ABSTRACT Background Effective treatment options remain limited for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), including patients who have progressed after platinum‐based chemotherapy and systemic‐therapy‐naïve patients. This Phase Ib trial evaluates the efficacy and safety of finotonlimab, a PD‐1 antibody, combined with SCT200, an EGFR antibody. Methods This prospective, multicenter, open‐label study enrolled patients into two cohorts: Cohort A (previously treated with platinum‐based chemotherapy and immune checkpoint inhibitors) and Cohort B (systemic therapy‐naïve). Patients received finotonlimab (200 mg every 3 weeks) and SCT200 (6 mg/kg weekly for 12 weeks, then 8 mg/kg every 2 weeks). The primary endpoint was objective response rate (ORR). Results Among 41 patients, Cohort A (n = 11) showed an ORR of 27.3%, median progression‐free survival (PFS) of 5.8 months, and median overall survival (OS) of 10.6 months. Cohort B (n = 30) had an ORR of 56.7%, median PFS of 9.6 months, and an estimated median OS of 13.6 months. Common treatment‐related adverse events included hypomagnesemia (63.4%), rash (41.5%), and acneiform dermatitis (36.6%), which were manageable. Conclusions The combination of finotonlimab and SCT200 demonstrates promising efficacy, particularly in systemic therapy‐naïve patients, warranting further investigation. Trial Registration ClinicalTrials.gov identifier: NCT05552807; Chinadrugtrials.org.cn identifier: CTR20220917

IMPORTANCE:Programmed cell death 1 protein (PD-1) or programmed cell death 1 ligand 1 inhibitors plus chemotherapy is the current standard first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). However, the long-term survival benefits at the 5-year benchmark remain uncertain. OBJECTIVE:To determine whether adding camrelizumab to chemotherapy significantly improved 5-year overall survival (OS) as first-line treatment for RM-NPC, compared with chemotherapy alone. DESIGN, SETTING, AND PARTICIPANTS:The CAPTAIN-1st trial was a randomized, double-blind, phase 3 trial conducted at 28 hospitals in China. Between November 13, 2018, and November 29, 2019, patients with treatment-naive RM-NPC were enrolled. This secondary analysis of the CAPTAIN-1st trial was prespecified. Data analysis was conducted on June 1, 2025. INTERVENTIONS:Patients were randomized (1:1) to receive camrelizumab or placebo in combination with gemcitabine and cisplatin for 4 to 6 cycles, followed by maintenance therapy with camrelizumab or placebo until disease progression, unacceptable toxic effects, or completion of 2 years of treatment. MAIN OUTCOME:The primary end point, progression-free survival per independent review committee, has been reported previously. Herein, the secondary end point of OS is reported as prespecified in the protocol. RESULTS:Among 263 randomized patients (134 in randomized to camrelizumab, 129 to placebo), baseline characteristics were generally balanced between groups, except for age. The mean (SD) age was 49 (11.25) years, and 218 patients (82.9%) were male individuals, 45 (17.1%) were female individuals. With a median survival follow-up of 63.5 (95% CI, 61.2-64.6) months for the camrelizumab group and 63.0 (95% CI, 60.8-64.6) months for the placebo group, 85 (63.4%) and 95 (73.6%) deaths occurred, respectively. Median OS was 34.5 months (95% CI, 29.4-45.7) with camrelizumab vs 26.6 months (95% CI, 19.8-33.5) with placebo (hazard ratio [HR], 0.74; 95% CI, 0.55-0.99; 2-sided P = .047). After adjusting for age imbalance, the HR was 0.65 (95% CI, 0.48-0.89; P = .01). The 5-year OS rates were 37.8% vs 24.2%, reflecting an absolute difference of 13.6% (95% CI, 2.4%-24.8%; P = .02) in favor of camrelizumab. The OS benefits were generally consistent across subgroups. In the camrelizumab group, patients who achieved rapid clearance of Epstein-Barr virus (EBV) DNA had significantly longer OS compared with those without EBV DNA clearance (HR, 0.32; 95% CI, 0.18-0.58; P < .001). CONCLUSIONS AND RELEVANCE:In this secondary analysis of a randomized clinical trial, the addition of camrelizumab to chemotherapy produced statistically significant and clinically meaningful 5-year OS benefits compared with chemotherapy alone in the first-line treatment of RM-NPC. These findings provided the first 5-year evidence supporting the benefit of PD-1-based chemoimmunotherapy in this setting. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03707509.

