1224P Detection of circulating tumor DNA (ctDNA) in untreated patients (pts) with cancer: Implications for early cancer detection (ECD)

Blood-based ECD is an emerging tool to identify cancer signals in asymptomatic individuals. ctDNA detection is impacted by several clinicopathologic factors. We report on ctDNA detection rates in pts with cancer prior to receiving treatment and in correlation with median tumor mutational burden (mTMB) rates. Pretreatment plasma samples were analyzed using a tumor-informed ctDNA assay (SignateraTM) in 1657 pts, including breast cancer (BC, N=131), lung cancer (LC, N=57), colorectal cancer (CRC, N=1382), epithelial ovarian cancer (OV, N=36), pancreatic cancer (PC, N=17), and diffuse large B cell lymphoma (DLBCL, N=37). Stage-agnostic, exome-based mTMB was reported for BC, CRC, PC, DLBCL (internal data), LC (pmid28420421), and OV (pmid35087563). Baseline ctDNA was detected in 1621 (87%) pts; rates were lower in stage I/II (707/858, 82.4%) vs III/IV (914/998, 91.6%). In BC (mTMB 4.4 mut/MB), ctDNA detection rates were lower in hormone receptor-positive tumors (stage I/II 61.2%[74/121], III 81% [17/21]) vs triple-negative breast cancer (I/II 81.5% [75/92], III 97% [58/60]) and HER2+ tumors (I/II 73.9% [17/23], III 87.5% [7/8]); rates increased by stage in all subtypes. In LC, detection rates were lower for adenocarcinoma (mTMB 6.3 mut/MB; I/II 25% [5/20], III 73% [11/15]) vs squamous cell carcinoma (mTMB 9.0 mut/MB; I/II 85% [11/13], III 100% [9/9]). In CRC (mTMB 4.31 mut/MB with a bi-modal distribution), detection rates for stage I/II/III-IV were [(74% (71/96), 94% (421/448) and 92% (773/838)]. In OV (mTMB 1.9 mut/MB), detection rates were 60% (9/15) in stage I/II and 72% (15/21) in stage III/IV. In PC (mTMB 1.47 mut/MB), detection rates were 65% (11/17) in stage I/II and 100% (2/2) in stage III/IV. In DLBCL (mTMB 4.58 mut/MB), detection rates were 100% (13/13) in stage I/II and 92% (22/24) in III/IV. Our study supports past findings that ctDNA positivity varies across cancers and histology and is higher in some later stage cancers and suggests that ctDNA detection in the presurgical setting can be detected in a majority of patients with a tumor-informed approach. Further studies are needed to understand the biological and technical factors that may impact assay’s performance.