We detected a significant rate of low-level pre-treatment T790M mutations in NSCLC using highly sensitive dPCR. It also correlated with increased mortality (HR 3.1 95%CI 1.2-8.1, p = 0.022) in patients who did not respond to TKI treatment. T790M positivity correlated with increased rate of early disease progression.
#Mical amanuel free
The median progression free survival was 10.7 (IQR 5.6-19.9) versus 6.7 (IQR 3.5-20.8) months in T790M negative and positive patients respectively. Overall response rate to first generation EGFR tyrosine kinase inhibitors (TKI) was 67% regardless of T790M status. Median variant allele frequency was 0.14% (range 0.02-28.5%). T790M was detected in 42 of 109 pre-treatment samples (38.5%). DNA extracted from pre-treatment NSCLC tumor tissue with known activating EGFR mutations, diagnosed between October 2010 and May 2017 at PathWest laboratory, was used to perform targeted dPCR for quantitative detection of T790M mutations. We utilized digital PCR (dPCR), a highly sensitive gene mutation detection method, to detect pre-treatment T790M mutations in NSCLC tumor samples and correlated the T790M status with clinical features and patient outcomes. Increasing evidence points to the presence of low-level de novo T790M mutations in patients with non-small cell lung carcinoma (NSCLC) harboring activating EGFR mutations. 9 School of Medical Science, Edith Cowan University, Joondalup, WA, Australia.8 Institute for Health Research, The University of Notre Dame Australia, Perth, Western Australia, Australia.7 Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, Western Australia, 6009, Australia.6 School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Western Australia, Australia. 5 School of Veterinary and Life Science, Murdoch University, Perth, Western Australia, Australia. 4 Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, Western Australia, 6009, Australia. 3 School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Western Australia, Australia.2 Faculty of Health and Medical Sciences, The University of Western Australia, Crawley, Western Australia, Australia.1 Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
0 kommentar(er)
