Background: Little is known about the nature of metaistasis to small cervical lymph nodes(SCLNS) in the patients with nasopharyngeal carcinoma(NPC)examined by using 18-fluoro-2-deoxy-glucose(^(18)F-FDG) positron emiss...Background: Little is known about the nature of metaistasis to small cervical lymph nodes(SCLNS) in the patients with nasopharyngeal carcinoma(NPC)examined by using 18-fluoro-2-deoxy-glucose(^(18)F-FDG) positron emission tomography/computed tomography(PET/CT).The present study aimed to evaluate the diagnostic values of PET/CT in identifying metastasis in SCLNs in NPC patients.Methods: Magnetic resonance images(MRI) and PET/CT scans for 470 patients with newly diagnosed, non-distant metastatic NPC were analyzed. Metastatic rates of SCLNs were defined by the positive number of SCLNs on PET/CT scans and total number of SCLNs on MRI scans. Receiver operating characteristic curve was applied to compare PET/CT-determined stage with MRI-determined stage.Results: In total, 2082 SCLNs were identified, with 808(38.8%) ≥ 5 and < 6 mm in diameter(group A), 526(25.3%)≥ 6 and < 7 mm in diameter(group B),374(18.0%)≥ 7 and < 8 mm in diameter(group C), 237(11.4%) ≥8 and<9 mm in diameter(group D),and 137(6.5%) ≥ 9 and <10 mm in diameter(group E).The overall metastatic rates examined by using PET/CT for groups A, B,C,D, and E were 3.5%, 8.0%, 31.3%, 60.0%, and 83.9%, respectively(P< 0.001). In level IV/Vb, the metastatic rate for nodes ≥ 8 mm was 84.6%. PET/CT examination resulted in modification of N category and overall stage for 135(28.7%) and 46(9.8%) patients, respectively. The areas under curve of MRIdetermined and PET/CT-determined overall stage were 0.659 and 0.704 for predicting overall survival, 0.661 and 0.711 for predicting distant metastasis-free survival, and 0.636 and 0.663 for predicting disease-free survival.Conclusions: PET/CT was more effective than MRI in identifying metastatic SCLNs, and the radiologic diagnostic criteria for metastatic lymph nodes in level IV/Vb should be re-defined.展开更多
Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses...Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra-and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy.This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules.Methods: In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+)T-cell density in primary tumors and PD-1 expression on CD8(+)T cells were detected with immunofluorescence. Univariate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival.Results: Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors(45.4% vs. 38.7%, P = 0.005); the positive rate of PD-1 on CD8(+)T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes(both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression,PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.Conclusion: The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stageT1-4 N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies.展开更多
Background:With industrial and economic development in recent decades in South China,cancer incidence may have changed due to the changing lifestyle and environment.However,the trends of lung cancer and the roles of s...Background:With industrial and economic development in recent decades in South China,cancer incidence may have changed due to the changing lifestyle and environment.However,the trends of lung cancer and the roles of smoking and other environmental risk factors in the development of lung cancer in rural areas of South China remain unclear.The purpose of this study was to explore the lung cancer incidence trends and the possible causes of these trends.Methods:Joinpoint regression analysis and the age-period-cohort(APC) model were used to analyze the lung cancer incidence trends in Sihui,Guangdong province,China between 1987 and 2011,and explore the possible causes of these trends.Results:A total of 2,397 lung cancer patients were involved in this study.A 3-fold increase in the incidence of lung cancer in both sexes was observed over the 25-year period.Joinpoint regression analysis showed that while the incidence continued to increase steadily in females during the entire period,a sharp acceleration was observed in males starting in 2005.The full APC model was selected to describe age,period,and birth cohort effects on lung cancer incidence trends in Sihui.The age cohorts in both sexes showed a continuously significant increase in the relative risk(RR)of lung cancer,with a peak in the eldest age group(80-84 years).The RR of lung cancer showed a fluctuating curve in both sexes.The birth cohorts identified an increased trend in both males and females;however,males had a plateau in the youngest cohorts who were born during 1955-1969.Conclusions:Increasing trends of the incidence of lung cancer in Sihui were dominated by the effects of age and birth cohorts.Social aging,smoking,and environmental changes may play important roles in such trends.展开更多
Background: Serum immunoglobulin A antibodies against Epstein–Barr virus(EBV), viral capsid antigen(VCA?Ig A) and early antigen(EA?Ig A), are used to screen for nasopharyngeal carcinoma(NPC) in endemic areas. However...Background: Serum immunoglobulin A antibodies against Epstein–Barr virus(EBV), viral capsid antigen(VCA?Ig A) and early antigen(EA?Ig A), are used to screen for nasopharyngeal carcinoma(NPC) in endemic areas. However, their routine use has been questioned because of a lack of specificity. This study aimed to determine the distributions of different subtypes of antibody and to illustrate how the natural variation patterns affect the specificity of screening in non?NPC participants.Methods: The distribution of baseline VCA?IgA was analyzed between sexes and across 10?year age groups in 18,286 non?NPC participants using Chi square tests. Fluctuations in the VCA?IgA level were assessed in 1056 non?NPC participants with at least two retests in the first 5?year period(1987–1992) after the initial screening using the Kaplan–Meier method.Results: The titers of VCA?Ig A increased with age(P < 0.001). Using a previous serological definition of high NPC risk, nasopharyngeal endoscopy and/or nasopharyngeal biopsy would be recommended in 55.5% of the non?NPC partici?pants with an initial VCA?Ig A?positive status and in 20.6% with an initial negative status during the 5?year follow?up. However, seroconversions were common; 85.2% of the participants with a VCA?Ig A?positive status at baseline con?verted to negative, and all VCA?Ig A?negative participants changed to positive at least once during the 5?year follow?up. The EA?Ig A status had a high seroconversion probability(100%) from positive to negative; however, it had a low probability(19.6%) from negative to positive.Conclusions: Age? and sex?specific cutoff titer values for serum anti?EBV antibodies as well as their specific titer fluc?tuation patterns should be considered when defining high NPC risk criteria for follow?up diagnostics and monitoring.展开更多
