Background:To investigate the mutation types and mutation rate of the epidermal growth factor receptor(EGFR)gene in patients with lung adenocarcinoma and the clinical features of lung adenocarcinoma with EGFR gene mut...Background:To investigate the mutation types and mutation rate of the epidermal growth factor receptor(EGFR)gene in patients with lung adenocarcinoma and the clinical features of lung adenocarcinoma with EGFR gene mutations in Karamay,Xinjiang,China.Methods:Paraffin-embedded tissue samples of adenocarcinoma patients were collected in the Karamay Central Hospital from March 2016 to June 2019,and mutations in exon 18–21 of the EGFR gene were detected by the allele-specific amplification polymerase chain reaction(Amplification RefractoryMutation System–PCR)method.The relationships between themutation types,mutation incidence,and clinical features were analyzed.Results:Of the 170 patients with lung adenocarcinoma,83 had EGFR mutations.The total mutation rate of EGFR in patients with lung adenocarcinoma was 48.8%,which included mutations in exons 18(1.2%[2/170]),19(19.4%[33/170]),20(2.4%[4/170]),and 21(20.6%[35/170]).Intriguingly,there was a case with 9 mutations in exons 20 and 21.The mutations in exon 19 of EGFR resulted in the deletion of codons 746 to 750.The main mutation in exon 21 was L858R(91.4%[32/35]).There was no significant difference in exons 19 and 21 mutation rates(P>0.05).The mutation rate of EGFR in female patients was significantly higher than that in male patients(P<0.05)but had no correlation with the age,smoking status,and clinical stage of patients with non–small cell lung cancer(P>0.05).The EGFR mutation rate may be related to the degree of tumor differentiation.Conclusions:Among patients with lung adenocarcinoma in Kelamayi(city in Xinjiang),EGFR mutations were more frequently detected in female patients,and the main sites of mutations were exons 19 and 21.展开更多
Objective:To investigate the genetic correlations between epithelial growth factor receptor(EGFR)mutation and FHIT methylation in patients diagnosed with lung adenocarcinoma(AC)and pulmonary tuberculosis(TB).Methods:T...Objective:To investigate the genetic correlations between epithelial growth factor receptor(EGFR)mutation and FHIT methylation in patients diagnosed with lung adenocarcinoma(AC)and pulmonary tuberculosis(TB).Methods:The presence of EGFR mutations and the methylation status of the FHIT gene in patients presenting with AC and TB were analyzed.The correlation between TB status and the observed genetic and epigenetic variations was also examined.Results:Among the 90 patients included in the study,38 exhibited EGFR mutations(14 among those with TB and 24 among those without TB),while 29 exhibited FHIT myelination(19 among those with TB and 10 among those without TB).Furthermore,the protein expression levels of EGFR and FHIT were significantly higher in patients diagnosed solely with AC compared to those presenting with both AC and TB.A robust inverse correlation was identified between TB status and the frequency of EGFR mutation(P<0.001).Moreover,significant associations were observed between TB status and FHIT methylation(P<0.01).Conclusion:The findings suggest a correlation between TB and the prevalence of EGFR mutation and FHIT methylation in the pathogenesis of AC.展开更多
Objective： The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal ...Objective： The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal growth factor receptor（EGFR） mutation-positive lung adenocarcinoma, and to analyze the effects of the different medication orders of first- and second-line drugs on third-line efficacy.Patients and methods： One hundred and sixteen cases of patients with EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or in combination with bevacizumab between March 2010 and March 2014 at Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively. Additionally, all the patients were treated with first-line gemcitabine and cisplatin（GP） chemotherapy and second-line EGFR tyrosine kinase inhibitor（TKI） or with first-line EGFR-TKI and second-line GP chemotherapy.Results： The median survival of 61 cases with third-line pemetrexed monotherapy was 36.22 months, the median survival time of 55 cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was a significant difference in survival time between