Utility of circulating tumor DNA in patients with resectable pancreatic cancer using a patient-specific panel: ARTEMIS-PC study.

747 Background: Tumor-informed circulating tumor DNA (ctDNA) assays for minimal residual disease (MRD) have demonstrated promise across multiple cancers. However, in pancreatic ductal adenocarcinoma (PDAC), clinical utility remains uncertain. We therefore conducted the multicenter prospective ARTEMIS-PC study to evaluate the utility of a personalized, tumor-informed MRD assay in patients with resectable PDAC. Methods: Of 50 patients who underwent panel creation, 40 (80%) were successful. Among these, 39 patients with treatment-naïve, preoperative tumor tissue and histopathologic confirmation of PDAC, as well as assessable longitudinal ctDNA, were included in the analysis. ctDNA was assessed using a patient-specific, tumor-informed assay (Invitae Personalized Cancer Monitoring). Plasma was collected longitudinally at specific timepoints: enrollment, after completion of neoadjuvant chemotherapy (NAC) when administered (36/39), 1 month postoperatively, every 3 months during year 1, and every 6 months thereafter through 24 months. Endpoints included panel-creation success rate, longitudinal ctDNA dynamics, and associations of ctDNA status with landmark recurrence-free survival (RFS) and overall survival (OS). Results: The majority of resectable patients in study were stage I (IA-12, 31%; IB-24, 62%) at diagnosis, with a small subset being stage II (IIA-1,2%; IIB-2, 5%). The median follow-up period was 17.7 months (range: 2.1-30.7 months). At baseline, 67% (26/39) patients were ctDNA positive. Among ctDNA-positive who received NAC (22/26), 45% (10/22) converted to negative, whereas 55% (12/22) remained positive. 50% (8/16) of ctDNA-positive patients were inoperable. Among 29 patients who underwent surgery, 21 (72.4%) remained ctDNA-negative, 6 (20.7%) converted to negative, and 2 (6.9%) remained positive at 1 month postoperatively. Recurrence occurred in 16 patients (55.2%), with a median lead time of 0 months (range: 0-6) in 12 evaluable patients, 4/12 had a 2-6 month lead time compared to imaging; 3/16 patients (18.8%) remained ctDNA-negative at recurrence, ctDNA positivity after NAC (if given)/ before surgery was associated with significantly worse RFS (HR = 4.69; P = .005) and OS (HR = 15.75; P = .031). Median RFS was 16.5 months for ctDNA-negative vs 4.6 months for ctDNA-positive. ctDNA negativity after NAC (if given)/before surgery remained the strongest independent predictor of RFS on multivariable analysis (HR = 3.95; P = .025). Conclusions: Tumor-informed ctDNA monitoring is feasible in patients with resectable PDAC. ctDNA positivity after NAC (if given)/before surgery strongly predicted inoperability and worse survival outcomes, supporting its use for risk stratification. Clinical trial information: UMIN000043561 .