Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genet...Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.展开更多
Objective： Although superior clinical benefits of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in the treatment of advanced non-small-cell lung cancer （NSCLC） had been reported, the...Objective： Although superior clinical benefits of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in the treatment of advanced non-small-cell lung cancer （NSCLC） had been reported, the survival difference between exon 19 deletion （Dell9） and exon 21 Leu858Arg substitution （L858R） remains controversial. The purpose of this study is to investigate the differences in progression-free survival （PFS） and overall survival （OS） between different EGFR mutant subtypes among advanced NSCLC patients receiving gefitinib. Methods： There were 204 advanced NSCLC patients with EGFR mutations treated with gefitinib were enrolled in this retrospective cohort study. Patients were divided into the EGFR Dell9 group and the L858R mutated group according to their mutant subtype. Propensity score matching （PSM） was conducted by using a nearest-neighbor algorithm （1：1） to adjust for demographical and clinical covariates. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Results： The PFS in Dell9 group was similar to that in the L858R group [before PSM 8.6 vs. 7.2 months, P=0.072; after PSM 7.3 vs. 7.2 months, P=0.155]. No differences were detected in OS between the L858R and the Dell9 group （before PSM 17.8 vs. 13.1 months, P=0.253; after PSM 16.9 vs. 13.1 months, P=0.339）. The Dell9 group was significantly younger compared with the L858R mutation group in age （P=0.015）. Conclusions： No significant difference was found in the PFS or OS between the Dell9 and L858R mutant NSCLC patients receiving gefitinib. The age gap might contribute to the survival differences between Dell9 and L858R groups. PSM is of important value to the elimination of potential bias.展开更多
Background： To determine the safety and therapeutic efficacy of nimotuzumab （h-R3） combined with docetaxel in advanced non-small-cell lung cancer （NSCLC） patients who have failed to respond to prior first-line ch...Background： To determine the safety and therapeutic efficacy of nimotuzumab （h-R3） combined with docetaxel in advanced non-small-cell lung cancer （NSCLC） patients who have failed to respond to prior first-line chemotherapy. Methods： In this single-center, open-label, dose-escalating phase I trial, patients with epidermal growth factor receptor （EGFR）-expressing stage IV NSCLC were treated with nimotuzumab plus doeetaxel according to a dose escalation schedule. The safety and efficacy of the combination treatment were observed and analyzed.Results： There were 12 patients with EGFR-expressing stage IV NSCLC enrolled. The dose of nimotuzumab was escalated from 200 to 600 mg/week. The longest administration of study drug was 40 weeks at the 600 mg/week dose level. Grade Ⅲ-Ⅳ toxicities included neutropenia and fatigue, and other toxicities included rash. Dose-limiting toxicity occurred with Grade 3 fatigue at the 200 mg dose level of nimotuzumab and Grade 4 neutropenia with pneumonia at the 600 mg dose level of nimotuzumab. No objective responses were observed, and stable disease was observed in eight patients （66.7%）. The median progression-free survival （PFS） was 4.4 months in all patients, 1.3 months in patients with the EGFR mutation, and 4.4 months in those with wild type EGFR （EGFR WT）. The median survival time （MST） was 21.1 months in all patients, 21.1 months in patients with EGFR mutation, and 26.4 months in patients with EGFR WT. Conclusions： Nimotuzumab and docetaxel combination therapy was found to be well tolerated and efficacious. Further study of nimotuzumab is warranted in advanced NSCLC patients.展开更多
Objective:Atezolizumab along with chemotherapy has prolonged the survival of patients with extensive-stage small-cell lung cancer(ES-SCLC)worldwide,although real-world(RW)data are lacking in China.This study was desig...Objective:Atezolizumab along with chemotherapy has prolonged the survival of patients with extensive-stage small-cell lung cancer(ES-SCLC)worldwide,although real-world(RW)data are lacking in China.This study was designed to evaluate the efficacy and clinical outcomes of atezolizumab plus etoposide/platinum(EP).Methods:Data obtained in this retrospective study were captured from six oncology units of five medical facilities from January 2019 to April 2022.For first-line treatments,atezolizumab combined with EP vs.EP alone,we primarily evaluated progression-free