UNION: Longitudinal ctDNA for Predicting Response to Short-Course Rectal Cancer Neoadjuvant RT

A group of researchers from China presented results of a phase 3 study that “offer valuable insights into the dynamic landscape of neoadjuvant therapy for locally advanced rectal cancer (LARC) management.”

Their presentation, given as a late-breaking abstract at the 2024 American Society of Clinical Oncology Annual Meeting, also emphasized the “potential of circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) assessment as a valuable tool for tailoring treatment strategies” in these patients.

UNION is a multicenter, randomized, open-label, phase 3 clinical trial evaluating the feasibility of short-course radiotherapy (shortRT) combined sequentially with camrelizumab and chemotherapy as a neoadjuvant therapy for LARC. Researchers aimed to better understand the value of ctDNA-based MRD in determining the comparative efficacy of short-course and long-course chemoradiotherapy.

A total of 244 plasma samples from 79 patients with LARC were included in the analysis. All patients underwent neoadjuvant therapy prior to curative surgery and had their plasma samples collected at baseline (C1), at the time of neoadjuvant therapy (C2), after neoadjuvant therapy (C3), and postsurgery (C4).

Researchers performed deep targeted panel sequencing of 556 known cancer-related genes. Changes in genomic features and ctDNA-based MRD status during treatment were noted, and the relationship between these changes and treatment response was evaluated.

During neoadjuvant therapy, researchers found that the ctDNA-based MRD positivity rate tended to decline significantly. Patients with high baseline tumor mutation burden often showed a significant inclination toward pathological response and tumor regression (grade 0/1) after neoadjuvant therapy, while no significant correlation was observed between baseline ctDNA-based MRD status and treatment response.

Additionally, they reported that microsatellite instability was more pronounced after shortRT compared with long-course radiotherapy (P=.042), and ctDNA negativity was significantly associated with pathological complete response (P=.022). Both ctDNA clearance (P=.049) and MRD clearance (P=.015) after shortRT was significantly correlated with pathological complete response, they added.

Furthermore, researchers developed a risk-scoring predictive model based on ctDNA-based MRD, which combined with MRD clearance and CEA, outperformed models that use only MRD clearance (area under the curve [AUC], 0.917; 95% CI, 0.753-1.000) or only CEA (AUC, 0.733; 95% CI, 0.449-1.000). This finding highlighted the model’s superior performance in predicting pathological complete response as well as nonpathological complete response (AUC, 0.983; 95% CI, 0.937-1.000).

“[UNION] contributes valuable insights into optimizing treatment decision-making and predicting treatment response in LARC patients, ultimately advancing the field of rectal cancer management,” they concluded, adding that “the differences observed between shortRT and long-course radiotherapy regimens underscore the need for personalized treatment approaches.”