Background: Pulmonary arterial hypertension is a rare but life-threatening condition in children, with hereditary forms often being linked to mutations in genes such as bone morphogenetic protein receptor type 2 (BMPR2), caveolin 1 (CAV1), and potassium channel subfamily K member 3 (KCNK3). Among these, CAV1 mutations are associated with severe disease phenotypes, though cases resulting from de novo heterozygous CAV1 mutations with multi-system involvement remain rarely reported. The CAV1 mutation (c.424C > T, p.Q142X) disrupts caveolin-1 function, leading to dysregulated pulmonary vascular remodeling and multi-system abnormalities. Methods: This was a retrospective case study of a pediatric patient with hereditary PAH. The patient was followed at our hospital from initial presentation until death. Clinical data were collected from medical records, including physical examinations, laboratory tests, echocardiography, chest X-ray, computed tomography pulmonary angiography (CTPA), and genetic analysis. The patient was treated sequentially with various PAH-targeted medications. This report also includes a review of the relevant literature on CAV1-associated PAH. Results: A female aged 3 years and 11 months was diagnosed with hereditary PAH associated with a de novo heterozygous CAV1 mutation (c.424C > T, p.Q142X). Both parents underwent genetic testing and were negative for the mutation, confirming its de novo origin. Clinical manifestations included special facial features, congenital telangiectasia, cutis marmorata (marbled skin), congenital cataract, hereditary lipodystrophy, and severe PAH. The patient presented with progressive exercise intolerance, syncope, and worsening dyspnea over nine years. Echocardiography revealed pulmonary hypertension with an estimated pulmonary artery systolic pressure of 69-105 mmHg, right heart enlargement, right ventricular hypertrophy, and moderate tricuspid regurgitation. Blood and urine metabolic screenings were normal. A chest X-ray showed progressive enlargement of the cardiac silhouette and bulging of the pulmonary artery segment. CTPA demonstrated pulmonary hypertension, secondary right heart dysfunction, decompensated right ventricular function, and mosaic perfusion in both lungs, suggestive of small arterial branch occlusion. Right heart catheterization was declined by the parents. Thus, the diagnosis of PAH was established based on clinical, echocardiographic, CTPA, and genetic findings. The patient was hospitalized four times and lost to follow-up from 2017 to 2023. She received sequential treatment with digoxin, hydrochlorothiazide, tadalafil, ambrisentan, selexipag, and treprostinil. Despite these therapies, pulmonary artery pressure continued to rise with progressive clinical deterioration. The patient ultimately died at 13 years of age due to a pulmonary hypertensive crisis and multiple organ failure following a severe episode of gastroenteritis. Conclusions: Despite aggressive treatment with multiple targeted reduced pulmonary artery pressure drug therapies, managing hereditary PAH caused by CAV1 mutations in children remains a significant challenge, with a high mortality rate. Early genetic diagnosis, regular follow-up, and individualized treatment are crucial. It requires the joint efforts of patients, parents, and healthcare providers.

Programmed cell death 1 protein (PD-1) or programmed cell death 1 ligand 1 inhibitors plus chemotherapy is the current standard first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). However, the long-term survival benefits at the 5-year benchmark remain uncertain. To determine whether adding camrelizumab to chemotherapy significantly improved 5-year overall survival (OS) as first-line treatment for RM-NPC, compared with chemotherapy alone. The CAPTAIN-1st trial was a randomized, double-blind, phase 3 trial conducted at 28 hospitals in China. Between November 13, 2018, and November 29, 2019, patients with treatment-naive RM-NPC were enrolled. This secondary analysis of the CAPTAIN-1st trial was prespecified. Data analysis was conducted on June 1, 2025. Patients were randomized (1:1) to receive camrelizumab or placebo in combination with gemcitabine and cisplatin for 4 to 6 cycles, followed by maintenance therapy with camrelizumab or placebo until disease progression, unacceptable toxic effects, or completion of 2 years of treatment. The primary end point, progression-free survival per independent review committee, has been reported previously. Herein, the secondary end point of OS is reported as prespecified in the protocol. Among 263 randomized patients (134 in randomized to camrelizumab, 129 to placebo), baseline characteristics were generally balanced between groups, except for age. The mean (SD) age was 49 (11.25) years, and 218 patients (82.9%) were male individuals, 45 (17.1%) were female individuals. With a median survival follow-up of 63.5 (95% CI, 61.2-64.6) months for the camrelizumab group and 63.0 (95% CI, 60.8-64.6) months for the placebo group, 85 (63.4%) and 95 (73.6%) deaths occurred, respectively. Median OS was 34.5 months (95% CI, 29.4-45.7) with camrelizumab vs 26.6 months (95% CI, 19.8-33.5) with placebo (hazard ratio [HR], 0.74; 95% CI, 0.55-0.99; 2-sided P = .047). After adjusting for age imbalance, the HR was 0.65 (95% CI, 0.48-0.89; P = .01). The 5-year OS rates were 37.8% vs 24.2%, reflecting an absolute difference of 13.6% (95% CI, 2.4%-24.8%; P = .02) in favor of camrelizumab. The OS benefits were generally consistent across subgroups. In the camrelizumab group, patients who achieved rapid clearance of Epstein-Barr virus (EBV) DNA had significantly longer OS compared with those without EBV DNA clearance (HR, 0.32; 95% CI, 0.18-0.58; P < .001). In this secondary analysis of a randomized clinical trial, the addition of camrelizumab to chemotherapy produced statistically significant and clinically meaningful 5-year OS benefits compared with chemotherapy alone in the first-line treatment of RM-NPC. These findings provided the first 5-year evidence supporting the benefit of PD-1–based chemoimmunotherapy in this setting. ClinicalTrials.gov Identifier: NCT03707509

