RESUMEN
With the development of molecular pathology,many types of epidermal growth factor receptor (EGFR) mutations have been identified.The efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with different types of EGFR mutations,especially in patients with single rare mutations or complex mutations (co-occurrence of two or more different mutations),has not been fully understood.This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations.Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital,Wuhan,were retrospectively reviewed.The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed.Among these patients,377 patients had only the EGFR del-19 mutation,362 patients the EGFR L858R mutation in exon 21,33 patients single rare mutations and 37 patients complex mutations.Among these 809 patients,239 patients were treated with EGFR-TKIs.In all the 239 patients,the disease control rate (DCR) was 93.7％ with two patients (0.2％) achieving complete response (CR),the median progression free survival (PFS) was 13.0 months (95％ confidence interval [CI],11.6-14.4 months),and the median overall survival (OS) was 55.0 months (95％ CI,26.3-83.7 months).Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858R mutation (P＜0.001).Patients with classic mutations (del-19 and/or L858R mutations) demonstrated longer PFS (P＜0.001) and OS (P=0.017) than those with uncommon mutations (single rare and/or complex mutations).Furthermore,the patients with single rare mutations had shorter median OS than in those with other mutations.Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS (hazard ratio [HR]=0.308,95％ CI,0.191-0.494,P＜0.001) and OS (HR=0.221,95％ CI,0.101-0.480,P＜0.001).The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations.The prognosis of the single rare EGFR mutations is depressing.EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR.Further studies in these patients with uncommon mutations (especially for the patients with single rare mutations) are needed to determine a better precision treatment.
RESUMEN
Objective To investigate the genotypic frequency of glucose-6-phosphate dehydrogenase (G6PD) (1376G ＞ T),G6PD 1311C ＞ T and G6PD IVS11-93T ＞ C in 50 newborns with G6PD deficiency in Guangdong region.Methods To identify G6PD deficiency in the patients of neonatal ward in Guangzhou First People's Hospital during 2010,detected by methemoglobin reduction test and measurement of G6PD/6-phosphate dehydrogenase (6PGD) ratio.Fifty G6PD deficiency subjects were classified into the experimental group,20 neonatal jaundice subjects were classified into the control group.Genomic DNA was extracted by standard method from the peripheral blood of each subject.PCR-direct DNA sequence analysis was used to identify G6PD 1376G ＞ T,1311C ＞ T and 11 intron 93T ＞ C mutations.Results The overall results of mutation analysis in the 50 G6PD deficiency subjects showed the existence of 3 different alleles:G6PD 1376G ＞T,1311C ＞T,11 intron 93T ＞ C(including 1311C ＞ T/IVS11-93T ＞ C and 1376G ＞T/1311C ＞T/IVS11-93T ＞ C complex mutations).The different genotypic frequency in the experimental group was G6PD 1376G ＞T 26.0％ (13/50 cases),1311C ＞ T 4.0％ (2/50 cases),11 intron 93T ＞ C 4.0％ (2/50 cases),1311C ＞ T/IVS11-93T ＞ C 2.0％ (1/50 cases),1376G ＞ T/1311C ＞ T/IVS11-93T ＞ C 2.0％ (1/50 cases).The G6PD enzyme activity of the subjects with 1311C ＞ T/IVS11-93T ＞ C and 1376G ＞ T/1311C ＞ T/IVS11-93T ＞ C complex mutation were reduced.These G6PD mutations were not found in the controls.Conclusions G6PD 1376G ＞ T is one of the commonest mutation in G6PD deficiency newborn in Guangdong region.A novel complex mutation 1376G ＞ T/1311C ＞ T/IVS11-93T ＞ C in this study was found.