Abstract

Introduction: Next-generation sequencing (NGS) tumor profiling is a mainstay for guiding therapy in oncology. Circulating tumor DNA (ctDNA) testing offers an additional, minimally invasive approach of detecting actionable alterations. We evaluated the concordance between solid tissue and liquid biopsy comprehensive genomic profiling (CGP) results in a largely rural cohort within the Great Plains.

Methods: Participants were enrolled in the Avera Cancer Sequencing and Analytics Protocol (ASAP; NCT05142033). Inclusion required an advanced unresectable or metastatic solid tumor and concurrent tumor and liquid biopsy CGP collected within 90 days. Concordance was calculated based on reported alterations after excluding those not covered by both panels (liquid biopsy panel: Tempus xF+; solid tissue panel: Labcorp OmniSeq INSIGHT®; analyzed alterations: 388 SNV, 7 CNV, 10 Fusions) and variants of unknown significance (VUS).

Results: Eighty-six patients met criteria (mean age +/- SD: 65 +/-10y; 52% female). Seventeen tumor types were represented; lung cancer (26%) and head-and-neck cancer (16%) were most frequent, and 20% had ≥ 2 cancer diagnoses. Patient-level full concordance, defined as identical sets of biologically relevant identified in both tissue and liquid biopsy, was 59%. Variant-level concordance across all alteration types was 31% (CNV [n=23]: 22%, Fusion [n=6]: 50%, SNV [n=365]: 30%). Among unique variants, most SNVs (54%) and CNVs (89%) were detected only in tissue. After filtering 17 genes related to clonal hematopoiesis (CH) from liquid biopsy, variant-level concordance across all alteration types was 35% (CNV [n=23]: 22%, fusion [n=6]: 50%, SNV [n=296]: 38%). OncoKB levels of therapeutic evidence (1-4 and R1-2) were applied to the variants and tumor types in which they were identified. Of the 112 variants with an annotated level of evidence in the data set, 42 were concordant variants, 45 unique to tissue, and 25 to liquid biopsy. MSI status was 100% concordant (2 MSI-high / 84 MSI-stable). High tumor mutational burden (TMB-H) showed 90% concordance (72/80 concordant, 8/80 discordant, 6 non-evaluable). Additional analyses will assess concordance by tumor type, tissue sampled, metastatic sites, treatment, time between liquid and tissue sample collection, and time from diagnosis to sample collection.

Conclusions: Tissue and liquid biopsy CGP each provide complementary, actionable information for therapy selection. Forty percent of patients had unique findings in liquid or tissue-based testing. These results support the value of a comprehensive CGP strategy in advanced solid tumors.

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