survival(PFS);other efficacy indicators,including overall survival(OS),objective response rate(ORR),and patterns of SCLC progression and adverse events(AEs)were assessed.Results:The primary analysis included data from 225 patients,of whom 133 received EP along with atezolizumab(atezolizumab group)and 92 received EP alone(EP group).The PFS duration of the atezolizumab group[7.10 months;95%confidence interval(95%CI),6.53-9.00]exceeded that of the EP group(6.50 months;95%CI,4.83-7.53).Overall,the hazard ratio(HR)was 0.69(95%CI,0.49-0.97)(P=0.029);particularly,the HR was 0.54(95%CI,0.36-0.80)among patients undergoing≥4 chemotherapy cycles and 0.33(95%CI,0.20-0.56)among individuals with atezolizumab maintenance.The ORR and disease-control rate(DCR)were similar between the two groups.Because of incomplete OS data,the median OS was not determined for either group.Bone marrow suppression was the most common AE detected(58.6%)in the atezolizumab group.Immune-related AEs occurred in 19 patients in the atezolizumab group(14.3%),with only one case of grade 3 encephalitis.Conclusions:This RW study in China demonstrated improved clinical outcomes of atezolizumab along with EP for ES-SCLC,particularly in the chemosensitive population.These results align with the results of the IMpower133 study,although the impact of this treatment modality on OS warrants additional follow-up studies.展开更多
The publisher regrets that some of the authors’affiliations were mistakenly annotated in the manuscript.Hence,the authors of the below article were contacted after publication to request a correction of the author af...The publisher regrets that some of the authors’affiliations were mistakenly annotated in the manuscript.Hence,the authors of the below article were contacted after publication to request a correction of the author affliction and responded with the correct by the time this erratum is being published.展开更多
Background:Small cell lung cancer(SCLC)transformation had previously been reported mainly in epidermal growth factor receptor(EGFR)mutant adenocarcinoma.However,the underlying genomic profile remains un-clear.Our stud...Background:Small cell lung cancer(SCLC)transformation had previously been reported mainly in epidermal growth factor receptor(EGFR)mutant adenocarcinoma.However,the underlying genomic profile remains un-clear.Our study aimed to find the evolution and genotypic characteristic of SCLC transformation.Methods:Thirty-one SCLC transformation patients who were initially diagnosed as non-small cell lung cancer(NSCLC)patients were included.Whole exome sequencing(WES)of both primary and transformed re-biopsy lesions was conducted on 12 patients.Clinical characteristics were analyzed using R software(v.3.6.1).Results:Our study included 31 patients,of whom,three had lung squamous cell carcinoma,6 patients did not carry EGFR mutations,and 30 patients received chemotherapy for SCLCs.The disease control rate(DCR)was 96.7%,and the median progression-free survival(PFS)was 4.03 months.The median time to transformation was 33.07 months,and the median overall survival(OS)was 62.08 months.Somatic mutation analysis showed that besides TP53,RB1,and EGFR,there was a high occurrence of mutations to CSMD3 and ADAMTS19,espe-cially in the EGFR-wild type(EGFR-wt)group.Concerning mutational signature,the EGFR-mutant(EGFR-mut)transformed group favored an apolipoprotein B(APOBEC)mRNA editing catalytic polypeptide-like-associated mutation pattern(P=0.16).DNA damage repair(DDR)-related signatures were significantly enriched in the EGFR-wt transformed group(P=0.034).Additionally,clonal evolution analysis revealed that all patients had the same main trunk genes in the phylogenetic tree.Transformed SCLCs are not sensitive to immunotherapy,possibly due to increased tumor heterogeneity.Conclusions:Our results indicate that the EGFR-wt patients could also transform to SCLCs,but they have different genetic features with EGFR-mut patients.SCLC-transformed patients respond to classical chemotherapy and have a better prognosis than those with classical SCLCs.展开更多
基金supported by the Major Program of National Natural Science Foundation of China (No. 91959205)National Natural Science Foundation of China (No. 82141117)+3 种基金The Capital’s Funds for Health Improvement and Research (CFH) (No. 2022-2-1023)Beijing Xisike Clinical Oncology Research Foundation Ypierrefabre (No. 202101-0099)Beijing Municipal Administration of Hospitals Incubating Program (No. PX2020045)Science Foundation of Peking University Cancer Hospital (No. 2020-4)。
文摘Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.
