P-117 Feasibility of tumor informed circulating tumor DNA in neoadjuvant rectal cancer

Circulating tumor DNA (ctDNA) is emerging as a biomarker to detect molecular evidence of residual disease and predict recurrence in patients with colorectal cancer in the adjuvant setting. Treatment paradigms have been evolving in stage II and III rectal with total neoadjuvant therapy (TNT). Prospective evaluation, feasibility and the utility of using ctDNA as a biomarker during neoadjuvant therapy in clinical practice has been limited to date. In this retrospective single institution study, data from commercial ctDNA testing in 12 patients with rectal cancer during their neoadjuvant management was analyzed. A personalized and tumor-informed multiplex PCR assay (Signatera TM 16-plex bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA. ctDNA testing was performed at the time of diagnosis and at completion of TNT. Primary objectives of the study are to determine the feasibility of tumor informed ctDNA testing in rectal cancer patients and the proportion of ctDNA positivity at diagnosis. Secondary objectives are to determine correlation of ctDNA response with clinical and pathologic responses. Agreement was assessed by concordance with 95% CI and was compared to 0.5 as a null hypothesis. ctDNA testing was performed in 12 patients; 1 patient did not have a pre-treatment test. Seven of the 11 evaluable patients were females and 4 patients were males. Ten out of 11 patients had at least T3 or T4 and N1 or N2 rectal cancer at presentation. Tumor-informed ctDNA was detected in 100% (11/11) of the patients at diagnosis. Ten patients had completed total neoadjuvant therapy with at least 2 time points of ctDNA testing. Six patients underwent rectal cancer surgery while 2 patients opted for a watch-and-wait approach. Nine out of 10 patients had a reduction in ctDNA levels with neoadjuvant therapy. Six out of 9 patients had cleared their ctDNA after TNT. The ctDNA clearance (N=6) correlated 100% (95% CI: 0.7-1.0, p=0.004) with overall clinical response (PR or CR), and the reduction in ctDNA levels (N=3) correlated with histologic evidence of treatment effect on definitive surgical pathology. Circulating tumor DNA was detected in 100% of rectal cancer patients at diagnosis prior to initiation of TNT. Clinical and pathological responses correlated with reduction or clearance in ctDNA. This study demonstrates the feasibility of tumor-informed ctDNA in patients with rectal cancer in the neoadjuvant setting. Further prospective data are required to determine the definitive utility of ctDNA as a correlative biomarker to assess clinical and pathological responses to neoadjuvant rectal cancer patient management.