio: 1.74; 95% confidence interavl: 1.32-2.29). The HALP score remained an independent predictor of OS. The HALP score is a useful, accessible, and cost-effective prognostic marker for MM, and may aid in risk stratification.

Childhood leukemia remains a critical global public health challenge, contributing significantly to disability and premature mortality. Despite progress in healthcare, comprehensive estimates of its burden across geographic and sociodemographic strata remain essential for formulating evidence-based interventions. Utilizing data from the Global Burden of Diseases 2021, this cross-sectional study analyzed leukemia incidence, deaths, and disability-adjusted life years (DALYs) among children aged 0 to 14 across 204 countries and territories from 1990 to 2021. Stratified analyses by region, nation, age, sex, leukemia type, and Sociodemographic Index (SDI) were conducted, with estimated annual percentage changes calculated to assess trends. In 2021, childhood leukemia caused 58,785 incident cases (95% uncertainty interval [UI], 43,200-73,139), 27,861 deaths, and 2,341,610 DALYs globally, corresponding to an incidence rate of 4.37 per 100,000 (95% UI, 3.51-5.46). From 1990 to 2021, global incidence and death rates declined by a total of 0.23% (95% UI, -0.44% to -0.11%) and 0.52% (95% UI, -0.64% to -0.35%), respectively. However, the low-SDI region exhibited rising incidence, mortality, and DALY rates. Australasia experienced the largest incidence increase (estimated annual percentage change: 0.67%, 95% confidence interval, 0.23%-1.11%). Nationally, San Marino reported the highest incidence (13.79 per 100,000; 95% UI, 8.03-21.07), while Tokelau had the highest mortality (7.92 per 100,000; 95% UI, 4.36-13.32) and DALY rates (116.39 per 100,000; 95% UI, 86.46-139.97). Despite global reductions in childhood leukemia burden over 3 decades, persistent disparities across SDI subgroups and regions underscore unmet needs in low-resource settings. Precision epidemiology and context-specific strategies are imperative to mitigate inequities and optimize prevention and care.

Tumor immune barriers (TIBs) are spatially organized stromal-immune niches that restrict lymphocyte entry. To explain persistent immune-checkpoint blockade (ICB) resistance in clear cell renal cell carcinoma (ccRCC), we mapped TIBs and defined a peritumoral variant built from POSTN⁺ cancer-associated fibroblasts (CAFs) interlaced with APOE⁺ tumor-associated macrophages (TAMs). This niche excluded CD8⁺ T cells from tumor cores, and was enriched in poor-prognosis, ICB-refractory patients. Spatial transcriptomics and single-cell profiling showed TIB regions enriched for extracellular-matrix remodeling, immunosuppressive ligand-receptor circuits, and metabolic reprogramming. Mechanistically, tumor-derived TGF-β1 activated CAFs via SMAD signaling, inducing POSTN and recruiting APOE⁺TAMs through integrin and chemokine axes. TAMs secreted TGF-β1 and VEGFA, amplifying stromal programs and sustaining exclusion. Blocking POSTN reprogrammed macrophages, reduced matrix-mediated suppression, and restored CD8⁺ infiltration. In vivo, POSTN inhibition combined with ICB boosted antitumor immunity, reduced tumor burden, and reversed immunosuppressive infiltration, nominating POSTN-directed strategies to potentiate ICB.