基金supported by the Beijing Natural Science Foundation(Commission No.7162038)the Beijing Municipal Administration of Hospitals’Youth Program(Commission No.QML20161101)
文摘Objective： Although superior clinical benefits of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in the treatment of advanced non-small-cell lung cancer （NSCLC） had been reported, the survival difference between exon 19 deletion （Dell9） and exon 21 Leu858Arg substitution （L858R） remains controversial. The purpose of this study is to investigate the differences in progression-free survival （PFS） and overall survival （OS） between different EGFR mutant subtypes among advanced NSCLC patients receiving gefitinib. Methods： There were 204 advanced NSCLC patients with EGFR mutations treated with gefitinib were enrolled in this retrospective cohort study. Patients were divided into the EGFR Dell9 group and the L858R mutated group according to their mutant subtype. Propensity score matching （PSM） was conducted by using a nearest-neighbor algorithm （1：1） to adjust for demographical and clinical covariates. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Results： The PFS in Dell9 group was similar to that in the L858R group [before PSM 8.6 vs. 7.2 months, P=0.072; after PSM 7.3 vs. 7.2 months, P=0.155]. No differences were detected in OS between the L858R and the Dell9 group （before PSM 17.8 vs. 13.1 months, P=0.253; after PSM 16.9 vs. 13.1 months, P=0.339）. The Dell9 group was significantly younger compared with the L858R mutation group in age （P=0.015）. Conclusions： No significant difference was found in the PFS or OS between the Dell9 and L858R mutant NSCLC patients receiving gefitinib. The age gap might contribute to the survival differences between Dell9 and L858R groups. PSM is of important value to the elimination of potential bias.
文摘Background： To determine the safety and therapeutic efficacy of nimotuzumab （h-R3） combined with docetaxel in advanced non-small-cell lung cancer （NSCLC） patients who have failed to respond to prior first-line chemotherapy. Methods： In this single-center, open-label, dose-escalating phase I trial, patients with epidermal growth factor receptor （EGFR）-expressing stage IV NSCLC were treated with nimotuzumab plus doeetaxel according to a dose escalation schedule. The safety and efficacy of the combination treatment were observed and analyzed.Results： There were 12 patients with EGFR-expressing stage IV NSCLC enrolled. The dose of nimotuzumab was escalated from 200 to 600 mg/week. The longest administration of study drug was 40 weeks at the 600 mg/week dose level. Grade Ⅲ-Ⅳ toxicities included neutropenia and fatigue, and other toxicities included rash. Dose-limiting toxicity occurred with Grade 3 fatigue at the 200 mg dose level of nimotuzumab and Grade 4 neutropenia with pneumonia at the 600 mg dose level of nimotuzumab. No objective responses were observed, and stable disease was observed in eight patients （66.7%）. The median progression-free survival （PFS） was 4.4 months in all patients, 1.3 months in patients with the EGFR mutation, and 4.4 months in those with wild type EGFR （EGFR WT）. The median survival time （MST） was 21.1 months in all patients, 21.1 months in patients with EGFR mutation, and 26.4 months in patients with EGFR WT. Conclusions： Nimotuzumab and docetaxel combination therapy was found to be well tolerated and efficacious. Further study of nimotuzumab is warranted in advanced NSCLC patients.