Salivary gland carcinomas(SGCs)are rare malignancies that remain poorly understood owing to their low incidence(Matsuba et al.,1986b;Liu et al.,2012).As per GLOBOCAN 2018.52.800 new cancers arising from salivary gland...Salivary gland carcinomas(SGCs)are rare malignancies that remain poorly understood owing to their low incidence(Matsuba et al.,1986b;Liu et al.,2012).As per GLOBOCAN 2018.52.800 new cancers arising from salivary glands were estimated to be diag-nosed across the world that year.Because of their high propensity to invade local and perineural structures.展开更多
Background GD-11,a novel brain cytoprotective drug,was designed to be actively taken up and transported across the blood-brain barrier via the glucose transporter.This study aimed to evaluate the safety and efficacy o...Background GD-11,a novel brain cytoprotective drug,was designed to be actively taken up and transported across the blood-brain barrier via the glucose transporter.This study aimed to evaluate the safety and efficacy of GD-11 for improving the recovery of patients with acute ischaemic stroke(AIS).Methods A double-blind,randomised,placebo-controlled,phase 2 trial was conducted at 15 clinical sites in China.Patients aged 18-80 years with AIS within 48 hours were randomly assigned(1:1:1)to receive 160 mg GD-11,80 mg GD-11 and placebo,two times a day for 10 days.The primary endpoint was a modified Rankin Scale(mRS)score of 0-1 at 90 days after treatment.The safety outcome was any adverse events within 90 days.Results From 17 November 2022 to 22 March 2023,a total of 80 patients in the 160 mg GD-11 group,79 patients in the 80 mg GD-11 group and 80 patients in the placebo group were included.The proportion of an mRS score of 0-1 at day 90 was 77.5%in the 160 mg GD-11 group,72.2%in the 80 mg GD-11 group and 67.5%in the placebo group.Though no significant difference was found(p=0.3671),a numerically higher proportion was observed in the GD-11 group,especially in the 160 mg GD-11 group.The incidence of adverse events was similar across the three groups(p=0.1992).Conclusion GD-11 was safe and well-tolerated.A dosage of GD-11160 mg two times a day was recommended for a large trial to investigate the efficacy.展开更多
Background The benefit of intravenous alteplase in acute ischaemic stroke(AIS)is time-dependent.Tenecteplase is non-inferior to alteplase among patients with AIS.We aimed to delineate the association of the stroke ons...Background The benefit of intravenous alteplase in acute ischaemic stroke(AIS)is time-dependent.Tenecteplase is non-inferior to alteplase among patients with AIS.We aimed to delineate the association of the stroke onset to treatment time(OTT)with tenecteplase compared with alteplase on therapeutic benefit and clinical risks.Methods This is a post hoc analysis of the Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-2 an open-label,randomised,controlled,non-inferior trial.A total of 1430 AIS within 4.5 hours onset at 53 sites in China from 12 June 2021 to 29 May 2022 were randomly assigned(1:1)to receive either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg.The primary efficacy outcome was the proportion of participants with a modified Rankin Scale score of 0–1 at 90 days.A post hoc subgroup analysis was conducted with the OTT divided into three intervals(0–90 min,91–180 min and 181–270 min).The primary safety outcome was symptomatic intracranial haemorrhage within 36 hours post-thrombolytic treatment.Results Treatment was initiated within 270 min of stroke onset in 1412 patients who were randomly allocated to either tenecteplase(n=707)or alteplase(n=705).The OR of primary efficacy outcome was similar as OTT increased(p=0.84).Adjusted odds of an excellent functional outcome were 0.99(95%CI 0.37 to 2.67)for 0–90 min,1.23(95%CI 0.88 to 1.71)for 91–180 min and 1.21(95%CI 0.88 to 1.65)for 181–270 min.All were in favour of the tenecteplase group.Meta-analysis of 2949 patients yielded a pooled risk difference of 5.54(95%CI-0.18 to 11.26;p=0.82)in favour of tenecteplase for more than 180 min and 1.77(95%CI-2.66 to 6.20;p=0.58)for 0–180 min.Conclusions In AIS patients who were treated with either tenecteplase or alteplase within 4.5 hours onset,there was no difference observed in the efficacy and safety between the two groups at the three different OTT time intervals.展开更多
Background and purpose Reteplase is the third generation of alternative thrombolytic agent.We hypothesis that reteplase will be non-inferior to alteplase in achieving excellent functional outcome at 90 days among elig...Background and purpose Reteplase is the third generation of alternative thrombolytic agent.We hypothesis that reteplase will be non-inferior to alteplase in achieving excellent functional outcome at 90 days among eligible patients with acute ischaemic stroke.Methods and design Reteplase versus alteplase for acute ischaemic stroke within 4.5hours(RAISE)trial is a multicentre,prospective,randomised,open-label,blinded endpoint(PROBE),controlled phase 3 non-inferiority trial.A total of 1412 eligible patients will be randomly assigned to receive either reteplase at a dose of 18 mg+18mg or alteplase 0.9mg/kg at a ratio of 1:1.An independent data monitoring committee will review the trail’s progress and safety data.Study outcomes The primary efficacy outcome of this study is proportion of individuals attaining an excellent functional outcome,defined as modified Rankin Scale(mRS)0–1 at 90 days.The secondary efficacy outcomes encompass favourable functional outcome defined as mRS 0–2,major neurological improvement on the National Institutes of Health Stroke Scale,ordinal distribution of mRS and Barthel Index score of at least 95 points at 90 days.The primary safety outcomes are symptomatic intracranial haemorrhage at 36 hours within 90 days.Discussion The RAISE trial will provide crucial insights into the selection of thrombolytic agents for stroke thrombolysis.Trial registration number NCT05295173.展开更多
