Longitudinal circulating tumor DNA monitoring in predicting response to short-course radiotherapy followed by neoadjuvant chemotherapy and camrelizumab in locally advanced rectal cancer: data from a Phase Ⅲ clinical trial (UNION).

This study, conducted as part of a multicenter phase III clinical trial, aimed to assess the utility of circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) in comparing the efficacy of short-course and long-course chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). A total of 244 plasma samples from 79 LARC patients undergoing neoadjuvant therapy (NAT) before surgery were collected at various time points. Targeted deep sequencing using a novel MRD panel was performed. During NAT, ctDNA levels declined significantly. Baseline ctDNA-MRD status did not correlate significantly with treatment response. Notably, compared to long-course radiotherapy, microsatellite instability increased significantly after short-course radiotherapy (shortRT). Additionally, ctDNA negativity or lower levels were significantly associated with pathological complete response (pCR). Clearance of ctDNA and MRD after shortRT correlated significantly with pCR. A predictive model based on ctDNA-MRD, combined with carcinoembryonic antigen (CEA), outperformed models using only MRD or only CEA in predicting pCR/non-pCR. These findings provide insights into NAT for LARC and highlight ctDNA-based MRD assessment's potential in tailoring treatment strategies, emphasizing the need for personalized approaches.