Evaluation of circulating tumor DNA (ctDNA) following liver resection in a high-risk population with colorectal liver metastases.

3556 Background: Liver resection is routinely performed for oligometastatic colorectal cancer (CRC). ctDNA analysis is becoming important in the management of primary CRC following surgery, but in patients with liver metastases, its role is less clear. This study aimed to evaluate the performance of a plasma ctDNA assay for early detection of recurrence in patients with liver only CRC metastases post surgical resection. The cohort included patients who had inoperable disease prior to induction chemotherapy and those having repeat resections. Patients with the primary cancer in situ were included if a synchronous resection was performed. Methods: 61 patients (42 male, median age 68 [range 41-85]) were studied. All patients had CRC liver metastases as the sole metastatic site on evaluation by CT and MRI. Patients were followed up clinically with regular CT imaging. Plasma samples were collected at baseline (pre-surgery, n = 55) and 5 days to 1+ year after surgery, and were tested retrospectively on a blood-only, tumor-agnostic, targeted methylation assay that interrogates informative methylation regions for signal indicative of ctDNA using a machine learning classifier (GRAIL, Inc., Menlo Park, CA). Results: ctDNA was detected in 94.5% (52/55) of patients at the pre-surgery timepoint. During clinical surveillance, 46 developed recurrence, 5 had no recurrence for at least 2 years after surgery, and 10 had follow-up for less than 2 years. Among patients with recurrence, ctDNA was detected in 80.4% (37/46) of patients before recurrence, with a median lead time of 245 days [IQR: 65 - 393 days]. All five patients who remained recurrence-free for at least 2 years had undetectable ctDNA following surgery. ctDNA was detected in 57.8% (26/45) of patients who recurred and had plasma collected within 3 months following surgery. Recurrence-free survival (RFS) was significantly lower in patients with ctDNA detected within 3 months after surgery (median RFS 272 vs. 593 days, log-rank p-value < 0.01). Conclusions: ctDNA analysis using a methylation-based assay allowed the detection of minimal residual disease and the prediction of recurrence in many patients following resection of CRC liver metastases. These data support the potential use of this biomarker for patient management pending confirmation in prospective clinical studies.