• Ultrasound-guided radiofrequency ablation versus laparoscopic adrenalectomy for unilateral isolated aldosterone-producing adenoma: a two-center retrospective study.
    2 weeks ago
    This study aimed to evaluate the safety and efficacy of Ultrasound-guided radiofrequency ablation (US-guided RFA) compared to laparoscopic adrenalectomy (LA) for the treatment of aldosterone-producing adenoma (APA).

    This retrospective, two-center study evaluated 100 patients with APA treated with either US-guided RFA or LA between January 2020 and June 2024. Patients were categorized based on treatment modality (US-guided RFA: n=36; LA: n=64). To minimize confounding, a 1:1 matching was performed based on sex, age, medical history, and disease characteristics. Post-treatment outcomes, including biochemical remission and blood pressure control, were compared using independent-samples t-tests or chi-square tests.

    A total of 36 patients (median age: 49.5 years [IQR: 33.25-57.00]; 23 women) underwent US-guided RFA, and 36 matched patients (median age: 52.00 years [IQR: 37.50-59.75]; 20 women) underwent LA. The technical success rate was 100% in both groups. During the follow-up period (median: 14 months [IQR: 6-22 months]), both groups achieved complete biochemical remission (36/36, P = 1.000), similar hypertension control rates (66.7% vs. 77.8%, P = 0.430), and no disease progression (0/36 in both groups). US-guided RFA was associated with significantly lower intraoperative blood loss (median: 3.0 mL vs. 30 mL) and shorter procedure time (77.5 min vs. 115 min; both P < 0.001).

    In patients with unilateral isolated APA, no significant differences were observed between US-guided RFA and LA in terms of disease progression, biochemical remission, or hypertension control in the short term.
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  • Honokiol Suppresses Stemness and Sensitizes Triple-Negative Breast Cancer to Chemotherapy via YAP/TAZ-TEAD Inhibition.
    2 weeks ago
    Objectives: As an aggressive subtype of breast cancer, triple-negative breast cancer (TNBC) is constrained by the limited availability of effective treatments and the absence of well-validated therapeutic targets. This study aimed to explore whether honokiol, a potent YAP/TAZ inhibitor, suppresses stem cell-like properties and enhances chemotherapeutic efficacy in TNBC by blocking YAP/TAZ-TEAD transcriptional complex. Methods: Through both in vitro and in vivo models of TNBC, the current study examined how honokiol influences cell proliferation, cancer stem cell (CSC) traits, and paclitaxel sensitivity. To uncover the molecular mechanisms, we analyzed the transcript levels and protein abundance of core YAP/TAZ-TEAD pathway members, including YAP, TAZ, TEADs, ANKRD1, and CYR61. Furthermore, we conducted immunofluorescence staining to examine the nuclear localization of YAP/TAZ. Potential direct interactions were identified using molecular docking, which also predicted the binding affinity between honokiol and the TAZ-TEAD complex. Results: Honokiol markedly suppressed the viability and stemness of TNBC cells. It also improved the antitumor efficacy of paclitaxel in both TNBC cells and xenograft models. Mechanistically, honokiol may directly target the TAZ-TEAD complex, as indicated by molecular docking analysis. This interaction led to decreased YAP/TAZ protein levels and blockade of their nuclear accumulation, thereby suppressing the downstream transcriptional targets ANKRD1 and CYR61 in TNBC cells. Conclusion: Collectively, our findings suggest that honokiol is a promising therapeutic agent against TNBC, acting at least in part by suppressing the transcriptional activity of the YAP/TAZ-TEAD complex, thus attenuating cancer stemness and overcoming chemoresistance. These findings highlight honokiol's translational potential.
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  • Rule-derived preoperative inflammatory-lymphocyte recovery phenotype and pathological response in resected osteosarcoma: a retrospective cohort study.
    2 weeks ago
    Pathological response after neoadjuvant chemotherapy is a key treatment milestone in osteosarcoma. We evaluated whether a rule-derived preoperative peripheral inflammatory-lymphocyte recovery phenotype constructed from routinely collected laboratory measurements was associated with poor pathological response.

