LAUSR

3579 Background: Recurrence of colorectal cancer has been linked to the presence of epigenetic circulating tumour DNA (ctDNA) in patient plasma after surgery. The prognostic significance of ctDNA prior to treatment remains unknown. This study investigated the correlation between pre-treatment ctDNA and current radiological (MRI) prognostic markers in patients with rectal cancer. Methods: Forty-two patients with rectal cancer were enrolled, with all having staging MRI prior to treatment. Plasma was taken for ctDNA at diagnosis. The presence of either methylated branched-chain amino acid transaminase 1 (BCAT1) or Ikaros family zinc finger (IKZF1) in cell-free DNA from plasma was deemed a positive ctDNA result. Correlation of MRI prognostic indicators and ctDNA results was assessed with chi-square tests. Univariable and multivariable cox regression analyses were performed to determine variables associated with overall survival (OS). Results: Mean age was 64.4 years (SD 12.5) and majority were male (30/42, 71.4%). 11, 13, 9 & 9 patients had stages I, II, III, IV respectively. Patients had a minimum follow-up of 36 months. Thirty-three (78.6%) patients received neoadjuvant chemoradiotherapy. 29 (69.0%) patients underwent surgical resection. 3-year survival rate was 64% in the overall group. 67% (n=28/42) of patients were positive for the methylated ctDNA at diagnosis. 11 out of 12 patients with a positive circumferential resection margin (CRM +) were ctDNA positive (p=0.03). Univariable analysis showed that prognostic indicators for OS were presence of extramural venous invasion (EMVI) (HR 3.0, 95% CI 1.1-8.4), CRM+ (HR 12.2, 95%CI 3.9-37.6), metastatic disease (HR 7.32, 95% CI 2.63-20.37) and ctDNA% methylation (HR 1.1, 95% CI 1.04-1.13) (Table 1). The presence of CRM+ and a positive ctDNA had a HR of 20.5 (95% CI 5.1-82.3). With multivariable analysis, including adjustment for age and EMVI, only CRM+/ctDNA+ variable was an independent predictor for poor survival (HR 20.2, 95% CI 4.5-90.9). Conclusions: In rectal cancer, almost all patients with CRM involvement have ctDNA, and these patients had the worst prognosis. Future studies with longitudinal ctDNA assessment pre and post treatment could potentially inform prognosis and help tailor patients’ treatment.[Table: see text]