Here we report long-term outcomes of adjuvant metronomic capecitabine in patients with locoregionally advanced nasopharyngeal carcinoma. In this multicenter, open-label, parallel-group, randomized, controlled, phase 3 trial, 406 patients who had completed definitive chemoradiotherapy were randomly assigned (1:1) to receive either adjuvant metronomic capecitabine (650 mg m-2 twice daily for 1 year) or observation. The primary endpoint was failure-free survival; secondary endpoints included overall survival (OS), distant failure-free survival, locoregional failure-free survival, and safety, as reported in this analysis. The trial met its primary endpoint. With a median follow-up of 71.3 months, metronomic capecitabine significantly improved OS (hazard ratio = 0.53, 95% confidence interval, 0.31-0.91, P = 0.019). Grade 3 adverse events occurred in 35 (17%) of 201 patients in the metronomic capecitabine group and 11 (6%) of 200 in the observation group; one (<1%) grade 4 neutropenia was reported. In a post hoc analysis, completion of the 1 year course was associated with improved OS, whereas dose reductions and relative dose intensity showed no association with OS. Patients with a higher post-radiotherapy neutrophil-to-lymphocyte ratio derived greater benefit from metronomic capecitabine. These findings support the long-term therapeutic benefit of adjuvant metronomic capecitabine in locoregionally advanced nasopharyngeal carcinoma. ClinicalTrials.gov identifier: NCT02958111 .

QuestionDoes first-line tislelizumab plus chemotherapy improve long-term outcomes compared with placebo plus chemotherapy in participants with recurrent or metastatic nasopharyngeal cancer?FindingsIn this randomized clinical trial including 263 participants, tislelizumab plus chemotherapy demonstrated sustained progression-free survival benefit (median, 9.6 months vs 7.4 months) and clinically meaningful overall survival improvement (median, 45.3 months vs 31.8 months) compared with placebo plus chemotherapy after 3 years of follow-up, which is consistent with the interim analysis.MeaningThese findings support tislelizumab plus chemotherapy as a first-line treatment for recurrent or metastatic nasopharyngeal cancer, with the potential to provide sustained, long-term survival benefit. This secondary analysis of a randomized clinical trial evaluates the 3-year efficacy and safety of tislelizumab plus chemotherapy vs placebo plus chemotherapy in participants with recurrent or metastatic nasopharyngeal carcinoma and explores potential biomarkers of treatment response. ImportanceNasopharyngeal carcinoma (NPC) is a major health concern in Asia, and treatment options for recurrent or metastatic disease are limited. Immunotherapy plus chemotherapy has shown promise, but long-term data are needed to guide first-line treatment.ObjectiveTo evaluate the 3-year efficacy and safety of tislelizumab plus chemotherapy vs placebo plus chemotherapy in participants with recurrent or metastatic NPC and explore potential biomarkers of treatment response.Design, Setting, and ParticipantsThe RATIONALE-309 trial was a double-blind, placebo-controlled phase 3 randomized clinical trial conducted in Asia from April 2019 to December 2023. Treatment-naive adults with histologically or cytologically confirmed recurrent or metastatic NPC were included. Data were analyzed from December 2023 to January 2024.InterventionsParticipants were randomized 1:1 to receive tislelizumab, 200 mg, intravenously or placebo every 3 weeks, both with gemcitabine and cisplatin for 4 to 6 cycles. Participants in the placebo arm could cross over to tislelizumab monotherapy at disease progression.Main Outcomes and MeasuresThe primary end point was progression-free survival (PFS) assessed by an independent review committee. The primary hypothesis (PFS superiority for tislelizumab vs placebo) was specified in the protocol prior to data collection. Secondary end points included overall survival (OS), PFS after next-line therapy, and safety.ResultsOf 263 included participants, 206 (78.3%) were male, and the median (range) age was 50 (23-74) years; the median (range) follow-up was 27.5 (0.1-53.0) months. A total of 131 were randomized to the tislelizumab group and 132 to the placebo group. Tislelizumab plus chemotherapy demonstrated improved PFS vs placebo plus chemotherapy (median PFS, 9.6 months [95% CI, 7.6-11.6] vs 7.4 months [95% CI, 5.6-7.6]; hazard ratio [HR], 0.53; 95% CI, 0.39-0.71). The median OS was 45.3 months (95% CI, 33.4 to not estimable) vs 31.8 months (95% CI, 25.0 to not estimable), respectively (HR, 0.73; 95% CI, 0.51-1.05). Rank-preserving structural failure time analysis (HR, 0.56; 95% CI, 0.27-1.19) and 2-stage crossover-adjusted analysis (HR, 0.62; 95% CI, 0.40-0.97) showed greater OS benefit. Treatment-emergent adverse events occurred in 133 of 133 participants (100%) in the tislelizumab arm and 129 of 130 participants (99.2%) in the placebo arm, with comparable grade 3 or higher adverse event rates. Immune-mediated adverse events were more frequent with tislelizumab (71 [53.4%] vs 49 [37.7%]) but mostly of grades 1 or 2. High B-cell gene expression was associated with greater OS benefit (HR, 0.41; 95% CI, 0.23-0.74).Conclusions and RelevanceIn this secondary analysis of the RATIONALE-309 randomized clinical trial, after 3 years of follow-up, tislelizumab plus chemotherapy provided sustained PFS and meaningful OS improvement vs placebo plus chemotherapy in recurrent or metastatic NPC, with an acceptable safety profile. Greater benefit was observed in participants with activated immune signatures, especially high B-cell expression.Trial RegistrationClinicalTrials.gov Identifier: NCT03924986