    This single-center retrospective cohort included patients with osteosarcoma who completed neoadjuvant chemotherapy, underwent definitive surgery, had pathological response assessed, and had valid baseline (T0) and preoperative (T3) laboratory measurements. A failure score combined standardized myeloid-inflammatory burden and lymphocyte-nutritional reserve. Patients were classified as favorable recovery, intermediate recovery phenotype, or persistent recovery failure using the primary T0-T3 rule. The primary outcome was tumor necrosis <90%. The primary association was estimated using parsimonious Firth logistic regression, with modified-Poisson risk ratios and standardized absolute risks. Model comparisons used nested full-pipeline repeated cross-validation. Event-related analyses were exploratory.

    Among 162 patients, 88 (54.3%) had poor pathological response; 65 were classified as favorable recovery, 45 as intermediate, and 52 as persistent recovery failure. Persistent failure was associated with poor pathological response versus favorable recovery (Firth OR, 5.72; 95% CI, 2.42-13.53; P<0.001; adjusted RR, 2.10; 95% CI, 1.46-3.01). Standardized risks were 37.2% for favorable recovery and 75.7% for persistent failure, corresponding to a risk difference of 38.6 percentage points (95% CI, 19.7-52.7). In nested full-pipeline cross-validation, the phenotype model had an AUC of 0.641 and did not outperform the continuous T3 score (AUC, 0.665); its out-of-fold calibration slope was 0.587 (95% CI, 0.220-0.953). Exploratory associations were observed for event-free survival (EFS) and pulmonary metastasis, whereas overall survival (OS) was immature with 24 deaths.

    A rule-derived preoperative peripheral inflammatory-lymphocyte recovery phenotype was associated with pathological response among patients who completed neoadjuvant chemotherapy and underwent definitive surgery for osteosarcoma. The association was robust across alternative definitions and sensitivity analyses; however, the categorical phenotype did not outperform the continuous preoperative T3 score, and out-of-fold calibration indicated residual overfitting. Event-related findings and biological interpretation require external validation.
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  • Early-onset CLL is characterized by enhanced microenvironment-driven metabolic fitness, increased proliferative bias, and accelerated disease progression.
    2 weeks ago
    Chronic lymphocytic leukemia (CLL) predominantly affects older adults; however, approximately 10% of patients are diagnosed at a younger age. Although overall survival appears comparable across age groups, emerging evidence suggests that early-onset CLL may represent a biologically distinct disease subset. Given the profound effects of aging on immune competence and tumor-host interactions, we investigated whether age at diagnosis influences leukemic cell behavior, microenvironmental responsiveness, and immune dysfunction in CLL. We first analyzed the clinical impact of age at diagnosis in a Uruguayan cohort of 462 CLL patients and subsequently explored the biological basis underlying age-associated differences. Patients were stratified according to age at diagnosis, and disease progression was assessed by time-to-first treatment (TTFT). Metabolic analysis evaluated leukemic cell responses to prototypical tumor microenvironment (TME) stimuli, including CD40L plus IL-4 and CpG-ODN plus IL-15. In parallel, we characterized proliferative and quiescent leukemic fractions in peripheral blood, assessed T-cell exhaustion profiles, and analyzed metabolic reprogramming following microenvironmental stimulation. Patients diagnosed at ≤55 years of age exhibited the shortest TTFT (median 39 months), whereas those aged ≥65 years showed a significantly longer TTFT (median 97,6) confirming the more aggressive clinical course of early-onset CLL, despite the longer overall survival as previously described. Metabolic studies revealed that leukemic cells from younger patients displayed enhanced responsiveness to TME-derived signals, characterized by increased metabolic fitness and greater metabolic reprogramming following stimulation. Moreover, early-onset CLL was enriched in proliferative leukemic fractions, whereas the frequency and distribution of exhausted T-cell subsets were comparable between age groups. Collectively, our findings indicate that age-dependent differences in CLL behavior are primarily associated with intrinsic leukemic cell properties rather than major alterations in T-cell dysfunction. Early-onset CLL is characterized by enhanced metabolic adaptability and enrichment of proliferative leukemic cells, supporting the concept that it constitutes a biologically distinct subset of the disease. Despite the absence of differences in survival between age groups, our results provide new insights into CLL heterogeneity and suggest that age-related differences in leukemic cell-microenvironment interactions may contribute to the more aggressive clinical behavior observed in younger patients.
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  • An exploratory case series of sequential stereotactic body radiotherapy and tislelizumab after platinum-doublet chemotherapy in stage IIIB/C-IV non-squamous NSCLC.
    2 weeks ago
    Patients with unresectable stage IIIB/C-IV non-squamous non-small cell lung cancer (NSCLC) lacking driver mutations (EGFR/ALK/ROS1/RET/BRAF/MET) face limited treatment options. This single-center prospective exploratory pilot case series, limited to a small pre-selected cohort, aims to descriptively characterize real-world efficacy, survival signals and safety profiles of sequential platinum-doublet chemotherapy followed by individualized stereotactic body radiotherapy (SBRT) combined with tislelizumab; this work cannot draw definitive therapeutic conclusions and only generates preliminary hypothesis-building observations.

