This study assessed the preclinical and clinical pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of ribupatide (HRS9531), a novel dual agonist of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors.

Preclinical assessments of ribupatide included in vitro functional receptor potency assays, PK evaluations in Sprague-Dawley (SD) rats and cynomolgus monkeys and PD assessments in diet-induced obese (DIO) mice. The Phase 1 study comprised single-ascending dose (SAD; 0.1, 0.3, 0.9, 2.7, 5.4 and 8.1 mg) and multiple-ascending dose (MAD; 0.9, 2.7 and 5.4 mg [2.7/2.7/4.0/5.4 mg]) parts. In the MAD part, ribupatide or placebo was administered subcutaneously once weekly for 4 weeks. The primary endpoints were safety and tolerability.

Ribupatide is a chemically synthesised polypeptide that activates both GLP-1 and GIP receptor signalling pathways in vitro. In SD rats and cynomolgus monkeys, ribupatide demonstrated good subcutaneous bioavailability. In DIO mice, it significantly reduced body weight and cumulative food intake over 28 days compared with vehicle-treated controls. These preclinical PK/PD findings provided a rationale for clinical studies. A total of 90 healthy Chinese participants were randomised and received study treatment, of whom 87 (96.7%) completed the study. Ribupatide was well tolerated across all dose levels, with all treatment-emergent adverse events (TEAEs) being mild-to-moderate in severity and no serious TEAEs or deaths reported. In the MAD, the mean half-life was 7-8 days across the dose range. Fasting plasma glucose decreased dose-dependently after single and multiple dosing. After four weekly doses, mean weight change in ribupatide groups ranged from -4.3 kg (-6.7%) to -7.7 kg (-9.6%), compared with -1.2 kg (-1.4%) in the placebo group.

Ribupatide exhibited a favourable safety and tolerability profile, along with PK properties consistent with once-weekly administration. Its glucose-lowering and weight-loss effects support further clinical development for the treatment of type 2 diabetes mellitus and obesity.

ClinicalTrials.gov identifier: NCT05152277.

To evaluate and compare the prognostic value of the 8th and 9th editions of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system in patients with non-metastatic nasopharyngeal carcinoma (NPC).

Clinical data from 470 patients with NPC treated between November 2019 and June 2022 were retrospectively analyzed. Patients were restaged according to the 8th and 9th editions of the AJCC/UICC staging system. OS was the primary endpoint; locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were secondary endpoints. Kaplan-Meier curves were compared using global and pairwise log-rank tests. Prognostic discriminative ability was evaluated using the concordance index (C-index) and Akaike information criterion (AIC).

Seventeen patients (3.6%) classified as T3 by TNM-8 were reclassified as T4 by TNM-9. Thirty-one patients (6.6%) were reclassified to N3 because of advanced iENE. TNM-9 improved discrimination for DMFS across N categories (log-rank p < 0.001 vs. p = 0.016 for TNM-8) and for OS (p < 0.001 vs. p = 0.042). T categories discriminated LRFS in both editions (p = 0.012 for each), whereas OS differences were not significant (TNM-8 p = 0.139; TNM-9 p = 0.137). TNM-9 overall stage discriminated OS (p = 0.002), unlike TNM-8 (p = 0.121). Both editions discriminated DFS (both p < 0.001), but TNM-9 provided better pairwise separation between early and advanced overall stages. The 9th edition exhibited enhanced predictive performance compared with the 8th edition, as evidenced by higher C-index values and lower Akaike information criterion (AIC) values for both DFS and OS prediction across overall stages.

The 9th edition of the AJCC/UICC staging system demonstrated superior prognostic discriminative ability compared with the 8th edition, enabling more accurate risk stratification and supporting more informed clinical decision-making for patients with NPC.

While psychological distress is a well-documented concern among cancer patients, the prevalence and severity of depression and anxiety in breast cancer patients in Saudi Arabia remain insufficiently explored. This study aimed to evaluate depression, anxiety, and quality of life (QoL) among patients with breast cancer undergoing adjuvant pharmacotherapy in Saudi Arabia.