Background Lung cancer is one of the leading causes of cancer-related deaths worldwide with limited treatment options available. The anti-tumor effects of the TrxR inhibitor Butaselen (BS/BS1801) on lung cancer and its underlying mechanisms remain unknown.Methods This study utilized lung cancer cell lines, LLC1-bearing mice models, and organoids to detect the inhibitory effects of BS on lung cancer. The ROS-induction and apoptotic role of BS on lung cancer cells and molecular mechanisms were assessed with flow cytometry, western blot, Co-IP, real-time PCR, ChIP, reporter gene assay, ELISA, and bisulfite pyrosequencing.Results BS can effectively inhibit lung cancer both in vitro and in vivo, by triggering ROS-induced apoptosis. The inactivation of NF-κB and MAPK signaling pathways, along with the activation of PI3K-Akt and HBP1 signaling pathways, are involved in BS's suppression of lung cancer. HBP1 is a novel downstream target of the Trx system. The activation of HBP1 by BS is dependent on ROS accumulation and further leads to the transcriptional inhibition of DNMT1 and the demethylation of the whole genome, as well as the promoters of p21 and HOXA9.Conclusion The TrxR/Trx inhibitor butaselen suppresses lung cancer by triggering ROS-induced apoptosis. This study provides a novel and effective regimen for treating lung cancer.

Background Most population-based sexual health research in China excludes older adults. To fill the gap, this study aims to characterise sexual dissatisfaction among people aged 50 years or older from a nationwide, population-representative sample and to explore its association with physical, mental, and self-reported overall health indicators. Methods Data were collected as part of the China Family Panel Studies in 2020, led by the Institute of Social Science Survey of Peking University. Multivariable logistic regressions with robust estimators were used to investigate the association between sexual dissatisfaction and health indicators and potential demographic confounders. Results Among the 8222 partnered Chinese adults aged 50 years or older (median age: 59, IQR: 54-66, 47% identified as women), 78% (6380/8222) reported being satisfied or very satisfied in their sex life. After adjusting for demographic variables, poor self-rated health status (aOR: 1.59, 95% CI: 1.42-1.77), experiencing depression symptoms (aOR: 2.02, 95% CI: 1.80-2.26), and having chronic diseases (aOR: 1.20, 95% CI: 1.07-1.36) were positively associated with sexual dissatisfaction in multivariable analyses. Among sociodemographic factors, younger age, female gender, and education level at senior high school or above were more likely to experience sexual dissatisfaction (all P < 0.05). Conclusion Based on our sample, more than one in five Chinese adults aged 50 years or older might face sexual dissatisfaction. Comorbidities common in older age likely exacerbate sexual dissatisfaction. Greater attention to sexual satisfaction research and sexual health programs among older adults is needed with respect to gender differences and chronic disease comorbidities.