    This exploratory pilot case series enrolled only patients who maintained disease control after 4-cycle platinum-based chemotherapy (introducing notable selection bias favoring chemo-sensitive tumors). Individualized SBRT with heterogeneous dose/fractionation schemes (3-10 Gy/fx) was delivered to metastatic lesions, with tislelizumab 200 mg q3w initiated within five SBRT fractions and maintained until progression or intolerable toxicity. We added standardized multi-modal toxicity surveillance and grading-based intervention protocols for differentiating radiation versus immune pneumonitis. Endpoints were analyzed purely for descriptive purposes, including 1-year PFS rate, median PFS, OS, ORR, DCR, and treatment-related adverse events (TRAEs).

    The 1-year PFS rate was 25%. The median PFS was 10.14 months (95%CI: 3.65-17.38). Median OS was 26.89 months (95%CI: 17.68-30.19), with 1-year and 2-year OS rates of 100% and 62.5%, respectively. The best overall response rate (BOR), defined as the best response recorded from the start of treatment until disease progression or initiation of new anticancer therapy, was 87.5%, with 7 patients achieving partial response (PR) and 1 patient achieving stable disease (SD) as best response. At the fixed 1-year time point, the ORR was 12.5% (1/8 patients in PR) and the DCR was 100% (1 patient in PR and 7 patients in SD). Treatment-related adverse events (TRAEs) were observed in all patients (100%). The incidence of grade ≥3 TRAEs was 62.5%.

    This small exploratory case series provides only preliminary, hypothesis-generating signals regarding the feasibility of sequential SBRT and tislelizumab after chemotherapy in selected patients with advanced nsNSCLC. The observed efficacy and safety data are insufficient to establish definitive conclusions or clinical recommendations. These findings require rigorous validation in larger, controlled trials before any therapeutic inference can be drawn.
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  • Association of the metabolic score for insulin resistance with bone mineral density and trabecular bone score in cancer patients: a cross-sectional study.
    2 weeks ago
    To investigate the association between the Metabolic Score for Insulin Resistance (METS-IR) and bone mineral density (BMD) and trabecular bone score (TBS) in adult cancer patients.

    This cross-sectional study enrolled 127 patients (median age 63 years, 44.9% female) with histopathologically confirmed malignancies. BMD at the lumbar spine, femoral neck, and total hip and lumbar spine TBS were measured by dual-energy X-ray absorptiometry. METS-IR was calculated using fasting glucose, triglycerides, high-density lipoprotein cholesterol, and body mass index. Multivariable linear regression was used to identify independent associations.

