Evaluation of concordance between blood-based and matched tissue molecular testing in a regional cancer center.
Authors: Sourat Darabi, Carlos E Zuazo, Taylor Brodie, David R. Braxton, Burton Larry Eisenberg, Michael J. Demeure
Journal: Journal of Clinical Oncology (2024)

e15062 Background: Next-generation sequencing (NGS) to identify cancer-associated mutations together with an increasing array of targeted drugs with FDA approval allows for matching patients with more effective therapies. Tumor tissue molecular profiling is most often used to identify actionable biomarkers. Blood-based tests to sequence cell-free circulating tumor DNA (ctDNA) are a less invasive approach. Both methods have high specificity and sensitivity and provide insights into actionable biomarkers; however, little is known about how these NGS tests compare when used for the same patient. This study assessed the concordance of paired ctDNA and solid tumor profiling in patients treated in our regional cancer center. Methods: We retrospectively reviewed ctDNA and matching tumor sequencing data test results from CLIA/CAP laboratories between June 2018, and October 2023. The average testing turnaround time was 12.9 days for solid tumor sequencing and 7.7 days for ctDNA testing. We analyzed genomic variants, gene fusions, and microsatellite status in these patient results. The NGS tests for ctDNA included 83 relevant genes which reported single nucleotide variants, small insertions and deletions, splice variants, and limited copy number alterations and gene fusions. The NGS tests for tumor testing were performed on Formalin-Fixed Paraffin Embedded tissue samples using either a 592 relevant gene panel or whole exome sequencing, and either an RNA-based targeted capture panel of 52 genes or RNA whole transcriptome sequencing. Concordance is defined as both ctDNA and tumor testing reporting the same alterations, whereas discordant reports are defined as each reporting different alterations that didn’t overlap between ctDNA and tumor sequencing. Results: A total of 186 patients had both ctDNA and solid tumor sequencing tests done. Cancer types included pancreatic cancer (n = 42), breast cancer (n = 29), lung cancer (n = 28), colorectal cancer (n = 14), and others (n = 73). We observed concordance between tests in 76 (41%) patients in identifying the same genomic alterations. In 103 (55%) patients, we found discordant genomic findings (in the remaining 7 (4%) patients, there were no alterations detected (ND)). Among 103 patients for whom we found discordant findings between the tests, 41 (40%) showed genomic alterations only from the ctDNA test, 46 (45%) had results only from solid tumor profiling, and 16 (15%) had abnormal gene findings from both solid tumor and ctDNA testing but the results did not overlap. Conclusions: Our retrospective analysis comparing sequencing of ctDNA and tumor tissue demonstrated about 40% concordance in genomic findings. Our study indicates that these tests may be complementary. If one accepts a degree of discordance, then testing of ctDNA may be used to identify actionable genomic alterations in the setting of inaccessible or inadequate tumor samples for sequencing.