A cross-sectional observational study was conducted among patients with breast cancer receiving adjuvant therapy. Data were collected using the Patient Health Questionnaire-9 (PHQ-9) for depression, the Generalized Anxiety Disorder-7 (GAD-7) for anxiety, and the Quality-of-Life Questionnaire-C30 (QLQ-C30) for QoL assessment.

Among 246 patients, the most prevalent cancer subtype was hormone receptor-positive (65.0%), followed by human epidermal growth factor receptor 2 (HER2)-positive (13.4%), triple-negative (11.0%), and HER2/hormone receptor-positive (10.6%). Trastuzumab (20.3%) and pembrolizumab (11.0%) were the most commonly administered biological therapies, while letrozole (45.5%) and tamoxifen (22.8%) were the most used hormonal agents. Notably, 48.4% of patients received chemotherapy. The mean ± standard deviation (SD) of PHQ-9 score was 12.87 ± 7.63, and the mean ± SD of GAD-7 score was 9.55 ± 5.53, with clinical significant depression and anxiety of 54.1% and 49.6%, respectively. The mean ± SD of the QLQ-C30 score was 58.84 ± 24.98. Multivariate analysis revealed that chemotherapy and the number of cycles were significantly associated with higher levels of depression and anxiety. Quality of life was negatively impacted by chemotherapy, endocrine therapy, and the number of treatment cycles.

Depression, anxiety, and reduced QoL are prevalent among breast cancer patients undergoing treatment in Saudi Arabia. Chemotherapy and endocrine therapy contribute significantly to psychological distress, and diminished QoL.

Pulmonary metastasis in high-grade conventional osteosarcoma remains a leading cause of treatment failure and mortality. Traditional monitoring methods are insufficient for early detection. This study aims to develop and validate an interpretable machine learning (ML) model using multi-dimensional data from electronic medical records (EMR) to predict the early risk of pulmonary metastasis in high-grade conventional osteosarcoma patients.

This retrospective study included data from 522 high-grade conventional osteosarcoma patients. After rigorous feature selection, 12 independent predictive factors were identified: prothrombin time (PT), international normalized ratio (INR), fibrinogen, globulin, prognostic nutritional index (PNI), eosinophil percentage, monocyte percentage, neutrophil percentage, monocyte count, maximum tumor diameter, gender, and amputation status. Eleven ML models were constructed and compared, with Shapley Additive Explanations (SHAP) analysis applied to enhance model interpretability and clinical transparency.

The gradient boosting model exhibited superior performance, achieving an area under the curve (AUC) of 0.891 in the training set and 0.742 in the independent test set. SHAP analysis revealed that tumor maximum diameter was the most influential predictor of pulmonary metastasis risk, while inflammation and coagulation-related indicators also demonstrated significant contributions.

The gradient boosting model effectively predicts the early risk of pulmonary metastasis in high-grade conventional osteosarcoma and provides interpretable risk factors. This model shows potential as a clinical decision support tool, facilitating personalized risk management and precision medicine, aiming to improve patient outcomes.

