Lung cancer genomic alterations in cell free DNA in pleural effusion compared to plasma
Sub-category:
Tumor-Based Biomarkers
Category:
Tumor Biology
Meeting:
2017 ASCO Annual Meeting
Abstract No:
e23206
Citation:
J Clin Oncol 35, 2017 (suppl; abstr e23206)
Author(s): Zhenzhen Zhou, Rongrong Chen, Yuxing Chu, Xingsheng Hu, Ling Yang, Xin Yi, HongbingZhang, Dongmei Zhang, Xuefeng Xia, Zhongxing X. Liao; Dalian Medical University, Dalian, China;
Geneplus-Beijing, Beijing, China; National Cancer Center /Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Chinical Study on
Anticancer Molecular Targeted Drugs, Beijing, China; State Key Laboratory of Medical Molecular Biology, Department of Physiology, Collaborative Innovation Center for Cancer Medicine, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and
Chinese Academy of Medical, Beijing, China; The Methodist Hospital Research Institute, Houston,TX; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center,
Houston, TX
Abstract Disclosures
Abstract
Background
Circulating tumor DNA (ctDNA) in plasma has been shown to be informative of the genomic alterations present in lung cancer and has been used to guide tumor treatment and monitor tumor progression. However, patients with lung cancer, even in advanced stage, usually present with small numbers of cancer-related genetic aberrations and low mutation allele frequency(MAF) on average. Malignant pleural effusion is one of common complications for lung cancer patients in advanced stage. Cell free DNA (cfDNA) in pleural effusion may be extensively diluted
once entering into the peripheral circulation system.
Methods
We implemented targeted capture NGS with a gene panel of 180 lung cancer-relevant genes on 23 paired plasma ctDNA and matched pleural cfDNA samples extracted simultaneously from the same patient with advanced lung cancer (n = 23), including 17 adenocarcinoma.
Results
Overall, actionable variations with on label, off-label, or experimental drugs available, were identified in 87% (n = 20) of pleural effusion samples, whereas plasma was 48% (n = 11). Median number of pleural somatic mutations was 4, predominantly located in TP53, EGFR, and ALK; while the median number was 2 in plasma samples. Of that, 39% and 74% of plasma ctDNA and pleural
cfDNA samples were observed at an average MAF above 1%, respectively. In addition, 48% and 78% of plasma ctDNA and pleural cfDNA samples were observed with the highest MAF above 1%.
The concordance rate for EGFR and ALK alterations with plasma NGS was 83% and 87%,respectively.
Conclusions
Our results suggest that pleural effusion-derived cfDNA is more sensitive than plasma for advanced lung cancer patients. With higher MAF and detection rate of actionable variations,pleural effusion-derived cfDNA might guide more precise lung cancer treatment.