Pan-Cancer Pre-Treatment ctDNA Detection Using a Highly Sensitive Tumor-Informed Assay

Circulating tumor DNA (ctDNA) has many potential applications in the management of cancer, including detection, monitoring, and treatment response assessment. This study evaluates pre-treatment ctDNA detection in a single-institution pan-cancer cohort using a highly sensitive tumor-informed ctDNA assay. Participant samples were collected at the University Health Network across six study cohorts. A total of 273 patients with stage II-IV cancers spanning 16 tumor types were analyzed using a personalized tumor-informed assay (RaDaR^®). Harmonized methods were employed to mitigate the impact of variables known to influence ctDNA detection and its quantification. Pre-treatment ctDNA was detected in 83% of participants (226/273) across all stages and cancer types. Detection rates varied by clinical characteristics, including cancer type and stage; ctDNA was detected in 100% of stage IV metastatic recurrent high-grade serous ovarian cancer (HGSOC) patients (n = 8/8) and 54% of stage IV melanoma patients (n = 6/11). The median estimated variant allele fraction (eVAF) across all patients with a positive ctDNA result was 0.25% (range: 0.000029-37.7%), varied by tumor type and increased with cancer stage. A total of 11% of positive samples (24/226) had an eVAF of <0.01%. This pan-cancer ctDNA analysis using a highly sensitive assay reveals high detection rates overall, including ~10% at low levels (<0.01% eVAF), offering a reference for future clinical ctDNA applications and furthering our understanding of factors influencing ctDNA measurements.