the two groups（P=0.04）. Subgroup analysis revealed that among the 55 cases with third-line bevacizumab plus pemetrexed treatment, the median survival of 29 patients with first-line GP and second-line EGFR-TKI was 42.80 months, while the median survival of 26 patients with first-line EGFR-TKI and second-line GP was only 34.46 months; additionally, there was a significant difference in the survival time between the two subgroups（P=0.001）. Among 61 cases with thirdline pemetrexed treatment, the median survival of 34 patients with first-line GP and second-line EGFR-TKI was 38.72 months, while the median survival of 27 patients with first-line EGFR-TKI and second-line GP was only 32.94 months; the survival time of the two subgroups was significantly different（P=0.001）.Conclusions： Regardless of the order of the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line therapy in patients with advanced EGFR-positive lung adenocarcinoma. However, this strategy is worth further investigation in prospective studies.展开更多
Background:Epidermal growth factor receptor(EGFR) mutations,including a known exon 19 deletion(19 del) and exon 21 L858 R point mutation(L858R mutation),are strong predictors of the response to EGFR tyrosine kinase in...Background:Epidermal growth factor receptor(EGFR) mutations,including a known exon 19 deletion(19 del) and exon 21 L858 R point mutation(L858R mutation),are strong predictors of the response to EGFR tyrosine kinase inhibitor(EGFR-TKI) treatment in lung adenocarcinoma.However,whether patients carrying EGFR 19 del and L858 R mutations exhibit different responsiveness to EGFR-TKls and what are the potential mechanism for this difference remain controversial.This study aimed to investigate the clinical outcomes of EGFR-TKI treatment in patients with EGFR 19 del and L858 R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes.Methods:Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858 R mutations,532 received EGFR-TKI treatment and were included in this study.EGFR 19 del and L858 R mutations were detected by using denaturing high-performance liquid chromatography(DHPLC).T790 M mutation,which is a common resistant mutation on exon 20 of EGFR,was detected by amplification refractory mutation system(ARMS).Next-generation sequencing(NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858 R mutations.Results:Of the 532 patients,319(60.0%) had EGFR 19 del,and 213(40.0%) had L858 R mutations.The patients with EGFR 19 del presented a significantly higher overall response rate(ORR) for EGFR-TKI treatment(55.2%vs.43.7%,P = 0.017) and had a longer progression-free survival(PFS) after first-line EGFR-TKI treatment(14.4 vs.11.4 months,P = 0.034) compared with those with L858 R mutations.However,no statistically significant difference in overall survival(OS) was observed between the two groups of patients.T790 M mutation status was analyzed in 88 patients before EGFR-TKI treatment and 134 after EGFR-TKI treatment,and there was no significant difference in the co-existence of T790 M mutation with EGFR 19 del and L858 R mutations before EGFR-TKI treatment(5.6%vs.8.8%,P = 0.554)or after treatment(24.4%vs.35.4%,P = 0.176).In addition,24 patients with EGFR 19 del and 19 with L858 R mutations were analyzed by NGS,and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes.Conclusions:Patients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858 R mutations.Whether the heterogeneity of tumors with EGFR 19 del and L858 R mutations contribute to a therapeutic response difference needs further investigation.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
目的探究贝伐珠单抗联合放疗治疗表皮生长因子受体(EGFR)野生型肺腺癌脑转移的临床效果。方法于2020年5月至2022年5月采用随机数字表法将40例EGFR野生型肺腺癌脑转移患者分为参照组(全脑放疗+瘤区推量调强放疗)和试验组(贝伐珠单抗联合...目的探究贝伐珠单抗联合放疗治疗表皮生长因子受体(EGFR)野生型肺腺癌脑转移的临床效果。方法于2020年5月至2022年5月采用随机数字表法将40例EGFR野生型肺腺癌脑转移患者分为参照组(全脑放疗+瘤区推量调强放疗)和试验组(贝伐珠单抗联合全脑放疗+瘤区推量调强放疗)各20例,对干预效果进行分析比较。结果与参照组20.00%相比,试验组50.00%治疗总有效率显著更高(P<0.05),治疗前研究对象的Karnofsky(KPS)评分、美国国立卫生研究院卒中量表(NIH Stroke Scale,NIHSS评分)、格拉斯哥昏迷计分(Glasgow Coma Scale,GCS)评分水平对比无显著差异(P>0.05),治疗后试验组KPS评分、GCS评分高于参照组,NIHSS评分低于参照组(P<0.05);在不良事件发生率上,参照组40.00%与试验组50.00%相比无显著差异(P>0.05);试验组无进展生存时间(PFS)、总生存期(OS)显著高于参照组(P<0.05)。结论将贝伐珠单抗联合放射治疗应用于EGFR野生型肺腺癌脑转移患者可显著提升疗效,改善精神状态、神经功能,提升生活质量,延长PFS、OS。展开更多
基金supported by a grant fromthe Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2021D01A24).