Objectives: To evaluate the safety, short-term efficacy and prognostic characteristics of spatially fractionated radiation therapy (SFRT) in patients with advanced or metastatic solid tumors. Methods: Clinical data of patients with advanced/recurrent metastatic malignant tumors who received SFRT in Shenzhen Hospital of Cancer Hospital, Chinese Academy of Medical Sciences from June 2023 to August 2024 were retrospectively analyzed. Patients were divided according to radiotherapy modality into the lattice radiation therapy (LRT) group (high-dose irradiation delivered in a spherical lattice pattern within the target area) and the stereotactic central ablative radiation therapy (SCART) group (ablative dose irradiation delivered to the tumor core area). All patients underwent at least one imaging follow-up after treatment. Results: A total of 49 patients were enrolled; 12 patients who did not complete imaging follow-up were excluded, and finally 37 patients were included in the analysis. The median age was 58 years (range, 28 to 77 years), male accounted for 67.6% (25/37), and the median Eastern Cooperative Oncology Group (ECOG) performance status score was 1 point (range, 1 to 2). The most common primary tumor type was gastrointestinal tumors (48.6%, 18/37). The median number of prior lines of chemotherapy before radiotherapy was 3 (range, 0 to 11). The median maximum diameter of the target area was 9.3 cm (range, 4.9 to 33.4 cm), and the median volume was 236.6 cc (range, 28.6 to 5 053.0 cc). There were 21 cases (56.8%, 21/37) in the LRT group and 16 cases (43.2%, 16/37) in the SCART group. The median SFRT vertex dose was 12 Gy (range, 6 to18 Gy), and the median number of fraction was 5 (range, 1 to 5). A total of 40.5% (15/37) of patients received conventional fractionated radiotherapy or stereotactic body radiotherapy (SBRT) before or after SFRT. Furthermore, 35.1% (13/37) of patients received sequential immunotherapy, with a median of 3 cycles (range, 2 to 4). As of May 16, 2025, the median follow-up time was 13.2 months (range, 9.4 to 22.7 months); 21 patients were alive, 12 died (11 due to tumor progression, 1 due to immune checkpoint inhibitor-related pneumonia), and 4 were lost to follow-up. Efficacy evaluation showed that the median time for first imaging assessment was 3 months (range, 0.5 to 6 months), the in-field disease control rate was 94.6%, and the 6-month in-field disease control rate was 85.0% (17/20). Among the 21 patients with pre-treatment symptoms, pain relief was achieved in 11 patients (11/15), and the overall symptom control rate was 81.0% (17/21). No grade Ⅲ or higher radiotherapy-related acute/chronic adverse events were observed. Grade Ⅰ-Ⅱ radiation gastroenteritis occurred in 9 patients, and grade Ⅰ elevated transaminase occurred in 3 patients. Conclusions: SFRT can effectively alleviate clinical symptoms and provide favorable local control in patients with advanced/recurrent metastatic large-volume malignant tumors, with manageable safety. Preliminary results suggest that SFRT can serve as a palliative treatment option for this patient population. The synergistic effect and long-term efficacy of sequential drug therapy (including immunotherapy) require validation with larger sample size or prospective studies.

Objective: To analyze the clinicopathological and molecular characteristics of non-small cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 (HER-2) variations (including mutations and amplifications) and their correlation with prognosis.​ Methods: Clinicopathological data of NSCLC patients with HER-2 variations who underwent targeted next-generation sequencing (NGS) at Ningbo Clinical Pathology Diagnostic Center from September 2022 to June 2024 were collected. The clinicopathological and molecular features were retrospectively analyzed, and a literature review was conducted. Results: Among 2 795 NSCLC patients, HER-2 variations were identified in 148 cases (5.3%, 148/2 795). Of these, 128 cases had HER-2 mutations [86.5%, 128/148, including 63 exon 20 (Exon20) mutations], 16 cases had HER-2 amplifications (10.8%, 16/148), and 4 cases had concurrent HER-2 mutation and amplification (2.7%, 4/148). Compared with the HER-2 mutation group, patients with HER-2 amplification were more likely to have larger tumor size, lymph node metastasis, distant metastasis and higher TNM stage (all P＜0.05). Among HER-2 mutations, Exon 20 mutations were more common in females and associated with lower risks of larger tumor size, lymph node metastasis and distant metastasis (all P＜0.05). Cox regression analysis indicated that HER-2 amplification, larger tumor size, lymph node metastasis, distant metastasis and higher TNM stage were associated with poor prognosis (P＜0.05). Molecular analysis revealed that Exon20 mutations rarely co-occurred with other gene variations, whereas non-Exon20 mutations were frequently accompanied by other genetic alternations, most commonly epidermal growth factor receptor (EGFR) mutations (55.4%, 36/65). In addition, 16 cases of HER-2 p.A270S mutation were identified, of which 11 were at advanced TNM stage (68.8%, 11/16), and 5 patient died.​ Conclusions: Different types of HER-2 variations (mutations/amplifications) exhibit distinct clinicopathological and molecular characteristics. Patients with HER-2 amplification have a poor prognosis, and the HER-2 p.A270S mutation may be associated with malignant phenotypes of NSCLC. It is necessary to integrate the characteristics of HER-2 variations to provide references for individualized treatment.​.

