Comprehensive analysis of genomic alterations detected by next-generation sequencing-based tissue and circulating tumor DNA assays in Chinese patients with non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20534-e20534
Author(s):  
Hua Yang ◽  
Junjie Zhang ◽  
Lemeng Zhang ◽  
Xiaoping Wen ◽  
Yongzhong Luo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Chinese Patients ◽  
Small Cell Lung ◽  
Genomic Alterations ◽  
Nsclc Patients ◽  
Tumor Dna ◽  
Generation Sequencing

e20534 Background: While tumor genotyping is the standard treatment for patients with non-small cell lung cancer (NSCLC), spatial and temporal tumor heterogeneity and insufficient specimens can lead to limitations in the use of tissue-based sequencing. Circulating tumor DNA (ctDNA) fully encompasses tumor-specific sequence alterations and offers an alternative to tissue sample biopsies. The aim of the study was to evaluate whether the frequency of multiple genomic alterations observed following ctDNA sequencing was similar to that observed following tissue sequencing in NSCLC. Methods: A total of 99 NSCLC patients were enrolled in this study, including 40 tissue and 59 plasma samples. All kinds of variants of oncogenic drivers in NSCLC were identified by next-generation sequencing (NGS) with Acornmed panel. Results: The frequencies of genetic alterations detected in ctDNA were significantly correlated to those detected via tissue profiling (Spearman’s r = 0.812, P = 0.022). Genomic data revealed significant mutual exclusivity between alterations in epidermal growth factor receptor ( EGFR) and tumor protein 53 ( TP53; P = 0.020) and between those in EGFR and Kirsten rat sarcoma viral oncogene homolog ( KRAS; P = 0.008), as well as potential mutual exclusivity between alterations in EGFR and Erb-B2 receptor tyrosine kinase 2 ( ERBB2; P = 0.059). Furthermore, the EGFR mutant allele frequency (MAF) was strongly correlated with the TP53 MAF in individual tumors (Spearman’s r = 0.773, P = 0.005), and there was a marked difference in the EGFR MAF between patients with and without the TP53 mutation (P = 0.001). Levels of the tumor serum marker CA242 in patients with ctDNA-detectable mutations were higher than those in patients without ctDNA-detectable mutations. Conclusions: This study provides a better understanding of the spectra of genomic alterations detected by tissue and plasma ctDNA assays in Chinese patients with NSCLC. The present data also highlights the importance of tissue and plasma ctDNA screening by NGS to guide personalized therapy and promote the clinical management of NSCLC patients.

Concordance of next-generation sequencing between tissue and liquid biopsies in non-small cell lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21547-e21547
Author(s):  
Fahmin Basher ◽  
Diana Saravia ◽  
Dino Fanfan ◽  
Jared Addison Cotta ◽  
Gilberto Lopes
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Liquid Biopsy ◽  
Median Number ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tumor Dna ◽  
Generation Sequencing ◽  
Gene Alterations

e21547 Background: While genetic profiling has become standard of care for patients diagnosed with non-small cell lung cancer (NSCLC), next-generation sequencing (NGS) provides a wealth of information about targetable mutations. Advances in genetic testing have led to sequencing platforms that utilize tissue itself or extracellular circulating tumor DNA in the blood, known as a “liquid biopsy.” Methods: We identified 55 patients with NSCLC who had undergone both tissue and liquid biopsy, using Foundation One and Guardant 360 at the University of Miami / Sylvester Comprehensive Cancer Center between January 2016 and December 2018, and performed retrospective analysis to determine patient characteristics as well concordance between different NGS platforms. Results: In our patient population, 34% of patients had never smoked prior to diagnosis, while 22% had more than a 30 pack-year smoking history. 64% of patients had no treatment prior to initial NGS. 40% of patients had both testing done essentially simultaneously, while 60% of patients had one test done after disease progression. Of these patients, therapy was changed as a result in 73%. Median number of days between tests was 21 days, with 56% of testing done within 90 days of the previous testing. Nine patients had an additional Foundation One tissue NGS performed. Concordance across all genes tested in both platforms was 98 ± 0.2%. Concordance with consideration of genetic alterations detected in both assays was 24.5 ± 3.0%. The median number of gene alterations determined by Foundation One testing was 4 (range 1-9), while the median for gene alterations detected by Guardant 360 was 3 (range 1-13). The median number of variants of unknown significance (VUS) was 10 (range 5-25). Conclusions: Our analysis indicates a role for both tissue-based and circulating tumor DNA-based NGS for determination of targetable mutations and thus appropriate treatment regimens. Low levels of concordance are potentially related to post-treatment changes in the tumor genetic profile as well as evolution in the testing itself.

scholarly journals Next-generation sequencing of circulating tumor DNA for metastatic non-small cell lung cancer: a discussion on its implementation in the Brazilian clinical practice

2020 ◽  
Author(s):  
Luiz H Araujo ◽  
Carlos Gil Ferreira ◽  
Clarissa S Baldotto ◽  
Clarissa Mathias ◽  
Gilberto Castro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Next Generation ◽  
Small Cell Lung ◽  
Tumor Dna ◽  
Generation Sequencing

The objective of this review is to address the barriers limiting access to next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) for metastatic nonsquamous non-small cell lung cancer in Brazil and to propose its implementation in practice. A selected panel of lung cancer experts was provided with relevant prompts to address at a conference; a paper was then compiled on the topic. The authors propose specific and realistic recommendations for implementing access to ctDNA NGS. Further, the authors address all barriers and impediments mentioned within this review. There is a great need to increase ctDNA NGS for cancer care in Brazil. Adapting the current cancer testing framework is essential to expanding the use of this tool.

Case series of EGFR C797S mutations in non-small cell lung cancer identified with cell-free circulating tumor DNA next generation sequencing.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e23021-e23021 ◽  
Author(s):  
Stephen R Fairclough ◽  
Oliver A. Zill ◽  
Darya Chudova ◽  
Christine Elaine Lee ◽  
Richard Burnham Lanman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Case Series ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tumor Dna ◽  
Generation Sequencing
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