Breast cancer is one of the most common malignant tumors among women in China,with approximately 306,000 new cases reported in 2016.Notably,around 33%(100,400)of these cases occurred in rural areas.County-level hospit...Breast cancer is one of the most common malignant tumors among women in China,with approximately 306,000 new cases reported in 2016.Notably,around 33%(100,400)of these cases occurred in rural areas.County-level hospitals,encompassing counties and county-level cities,serve as the primary diagnostic units for the majority of rural breast cancer patients.These hospitals are integral to cancer prevention,screening,maintenance treatment,rehabilitation,follow-up,and referral processes.However,economic and geographical constraints result in county-level hospitals being relatively deficient in medical equipment,health human resources,and drug accessibility.Consequently,there is a critical need for breast cancer prevention and management guidelines that are tailored to the specific conditions of China's counties.In response to this need,and within the policy framework of hierarchical diagnosis and treatment,a Chinese expert group has developed the Guideline for the Management Pathway and Quality Control of Breast Cancer Prevention and Treatment in China's Counties(2023 Edition).This guideline aims to expand the availability of quality medical resources,ensure better distribution of these resources across regions,and enhance the capacity for breast cancer prevention and treatment.Ultimately,the goal is to improve the prognosis and quality of life for breast cancer patients in China's counties.This guideline includes clear and concise path diagrams that are easy to implement in clinical practice,serving as a valuable reference for clinicians in countylevel hospitals.展开更多
Treatment of breast cancer with low expression of human epidermal growth factor receptor 2(HER2;HER2-low)has drawn much attention in recent years.With the proven therapeutic effect of trastuzumab deruxtecan(T-DXd)in p...Treatment of breast cancer with low expression of human epidermal growth factor receptor 2(HER2;HER2-low)has drawn much attention in recent years.With the proven therapeutic effect of trastuzumab deruxtecan(T-DXd)in patients with HER2-low(immunohistochemistry[IHC]1+,or IHC2+/in situ hybridization[ISH]-)breast cancer,HER2-low may become a new subtype of targeted therapy for breast cancer.The expert committee formulated this consensus based on the current clinical studies and clinical medication experience.The current consensus is the collaborative work of an interdisciplinary working group,including experts in the fields of pathology and oncology.The purpose of this consensus was to guide the clinical diagnosis and treatment of HER2-low breast cancer,thereby prolonging the overall survival of patients.展开更多
Objectives:To describe and compare the research and development(R&D)pipeline of cancer new drugs and newly approved drugs in China and the USA in 2020,thus to provide decision-making evidence for related stakehold...Objectives:To describe and compare the research and development(R&D)pipeline of cancer new drugs and newly approved drugs in China and the USA in 2020,thus to provide decision-making evidence for related stakeholders.Methods:Clinical trials and tested cancer new drugs information in China and the USA were respectively ac-quired from Information Disclosure Platform for Drug Clinical Studies and Trialtrove database.Drug approval was tracked from the official release.Subgroup comparison in terms of initiated trials and drugs were conducted between the two countries.Results:In 2020,577 trials on 335 cancer new drugs were registered in China,accounting for 22.6%of all clinical drug trials,while in the USA,916 trials on 678 cancer new drug trials were captured,accounting for 19.9%of the total.Relatively,a lower proportion of earlier phase(76.9%vs 87.4%),global(17.7%vs 39.0%),and top 20 pharmaceutics contribution(15.8%vs 43.2%)were found for cancer drug trials initiated in China.The fight against solid tumor took top billing in both countries,and the different distribution of cancer indications associated with cancer spectrum was also observed.Compared with the USA,more targeted agents(87.5%vs 77.0%,P<0.001)and less immune agents(30.7%vs 41.6%,P<0.001)were tested in China.In addition,16 and 18 anticancer new drugs were approved in China and the USA,with 6(37.5%)and 17(94.4%)drugs being firstly approved worldwide,respectively.Among them,32 drugs were granted by at least one expedited program,and 31 drugs were approved based on evidence from surrogate endpoints.A total of 17 cancer types were covered,and only one drug was targeted on digestive cancers,including gastric,liver,and esophageal cancers.Conclusions:R&D of anticancer new drugs is substantial,and great progress has been made in both China and the USA in 2020.The difference and gap between China and the USA highlight that more efforts should be paid to anticancer drug R&D on innovative agents and cancers unique to Chinese populations,as well as to facilitate global synchronous R&D in China.展开更多
Objective Limited evidence is available regarding the risk-benefit ratio of thrombolytic therapy in patients with stroke and renal impairment complications,particularly for the drug tenecteplase.Therefore,we examined ...Objective Limited evidence is available regarding the risk-benefit ratio of thrombolytic therapy in patients with stroke and renal impairment complications,particularly for the drug tenecteplase.Therefore,we examined the association of impaired renal function with the safety and efficacy of intravenous thrombolytic treatment(IVT)in patients with acute ischaemic stroke(AIS).Methods A post hoc analysis of a randomised controlled trial(ClinicalTrials gov.NCT04797013)was conducted.Participants who received IVT with tenecteplase and alteplase(0.25 and 0.9 mg/kg,respectively)within 4.5 hours of symptoms onset were categorised based on their estimated glomerular filtration rate as follows:(1)≥90 mL/min/1.73 m2,normal renal function;(2)60-89 mL/min/1.73 m2,mildly decreased renal function;and(3)<60 mL/min/1.73 