文摘Background:To investigate the mutation types and mutation rate of the epidermal growth factor receptor(EGFR)gene in patients with lung adenocarcinoma and the clinical features of lung adenocarcinoma with EGFR gene mutations in Karamay,Xinjiang,China.Methods:Paraffin-embedded tissue samples of adenocarcinoma patients were collected in the Karamay Central Hospital from March 2016 to June 2019,and mutations in exon 18–21 of the EGFR gene were detected by the allele-specific amplification polymerase chain reaction(Amplification RefractoryMutation System–PCR)method.The relationships between themutation types,mutation incidence,and clinical features were analyzed.Results:Of the 170 patients with lung adenocarcinoma,83 had EGFR mutations.The total mutation rate of EGFR in patients with lung adenocarcinoma was 48.8%,which included mutations in exons 18(1.2%[2/170]),19(19.4%[33/170]),20(2.4%[4/170]),and 21(20.6%[35/170]).Intriguingly,there was a case with 9 mutations in exons 20 and 21.The mutations in exon 19 of EGFR resulted in the deletion of codons 746 to 750.The main mutation in exon 21 was L858R(91.4%[32/35]).There was no significant difference in exons 19 and 21 mutation rates(P>0.05).The mutation rate of EGFR in female patients was significantly higher than that in male patients(P<0.05)but had no correlation with the age,smoking status,and clinical stage of patients with non–small cell lung cancer(P>0.05).The EGFR mutation rate may be related to the degree of tumor differentiation.Conclusions:Among patients with lung adenocarcinoma in Kelamayi(city in Xinjiang),EGFR mutations were more frequently detected in female patients,and the main sites of mutations were exons 19 and 21.
文摘Objective:To investigate the genetic correlations between epithelial growth factor receptor(EGFR)mutation and FHIT methylation in patients diagnosed with lung adenocarcinoma(AC)and pulmonary tuberculosis(TB).Methods:The presence of EGFR mutations and the methylation status of the FHIT gene in patients presenting with AC and TB were analyzed.The correlation between TB status and the observed genetic and epigenetic variations was also examined.Results:Among the 90 patients included in the study,38 exhibited EGFR mutations(14 among those with TB and 24 among those without TB),while 29 exhibited FHIT myelination(19 among those with TB and 10 among those without TB).Furthermore,the protein expression levels of EGFR and FHIT were significantly higher in patients diagnosed solely with AC compared to those presenting with both AC and TB.A robust inverse correlation was identified between TB status and the frequency of EGFR mutation(P<0.001).Moreover,significant associations were observed between TB status and FHIT methylation(P<0.01).Conclusion:The findings suggest a correlation between TB and the prevalence of EGFR mutation and FHIT methylation in the pathogenesis of AC.
基金funded by National Key Scientific & Technology Support Program: Collaborative innovation of Clinical Research for chronic obstructive pulmonary disease and lung cancer (NO. 2013BAI09B09)
文摘Objective： The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal growth factor receptor（EGFR） mutation-positive lung adenocarcinoma, and to analyze the effects of the different medication orders of first- and second-line drugs on third-line efficacy.Patients and methods： One hundred and sixteen cases of patients with EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or in combination with bevacizumab between March 2010 and March 2014 at Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively. Additionally, all the patients were treated with first-line gemcitabine and cisplatin（GP） chemotherapy and second-line EGFR tyrosine kinase inhibitor（TKI） or with first-line EGFR-TKI and second-line GP chemotherapy.Results： The median survival of 61 cases with third-line pemetrexed monotherapy was 36.22 months, the median survival time of 55 cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was a significant difference in survival time between the two groups（P=0.04）. Subgroup analysis revealed that among the 55 cases with third-line bevacizumab plus pemetrexed treatment, the median survival of 29 patients with first-line GP and second-line EGFR-TKI was 42.80 months, while the median survival of 26 patients with first-line EGFR-TKI and second-line GP was only 34.46 months; additionally, there was a significant difference in the survival time between the two subgroups（P=0.001）. Among 61 cases with thirdline pemetrexed treatment, the median survival of 34 patients with first-line GP and second-line EGFR-TKI was 38.72 months, while the median survival of 27 patients with first-line EGFR-TKI and second-line GP was only 32.94 months; the survival time of the two subgroups was significantly different（P=0.001）.Conclusions： Regardless of the order of the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line therapy in patients with advanced EGFR-positive lung adenocarcinoma. However, this strategy is worth further investigation in prospective studies.
