Objective:An understanding of the leading causes of death in patients with head and neck squamous cell carcinoma(HNSCC)would be helpful to inform doctors,patients,and healthcare providers on disease management.This st...Objective:An understanding of the leading causes of death in patients with head and neck squamous cell carcinoma(HNSCC)would be helpful to inform doctors,patients,and healthcare providers on disease management.This study aimed to comprehensively study the leading causes of death in these survivors.展开更多
Background:Circulating tumor DNA(ctDNA)is a promising biomarker for non-invasive epidermal growth factor receptor mutations(EGFRm)detection in lung cancer patients,but existing methods have limitations in sensitivity ...Background:Circulating tumor DNA(ctDNA)is a promising biomarker for non-invasive epidermal growth factor receptor mutations(EGFRm)detection in lung cancer patients,but existing methods have limitations in sensitivity and availability.In this study,we used theΔCt value(mutant cycle threshold[Ct]value-internal control Ct value)generated during the polymerase chain reaction(PCR)assay to convert super-amplification-refractory mutation system(superARMS)from a qualitative method to a semi-quantitative method named reformed-superARMS(R-superARMS),and evaluated its performance in detectingEGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma.Methods:A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had knownEGFRm in tumor tissue and were previously untreated.EGFRm in ctDNA was identified by using superARMS.Through making use ofΔCt value generated during the detection process of superARMS,we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method,named R-superARMS.Both qualitative and quantitative analyses of the data were performed.Kaplan-Meier analysis was performed to estimate the progression-free survival(PFS)and overall survival(OS).Fisher exact test was used for categorical variables.Results:The concordance rate ofEGFRm in tumor tissues and matched plasma samples was 68.3%(28/41).At baseline,EGFRm-positive patients were divided into two groups according to the cut-offΔCt value ofEGFRm set at 8.11.A significant difference in the median OS(mOS)between the two groups was observed(EGFRmΔCt≤8.11vs.>8.11:not reachedvs.11.0 months;log-rankP=0.024).Patients were divided into mutation clearance(MC)group and mutation incomplete clearance(MIC)group according to whether theΔCt value ofEGFRm test turned negative after 1 month of treatment.We found that there was also a significant difference in mOS(not reachedvs.10.4 months;log-rankP=0.021)between MC group and MIC group.Although there was no significant difference in PFS between the two groups,the two curves were separated and the PFS of MC group tended to be higher than the MIC group(not reachedvs.27.5 months;log-rankP=0.088).Furthermore,EGFRm-positive patients were divided into two groups according to the cut-off of the changes inΔCt value ofEGFRm after 1 month of treatment,which was set at 4.89.A significant difference in the mOS between the two groups was observed(change value ofΔCt>4.89vs.≤4.89:not reachedvs.11.0 months;log-rankP=0.014).Conclusions:DetectingEGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy,reflect the molecular load of patients,and predict the therapeutic efficacy and clinical outcomes of patients.展开更多
基金This work was funded by the General Program of the National Natural Science Foundation of China(No.81673090),Natural Science Foundation of Science and Technology Agency of Jilin Province(Bethune special foundation)。
文摘Objective:An understanding of the leading causes of death in patients with head and neck squamous cell carcinoma(HNSCC)would be helpful to inform doctors,patients,and healthcare providers on disease management.This study aimed to comprehensively study the leading causes of death in these survivors.
基金supported by the National Key Research&Development Program of China(No.2016YFC1303800)Innovation Project of Health and Technology in Jilin Province(No.2017J064)+1 种基金Special Project of Development and Reform Commission in Jilin Province(No.2017C022)Key Laboratory Construction Project of Department of Science and Technology of Jilin Province(No.20170622011JC)。
文摘Background:Circulating tumor DNA(ctDNA)is a promising biomarker for non-invasive epidermal growth factor receptor mutations(EGFRm)detection in lung cancer patients,but existing methods have limitations in sensitivity and availability.In this study,we used theΔCt value(mutant cycle threshold[Ct]value-internal control Ct value)generated during the polymerase chain reaction(PCR)assay to convert super-amplification-refractory mutation system(superARMS)from a qualitative method to a semi-quantitative method named reformed-superARMS(R-superARMS),and evaluated its performance in detectingEGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma.Methods:A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had knownEGFRm in tumor tissue and were previously untreated.EGFRm in ctDNA was identified by using superARMS.Through making use ofΔCt value generated during the detection process of superARMS,we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method,named R-superARMS.Both qualitative and quantitative analyses of the data were performed.Kaplan-Meier analysis was performed to estimate the progression-free survival(PFS)and overall survival(OS).Fisher exact test was used for categorical variables.Results:The concordance rate ofEGFRm in tumor tissues and matched plasma samples was 68.3%(28/41).At baseline,EGFRm-positive patients were divided into two groups according to the cut-offΔCt value ofEGFRm set at 8.11.A significant difference in the median OS(mOS)between the two groups was observed(EGFRmΔCt≤8.11vs.>8.11:not reachedvs.11.0 months;log-rankP=0.024).Patients were divided into mutation clearance(MC)group and mutation incomplete clearance(MIC)group according to whether theΔCt value ofEGFRm test turned negative after 1 month of treatment.We found that there was also a significant difference in mOS(not reachedvs.10.4 months;log-rankP=0.021)between MC group and MIC group.Although there was no significant difference in PFS between the two groups,the two curves were separated and the PFS of MC group tended to be higher than the MIC group(not reachedvs.27.5 months;log-rankP=0.088).Furthermore,EGFRm-positive patients were divided into two groups according to the cut-off of the changes inΔCt value ofEGFRm after 1 month of treatment,which was set at 4.89.A significant difference in the mOS between the two groups was observed(change value ofΔCt>4.89vs.≤4.89:not reachedvs.11.0 months;log-rankP=0.014).Conclusions:DetectingEGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy,reflect the molecular load of patients,and predict the therapeutic efficacy and clinical outcomes of patients.