Objective: To analyze the disease burden of malignant neoplasms of bone and articular cartilage (MNBAC) in the East Asian (China, Democratic People's Republic of Korea, Japan, Mongolia, and South Korea) from 1990 to 2023, so as to formulate and adjust prevention and treatment strategies for MNBAC. Methods: The average annual percentage change (AAPC) was used to comprehensively evaluate the changing trend of MNBAC disease burden from 1990 to 2023. Decomposition analysis was conducted on the corresponding burden of MNBAC in Ease Asian countries, along with subgroup analyses by age and gender. Based on the autoregressive integrated moving average (ARIMA) model, the future standardized rates of MNBAC in China were predicted. Results: In 2023, there were significant differences in the disease burden of MNBAC among East Asia countries, with China, Democratic People's Republic of Korea, and Mongolia bearing the heavier burden. From 1990 to 2023, the standardized prevalence, disability-adjusted life years (DALYs) rate, and mortality rate of MNBAC in China and Democratic People's Republic of Korea all showed upward trends (AAPC value of 2.86%, 1.74%, 1.96% for China; and 1.15%, 0.84%, 1.26% for Democratic People's Republic of Korea, respectively), whereas those in Japan and Mongolia showed downward trends (AAPC values of -0.36%, -1.40%, -1.37% for Japan; and -0.58%, -0.77%, -0.82% for Mongolia, respectively). The standardized prevalence, DALYs rate, and mortality rate in South Korea remained relatively stable (AAPC=0.12%). Decomposition analysis indicated that epidemiological changes were the main drivers of the increases in prevalence and DALYs burden in China and Democratic People's Republic of Korea, but were negative contributors to the prevalence, DALYs and mortality burden in Mongolia. Gender subgroup analysis showed that the overall burden of MNBAC in males was significantly higher than that in females in East Asia. Age subgroup analysis indicated that the prevalence and DALYs rate exhibited an M-shaped pattern with increasing age, while the mortality rate increased with age. Additionally, over the next the corresponding burden of MNBAC in China is projected to show a downward trend. Conclusions: The disease burden of MNBAC varies significantly cross countries, genders, and age groups. It is necessary to further develop more targeted prevention and treatment measures based on the distribution characteristics of the disease burden, so as to effectively reduce the burden of MNBAC.

Developing effective nursing support for cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer requires understanding nurses' knowledge and nursing practices regarding CTRCD. This study elucidated these aspects among Certified Nurse Specialists (CNSs) and Certified Nurses (CNs) in Japan.

A web-based survey was administered to 1490 nurses, including CNSs in cancer nursing and CNs in cancer chemotherapy, breast cancer, and heart failure. The survey assessed participants' characteristics, knowledge of CTRCD, nursing practices, consultation experiences, and interprofessional collaboration. We calculated descriptive statistics and conducted group comparisons between oncology nurses specializing in cancer nursing and cardiology nurses specializing in heart failure nursing.

We obtained 261 responses, including 214 (82.0%) from oncology nurses and 47 (18.0%) from cardiology nurses. These two groups exhibited significant differences in their knowledge of CTRCD definitions, risk factors, and related agents (p < 0.01). Among oncology nurses, 88 (56.8%) provided patient education on CTRCD risk and 94 (63.9%) monitored CTRCD symptoms; thus, practice implementation remained around half. A higher proportion of cardiology nurses reported having received questions or consultations regarding CTRCD from patients or staff (p < 0.05). Only 27 participants (10.3%) reported access to onco-cardiology educational opportunities at their respective institutions.