基金supported by grants from the National Natural Sciences Foundation Key Program(No.81330062)Education Ministry Innovative Research Team Program(No.IRT13003)+1 种基金Peking University-Tsinghua University Joint Center for Life Sciences Clinical Investigator,National High Technology Research and Development Program 863(No.SS2015AA020403)Beijing Technology Project(No.Z141100000214013)
文摘Background:Epidermal growth factor receptor(EGFR) mutations,including a known exon 19 deletion(19 del) and exon 21 L858 R point mutation(L858R mutation),are strong predictors of the response to EGFR tyrosine kinase inhibitor(EGFR-TKI) treatment in lung adenocarcinoma.However,whether patients carrying EGFR 19 del and L858 R mutations exhibit different responsiveness to EGFR-TKls and what are the potential mechanism for this difference remain controversial.This study aimed to investigate the clinical outcomes of EGFR-TKI treatment in patients with EGFR 19 del and L858 R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes.Methods:Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858 R mutations,532 received EGFR-TKI treatment and were included in this study.EGFR 19 del and L858 R mutations were detected by using denaturing high-performance liquid chromatography(DHPLC).T790 M mutation,which is a common resistant mutation on exon 20 of EGFR,was detected by amplification refractory mutation system(ARMS).Next-generation sequencing(NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858 R mutations.Results:Of the 532 patients,319(60.0%) had EGFR 19 del,and 213(40.0%) had L858 R mutations.The patients with EGFR 19 del presented a significantly higher overall response rate(ORR) for EGFR-TKI treatment(55.2%vs.43.7%,P = 0.017) and had a longer progression-free survival(PFS) after first-line EGFR-TKI treatment(14.4 vs.11.4 months,P = 0.034) compared with those with L858 R mutations.However,no statistically significant difference in overall survival(OS) was observed between the two groups of patients.T790 M mutation status was analyzed in 88 patients before EGFR-TKI treatment and 134 after EGFR-TKI treatment,and there was no significant difference in the co-existence of T790 M mutation with EGFR 19 del and L858 R mutations before EGFR-TKI treatment(5.6%vs.8.8%,P = 0.554)or after treatment(24.4%vs.35.4%,P = 0.176).In addition,24 patients with EGFR 19 del and 19 with L858 R mutations were analyzed by NGS,and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes.Conclusions:Patients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858 R mutations.Whether the heterogeneity of tumors with EGFR 19 del and L858 R mutations contribute to a therapeutic response difference needs further investigation.
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.
文摘目的探究贝伐珠单抗联合放疗治疗表皮生长因子受体(EGFR)野生型肺腺癌脑转移的临床效果。方法于2020年5月至2022年5月采用随机数字表法将40例EGFR野生型肺腺癌脑转移患者分为参照组(全脑放疗+瘤区推量调强放疗)和试验组(贝伐珠单抗联合全脑放疗+瘤区推量调强放疗)各20例,对干预效果进行分析比较。结果与参照组20.00%相比,试验组50.00%治疗总有效率显著更高(P<0.05),治疗前研究对象的Karnofsky(KPS)评分、美国国立卫生研究院卒中量表(NIH Stroke Scale,NIHSS评分)、格拉斯哥昏迷计分(Glasgow Coma Scale,GCS)评分水平对比无显著差异(P>0.05),治疗后试验组KPS评分、GCS评分高于参照组,NIHSS评分低于参照组(P<0.05);在不良事件发生率上,参照组40.00%与试验组50.00%相比无显著差异(P>0.05);试验组无进展生存时间(PFS)、总生存期(OS)显著高于参照组(P<0.05)。结论将贝伐珠单抗联合放射治疗应用于EGFR野生型肺腺癌脑转移患者可显著提升疗效,改善精神状态、神经功能,提升生活质量,延长PFS、OS。