    After adjustment for confounders, METS-IR was independently and positively associated with BMD at lumbar spine (β = 0.006, 95% CI 0.002-0.011, P = 0.007), femoral neck (β = 0.007, 95% CI 0.003-0.011, P < 0.001), and total hip (β = 0.007, 95% CI 0.003-0.010, P < 0.001). Age was inversely associated with lumbar spine and femoral neck BMD, but not with total hip BMD; bone metastasis was linked to higher lumbar spine and total hip BMD. In contrast, METS-IR showed no significant association with lumbar spine TBS (P = 0.374). For TBS, age and male sex, but not METS-IR, were independent determinants.

    In cancer patients, higher METS-IR is independently associated with greater BMD but not with better trabecular microarchitecture. This discordance between bone quantity and quality suggests that insulin resistance may mask impaired bone quality despite preserved BMD. Clinicians should consider bone quality assessments when evaluating fracture risk in metabolically compromised cancer patients. Longitudinal studies are warranted to confirm these findings.
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  • National-level estimation of long-term economic burden for lung cancer patients in China.
    2 weeks ago
    With the rapid increase in the incidence and mortality of lung cancer, a growing number of patients with lung cancer and their families are facing a tremendous economic burden owing to the high cost of treatment in China. This study aimed to estimate the long-term (5 years post-diagnosis) economic burden on patients with lung cancer newly diagnosed in 2015 in China.

    This study utilized data from a multicenter survey, involving 469 patients in eastern, central, and western China. From the survey, direct and indirect economic burdens were calculated, and the number of survivors 5 years later based on the national incidence of lung cancer and the observed survival rate in 2015 were estimated. Based on this, we performed descriptive statistical analysis using Excel and calculated the long-term economic burden on patients with lung cancer across the country in 2015 during the 5 years after disease onset.

    The total economic burden for the 2015 cohort 5 years post-diagnosis was $12.7 billion, equivalent to 0.13% of China's 2015 gross domestic product. Direct costs accounted for 64% ($8.1 billion), while indirect costs accounted for 36% ($4.6 billion). Among the investigated components, direct medical costs constituted the largest share (57% of the total burden), followed by indirect costs from missed work (26%), indirect costs from premature death (10%), and direct non-medical costs (7%).

    The economic burden of lung cancer in China is substantial and is dominated by direct medical costs. There is an urgent need for policy measures focusing on multi-tiered medical insurance system improvements, cost-control mechanisms, and the promotion of early screening and diagnosis to alleviate this burden on patients, families, and the healthcare system.
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  • Risk factors for central lymph node metastasis in papillary thyroid microcarcinoma: a simplified risk scoring system.
    2 weeks ago
    Central lymph node metastasis (CLNM) occurs in 20-50% of papillary thyroid microcarcinoma (PTMC) patients and influences surgical decision-making. Existing predictive models require complex calculations or specialized tools, limiting clinical utility. This study aimed to develop a simplified risk scoring system for preoperative CLNM prediction using readily available clinical variables.

    This retrospective cohort study included 486 PTMC patients who underwent thyroid surgery with prophylactic central neck dissection between January 2022 and January 2026. Multivariate logistic regression identified independent predictors of CLNM. A simplified risk scoring system was developed by multiplying regression coefficients (β) by 2 and rounding to integers. Internal validation was performed using bootstrap resampling (1000 iterations).

    Four independent predictors were identified: male gender (β=0.52, adjusted OR 1.68, 95% CI 1.12-2.53), tumor size >5 mm (β=0.76, adjusted OR 2.14, 95% CI 1.45-3.16), multifocality (β=0.64, adjusted OR 1.89, 95% CI 1.23-2.91), and extrathyroidal extension (β=1.02, adjusted OR 2.76, 95% CI 1.68-4.53). The scoring system assigned 1 point each for male gender and multifocality, and 2 points each for tumor size >5 mm and extrathyroidal extension (total score 0-6). The apparent AUC was 0.742 (95% CI 0.698-0.786), with optimism-corrected AUC of 0.738. Risk stratification demonstrated progressive CLNM rates: very low-risk (score 0, 0%), low-risk (score 1, 22.3%), intermediate-risk (scores 2-3, 34.6%), and high-risk (scores 4-6, 62.2%) (p for trend <0.001).

