Circulating tumor DNA (ctDNA) analysis guiding adjuvant therapy in patients (pts) with colorectal cancer (CRC): Impact on fear of cancer recurrence (FCR).

Abstract

11125 Background: ctDNA detection following curative intent treatment is highly prognostic, with potential to impact patient fear of cancer recurrence (FCR). In 3 separate randomized trials (DYNAMIC II, III, rectal), pts with early-stage CRC were randomly assigned to treatment decision guided by ctDNA results (adjuvant chemotherapy escalation if ctDNA positive, de-escalation or no treatment if ctDNA negative), or according to standard clinicopathological features. The relationship between being informed of a high recurrence risk, or treatment de-escalation, and FCR is unclear. This study aims to explore the relationship between biomarker-informed adjuvant chemotherapy (ACT) decision making and FCR, including changes over time. Methods: A subset of pts from the 3 DYNAMIC studies completed validated self-report questionnaires measuring FCR, anxiety, depression and quality of life. Data were collected at three time points: after surgery (T1), at the time of the ACT decision (T2), and 9-12 months later (T3). Pts randomized to the ctDNA-guided group received a ctDNA test result (positive or negative) at T2, while those in the standard of care (SOC) group did not. The primary endpoint was the FCR Inventory Short Form score (FCRI-SF). FCR patterns over time were analyzed using a mixed model 2 (Randomization) x 3 (Time) ANCOVA. A 2 (Randomization) x 2 (Chemotherapy Status) ANCOVA was used to assess ACT’s impact on FCR at follow-up. Gender, age, and cancer stage were included as covariates. Results: 317 pts from 35 Australian sites participated in the FCR substudy (74% response rate for all timepoints). Two-thirds were male, and the mean age was 60 years. Of the ctDNA-guided group (n=176), 73% had a negative ctDNA result. At baseline, 63% of patients exhibited clinically significant levels of FCR (FCRI-SF >13). Younger age, female gender, anxiety, and higher cancer stage all predicted higher baseline FCR. FCR significantly decreased over time for all pts ( F (2,176) = 3.64, p = .03). This reduction was more pronounced in the ctDNA-guided group compared to the SOC group ( F (2, 176) = 3.83; p = .02), although the effect size was small (Cohen’s d =0.24). In the ctDNA-guided group, no differences in FCR were found between pts based on ctDNA result (positive vs. negative). High baseline anxiety was the only independent predictor of FCR at 12 months. Chemotherapy receipt, cancer stage, depression, and quality of life scores were not predictive of FCR over time. Conclusions: In pts with early-stage CRC, neither a positive nor negative ctDNA result impacted FCR. ctDNA-guided approach to determining ACT was associated with a greater reduction in FCR over time compared to SOC. This biomarker-guided treatment approach has potential to improve ACT selection as well as psychosocial outcomes. Temporal reduction in FCR is likely driven by increased prognostic certainty over time. Clinical trial information: 12615000381583 .