m2,moderately to severely decreased renal function.Patients stratified based on the normal renal function were used as the references.The primary efficacy and safety outcome were the percentage of patients achieving a modified Rankin Scale score of 0-1 at 90 days and the symptomatic intracranial haemorrhage(sICH)occurrence within 36 hours,respectively.Results In intravenous tenecteplase-treated patients,mildly decreased renal function(OR 3.10;95%CI:1.41 to 6.78)and moderately to severely decreased renal function(OR:8.03;95%CI:2.76 to 23.38)showed an association with a higher risk of all-cause mortality but not with sICH incidence compared with normal renal function.Among patients administered intravenous alteplase,those with a moderate-to severe decrease in renal function exhibited an elevated risk of sICH(adjusted OR:10.01;95%CI:1.61 to 62.15)and all-cause mortality(adjusted OR:4.54;95%CI:1.48 to 13.91).Comparative treatment effects between tenecteplase and alteplase according to renal function grades showed no heterogeneity.Conclusions A significant correlation was noted between kidney dysfunction and unfavourable outcomes in individuals with AIS who received treatment with either tenecteplase or alteplase.展开更多
Background:The National Comprehensive Cancer Network guidelines recommend intensity-modulated radiotherapy(IMRT)as the primary curative treatment for newly diagnosed nasopharyngeal carcinoma(NPC),but the radiation-rel...Background:The National Comprehensive Cancer Network guidelines recommend intensity-modulated radiotherapy(IMRT)as the primary curative treatment for newly diagnosed nasopharyngeal carcinoma(NPC),but the radiation-related complications and relatively high medical costs remain a consequential burden for the patients.Endoscopic nasopharyngectomy(ENPG)was successfully applied in recurrent NPC with radiation free and relatively low medical costs.In this study,we examined whether ENPG could be an effective treatment for localized stage I NPC.Methods:Ten newly diagnosed localized stage I NPC patients voluntarily received ENPG alone from June 2007 to September 2017 in Sun Yat-sen University Cancer Center.Simultaneously,the data of 329 stage I NPC patients treated with IMRT were collected and used as a reference cohort.The survival outcomes,quality of life(QOL),and medical costs between two groups were compared.Results:After a median follow-up of 59.0 months(95%CI 53.4-64.6),no death,locoregional recurrence,or distant metastasis was observed in the 10 patients treated with ENPG.The 5-year overall survival,local relapse-free survival,regional relapse-free survival,and distant metastasis-free survival among the ENPG-treated patients was similar to that among the IMRT-treated patients(100%vs.99.1%,100%vs.97.7%,100%vs.99.0%,100%vs.97.4%,respectively,P>0.05).In addition,compared with IMRT,ENPG was associated with decreased total medical costs($4090.42±1502.65 vs.$12620.88±4242.65,P<0.001)and improved QOL scores including dry mouth(3.3±10.5 vs.34.4±25.8,P<0.001)and sticky saliva(3.3±10.5 vs.32.6±23.3,P<0.001).Conclusions:ENPG alone was associated with promising long-term survival outcomes,low medical costs,and satisfactory QOL and might therefore be an alternative strategy for treating newly diagnosed localized stage I NPC patients who refused radiotherapy.However,the application of ENPG should be prudent,and prospective clinical tri-als were needed to further verify the results.展开更多
Background:Famitinib is a tyrosine kinase inhibitor against multiple targets,including vascular endothelial growth factor receptor 2/3,platelet-derived growth factor receptor,and stem cell factor receptor(c-kit).Previ...Background:Famitinib is a tyrosine kinase inhibitor against multiple targets,including vascular endothelial growth factor receptor 2/3,platelet-derived growth factor receptor,and stem cell factor receptor(c-kit).Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers.We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy(CCRT)in patients with locoregionally advanced nasopharyngeal carcinoma(NPC).We also evaluated the feasibility of contrast-enhanced ultrasound(D-CEUS)as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy.Methods:The trial was conducted in subjects with stage III or IVa-b NPC using a 3+3 design of escalating fami-tinib doses.Briefly,subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT.D-CEUS of the neck lymph nodes was performed at day 0,8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy.End points included safety,tolerability and anti-tumour activity.Results:Twenty patients were enrolled(six each for 12.5,16.5 and 20 mg and two for 25 mg).Two patients in the 25 mg cohort developed dose-limiting toxicities,including grade 4 thrombocytopenia and grade 3 hypertension.The most common grade 3/4 adverse events were leukopenia,neutropenia and radiation mucositis.D-CEUS tests showed that more than 60%of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone,and the parameter response was associated with disease improvement.In the famitinib monotherapy stage,three patients(15%)showed partial responses.The complete response rate was 65%at the completion of treatment and 95%3 months after the treatment ended.After a median follow-up of 44 months,the 3-year progression-free survival(PFS)and distant metastasis-free survival were 70%and 75%,respectively.Subjects with a decrease of perfusion parameter response,such as peak intensity decreased at least 30%after 1 week of famitinib treatment,had higher 3-year PFS(90.9%vs.44.4%,95%CI 73.7%-100%vs.11.9%-76.9%,P<0.001)than those with an increase or a reduction of less than 30%.Conclusions:The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC.D-CEUS is a reliable and early measure of efficacy for famitinib therapies.Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.展开更多
基金supported by grants from the Science and Technology Project of Guangzhou City,China(No.14570006)the Planned Science and Technology Project of Guangdong Province,China(No.2013B020400004)