Background: Various studies support the use of programmed cell death protein 1 (PD -1) blockades, also known as immune checkpoint inhibitors (ICIs), to treat head and neck cancer (HNC). Tislelizumab is a humanised immunoglobulin G4 (IgG4) monoclonal antibody with a high affinity and specificity for PD -1. However, the "real -world" clinical evidence of tislelizumab for HNC is limited. Methods: In this study, the medical records of 39 patients with head and neck squamous cell carcinoma (HNSCC) or nasopharyngeal carcinoma (NPC) who received tislelizumab between January 2021 and March 2022 were reviewed retrospectively. Tislelizumab was administered to 15 patients during neoadjuvant therapy (Group 1), five patients during adjuvant therapy (Group 2), 14 patients during consolidation therapy (Group 3), and five patients during salvage therapy (Group 4). The Kaplan -Meier method was used to calculate progression -free survival (PFS) and overall survival (OS). Results: The median age of enrolled patients was 55 (range, 28-83) years. The median follow-up time was 27.1, 26.1, 28.6, and 20.9 months for Groups 1, 2, 3, and 4, respectively. The mean PFS and OS of Groups 1, 2, 3, and 4 were 21.5 and 22.8; 24.1 and 24.2; 26.9 and 28.1; and 13.9 and 17.1 months, respectively. In Groups 1 and 4, the objective response rate (ORR) was 86.7% and 60%, respectively. Meanwhile, except for one (2.6%) patient with grade 4 enteritis, the other observed non -haematological adverse events (AEs) were <= grade 2. Conclusions: Tislelizumab demonstrated promising efficacy and tolerability in patients with HNSCC or NPC in a real -world setting, consistent with previous reports.

This study aimed to explore the distribution, characteristics and prognostic value of baseline peripheral blood lymphocyte subsets in patients with extranodal NK/T-cell lymphoma (NKTCL). We conducted this cross-sectional study of 205 newly-diagnosed NKTCL patients receiving first-line chemotherapy and radiation at our institute between 2010 and 2020. Baseline peripheral blood lymphocytes were detected using flow cytometry, and the clinical value was analyzed. Compared with healthy controls, patients with NKTCL presented with a distinct peripheral immunity with higher levels of cytotoxic CD8+ T cells (33.230 ± 12.090

Objective: To assess whether isolated very low QRS voltage of <= 0.3 mV in the frontal leads might be a marker for diagnosing paediatric vasovagal syncope and the risk of recurrence. Methods: We included 118 children with vasovagal syncope, comprising 70 males and 48 females in our retrospective analysis. All patients underwent head-up tilt test and supine 12-lead electrocardiography. Furthermore, the QRS voltage was measured from each one of the 12 leads on basal electrocardiography. Patients were followed up for 6-24 months (average, 16 months). Results: Eighty-six patients (73%) patients displayed isolated very low QRS voltage in frontal leads. Furthermore, the patients were classified into two groups based on the presence or absence of isolated very low QRS voltage. Enhanced syncopic spells over the past 6 months, and the positive rates of head-up tilt test were observed in patients having isolated very low QRS voltage in the frontal leads than those without isolated very low QRS voltage (p < 0.05). The single factor and time-to-event analyses also showed an increased syncope recurrence rate in patients with isolated very low QRS voltage in frontal leads when compared with those without isolated very low QRS voltage (p < 0.01). Conclusions: Isolated very low QRS voltage in frontal leads is correlated with the positive response of the head-up tilt test in children who experience syncope and its recurrence post-treatment. Hence, isolated very low QRS voltage in frontal leads might become a novel diagnostic indicator and a risk factor for syncope recurrence in children with vasovagal syncope.

Background Adult head and neck rhabdomyosarcoma (HNRMS) is an exceptionally rare malignancy, and there is a paucity of data and research dedicated to understanding its characteristics and management in adult populations. This study aimed to assess the outcomes and identify survival predictors in adult HNRMS. Methods We retrospectively evaluated 42 adult patients (> 16 years) with HNRMS who received radiotherapy (RT)-based treatment at our institute between 2008 and 2022. We analysed the clinical characteristics and prognosis of these patients, including the locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS), using the Kaplan–Meier method. The chi-square and Fisher’s exact tests were used to analyse differences between groups for dichotomous and categorical variables, respectively. Survival rates were calculated using the Kaplan–Meier method. Prognostic variables were assessed through univariate Cox analyses. Results The median patient age was 28 years (range, 16–82 years). Alveolar RMS was the most common histological type, observed in 21 patients (50.0%), followed by embryonal in 16 patients (38.1%). The anatomic sites of origin were orbital in one (2.4%), parameningeal in 26 (61.9%), and non-orbital/non-parameningeal in 15 (35.7%) patients. Nineteen patients (45.2%) had regional lymph node metastasis, and five patients (11.9%) presented with distant metastatic disease. Distant metastasis ( n = 17) was the primary cause of treatment failure. At a median follow-up of 47.0 months, the 5-year LRFS, PFS, and OS rates were 69.0%, 39.7%, and 41.0%, respectively. Univariate analysis revealed that tumour size, lymph node involvement, and the local treatment pattern (surgery and RT vs. RT alone) were significant predictors of survival. Conclusions The main failure pattern in patients with HNRMS receiving RT-based treatment was distant metastasis. Tumour size > 5 cm and lymph node involvement were predictors of worse LRFS. Multimodality local treatment, combining surgery and RT, is effective and provides survival benefits.

