title: Estimation of cell-free circulating EGFR mutation concentration predicts outcomes in NSCLC patients treated with EGFR-TKIs.
abstract: Detection of circulating tumor DNA using droplet digital polymerase chain reaction (ddPCR) is a highly-sensitive, minimally invasive alternative to serial biopsies for assessment and management of cancer. We used ddPCR to assess the utility of measuring plasma concentrations of common epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, and T790M) in 57 non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). High baseline plasma EGFR mutation (pEGFRmut) concentrations were associated with shorter progression-free survival (8.43 months) than low baseline pEGFRmut (16.23 months; p = 0.0019). By contrast, there were no differences in tumor shrinkage or overall survival between groups. During EGFR-TKI treatment, pEGFRmut levels decreased to zero in 89.58% of patients. Twenty-five of the 27 patients who progressed had basal pEGFRmut, and 18 also had circulating T790M. All 20 patients with dramatic progression (according to a categorization system for EGFR-TKIs failure) had basal pEGFRmut, and 13 had T790M mutation at progression. These results support the use of ddPCR for analysis of plasma EGFR mutations for prediction of PFS and to monitor clinical responses to EGFR-TKIs in NSCLC patients.
authors.affiliation: Oncology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, China.
authors.forename: Yan-Juan
authors.initials: YJ
authors.lastname: Zhu
authors.affiliation: Oncology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Zhang
authors.affiliation: Oncology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, China.
authors.forename: Yi-Hong
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Oncology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, China.
authors.forename: Fu-Li
authors.initials: FL
authors.lastname: Zhang
authors.affiliation: Pathology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, China.
authors.forename: Ya-Zhen
authors.initials: YZ
authors.lastname: Zhu
authors.affiliation: Oncology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Oncology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Bai
authors.affiliation: Oncology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, China.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Liu
authors.affiliation: Oncology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, China.
authors.forename: Yan-Chun
authors.initials: YC
authors.lastname: Qu
authors.affiliation: Oncology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Qu
authors.affiliation: Oncology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Chen
authors.affiliation: Oncology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Pathology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, China.
authors.forename: Guang-Juan
authors.initials: GJ
authors.lastname: Zheng
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use; D005260:Female; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: blood biopsy; droplet digital polymerase chain reaction; epidermal growth factor receptor; non-small cell lung cancer