文摘Background: Little is known about the nature of metaistasis to small cervical lymph nodes(SCLNS) in the patients with nasopharyngeal carcinoma(NPC)examined by using 18-fluoro-2-deoxy-glucose(^(18)F-FDG) positron emission tomography/computed tomography(PET/CT).The present study aimed to evaluate the diagnostic values of PET/CT in identifying metastasis in SCLNs in NPC patients.Methods: Magnetic resonance images(MRI) and PET/CT scans for 470 patients with newly diagnosed, non-distant metastatic NPC were analyzed. Metastatic rates of SCLNs were defined by the positive number of SCLNs on PET/CT scans and total number of SCLNs on MRI scans. Receiver operating characteristic curve was applied to compare PET/CT-determined stage with MRI-determined stage.Results: In total, 2082 SCLNs were identified, with 808(38.8%) ≥ 5 and < 6 mm in diameter(group A), 526(25.3%)≥ 6 and < 7 mm in diameter(group B),374(18.0%)≥ 7 and < 8 mm in diameter(group C), 237(11.4%) ≥8 and<9 mm in diameter(group D),and 137(6.5%) ≥ 9 and <10 mm in diameter(group E).The overall metastatic rates examined by using PET/CT for groups A, B,C,D, and E were 3.5%, 8.0%, 31.3%, 60.0%, and 83.9%, respectively(P< 0.001). In level IV/Vb, the metastatic rate for nodes ≥ 8 mm was 84.6%. PET/CT examination resulted in modification of N category and overall stage for 135(28.7%) and 46(9.8%) patients, respectively. The areas under curve of MRIdetermined and PET/CT-determined overall stage were 0.659 and 0.704 for predicting overall survival, 0.661 and 0.711 for predicting distant metastasis-free survival, and 0.636 and 0.663 for predicting disease-free survival.Conclusions: PET/CT was more effective than MRI in identifying metastatic SCLNs, and the radiologic diagnostic criteria for metastatic lymph nodes in level IV/Vb should be re-defined.
文摘Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra-and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy.This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules.Methods: In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+)T-cell density in primary tumors and PD-1 expression on CD8(+)T cells were detected with immunofluorescence. Univariate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival.Results: Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors(45.4% vs. 38.7%, P = 0.005); the positive rate of PD-1 on CD8(+)T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes(both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression,PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.Conclusion: The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stageT1-4 N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies.
基金supported by the National High Technology Research and Development Program of China(No.2012AA02A501)the Special Fund for Public Health Trade(No.201202014)
文摘Background:With industrial and economic development in recent decades in South China,cancer incidence may have changed due to the changing lifestyle and environment.However,the trends of lung cancer and the roles of smoking and other environmental risk factors in the development of lung cancer in rural areas of South China remain unclear.The purpose of this study was to explore the lung cancer incidence trends and the possible causes of these trends.Methods:Joinpoint regression analysis and the age-period-cohort(APC) model were used to analyze the lung cancer incidence trends in Sihui,Guangdong province,China between 1987 and 2011,and explore the possible causes of these trends.Results:A total of 2,397 lung cancer patients were involved in this study.A 3-fold increase in the incidence of lung cancer in both sexes was observed over the 25-year period.Joinpoint regression analysis showed that while the incidence continued to increase steadily in females during the entire period,a sharp acceleration was observed in males starting in 2005.The full APC model was selected to describe age,period,and birth cohort effects on lung cancer incidence trends in Sihui.The age cohorts in both sexes showed a continuously significant increase in the relative risk(RR)of lung cancer,with a peak in the eldest age group(80-84 years).The RR of lung cancer showed a fluctuating curve in both sexes.The birth cohorts identified an increased trend in both males and females;however,males had a plateau in the youngest cohorts who were born during 1955-1969.Conclusions:Increasing trends of the incidence of lung cancer in Sihui were dominated by the effects of age and birth cohorts.Social aging,smoking,and environmental changes may play important roles in such trends.
基金supported by Grants from the National High Technology Research and Development Program of China(No.2012AA02A501)the Special Fund for Public Health Trade(No.201202014)+1 种基金National Natural Science Foundation of China(No.81373068)the 5010 Clinical Trail Study of Sun Yat-sen University(No.2013012)
文摘Background: Serum immunoglobulin A antibodies against Epstein–Barr virus(EBV), viral capsid antigen(VCA?Ig A) and early antigen(EA?Ig A), are used to screen for nasopharyngeal carcinoma(NPC) in endemic areas. However, their routine use has been questioned because of a lack of specificity. This study aimed to determine the distributions of different subtypes of antibody and to illustrate how the natural variation patterns affect the specificity of screening in non?NPC participants.Methods: The distribution of baseline VCA?IgA was analyzed between sexes and across 10?year age groups in 18,286 non?NPC participants using Chi square tests. Fluctuations in the VCA?IgA level were assessed in 1056 non?NPC participants with at least two retests in the first 5?year period(1987–1992) after the initial screening using the Kaplan–Meier method.Results: The titers of VCA?Ig A increased with age(P < 0.001). Using a previous serological definition of high NPC risk, nasopharyngeal endoscopy and/or nasopharyngeal biopsy would be recommended in 55.5% of the non?NPC partici?pants with an initial VCA?Ig A?positive status and in 20.6% with an initial negative status during the 5?year follow?up. However, seroconversions were common; 85.2% of the participants with a VCA?Ig A?positive status at baseline con?verted to negative, and all VCA?Ig A?negative participants changed to positive at least once during the 5?year follow?up. The EA?Ig A status had a high seroconversion probability(100%) from positive to negative; however, it had a low probability(19.6%) from negative to positive.Conclusions: Age? and sex?specific cutoff titer values for serum anti?EBV antibodies as well as their specific titer fluc?tuation patterns should be considered when defining high NPC risk criteria for follow?up diagnostics and monitoring.
