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Analysis of plasma-derived cell-free DNA can identify BRAF mutations as accurately as formalin-fixed paraffin-embedded tumor sample analysis, investigators report.
Of 160 patients with advanced solid tumors, BRAF V600 mutations were detected in 62 (39%) archival formalin-fixed paraffin-embedded (FFPE) tumor samples and 47 (29%) plasma cell-free (cf) DNA samples. The two methods had overall agreement in 141 patients (88%; kappa coefficient, 0.74; SE, 0.06; 95% confidence interval, 0.63-0.85), Dr. Filip Janku of the University of Texas and his associates reported (Mol Cancer Ther. 2016 May 20. doi: 10.1158/1535-7163.MCT-15-0712).
BRAF mutations are prevalent in many types of advanced cancers, and targeting these mutations has demonstrated efficacy, but current assessment of BRAF mutations is limited by a lack of tissue samples and complicated by constantly changing mutation status.
cfDNA is secreted into the circulation by tumor cells and cells in the tumor microenvironment that are undergoing apoptosis or necroptosis and might serve as an alternate source for determining BRAF mutation.
“Collecting plasma cfDNA is a minimally invasive procedure that can be repeated at multiple times for diagnostic and disease-monitoring purposes,” Dr. Janku and associates said.
The investigators analyzed plasma samples from 160 patients with advanced solid tumors – most commonly colorectal cancer and melanoma –who had available archival FFPE tumor samples. cfDNA was isolated and extracted from whole blood and analyzed using the Idylla BRAF Mutation Test, a fully integrated real-time polymerase chain reaction–based test with a turnaround time of about 90 minutes.
Dr. Janku and associates found that a higher amount of mutant cfDNA was associated with shorter overall survival. Mean overall survival for patients with a BRAF-mutant cfDNA percentage of less than 2% (10.7 months; 95% CI, 9-12.4) was significantly longer than patients with a BRAF-mutant cfDNA percentage of greater than 2% (4.4 months; 95% CI, 3.2-5.6). Similar results were observed using different percentage cutoffs.
“Our study shows that the Idylla system can detect BRAF V600 mutations in plasma-derived cfDNA from patients with advanced cancers and has acceptable concordance (baseline, 88%; any time point, 90%); sensitivity (baseline, 73%; any time, 77%); and specificity (baseline, 98%; any time, 98%), compared with CLIA-certified laboratory testing of FFPE tumor tissue obtained at different times during routine care,” investigators wrote.
This study was supported by Biocartis, the Elsa U. Pardee Foundation, and the Sidney Kimmel Foundation for Cancer Research. Five of the investigators reported serving in an advisory role for, having ownership interest in, or receiving financial compensation or honoraria from multiple companies. The other investigators reported having no disclosures.
On Twitter @JessCraig_OP
Analysis of plasma-derived cell-free DNA can identify BRAF mutations as accurately as formalin-fixed paraffin-embedded tumor sample analysis, investigators report.
Of 160 patients with advanced solid tumors, BRAF V600 mutations were detected in 62 (39%) archival formalin-fixed paraffin-embedded (FFPE) tumor samples and 47 (29%) plasma cell-free (cf) DNA samples. The two methods had overall agreement in 141 patients (88%; kappa coefficient, 0.74; SE, 0.06; 95% confidence interval, 0.63-0.85), Dr. Filip Janku of the University of Texas and his associates reported (Mol Cancer Ther. 2016 May 20. doi: 10.1158/1535-7163.MCT-15-0712).
BRAF mutations are prevalent in many types of advanced cancers, and targeting these mutations has demonstrated efficacy, but current assessment of BRAF mutations is limited by a lack of tissue samples and complicated by constantly changing mutation status.
cfDNA is secreted into the circulation by tumor cells and cells in the tumor microenvironment that are undergoing apoptosis or necroptosis and might serve as an alternate source for determining BRAF mutation.
“Collecting plasma cfDNA is a minimally invasive procedure that can be repeated at multiple times for diagnostic and disease-monitoring purposes,” Dr. Janku and associates said.
The investigators analyzed plasma samples from 160 patients with advanced solid tumors – most commonly colorectal cancer and melanoma –who had available archival FFPE tumor samples. cfDNA was isolated and extracted from whole blood and analyzed using the Idylla BRAF Mutation Test, a fully integrated real-time polymerase chain reaction–based test with a turnaround time of about 90 minutes.
