@article{TLCR34468,
author = {Zhichao Liu and Zhanhong Xie and Shen Zhao and Dawei Ye and Xiuyu Cai and Bo Cheng and Caichen Li and Shan Xiong and Jianfu Li and Hengrui Liang and Zisheng Chen and Peng Liang and Jun Liu and Jianxing He and Wenhua Liang},
title = {Presence of allele frequency heterogeneity defined by ctDNA profiling predicts unfavorable overall survival of NSCLC},
journal = {Translational Lung Cancer Research},
volume = {8},
number = {6},
year = {2019},
keywords = {},
abstract = {Background: The generation of subclonal (low-frequency) mutations is driven by tumor mutations and the relationship between the heterogeneity of tumor mutation abundance and non-small cell lung cancer (NSCLC) remains unknown. We investigate the role of allele frequency heterogeneity (AFH) defined by circulating tumor DNA (ctDNA) profiling in predicting prognosis in advanced NSCLC patients.
Methods: Publicly available data set of POPLAR (N=211) and OAK (N=642) trials were used for analyzing. A low ratio of allele frequency (AF) of a mutation to the maximum-somatic-allele-frequency (MSAF) was used to define the presence of AFH. The prognostic value of AF/MSAF ratio that was below a defined cutoff point in overall survival (OS) was evaluated using Cox-proportional hazards regression; and the structural break point was determined by LOESS regression and Chow test. The derived AFH was also explored in an independent cohort (N=259) of advanced NSCLC receiving first-line EGFR-TKIs from the First Affiliated Hospital of Guangzhou Medical University.
Results: In the POPLAR and OAK cohort, low AF/MSAF ratio was found to be significantly associated with unfavorable OS in univariate and multivariate analysis. The structural break point analysis demonstrated that AF/MSAF },
issn = {2226-4477}, url = {https://tlcr.amegroups.org/article/view/34468}
}