Clinical utility and tissue concordance of circulating tumor DNA in pancreatic ductal adenocarcinoma

Abstract Importance The utility of ctDNA in addressing challenges of molecular tissue profiling and complementing NGS is undefined in pancreas ductal adenocarcinoma (PDAC). Objective To assess ctDNA detection rates by stage, disease burden, metastasis patterns, compare overall survival (OS) between ctDNA-positive and ctDNA-negative cases, and determine concordance between ctDNA and matched-tissue biopsies. Design Single-institution study, 2019- 2022. Setting Memorial Sloan Kettering. Participants Patients with PDAC and ctDNA profiling. Main Outcomes and Measures Clinical, survival data abstracted from medical records. NGS by MSK-ACCESS ctDNA assay. Results Four hundred and fourteen patients with PDAC: 28% stage I/II, 21% stage III, 51% stage IV. ctDNA detection highest among patients with advanced disease: 75% stage IV, 38% stage III, 34% stage I/II disease. For stage IV, ctDNA more frequently detected with ≥2 organs involved than with <2 organs (76% vs 38%, P = .025). Higher rates ctDNA detection observed in patients with liver metastases vs without (82% vs 52%, P < .001). In untreated stage IV cohort (N = 120), median OS was 10 months for those with detectable ctDNA (95% CI 6.9, 14) vs 19 months (95% CI 13, Not Reached) for those with undetectable ctDNA (P = .1). Concordance between ctDNA and matched tissue NGS lower in untreated stage I-III disease, but high for untreated stage IV PDAC, including critical success index of 93.1% of KRAS variants. Conclusion ctDNA is a promising tool in detection of somatic variants in PDAC. Concordance between ctDNA and tissue is high for patients with untreated metastatic disease, notably for detection of KRAS variants.