基金supported by National Natural Science Foundation of China(No.82141117)the Capital Health Research and Development of Special Fund(No.2022-21023)+2 种基金Beijing Municipal Administration of Hospitals Incubating Program(No.PX2020045)Science Foundation of Peking University Cancer Hospital(No.2020-4)Wu Jieping Medical Foundation(No.320.6750.2021-16-19)。
文摘Objective:Atezolizumab along with chemotherapy has prolonged the survival of patients with extensive-stage small-cell lung cancer(ES-SCLC)worldwide,although real-world(RW)data are lacking in China.This study was designed to evaluate the efficacy and clinical outcomes of atezolizumab plus etoposide/platinum(EP).Methods:Data obtained in this retrospective study were captured from six oncology units of five medical facilities from January 2019 to April 2022.For first-line treatments,atezolizumab combined with EP vs.EP alone,we primarily evaluated progression-free survival(PFS);other efficacy indicators,including overall survival(OS),objective response rate(ORR),and patterns of SCLC progression and adverse events(AEs)were assessed.Results:The primary analysis included data from 225 patients,of whom 133 received EP along with atezolizumab(atezolizumab group)and 92 received EP alone(EP group).The PFS duration of the atezolizumab group[7.10 months;95%confidence interval(95%CI),6.53-9.00]exceeded that of the EP group(6.50 months;95%CI,4.83-7.53).Overall,the hazard ratio(HR)was 0.69(95%CI,0.49-0.97)(P=0.029);particularly,the HR was 0.54(95%CI,0.36-0.80)among patients undergoing≥4 chemotherapy cycles and 0.33(95%CI,0.20-0.56)among individuals with atezolizumab maintenance.The ORR and disease-control rate(DCR)were similar between the two groups.Because of incomplete OS data,the median OS was not determined for either group.Bone marrow suppression was the most common AE detected(58.6%)in the atezolizumab group.Immune-related AEs occurred in 19 patients in the atezolizumab group(14.3%),with only one case of grade 3 encephalitis.Conclusions:This RW study in China demonstrated improved clinical outcomes of atezolizumab along with EP for ES-SCLC,particularly in the chemosensitive population.These results align with the results of the IMpower133 study,although the impact of this treatment modality on OS warrants additional follow-up studies.
文摘The publisher regrets that some of the authors’affiliations were mistakenly annotated in the manuscript.Hence,the authors of the below article were contacted after publication to request a correction of the author affliction and responded with the correct by the time this erratum is being published.
基金supported by the Beijing Municipal Administration of Hospitals Incubating Program(PX2019038,PX2020044)Beijing Youth Program for Outstanding Talents(2018000021469G262)+3 种基金National Key Research and Development Project(2019YFC1315700)NSFC Key Program(81630071)NSFC General Program(81871889,81972905)CAMS Key Lab of Translational Research on Lung Cancer(2018PT31035)and Aiyou Foundation(KY201701).
文摘Background:Small cell lung cancer(SCLC)transformation had previously been reported mainly in epidermal growth factor receptor(EGFR)mutant adenocarcinoma.However,the underlying genomic profile remains un-clear.Our study aimed to find the evolution and genotypic characteristic of SCLC transformation.Methods:Thirty-one SCLC transformation patients who were initially diagnosed as non-small cell lung cancer(NSCLC)patients were included.Whole exome sequencing(WES)of both primary and transformed re-biopsy lesions was conducted on 12 patients.Clinical characteristics were analyzed using R software(v.3.6.1).Results:Our study included 31 patients,of whom,three had lung squamous cell carcinoma,6 patients did not carry EGFR mutations,and 30 patients received chemotherapy for SCLCs.The disease control rate(DCR)was 96.7%,and the median progression-free survival(PFS)was 4.03 months.The median time to transformation was 33.07 months,and the median overall survival(OS)was 62.08 months.Somatic mutation analysis showed that besides TP53,RB1,and EGFR,there was a high occurrence of mutations to CSMD3 and ADAMTS19,espe-cially in the EGFR-wild type(EGFR-wt)group.Concerning mutational signature,the EGFR-mutant(EGFR-mut)transformed group favored an apolipoprotein B(APOBEC)mRNA editing catalytic polypeptide-like-associated mutation pattern(P=0.16).DNA damage repair(DDR)-related signatures were significantly enriched in the EGFR-wt transformed group(P=0.034).Additionally,clonal evolution analysis revealed that all patients had the same main trunk genes in the phylogenetic tree.Transformed SCLCs are not sensitive to immunotherapy,possibly due to increased tumor heterogeneity.Conclusions:Our results indicate that the EGFR-wt patients could also transform to SCLCs,but they have different genetic features with EGFR-mut patients.SCLC-transformed patients respond to classical chemotherapy and have a better prognosis than those with classical SCLCs.
