Handbook of Targeted Cancer Therapy and Immunotherapy

98 Other clinical trials exploring the utility of ctDNA for informing adjuvant chemo therapy include the Australian DYNAMIC III study (ACTRN12617001566325) in stage III colon cancer, and the CIRCULATE-Japan and US trials (NCT04120701) (13). Data from the observational GALAXY study within CIRCULATE-Japan evaluating a total of 1,365 patients with stage I–IV CRC showed improved 6-month disease-free survival (DFS) rate in patients with positive ctDNA at 4 weeks who turned negative at 12 weeks post-op ( N = 58) compared to those whose ctDNA remained positive at 4 and 12 weeks ( N = 78) (DFS 100% vs. 45%; HR 52.3; p < 0.001). Clearance of ctDNA at 12 weeks was significantly higher in those who received adjuvant chemotherapy (57% vs. 8%, all stages p < 0.001), and 6-month DFS rate was significantly higher in ctDNA-positive patients who received adjuvant chemotherapy (84% vs. 34%; HR 0.15; p < 0.001) (14,15). ctDNA informed therapy escalation/deescalation is ongoing. These studies are summarized in Table 10.1. ctDNA (MRD positivity) has also shown to be prognostic in patients with oligometastatic co lon cancer. In a cohort of 112 patients with metastatic CRC (mCRC) from the PREDATOR clinical trial, ctDNA was positive in 54.4% of patients postoperatively (median testing at 27 days post-op; range 8–99.5 days) (16). Approximately 97% of patients with MRD had progressed at time of data cutoff (HR 5.8; 95% CI 3.9–68; p < 0.001). MRD-positive patients also had lower overall survival. MRD-positive patients that had not received postoperative chemotherapy had a markedly reduced DFS (HR 15; 95% CI 4.3–49; p < 0.001). MiRDA-C (minimal residual disease assessment in patients with CRC, NCT04739072) is an ongoing prospective observational clinical trial evaluating ctDNA levels at baseline, during neoadjuvant therapy, prior to surgery, and during surveillance to deter mine feasibility and ability of MRD/ctDNA to improve detection of recurrence after completion of curative-intent therapy. Similar to colon cancer, the presence of ctDNA detected in locally ad vanced rectal cancer (LARC) patients postoperatively is a strong indicator of recurrence of disease. In a study of 47 patients with localized rectal cancer who underwent chemo-radiotherapy (CRT) followed by resection with serial plasma sampling, ctDNA was detected in 74% pretreatment, 21% mid- and post-CRT, and 13% postoperatively (17). Post-CRT ctDNA levels were associated with magnetic resonance imaging (MRI) tumor regression, and metastasis-free survival was shorter in those with detectable ctDNA post-CRT (HR 7.1; 95% CI 2.4–21.5; p < 0.001) compared to those with undetectable ctDNA. In another study of LARC, detection of ctDNA postoperatively was a strong

Copyright © 2023 Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited.