Concordance of circulating and solid tumor DNA through comprehensive genomic profiling in a large integrated cancer network.
Authors: LaFramboise William , Zaidi Ali Hussainy , Allen Casey Jackson , Bizhanova Zhadyra , Dalton Emily , Bapat Bela , Petrosko Patti , Gallo Phillip , Gil Louis , Lam Jasmyne Tong , Cebula Robin , Wagner Patrick , Bartlett David L. 
Published: June 2023

3059

Background: Comprehensive Genomic Profiling (CGP) of solid tumors is crucial in diagnosing and treating cancer patients. Circulating Tumor DNA (ctDNA) is a potential biomarker for detecting mutations when tissue samples are limited or unavailable. However, the sensitivity of ctDNA tests vary greatly, making concordance studies with tissue samples critical to validate clinical use. This study presents results of CGP in paired tumor tissue and plasma samples from representative cancer patients treated in a community-based, Integrated Network Cancer Program. Methods: Over 2000 cancer patients have provided solid tumor and/or blood samples to date including serial follow-up blood samples. To optimize ctDNA integrity, we collected blood using a membrane stabilizer (Streck), ensured courier transport in ≤ 72 hours, separated plasma via differential centrifugation x 3, extracted cell free DNA with magnetic beads, and performed Next Generation Sequencing (NGS) using the ct-TSO500 assay (Illumina). In cases where patients provided both a solid tumor and concurrent blood sample, st-TSO500 NGS results from the solid tumor were compared to the ctDNA results for these matching specimens. Clinical actionability of variants was determined using the OncoKB database at levels 1, 2, and R1. Results: 146 matched blood and solid tumor specimens were analyzed to date. CGP studies revealed 1179 ± 102 unique variants across 20 different cancer types. Coding mutations from these specimens averaged 183 ± 25 variants. The ctDNA contained 96.5% of initial variants (1088 ± 95) and 95.1% of coding mutations (163 ± 20) found in the respective matched solid tumor. 76 patients had one or more oncogenic mutations detected only in the ctDNA and 28 (36.8%) of these included an actionable anticancer pharmacotherapy. Concordance by selective tumor type for clinical oncogenic variants was 95.8% (prostate), 95.0% (pancreas), 92.8% (lung and ovarian), 90.0% (endometrium), 84.3% (colon) and 82.4% for breast cancer. There was no difference in concordance between stage IV (91.0%) and stage I-III (86.5%) tumors (p = 0.14). An average of 6.2 ± 2.5 oncogenic variants were detected in both ctDNA and tissue. 99.3% of all patients contained an oncogenic biomarker in both ctDNA and tissue assays. Conclusions: We developed a prospective tissue and plasma repository of patients across a large integrated cancer network. These data demonstrate high concordance between circulating and solid tumor DNA using an “in-house” CGP assay. With no loss of concordance across cancer stages, ctDNA can identify actionable mutations not found in solid tumor analysis. This study is an important step toward incorporating “in-house” ctDNA CGP into routine cancer care. Future goals are to utilize these data for development of novel prognostic and predictive classifiers for use in a community-based hospital system across various disease sites.