Differential detection of actionable alterations across CGP panels in biliary tract cancer: implications for panel selection
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Published on: April 11, 2016
Keisuke Kudo1, Rei Suzuki2, Hiroyuki Asama1
1Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
Background:
Comprehensive genomic profiling (CGP) is recommended for unresectable biliary tract cancer (BTC) to identify actionable biomarkers; however, evidence guiding optimal panel selection remains limited.
Methods:
We analyzed patients with BTC registered in the nationwide C-CAT database. Actionable alterations were defined according to guideline-recommended targets. Detection rates were compared among three tissue and two liquid CGP panels using multivariable logistic regression. Exploratory analyses compared tissue and liquid CGP according to a four-factor score based on clinical features associated with circulating tumor DNA detectability.
Results:
Among 8,840 complete-case patients, CGP panel type was independently associated with actionable alteration detection. Among tissue assays, FoundationOne CDx showed the highest adjusted detection rate (25.5%), followed by GenMine TOP (20.3%) and the OncoGuide NCC Oncopanel (15.9%), with the largest difference for ERBB2 amplification. FoundationOne Liquid CDx and Guardant360 CDx showed comparable adjusted detection rates (14.1% and 16.4%). In the four-factor analysis, liquid CGP showed lower detection than the OncoGuide NCC Oncopanel in the score 0-2 group but higher detection in the score 3-4 group. Compared with FoundationOne CDx, liquid CGP showed lower detection in the score 0-2 group, with no significant difference in the score 3-4 group.
Conclusion:
CGP platforms differ in actionable alteration detection in BTC, particularly for ERBB2 amplification among tissue assays. The relative yield of liquid CGP may vary according to clinical features associated with circulating tumor DNA detectability and the tissue assay used for comparison. Panel selection should consider assay characteristics, tissue availability, and clinical context.