The association of ctDNA with recurrence in patients with stage II-IV colorectal cancer: The β-CORRECT study.

3590 Background: CRC is a leading cause of cancer-related mortality globally. Detection of molecular residual disease (MRD) is an early indicator of recurrence and may allow for timely intervention. Here, we evaluated an analytically validated tumor-informed ctDNA MRD assay (Oncodetect) in a cohort of patients with CRC. Methods: This retrospective study utilized data and specimens from 468 patients with Stage II, III or resectable Stage IV CRC consecutively enrolled from June 1, 2020 through November 30, 2022 in the GALAXY study with available residual samples. Tumor tissue underwent whole-exome sequencing to identify up to 200 tumor-specific variants for designing a personalized MRD test. The test was used to assess ctDNA status in plasma at three timepoints: post-surgical (PS), post-definitive therapy (PDT) and in the surveillance period, which included the PDT and subsequent timepoints. The primary endpoint was the association of ctDNA status during surveillance with disease-free survival (DFS). An analysis of the association between RNA-seq expression and DFS was also planned. Results: Analysis included a total of 1648 ctDNA results from 417 patients with ≥1ctDNA result from ≥1 timepoint. Among these patients, 296 (71.0%) had colon and 121 (29.0%) had rectal cancer, 141 (33.8%) had Stage II, 249 (59.7%) Stage III and 27 (6.5%) Stage IV disease, and 255 (61.2%) received adjuvant chemotherapy. Median follow-up was 1.9 years. The median ctDNA level among detections, measured in mean tumor molecules per ml (MTM/ml) was 1.187 (range 0.006-3180.5). During surveillance, ctDNA detection was strongly prognostic for DFS (HR 36.6; CI 21.9 – 61.2; ctDNA status as a time-dependent variable). Similarly, ctDNA detection was strongly associated with DFS at the PS and PDT timepoints (Table). Multivariable analysis showed ctDNA status remained strongly associated with DFS while other clinicopathological factors did not. The median lead time between ctDNA detection and clinical recurrence was 97 days (95% CI: 51-114). RNA-seq analysis is ongoing. Conclusions: In a cohort of 468 patients who underwent curative-intent surgery for stage II-IV CRC, a tumor-informed quantitative ctDNA assay using up to 200 variants was strongly prognostic for DFS at all timepoints. The prognostic ability of RNA-seq expression analysis for ctDNA status and outcome in this cohort is currently being determined. Association of ctDNA status with DFS. Statistic Result Surveillance (n= 398) HR (95% CI) 36.6 (21.9 – 61.2), p<0.0001 Sensitivity (95% CI) 64.8% (53.2 - 74.9%) Specificity (95% CI) 98.8% (96.8 - 99.5%) PS (n = 241) HR (95% CI) 7.5 (4.3 – 13.1), p<0.0001 Sensitivity (95% CI) 44.2% (31.6% - 57.7%) Specificity (95% CI) 95.6% (91.6% - 97.8%) PDT (n = 367) HR (95% CI) 24.0 (13.8 – 41.7), p<0.0001 Sensitivity (95% CI) 45.5% (34.0% - 57.4%) Specificity (95% CI) 99.0% (97.1% - 99.7%)