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Relationship between tumor mutational burden and efficacy of targeted therapies in patients with advanced nonsmall cell lung cancer
Received:February 02, 2019  Revised:March 06, 2019  Click here to download the full text
Citation of this paper:童 琳,丁 宁,李佳旻,徐晓波,张 勇,叶茂松,李 春,张 新,洪群英,周 建,白春学,胡 洁.Relationship between tumor mutational burden and efficacy of targeted therapies in patients with advanced nonsmall cell lung cancer[J].Chinese Journal of Clinical Medicine,2019,26(4):538-542
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童 琳,丁 宁,李佳旻,徐晓波,张 勇,叶茂松,李 春,张 新,洪群英,周 建,白春学,胡 洁 复旦大学附属中山医院呼吸科上海市呼吸病研究所上海 200032 
Abstract:Objective:To explore the relationship between tumor mutational burden (TMB) and efficacy of targeted therapies in patients with advanced nonsmall cell lung cancer (NSCLC).Methods:Between Jan. 2016 and Jan. 2018, fiftyone NSCLC patients receiving targeted therapy were enrolled in Zhongshan Hospital, Fudan University. TMB levels in tumor tissue samples from these patients were examined using targeted nextgeneration sequencing.Results:The median TMB level of NSCLC patients with driver mutations and receiving targeted therapy was 6.2 mutations/Mb, with TMB levels in smokers significantly higher than nonsmokers (P=0.046). All enrolled patients were divided into high TMB and moderate/low TMB groups. Survival analysis showed that patients with moderate/low TMB had longer progressionfree survival (PFS) compared with patients with high TMB (410 d vs 217 d, HR= 0.331, 95% CI 0.1650.665, P=0.001 2). Subgroup analysis showed that the median PFS was longer in the moderate/low TMB group than that in the high TMB group among the subgroups of gender, whether smoking, and TP53 gene mutation status. In the subgroups of adenocarcinoma who harbor epidermal growth factor receptor (EGFR) mutations, EGFR exon 19 deletion, and EGFR L858R, the median PFS was also longer in the moderate/low TMB group than that in the high TMB group (P<0.05).Conclusions:For advanced NSCLC patients with driver mutations, the TMB level of tumor tissue is a predictor of the efficacy of targeted therapy. High TMB level suggests that PFS is shorter in patients receiving targeted therapy.
keywords:tumor mutational burden  advanced nonsmall cell lung cancer  targeted therapy  progressionfree survival
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