Dr. Janku and associates found that a higher amount of mutant cfDNA was associated with shorter overall survival. Mean overall survival for patients with a BRAF-mutant cfDNA percentage of less than 2% (10.7 months; 95% CI, 9-12.4) was significantly longer than patients with a BRAF-mutant cfDNA percentage of greater than 2% (4.4 months; 95% CI, 3.2-5.6). Similar results were observed using different percentage cutoffs.
“Our study shows that the Idylla system can detect BRAF V600 mutations in plasma-derived cfDNA from patients with advanced cancers and has acceptable concordance (baseline, 88%; any time point, 90%); sensitivity (baseline, 73%; any time, 77%); and specificity (baseline, 98%; any time, 98%), compared with CLIA-certified laboratory testing of FFPE tumor tissue obtained at different times during routine care,” investigators wrote.
This study was supported by Biocartis, the Elsa U. Pardee Foundation, and the Sidney Kimmel Foundation for Cancer Research. Five of the investigators reported serving in an advisory role for, having ownership interest in, or receiving financial compensation or honoraria from multiple companies. The other investigators reported having no disclosures.
On Twitter @JessCraig_OP
Analysis of plasma-derived cell-free DNA can identify BRAF mutations as accurately as formalin-fixed paraffin-embedded tumor sample analysis, investigators report.
Of 160 patients with advanced solid tumors, BRAF V600 mutations were detected in 62 (39%) archival formalin-fixed paraffin-embedded (FFPE) tumor samples and 47 (29%) plasma cell-free (cf) DNA samples. The two methods had overall agreement in 141 patients (88%; kappa coefficient, 0.74; SE, 0.06; 95% confidence interval, 0.63-0.85), Dr. Filip Janku of the University of Texas and his associates reported (Mol Cancer Ther. 2016 May 20. doi: 10.1158/1535-7163.MCT-15-0712).
BRAF mutations are prevalent in many types of advanced cancers, and targeting these mutations has demonstrated efficacy, but current assessment of BRAF mutations is limited by a lack of tissue samples and complicated by constantly changing mutation status.
cfDNA is secreted into the circulation by tumor cells and cells in the tumor microenvironment that are undergoing apoptosis or necroptosis and might serve as an alternate source for determining BRAF mutation.
“Collecting plasma cfDNA is a minimally invasive procedure that can be repeated at multiple times for diagnostic and disease-monitoring purposes,” Dr. Janku and associates said.
The investigators analyzed plasma samples from 160 patients with advanced solid tumors – most commonly colorectal cancer and melanoma –who had available archival FFPE tumor samples. cfDNA was isolated and extracted from whole blood and analyzed using the Idylla BRAF Mutation Test, a fully integrated real-time polymerase chain reaction–based test with a turnaround time of about 90 minutes.
Dr. Janku and associates found that a higher amount of mutant cfDNA was associated with shorter overall survival. Mean overall survival for patients with a BRAF-mutant cfDNA percentage of less than 2% (10.7 months; 95% CI, 9-12.4) was significantly longer than patients with a BRAF-mutant cfDNA percentage of greater than 2% (4.4 months; 95% CI, 3.2-5.6). Similar results were observed using different percentage cutoffs.
“Our study shows that the Idylla system can detect BRAF V600 mutations in plasma-derived cfDNA from patients with advanced cancers and has acceptable concordance (baseline, 88%; any time point, 90%); sensitivity (baseline, 73%; any time, 77%); and specificity (baseline, 98%; any time, 98%), compared with CLIA-certified laboratory testing of FFPE tumor tissue obtained at different times during routine care,” investigators wrote.
This study was supported by Biocartis, the Elsa U. Pardee Foundation, and the Sidney Kimmel Foundation for Cancer Research. Five of the investigators reported serving in an advisory role for, having ownership interest in, or receiving financial compensation or honoraria from multiple companies. The other investigators reported having no disclosures.
On Twitter @JessCraig_OP
FROM MOLECULAR CANCER THERAPEUTICS
Key clinical point: Analysis of plasma-derived cfDNA can identify BRAF mutations as accurately as FFPE tumor sample analysis.
Major finding: Concordance between mutation analysis of FFPE tumor samples and plasma cfDNA was in overall agreement (88%; kappa, 0.74; SE, 0.06; 95% CI, 0.63-0.85).
Data source: Analysis of FFPE tumor samples and plasma-derived cfDNA for 160 patients with advanced cancers.
Disclosures: This study was supported by Biocartis, the Elsa U. Pardee Foundation, and the Sidney Kimmel Foundation for Cancer Research. Five of the investigators reported serving in an advisory role for, having ownership interest in, or receiving financial compensation or honoraria from multiple companies. The other investigators reported having no disclosures.