OBJECTIVE:The objective of this systematic review was to explore the evidence regarding shared decision-making (SDM) in the management of pulmonary nodules. DESIGN:Systematic review of quantitative and qualitative studies. DATA SOURCE:Studies published in English or Chinese up to April 2022 were extracted from nine databases: PubMed, PsycINFO, EMBASE, Cochrane Library, Web of Science and CINAHL, China National Knowledge Infrastructure, Wanfang Data and SinoMed Data. ELIGIBILITY CRITERIA:Studies were eligible if patients or healthcare providers are faced with pulmonary nodule management options or the interventions or experiences were focused on the patient-healthcare provider relationship or health education to make, increase or support shared decisions. All types of studies were included, including quantitative and qualitative studies. Grey literature and literature that had not been peer reviewed were excluded. Poster abstracts and non-empirical publications such as editorials, letters, opinion papers and review articles were excluded. DATA EXTRACTION AND SYNTHESIS:Two reviewers independently screened abstracts and full texts, assessed quality using Joanna Briggs Institute's critical appraisal tools, and extracted data from included studies. Thematic syntheses were used to identify prominent themes emerging from the data. RESULTS:A total of 12 studies met the inclusion criteria, 11 of which were conducted in USA. These included six qualitative studies and six quantitative studies (including both survey and quasi-experimental designs). Three major themes with specific subthemes emerged: (1) Opportunity (uncertainty in the diagnosis and treatment of pulmonary nodules, willingness to participate in decision-making); (2) Ability (patient's lack of knowledge, physician's experience); and (3) Different worldview (misconception, distress among patients, preference for diagnosis and treatment). CONCLUSIONS:Uncertainty in the management of pulmonary nodules is the opportunity to implement SDM. Patients' lack of knowledge, distress, and misunderstandings between healthcare providers and patients are both the main obstacles and the causes of the application of SDM.

Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR) per RECIST (version 1.1), as assessed by an independent radiological review committee. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). One hundred thirty patients were enrolled and 125 were efficacy evaluable. At the data cutoff date (September 28, 2022), 1 patient achieved complete response and 34 patients attained partial response. The ORR was 28.0% (95% CI 20.3–36.7%). The response was durable, with 66.8% still in response at 9 months. Thirty-three patients (26.4%) were still on treatment. The median PFS and OS were 3.6 months (95% CI = 1.9–7.3 months) and 22.8 months (95% CI = 17.1 months to not reached), respectively. Ten (7.6%) patients experienced grade 3 or higher irAEs. Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development as third-line treatment of metastatic NPC.

PURPOSE:To analyze the impact of sarcopenia and obesity on overall survival (OS) in patients with head and neck cancer (HNC) receiving radiotherapy (RT). METHODS:This prospective longitudinal study recruited 494 patients using convenient sampling. Weight and body composition were assessed before RT (T1), and at the end of RT (T2) using bioelectrical impedance analysis (BIA). The appendicular skeletal mass index was used to define sarcopenia, while the body mass index and fat mass index were used to define obesity. Patient OS was followed and described using Kplan-Meier analysis. Cox proportional hazard regression was used to analyze influencing factors of OS. RESULTS:The median follow-up time was 26.2 months (IQR: 18.4-34.4 months). Multivariable models indicated that sarcopenia/obesity type assessed at T1 was not significantly associated with OS. Multivariable models involving body composition at T2 showed that age (P < 0.001), tumor site (P = 0.003), tumor stage (P = 0.024), and sarcopenia/obesity type (P = 0.040) were significantly associated with OS, while sarcopenic patients without obesity at T2 had worse OS. CONCLUSIONS:Patients with sarcopenia and no obesity at the end of RT might have worse OS. Healthcare professionals should enhance HNC patients' management during RT, helping them maintain a certain amount of muscle mass and fat mass to improve their survival.

