Concordance Study of a 520-Gene Next-Generation Sequencing-Based Genomic Profiling Assay of Tissue and Plasma Samples.

Abstract

Next-generation sequencing (NGS) enables simultaneous detection of actionable somatic variants and estimation of genomic signatures such as tumor mutational burden (TMB) or microsatellite instability (MSI) status, which empowers therapeutic decisions in clinical oncology. Our retrospective study investigated the clinical performance of somatic variant detection in paired tissue and blood samples using a large targeted gene panel, the OncoScreen Plus, which interrogates 520 cancer-related genes. We analyzed sequencing data derived from paired tissue and blood samples of 3005 patients spanning 20 solid tumor types, including lung (n = 1971), gastrointestinal (n = 625), breast (n = 120) and gynecological (n = 110), genitourinary (n = 38), and other cancers (n = 141). Across tumor types, the OncoScreen Plus panel achieved a high tissue detection rate, with an average of 97.9%. The average plasma detection rate was 72.2%, with an average tissue concordance rate of 36.6%. Considering all variant types, the plasma assay yielded an average sensitivity/true positive rate of 45.7%, with a positive predictive value of 64.7% relative to tissue assay. Pearson correlation analysis revealed a strong correlation in TMB estimated from blood and tissue samples (correlation coefficient 0.845, R2 = 0.756). MSI-high status was identified in five tumor types, including endometrial cancer (28.6%), colorectal cancer (2.5%), ovarian cancer (2.0%), gastric cancer (1.5%), and lung adenocarcinoma (0.2%). Paired tumor and blood samples from a large cohort of patients spanning 20 tumor types demonstrated that the OncoScreen Plus is a reliable pan-cancer panel for the accurate detection of somatic variants and genomic signatures that could guide individualized treatment strategies to improve the care of patients with advanced cancer.