基金the Chinese Academy of Medical Sciences(grant No.2019XK320068)。
文摘Salivary gland carcinomas(SGCs)are rare malignancies that remain poorly understood owing to their low incidence(Matsuba et al.,1986b;Liu et al.,2012).As per GLOBOCAN 2018.52.800 new cancers arising from salivary glands were estimated to be diag-nosed across the world that year.Because of their high propensity to invade local and perineural structures.
基金supported by Beijing Municipal Science&Technology Commission(Z221100007422050)Capital's Funds for Health Improvement and Research(2020-1-2041,2022-2G 2049).
文摘Background GD-11,a novel brain cytoprotective drug,was designed to be actively taken up and transported across the blood-brain barrier via the glucose transporter.This study aimed to evaluate the safety and efficacy of GD-11 for improving the recovery of patients with acute ischaemic stroke(AIS).Methods A double-blind,randomised,placebo-controlled,phase 2 trial was conducted at 15 clinical sites in China.Patients aged 18-80 years with AIS within 48 hours were randomly assigned(1:1:1)to receive 160 mg GD-11,80 mg GD-11 and placebo,two times a day for 10 days.The primary endpoint was a modified Rankin Scale(mRS)score of 0-1 at 90 days after treatment.The safety outcome was any adverse events within 90 days.Results From 17 November 2022 to 22 March 2023,a total of 80 patients in the 160 mg GD-11 group,79 patients in the 80 mg GD-11 group and 80 patients in the placebo group were included.The proportion of an mRS score of 0-1 at day 90 was 77.5%in the 160 mg GD-11 group,72.2%in the 80 mg GD-11 group and 67.5%in the placebo group.Though no significant difference was found(p=0.3671),a numerically higher proportion was observed in the GD-11 group,especially in the 160 mg GD-11 group.The incidence of adverse events was similar across the three groups(p=0.1992).Conclusion GD-11 was safe and well-tolerated.A dosage of GD-11160 mg two times a day was recommended for a large trial to investigate the efficacy.
基金National Natural Science Foundation of China(81870905,U20A20358,82111530203)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M 5-029)The National Science and Technology Major Project(2017ZX09304018).
文摘Background The benefit of intravenous alteplase in acute ischaemic stroke(AIS)is time-dependent.Tenecteplase is non-inferior to alteplase among patients with AIS.We aimed to delineate the association of the stroke onset to treatment time(OTT)with tenecteplase compared with alteplase on therapeutic benefit and clinical risks.Methods This is a post hoc analysis of the Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-2 an open-label,randomised,controlled,non-inferior trial.A total of 1430 AIS within 4.5 hours onset at 53 sites in China from 12 June 2021 to 29 May 2022 were randomly assigned(1:1)to receive either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg.The primary efficacy outcome was the proportion of participants with a modified Rankin Scale score of 0–1 at 90 days.A post hoc subgroup analysis was conducted with the OTT divided into three intervals(0–90 min,91–180 min and 181–270 min).The primary safety outcome was symptomatic intracranial haemorrhage within 36 hours post-thrombolytic treatment.Results Treatment was initiated within 270 min of stroke onset in 1412 patients who were randomly allocated to either tenecteplase(n=707)or alteplase(n=705).The OR of primary efficacy outcome was similar as OTT increased(p=0.84).Adjusted odds of an excellent functional outcome were 0.99(95%CI 0.37 to 2.67)for 0–90 min,1.23(95%CI 0.88 to 1.71)for 91–180 min and 1.21(95%CI 0.88 to 1.65)for 181–270 min.All were in favour of the tenecteplase group.Meta-analysis of 2949 patients yielded a pooled risk difference of 5.54(95%CI-0.18 to 11.26;p=0.82)in favour of tenecteplase for more than 180 min and 1.77(95%CI-2.66 to 6.20;p=0.58)for 0–180 min.Conclusions In AIS patients who were treated with either tenecteplase or alteplase within 4.5 hours onset,there was no difference observed in the efficacy and safety between the two groups at the three different OTT time intervals.
基金National Natural Science Foundation of China(U20A20358)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M 5-029)+3 种基金Beijing Municipal Science&Technology Commission(No.2221100007422050)National Natural Science Foundation of China(U20A20358)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M 5-029)Beijing Municipal Science&Technology Commission(No.2221100007422050).
文摘Background and purpose Reteplase is the third generation of alternative thrombolytic agent.We hypothesis that reteplase will be non-inferior to alteplase in achieving excellent functional outcome at 90 days among eligible patients with acute ischaemic stroke.Methods and design Reteplase versus alteplase for acute ischaemic stroke within 4.5hours(RAISE)trial is a multicentre,prospective,randomised,open-label,blinded endpoint(PROBE),controlled phase 3 non-inferiority trial.A total of 1412 eligible patients will be randomly assigned to receive either reteplase at a dose of 18 mg+18mg or alteplase 0.9mg/kg at a ratio of 1:1.An independent data monitoring committee will review the trail’s progress and safety data.Study outcomes The primary efficacy outcome of this study is proportion of individuals attaining an excellent functional outcome,defined as modified Rankin Scale(mRS)0–1 at 90 days.The secondary efficacy outcomes encompass favourable functional outcome defined as mRS 0–2,major neurological improvement on the National Institutes of Health Stroke Scale,ordinal distribution of mRS and Barthel Index score of at least 95 points at 90 days.The primary safety outcomes are symptomatic intracranial haemorrhage at 36 hours within 90 days.Discussion The RAISE trial will provide crucial insights into the selection of thrombolytic agents for stroke thrombolysis.Trial registration number NCT05295173.