e18035 Background: Neoadjuvant chemotherapy (NCT) combination with PD-1 inhibitor has a significant efficacy and approved indications in the first-line treatment of R/M head and neck squamous cell carcinoma (HNSCC), but the efficacy of the combination therapy in locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) remains unexplored. This study aimed to explore the efficacy and safety of NCT with PD-1 inhibitor for laryngeal preservation in patients with HPSCC. Methods: Patients with cT1N1-3M0 or cT2-3N0-3M0 (AJCC 8th) were eligible after multidisciplinary team (MDT) discussion. All patients received 2 cycles of intravenous docetaxel (60mg/m2 on d1), cisplatin (60mg/m2 on d1), fluorouracil (600mg/m2 per day as a continuous 120h infusion on d1-5) and toripalimab (240mg on d1) every 21 days. And the MDT underwent efficacy evaluation according to RECIST 1.1. Patients with complete response (CR)/partial response (PR) of the primary lesion(P) and no progressive disease (PD) in neck lymph nodes (LN) received definitive radiotherapy (RT) combined with toripalimab. Patients with stable disease (SD)/PD of P and no PD in LN or with PD in LN underwent surgery. Patients completed the third cycle of neoadjuvant therapy(NAT) before RT or surgery. The primary endpoint was the CR rate at 3 months (3m-CR) after NAT and definitive RT, and the secondary endpoints were the objective response rate (ORR) of NAT, laryngeal preservation rate, and adverse effects(AE). The sample size was calculated by the Simon-II-stage method: 27 patients in first stage (if ≥9 patients got 3m-CR, second stage started) , and a cumulative total of 81 patients in second stage. Results: From October 2020 to August 2023, 23 patients (median age:59, range:51-69, male:100%, stage II/III/IVA/IVB:4.3%/4.3%/26.1%/65.2%) were enrolled. After NAT, the ORR of primary tumor was 78.3% (18/23, including 2 CR), the ORR of lymph node was 65.2%% (15/23, including 9 CR), and the overall ORR was 70.0% (16/23). Fifteen patients received non-surgical treatment after NAT, and 8 patients underwent surgery (6 underwent laryngeal preservation surgery). At 3 months after RT or surgery, 18 patients completed evaluation. The CR rate was 77.8%, and the laryngeal preservation rate was 88.9%. In 13 evaluable patients who received NAT followed by definitive RT, 10 patients (76.9%) had an overall response of 3m-CR. During the NAT, 43.5% (10/23) of patients experienced grade 3-4 AEs, with grade 3-4 leukopenia or neutropenia in 30.4% (7/23) and grade 3 immune enteritis in 13.0% (3/23). Conclusions: NCT combination with PD-1 inhibitor may improve the ORR of HPSCC, potentially further increasing the laryngeal preservation rate, with manageable treatment-related AEs. The study results are pending publication after completion of the enrollment. Clinical trial information: NCT04624308 .

Background In 2019, the Chinese government launched the national volume-based procurement (NVBP). 7 antihypertensive drugs were selected in the first round of NVBP. This study aimed to evaluate the impact of NVBP on the expenditure of patients with hypertension. Methods The Guangzhou claims data of patients diagnosed with hypertension was extracted from the China Health Insurance Research Association (CHIRA) database, covering 36 months from January 2017 to December 2019. Adopting the interrupted time series (ITS) and difference-in-difference (DID) approach, we evaluated the impacts of the NVBP policy on total healthcare expenditure, health insurance expenditure, and patients’ financial burden at both the collective level and individual level. We also examined how patients and health facilities’ characteristics affected the association. Results At the collective level, we found that the introduction of the NVBP policy reduced total healthcare expenditures and health insurance expenditures for outpatient services by 11.40% and 15.63%, respectively (all p<0.01), while it appeared to have no impact on inpatient services. At the individual level, the DID analysis showed that the total healthcare expenditures per visit decreased by 35.40% (p<0.01), among which healthcare insurance expenditures decreased by 36.81% and out-of-pocket expenditures decreased by 24.65% for outpatients treated with NVBP-list drugs. However, we did not detect any changes in healthcare expenditures per admission. In subgroup analysis, we found a greater decrease in healthcare expenditure per visit for secondary and tertiary hospitals, as well as patients with Urban and Rural Residents Medical Insurance (URRMI). Conclusion This study provides additional evidence that the NVBP policy was associated with achieving cost-containment, alleviating patients’ burdens, and relieving pressure on health insurance funds, which provides important lessons for other countries that are seeking to improve their drug procurement processes. However, the impact of NVBP policy is likely to differ across facilities level and health insurance schemes.

