Abstract A042: ctDNA KRAS detection in pancreatic ductal adenocarcinoma: Platform concordance, sensitivity and clinical associations in a contemporary cohort
Jennifer Guo, Michael May, Michael F. Berger, Emma Cismas, Marc Hilmi, Anupriya Singhal, Fiyinfolu Balogun, Joshua D. Schoenfeld, Wungki Park, Eileen M. O'Reilly, Kenneth H. YuAbstract
Background:
Multiple circulating tumor DNA (ctDNA) platforms are available for KRAS mutation detection in pancreatic ductal adenocarcinoma (PDAC), including broad next-generation sequencing (NGS) and targeted quantitative polymerase chain reaction (qPCR) assays, yet comparisons of performance and concordance are limited. We characterized ctDNA KRAS detection rates, inter-platform concordance, and associated clinical features in a contemporary PDAC cohort at Memorial Sloan Kettering (MSK).
Methods:
We reviewed all patients with PDAC who underwent ctDNA testing with MSK-ACCESS (in-house, NGS, ∼150 genes), Guardant360 (commercial, NGS, ∼700 genes), and/or Idylla ctKRAS (qPCR assay detecting 21 specific KRAS mutations) at MSK in 2025. Clinical data (disease stage, metastatic site/burden, CA 19-9, CEA, somatic NGS) were collected at time of ctDNA testing. KRAS variant allele frequencies (VAF) were reported for ACCESS and Guardant. Equivocal results were classified as positive if a specific KRAS allele was identified and confirmed on a second platform. Inter-test concordance was evaluated in patients with KRAS detected by ≥1 platform. Mann-Whitney U and Fisher's exact tests were used for statistical comparisons between groups.
Results:
We identified 922 patients with PDAC who underwent ctDNA testing and analyzed 87 patients tested with ≥2 assays within a 28-day interval. Idylla had the shortest median turnaround time (4 days, range 2-21) compared to Guardant (7 days, range 5-15) and MSK-ACCESS (17 days, range 12-36). Among tissue KRAS+ cases, ctDNA KRAS detection rates favored the NGS platforms (ACCESS 70%, Guardant 67%, Idylla 56%). KRAS mutations were detected by ≥1 ctDNA platform in 54 patients. Compared to ctDNA KRAS-not detected patients, ctDNA KRAS+ patients had higher rates of Stage IV disease (100% vs. 85%, p=0.006), number of metastases (median 2 vs. 1, p=0.005), CEA (median 16.4 vs. 4.3 ng/mL, p<0.001) and incidence of liver metastases (89% vs. 55%, p<0.001). Among ctDNA KRAS+ patients, 42 (78%) were concordant and 12 (22%) discordant across the platforms. When comparing platforms pairwise, the two NGS platforms (ACCESS & Guardant) showed numerically higher concordance than the NGS/qPCR pairing (ACCESS & Idylla) (94% vs. 72%, p=0.08), with most discordant cases detected by ACCESS alone (9 ACCESS-only vs. 2 Idylla-only detections). KRAS VAF was significantly lower in discordant vs. concordant cases (median 0.60% vs 4.59%, p-value <0.001).
Conclusions:
In this contemporary cohort, detection of KRAS in ctDNA is associated with increased metastatic burden, higher CEA and liver metastases, supporting its use as a surrogate of disease extent. Although qPCR had the shortest turnaround time, NGS platforms had increased sensitivity for KRAS detection, especially at low VAF.
Citation Format:
Jennifer Guo, Michael May, Michael F. Berger, Emma Cismas, Marc Hilmi, Anupriya Singhal, Fiyinfolu Balogun, Joshua D. Schoenfeld, Wungki Park, Eileen M. O'Reilly, Kenneth H. Yu. ctDNA KRAS detection in pancreatic ductal adenocarcinoma: Platform concordance, sensitivity and clinical associations in a contemporary cohort [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr A042.