文摘Breast cancer is one of the most common malignant tumors among women in China,with approximately 306,000 new cases reported in 2016.Notably,around 33%(100,400)of these cases occurred in rural areas.County-level hospitals,encompassing counties and county-level cities,serve as the primary diagnostic units for the majority of rural breast cancer patients.These hospitals are integral to cancer prevention,screening,maintenance treatment,rehabilitation,follow-up,and referral processes.However,economic and geographical constraints result in county-level hospitals being relatively deficient in medical equipment,health human resources,and drug accessibility.Consequently,there is a critical need for breast cancer prevention and management guidelines that are tailored to the specific conditions of China's counties.In response to this need,and within the policy framework of hierarchical diagnosis and treatment,a Chinese expert group has developed the Guideline for the Management Pathway and Quality Control of Breast Cancer Prevention and Treatment in China's Counties(2023 Edition).This guideline aims to expand the availability of quality medical resources,ensure better distribution of these resources across regions,and enhance the capacity for breast cancer prevention and treatment.Ultimately,the goal is to improve the prognosis and quality of life for breast cancer patients in China's counties.This guideline includes clear and concise path diagrams that are easy to implement in clinical practice,serving as a valuable reference for clinicians in countylevel hospitals.
文摘Treatment of breast cancer with low expression of human epidermal growth factor receptor 2(HER2;HER2-low)has drawn much attention in recent years.With the proven therapeutic effect of trastuzumab deruxtecan(T-DXd)in patients with HER2-low(immunohistochemistry[IHC]1+,or IHC2+/in situ hybridization[ISH]-)breast cancer,HER2-low may become a new subtype of targeted therapy for breast cancer.The expert committee formulated this consensus based on the current clinical studies and clinical medication experience.The current consensus is the collaborative work of an interdisciplinary working group,including experts in the fields of pathology and oncology.The purpose of this consensus was to guide the clinical diagnosis and treatment of HER2-low breast cancer,thereby prolonging the overall survival of patients.
基金the manuscript was sup-ported by Chinese National Key Research and Development Project(2018YFC1315600)“Platform Improvement of Clinical Trial Ca-pability”(2020-I2M-2-007)。
文摘Objectives:To describe and compare the research and development(R&D)pipeline of cancer new drugs and newly approved drugs in China and the USA in 2020,thus to provide decision-making evidence for related stakeholders.Methods:Clinical trials and tested cancer new drugs information in China and the USA were respectively ac-quired from Information Disclosure Platform for Drug Clinical Studies and Trialtrove database.Drug approval was tracked from the official release.Subgroup comparison in terms of initiated trials and drugs were conducted between the two countries.Results:In 2020,577 trials on 335 cancer new drugs were registered in China,accounting for 22.6%of all clinical drug trials,while in the USA,916 trials on 678 cancer new drug trials were captured,accounting for 19.9%of the total.Relatively,a lower proportion of earlier phase(76.9%vs 87.4%),global(17.7%vs 39.0%),and top 20 pharmaceutics contribution(15.8%vs 43.2%)were found for cancer drug trials initiated in China.The fight against solid tumor took top billing in both countries,and the different distribution of cancer indications associated with cancer spectrum was also observed.Compared with the USA,more targeted agents(87.5%vs 77.0%,P<0.001)and less immune agents(30.7%vs 41.6%,P<0.001)were tested in China.In addition,16 and 18 anticancer new drugs were approved in China and the USA,with 6(37.5%)and 17(94.4%)drugs being firstly approved worldwide,respectively.Among them,32 drugs were granted by at least one expedited program,and 31 drugs were approved based on evidence from surrogate endpoints.A total of 17 cancer types were covered,and only one drug was targeted on digestive cancers,including gastric,liver,and esophageal cancers.Conclusions:R&D of anticancer new drugs is substantial,and great progress has been made in both China and the USA in 2020.The difference and gap between China and the USA highlight that more efforts should be paid to anticancer drug R&D on innovative agents and cancers unique to Chinese populations,as well as to facilitate global synchronous R&D in China.
基金funded by Key R&D Program of China(2017YFC1308204)This study was funded by Key R&D Program of China(2017YFC1308204),。
文摘Objective Limited evidence is available regarding the risk-benefit ratio of thrombolytic therapy in patients with stroke and renal impairment complications,particularly for the drug tenecteplase.Therefore,we examined the association of impaired renal function with the safety and efficacy of intravenous thrombolytic treatment(IVT)in patients with acute ischaemic stroke(AIS).Methods A post hoc analysis of a randomised controlled trial(ClinicalTrials gov.NCT04797013)was conducted.Participants who received IVT with tenecteplase and alteplase(0.25 and 0.9 mg/kg,respectively)within 4.5 hours of symptoms onset were categorised based on their estimated glomerular filtration rate as follows:(1)≥90 mL/min/1.73 m2,normal renal function;(2)60-89 mL/min/1.73 m2,mildly decreased renal function;and(3)<60 mL/min/1.73 m2,moderately to severely decreased renal function.Patients stratified based on the normal renal function were used as the references.The primary efficacy and safety outcome were the percentage of patients achieving a modified Rankin Scale score of 0-1 at 90 days and the symptomatic intracranial haemorrhage(sICH)occurrence within 36 hours,respectively.Results In intravenous tenecteplase-treated patients,mildly decreased renal function(OR 3.10;95%CI:1.41 to 6.78)and moderately to severely decreased renal function(OR:8.03;95%CI:2.76 to 23.38)showed an association with a higher risk of all-cause mortality but not with sICH incidence compared with normal renal function.Among patients administered intravenous alteplase,those with a moderate-to severe decrease in renal function exhibited an elevated risk of sICH(adjusted OR:10.01;95%CI:1.61 to 62.15)and all-cause mortality(adjusted OR:4.54;95%CI:1.48 to 13.91).Comparative treatment effects between tenecteplase and alteplase according to renal function grades showed no heterogeneity.Conclusions A significant correlation was noted between kidney dysfunction and unfavourable outcomes in individuals with AIS who received treatment with either tenecteplase or alteplase.