Differences in knowledge and practices regarding CTRCD were identified between oncology and cardiology nurses. Improving nursing practices, particularly patient education and symptom observation, is essential for early CTRCD detection and treatment. Furthermore, systematic educational programs and structured collaborative frameworks, including interprofessional collaboration, are needed at both the institutional and national levels.

The FDA's Project Optimus CALLS for randomized exploration of multiple doses to better refine selection of the optimal biologic dose (OBD). Project FrontRunner encourages the use of randomized controlled trials earlier in the drug development process. We propose a seamless three-stage trial design that addresses both goals by incorporating biomarker-subgroup stratified randomization in both the dose-ranging and efficacy stages. Stratification in the dose-ranging stage allows for possibly different OBDs within each biomarker subgroup. A Bayesian optimal interval design guides dose escalation, followed by a one-sample Bayesian optimal efficiency predictive probability design in the dose-ranging stage. A Bayesian optimal efficiency stratified control arm design is employed in the efficacy stage. The components are linked by two novel decisions: (1) selecting sufficiently safe doses to advance from escalation to dose-ranging, and (2) ranking doses based jointly on safety and efficacy to choose an OBD for the efficacy stage. In simulation studies of three potential dose levels, correct selection of the true OBD in the dose-ranging stage was challenging in some settings, with rates of correct selection ranging from 12% when the true OBD was the same as the true MRD to 80% when the true OBD was below the MTD. In many settings the proposed design outperformed BOIN12 and DROID in selection of the true OBD. Over the entire seamless study, adequate power of at least 80% was never achieved and the Type I error was controlled at too low rates, below the target of 10%. This novel design provides an important option for both settings with well-defined molecularly targeted subgroups and in settings where the molecular target is still being refined. By gathering multifaceted information across both dose levels and targeted subgroups, more efficient and better-informed decisions can be made about targeted dosing.

Robotic gastrectomy (RG) for gastric cancer reduces morbidity and achieves long-term outcomes comparable to laparoscopy. However, RG is typically a solo-surgeon procedure performed by expert console surgeons, limiting trainees' operative experience. To address this issue, we developed Laparoscopic and Robotic procedures Combined Surgery (LARCS), in which the patient-side surgeon (PSS) performs selected surgical maneuvers, including dissection, clipping, and stapling, using laparoscopic instruments under the supervision of the console surgeon.

We retrospectively analyzed 96 patients who underwent robotic distal or subtotal gastrectomy at Kitasato University Hospital between January 2019 and December 2023. Patients were divided into a conventional RG group (CRG; n = 60) and a LARCS group (n = 36). Propensity scores were estimated based on age, sex, body mass index, American Society of Anesthesiologists status, and clinical T and N categories. Cardinality matching within a 0.2-standard-deviation caliper of the logit of the propensity score yielded 23 matched pairs, with all absolute standardized mean differences for the matching covariates < 0.1. Perioperative outcomes and PSS participation were compared.

After matching, adequate balance was achieved for all matching covariates, with absolute standardized mean differences ranging from 0 to 0.062. Operative time was 406 min in the LARCS group and 373 min in the CRG group (p = 0.110). Estimated blood loss tended to be greater with LARCS (51 vs. 6 mL, p = 0.070). Any postoperative complication occurred in 6 and 5 patients, respectively (p = 1.000), and major complications occurred in 2 and 0 patients, respectively (p = 0.500). Median PSS operative time was 108 min, corresponding to 26.6% of the total operative time in LARCS, versus 0 min in CRG (p < 0.001).

LARCS provided patient-side trainees with supervised, instrument-based first-operator participation for approximately one-quarter of the operative time, supporting its feasibility as a complementary approach to trainee participation during robotic gastrectomy. Further prospective studies incorporating objective competency-based assessments are required to determine its educational effectiveness and safety.