    This simplified four-variable scoring system effectively stratifies CLNM risk in PTMC using preoperatively available data. Patients with score ≤1 may be considered for less extensive surgery or active surveillance, while those with score ≥4 should be considered for prophylactic central neck dissection. This practical tool enables immediate bedside risk assessment without specialized software, though external validation is warranted.
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  • Impaired bone health after pediatric acute lymphoblastic leukemia treatment despite normal DXA: insights from high-resolution peripheral quantitative computed tomography.
    2 weeks ago
    Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood. With improved survival rates, more attention has turned to long-term outcomes such as bone health. High-resolution peripheral quantitative computed tomography (HR-pQCT) allows a three-dimensional assessment of cortical and trabecular bone and may have advantages over standard dual-energy X-ray absorptiometry (DXA). The aim of this study was to evaluate whether HR-pQCT can detect early bone health impairment in children following ALL treatment.

    In this cross-sectional study, HR-pQCT findings in children within 5 years after completion of ALL therapy were compared with healthy controls. Additional assessments for ALL patients included lumbar spine bone mineral density (LSBMD) assessed by DXA and vertebral fracture (VF) assessment using EOS.

    HR-pQCT data from 30 ALL patients (14 male patients; median age 8.8 years) and 64 healthy controls (30 male controls; median age 9.4 years) were analyzed. Five ALL patients (17%) showed evidence of one or more VFs. LSBMD z-scores were within the normal range for all patients (mean 0.09 SDS). Compared with healthy controls, children after ALL treatment showed significantly reduced cortical area (p = 0.013), cortical BMD (p = 0.001), and cortical thickness (p = 0.006) at the tibia, and reduced cortical area (p = 0.046) and cortical BMD (p = 0.008) at the radius on HR-pQCT.

    Despite normal LSBMD DXA z-scores, a substantial proportion of pediatric ALL patients had vertebral fractures and lower values for several cortical parameters at both the radius and tibia on HR-pQCT. These findings suggest that HR-pQCT may serve as a valuable adjunctive tool to detect bone health impairment in children after ALL treatment.
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  • Estimating the Fraction of Hepatocellular Carcinoma and Decompensated Cirrhosis Attributable to Viral Hepatitis in England Using Electronic Health Records and Case-Notes Review.
    2 weeks ago
    Viral hepatitis mortality is an impact target required to evidence the elimination of viral hepatitis with a combined mortality rate of less than or equal to six deaths per 100,000 population. Within England, routine healthcare data linked with death registrations are used; however, where these data are not available, the World Health Organization (WHO) recommends overlaying the attributable fraction (AF) over the mortality envelope for decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC). We aimed to estimate viral hepatitis mortality using the attributable fraction and compared it to surveillance methods. Six acute NHS trusts participated across England and reviewed the case records of individuals identified retrospectively up to 31 December 2023 through hospital episode statistics to confirm the diagnosis and complete a proforma on possible exposures and likely cause of DC/HCC. Overall, 563 individuals were identified, 390 for DC review with 127 (32.6%) confirmed and 173 for HCC review with 157 (91.8%) confirmed. The AF for DC was 0.008 for HCV and 0.016 for HBV, equivalent to a crude mortality rate of 0.09 per 100,000 population and 0.17 per 100,000 population, respectively. For HCC 0.1806 for HCV and 0.0645 for HBV, equivalent to 0.85 per 100,000 population and 0.30 per 100,000 population respectively. These results are comparable to applying the attributable fraction methodology to linking healthcare data sets and demonstrate that England continues to meet the WHO impact target.
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