LBA11516 Background: ctDNA assays can noninvasively assess tumor burden and biology by identifying tumor-derived somatic alterations. For broad applicability, including early cancer detection, an unprecedented high-intensity approach (ultra-deep sequencing of plasma cell-free DNA (cfDNA) with broad genomic coverage) is needed to address intra-patient and population-level heterogeneity. We present initial results with this approach in patients (pts) with metastatic breast (BC), non-small cell lung (NSCLC), and castration-resistant prostate cancer (CRPC). Methods: Blood and tissue were prospectively collected w/in 6 wks with no intervening therapy change from pts with de novo or progressive cancer. cfDNA and white blood cell (WBC) genomic DNA from each pt were sequenced with a 508-gene panel (2 Mb; >60,000X raw depth). cfDNA variant calling used molecular barcoding for error correction and filtering for WBC variants. Tissue was sequenced using the MSK-IMPACT assay (410 genes, 1.4 Mb, >500X depth) blinded to plasma/WBC sequencing. Variants were classified as clonal or subclonal based on tumor sequencing in BC and NSCLC. Results: Of 161 eligible pts, 124 (39 BC, 41 NSCLC, and 44 CRPC) were evaluable for concordance. In tissue, 864 variants were detected across the 3 tumor types, with 627 (73%) also detected in plasma: single nucleotide variants/indels - 75%, fusions - 67%, and copy number alterations - 58%. In 90% of pts, at least 1 of the variants detected in tumor tissue was also detected in plasma: BC - 97%, NSCLC - 85%, CRPC - 84%. Most actionable mutations detected in tissue were also detected in plasma (54/71, 76%; SNVs only: 28/31, 90%). A subset of driver mutations (eg. in ESR1, PIK3CA, ERBB2, EGFR) were observed in plasma but not tissue. Clonal variants in tissue were more likely to be detected in plasma than subclonal variants (p<.001). Conclusions: This novel, high-intensity ctDNA assay enabled broad detection of genomic variants in plasma at high rates of concordance with corresponding tumor tissue, providing strong evidence for tumor-derivation of these signals. This study will inform development of a high-intensity sequencing approach for early cancer detection.
Role of endoscopic screening for de novo occurrence of gastric cancer and colorectal cancer in Korean liver transplant recipients