Spectrum of driver mutations and clinical impact of circulating tumor DNA analysis in non–small cell lung cancer: Analysis of over 8000 cases
| العنوان: | Spectrum of driver mutations and clinical impact of circulating tumor DNA analysis in non–small cell lung cancer: Analysis of over 8000 cases |
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| المؤلفون: | David R. Gandara, Stefanie Mortimer, Amir Ali Talasaz, Jonathan W. Riess, Rebekah A. Burich, Christine E. Lee, Oliver A. Zill, Richard B. Lanman, Carin R. Espenschied, Philip C. Mack, Kimberly C. Banks |
| المصدر: | Cancer |
| بيانات النشر: | John Wiley and Sons Inc., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Subset Analysis, Male, Cancer Research, Lung Neoplasms, medicine.medical_treatment, Adenocarcinoma of Lung, Targeted therapy, Circulating Tumor DNA, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, non–small cell lung cancer, circulating cell‐free tumor DNA (ctDNA), Carcinoma, Non-Small-Cell Lung, medicine, ROS1, Biomarkers, Tumor, Humans, 030212 general & internal medicine, Liquid biopsy, Lung cancer, Protein Kinase Inhibitors, Alleles, liquid biopsy, business.industry, High-Throughput Nucleotide Sequencing, Original Articles, Oncogenes, Sequence Analysis, DNA, medicine.disease, epidermal growth factor receptor (EGFR), ErbB Receptors, Treatment Outcome, Oncology, anaplastic lymphoma kinase (ALK), Chest and Lung Disease, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Mutation, Cancer research, Disease Progression, Adenocarcinoma, Population study, Original Article, Female, Disease Site, business, Progressive disease, Signal Transduction |
| الوصف: | Background Circulating cell‐free tumor DNA (ctDNA)‐based mutation profiling, if sufficiently sensitive and comprehensive, can efficiently identify genomic targets in advanced lung adenocarcinoma. Therefore, the authors investigated the accuracy and clinical utility of a commercially available digital next‐generation sequencing platform in a large series of patients with non–small cell lung cancer (NSCLC). Methods Plasma‐based comprehensive genomic profiling results from 8388 consecutively tested patients with advanced NSCLC were analyzed. Driver and resistance mutations were examined with regard to their distribution, frequency, co‐occurrence, and mutual exclusivity. Results Somatic alterations were detected in 86% of samples. The median variant allele fraction was 0.43% (range, 0.03%‐97.62%). Activating alterations in actionable oncogenes were identified in 48% of patients, including EGFR (26.4%), MET (6.1%), and BRAF (2.8%) alterations and fusions (ALK, RET, and ROS1) in 2.3%. Treatment‐induced resistance mutations were common in this cohort, including driver‐dependent and driver‐independent alterations. In the subset of patients who had progressive disease during EGFR therapy, 64% had known or putative resistance alterations detected in plasma. Subset analysis revealed that ctDNA increased the identification of driver mutations by 65% over standard‐of‐care, tissue‐based testing at diagnosis. A pooled data analysis on this plasma‐based assay demonstrated that targeted therapy response rates were equivalent to those reported from tissue analysis. Conclusions Comprehensive ctDNA analysis detected the presence of therapeutically targetable driver and resistance mutations at the frequencies and distributions predicted for the study population. These findings add support for comprehensive ctDNA testing in patients who are incompletely tested at the time of diagnosis and as a primary option at the time of progression on targeted therapies. Circulating cell‐free tumor DNA‐based liquid biopsy using next‐generation sequencing detects a spectrum of targetable alterations at frequencies expected in patients with advanced non–small cell lung cancer. These findings support the concept of a plasma‐first algorithm at the time of progression on targeted therapy for this population. |
| اللغة: | English |
| تدمد: | 1097-0142 0008-543X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::96c9c95edac568d8c59a189e19fc97d0 http://europepmc.org/articles/PMC7383626 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....96c9c95edac568d8c59a189e19fc97d0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970142 0008543X |
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