基金Funding was provided by the National Natural Science Foundation of China(Nos.81572912,81772895)Guangdong Public Welfare Research and Capacity Building Projects(2014B020212005)+1 种基金the Program of Sun Yat-Sen University for Clinical Research 5010 Program(No.201310)the Major Project of Sun Yat-Sen University for the New Cross Subject,the Special Support Program for High-level Talents in Sun Yat-Sen University Cancer Center(to M.Y.Chen),Guangdong Province Science and Technology Development Special Funds(Frontier and Key Technology Innovation Direction-Major Science and Technology Project),Guangzhou Science and Technology Planning Project-Production and Research Collaborative Innovation Major Project
文摘Background:The National Comprehensive Cancer Network guidelines recommend intensity-modulated radiotherapy(IMRT)as the primary curative treatment for newly diagnosed nasopharyngeal carcinoma(NPC),but the radiation-related complications and relatively high medical costs remain a consequential burden for the patients.Endoscopic nasopharyngectomy(ENPG)was successfully applied in recurrent NPC with radiation free and relatively low medical costs.In this study,we examined whether ENPG could be an effective treatment for localized stage I NPC.Methods:Ten newly diagnosed localized stage I NPC patients voluntarily received ENPG alone from June 2007 to September 2017 in Sun Yat-sen University Cancer Center.Simultaneously,the data of 329 stage I NPC patients treated with IMRT were collected and used as a reference cohort.The survival outcomes,quality of life(QOL),and medical costs between two groups were compared.Results:After a median follow-up of 59.0 months(95%CI 53.4-64.6),no death,locoregional recurrence,or distant metastasis was observed in the 10 patients treated with ENPG.The 5-year overall survival,local relapse-free survival,regional relapse-free survival,and distant metastasis-free survival among the ENPG-treated patients was similar to that among the IMRT-treated patients(100%vs.99.1%,100%vs.97.7%,100%vs.99.0%,100%vs.97.4%,respectively,P>0.05).In addition,compared with IMRT,ENPG was associated with decreased total medical costs($4090.42±1502.65 vs.$12620.88±4242.65,P<0.001)and improved QOL scores including dry mouth(3.3±10.5 vs.34.4±25.8,P<0.001)and sticky saliva(3.3±10.5 vs.32.6±23.3,P<0.001).Conclusions:ENPG alone was associated with promising long-term survival outcomes,low medical costs,and satisfactory QOL and might therefore be an alternative strategy for treating newly diagnosed localized stage I NPC patients who refused radiotherapy.However,the application of ENPG should be prudent,and prospective clinical tri-als were needed to further verify the results.
基金supported by Jiangsu Hengrui Medicine Co.,Ltd[The National Natural Science Foundation of China(Grant No.81230056)The National Science&Technology Pillar Program during the Twelfth Five-year Plan Period(Grand No.2014BAI09B10+4 种基金The Natural Science Foundation of Guangdong Province(Grand Nos.S2013010012220,2017A030312003)the Science and Technology Project of Guangzhou City,China(Grand No.132000507)The Health&Medical Collaborative Innovation Project of Guangzhou City,China(Grand No.201400000001)The Innovation Team Development Plan of the Ministry of Education(Grand No.IRT_17R110)the Program of Introducing Talents of Discipline to Universities(Grand No.B14035)].
文摘Background:Famitinib is a tyrosine kinase inhibitor against multiple targets,including vascular endothelial growth factor receptor 2/3,platelet-derived growth factor receptor,and stem cell factor receptor(c-kit).Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers.We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy(CCRT)in patients with locoregionally advanced nasopharyngeal carcinoma(NPC).We also evaluated the feasibility of contrast-enhanced ultrasound(D-CEUS)as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy.Methods:The trial was conducted in subjects with stage III or IVa-b NPC using a 3+3 design of escalating fami-tinib doses.Briefly,subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT.D-CEUS of the neck lymph nodes was performed at day 0,8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy.End points included safety,tolerability and anti-tumour activity.Results:Twenty patients were enrolled(six each for 12.5,16.5 and 20 mg and two for 25 mg).Two patients in the 25 mg cohort developed dose-limiting toxicities,including grade 4 thrombocytopenia and grade 3 hypertension.The most common grade 3/4 adverse events were leukopenia,neutropenia and radiation mucositis.D-CEUS tests showed that more than 60%of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone,and the parameter response was associated with disease improvement.In the famitinib monotherapy stage,three patients(15%)showed partial responses.The complete response rate was 65%at the completion of treatment and 95%3 months after the treatment ended.After a median follow-up of 44 months,the 3-year progression-free survival(PFS)and distant metastasis-free survival were 70%and 75%,respectively.Subjects with a decrease of perfusion parameter response,such as peak intensity decreased at least 30%after 1 week of famitinib treatment,had higher 3-year PFS(90.9%vs.44.4%,95%CI 73.7%-100%vs.11.9%-76.9%,P<0.001)than those with an increase or a reduction of less than 30%.Conclusions:The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC.D-CEUS is a reliable and early measure of efficacy for famitinib therapies.Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.