ObjectivesIn December 2018, China launched national volume-based procurement (NVBP) to negotiate drug prices with manufacturers. Gefitinib was one of the 25 pilot drugs, which is used for treatment of non-small cell lung cancer. Lung cancer is the most common type of cancer in China and targeted drugs like gefitinib have been proven to provide clinical benefits to patients. This study aims to explore the impact of NVBP policy on the usage and expenditure of anticancer drugs. MethodsGefitinib and alternative drugs (icotinib and erlotinib) were used as objects of study. Quarterly data from the China Hospital Pharmaceutical Audit database in 9454 hospitals in China were used for analysis. Descriptive analysis was conducted using purchase volume and expenditure as variables. Interrupted time-series (ITS) analysis was applied to further analyse the effect of NVBP policy on the medicines under study. ResultsDuring the 12-month period before (2018Q2-2019Q1) and after (2019Q2-2020Q1) the NVBP policy, the total purchase volume of medicines rose from 4.48 million defined daily dose (DDD) to 7.02 million DDD, with an increase of 56.66%. Purchase volume of gefitinib and alternative drugs increased 100.61% and 14.88%, respectively. After the implementation of NVBP policy, procurement volume of alternative drugs decreased by 72 051 DDD (p value=0.044) and trend change decreased by 56 738 DDD (p value<0.01). The overall expenditure reduction was 14.7%, with the expenditure of gefitinib reducing by 38.47% and alternative drugs increasing by 10.70%. ITS analysis indicated statistically significant differences in level and trend changes for expenditure of total drugs and gefitinib. ConclusionsThe evidence provided in this study indicated that the implementation of NVBP policy was related to the expenditure reduction of the first generation of anti-EGFR lung cancer drugs. The policy effectively controlled the increase in expenditures for corresponding drugs while ensuring the use of drugs.

Background: To provide real-world outcomes for the combination of etoposide and platinum as a first-line treatment for advanced thymic neuroendocrine neoplasms (TNENs).Methods: Retrospective analysis was performed on patients with advanced TNENs confirmed by pathology who received etoposide combined with platinum as a first-line chemotherapy in our institution between 2010 and 2022.Results: A total of 16 patients were included in this study. Twelve patients (75%) received etoposide combined with cisplatin, and four patients (25%) received etoposide combined with carboplatin. Efficacy was evaluated in all patients, with an objective response rate of 31.3%. One patient achieved a complete response, four achieved a partial response, and in eight patients the disease remained stable; the disease control rate was 81.3%. The median progression-free survival (PFS) was 7.2 months with a 95% confidence interval (CI) of 2.1-12.3 months. The median overall survival (OS) was 50.4 months with a 95% CI of 32.1-68.8 months. No significant difference in efficacy was observed between the treatment groups with regards to PFS (p = 0.095) and OS (p = 0.061). Treatment-related adverse events were observed in all 12 patients when evaluated for toxicity, manifesting as hematologic toxicity. Grade 3-4 bone marrow suppression occurred in six patients (50%). No treatment-related deaths were recorded.Conclusion: This retrospective analysis, conducted in a real-life setting, suggests that the combination of etoposide and platinum has a promising anti-tumor activity in advanced TNENs, with a clinically significant overall response rate.

目的 探讨基于深度学习实现对三翻转角2D SPGR MRI序列定量估算单侧肾动脉狭窄动物模型肾脏R1参数图的可行性.方法 共纳入12只平均体重3.2 kg的健康新西兰大白兔,对每只兔子施行左肾动脉部分结扎手术以建立单侧肾动脉狭窄(RAS)动物模型.RAS术前和术后每隔10 min采集一次2D单层三翻转角SPGR MRI数据,其中术前2次和术后9次,以获得单侧RAS造成肾脏水含量水平改变前后的肾脏R1参数图.最终获得127个2D图像对,每对图像包括一个由相同层面3个翻转角(15°,24°和33°)的SPGR序列图像组成三通道2D图像和一个传统可变翻转角R1估算方法得到相应层面的R1参数图图像.应用基于深度学习的编码器-解码器结构训练R1参数图生成模型.将RAS术后采集的92例数据分为训练集(74对)和调优集(18对),将RAS术前采集的34例数据及1例RAS术后的数据作为测试集(35对).以测试集的峰值信噪比和结构相似性结果为R1参数图生成模型的评价指标.结果 在测试集中,R1参数图生成模型的峰值信噪比(dB)和结构相似性(％)分别为22.08±2.33和79.49±6.49.结论 基于深度学习模型可实现对兔子肾脏R1参数图的定量估算进而定量评估其肾实质的水含量.