Abstract 2522: Exploring the prognostic and predictive value of circulating tumor DNA in patients with advanced colorectal cancer and chemotherapy

Abstract Background: Chemotherapy improves the survival of advanced colorectal cancer (CRC) patients but recurrences do happen frequently. Early indicators of reccurence/relapse post-chemotherapy are essential for optimal clinical decision. Circulating tumor DNA (ctDNA) are cancer-specific DNA fragments in plasma. They have been considered as predictive biomarkers of early stage CRC. However, the predictive value of ctDNA in advanced CRC is still undetermined. Here, we evaluate the applicability of early changes in ctDNA as a marker that might predict clinical course in advanced CRC patients after chemotherapy. Methods: 122 patients with CRC were enrolled and their ctDNA fingerprints, designed based on individual patient's top somatic mutated genes, were determined and monitored over time (~ 3-6 months interval). The patients were classified into high- and low-ctDNA groups divided by the median concentration of ctDNA. We subsequently analyzed the correlation between overall survival (OS) and ctDNA levels in patients with or without chemotherapy. The dynamics of ctDNA were used to assess the prognosis and OS. Results: In the 122 patients, higher ctDNA levels (above median) were associated with shorter OS (HR, 2.89; CI 95% 1.45-5.79, P=0.0027). The conclusion upheld in a subset of 48 who had advanced CRC (stage IV) and received chemotherapy (HR, 1.601, CI 95% 0.61-4.17, p=0.037). Moreover, changes of ctDNA were detected early during the chemotherapy treatment course. In the same 48 patients with advanced CRC and chemotherapy, those who had undetectable and decreased ctDNA had longer OS overall, suggesting that ctDNA dynamics is predictive of clinic change in chemotherapy in advanced CRC. Finally, compared with clinical imaging diagnosis, we found that approximately 52.9% (18/34) patients belonged to a “consistent” group, in which patients with decreased/undetectable ctDNA had relieved clinical diagnosis and patients with increased ctDNA had elevated diagnosis. However, 14.7% (5/34) patients had inconsistent results between imaging diagnosis and ctDNA monitoring, and 32.4% (11/34) patients were uncertain due to unstable ctDNA levels. Conclusion: This study confirms the association between baseline levels of ctDNA and survival times of CRC patients. Additionally, it also suggests the use of early change of ctDNA as a potential biomarker of therapeutic efficacy in CRC chemotherapy. Oncologists may be able to use ctDNA fingerprints to guide treatment decisions and predict individual patient's prognosis. Citation Format: Xiu Liu, Xuan Zhang, Kai Ou, Chelong Lu, Dong Zheng, Jun Liu, Qiang Xu, Lin Yang. Exploring the prognostic and predictive value of circulating tumor DNA in patients with advanced colorectal cancer and chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2522.