European journal of cancer (Oxford, England : 1990) · 2025
Feasibility of ctDNA-guided precision neoadjuvant therapy in locally advanced rectal cancer: Insights from the ongoing CINTS-R trial.
Клиническое исследование II фазыСтатьяМногоцентровое исследованиеРандомизированное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Zhang Xiao, Zhou Jiaolin, Geng Jianhao, Li Yongheng, Huang Fei, Shu Wenlong, Fu Wei, Zhou Xin, Wu Guoju, Jia Wenzhuo, Cui Jian, Wang Zhenjun, Han Jiagang, Shi Bohao, Li Lifeng, Rui Jinqiu, Xue Huadan, Hu Ke, Xu Tao, Chen Weijie, Lu Junyang, Yao Hongwei, Liu Qian, Lin Guole
Аннотация
BACKGROUND: Accurate risk stratification is essential to optimize neoadjuvant therapy for locally advanced rectal cancer (LARC) in the era of precision medicine. This study assessed the feasibility and safety of a circulating tumor DNA (ctDNA)-guided neoadjuvant strategy.
METHODS: This interim analysis included patients with mid-low rectal adenocarcinoma (cT3-4N0M0 or cT1-4N1-2M0) from the multicenter, randomized CINTS-R trial using a 2:1 allocation to an experimental or control group. The control group received conventional nCRT (long-course radiotherapy with concurrent capecitabine followed by one XELOX cycle). In the experimental group, treatment was stratified as follows: (1) ctDNA-defined high-risk patients received TNT, consisting of the same nCRT followed by five additional XELOX cycles (six in total); (2) ctDNA-defined low-risk patients proceeded directly to surgery after nCRT; and (3) patients with dMMR/MSI-H/TMB-H tumors received neoadjuvant tislelizumab (≥6 cycles). The analysis focuses on feasibility and safety outcomes.
RESULTS: Between February 2023 and September 2024, 349 patients were randomized and 316 included in analysis (experimental: 210; control: 106). Among the experimental group, 115 were ctDNA-high-risk and 89 ctDNA-low-risk. High-risk patients were significantly older and more often male, with larger tumors, longer tumor-to-anal verge distance, greater circumferential involvement, and higher EMVI rates (all p ＜0.05). Serious adverse events (SAEs, CTCAE v5.0, grade 3-4) occurred in 10.0 % vs. 6.6 % of patients in the experimental and control groups (p = 0.316). Notably, 15.7 % of TNT-treated patients discontinued chemotherapy due to SAEs, whereas all nCRT recipients completed treatment.
CONCLUSION: This interim analysis demonstrates the feasibility and safety of a ctDNA-guided, risk-adapted neoadjuvant strategy for LARC. Final outcomes will further clarify its clinical efficacy.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05601505.
METHODS: This interim analysis included patients with mid-low rectal adenocarcinoma (cT3-4N0M0 or cT1-4N1-2M0) from the multicenter, randomized CINTS-R trial using a 2:1 allocation to an experimental or control group. The control group received conventional nCRT (long-course radiotherapy with concurrent capecitabine followed by one XELOX cycle). In the experimental group, treatment was stratified as follows: (1) ctDNA-defined high-risk patients received TNT, consisting of the same nCRT followed by five additional XELOX cycles (six in total); (2) ctDNA-defined low-risk patients proceeded directly to surgery after nCRT; and (3) patients with dMMR/MSI-H/TMB-H tumors received neoadjuvant tislelizumab (≥6 cycles). The analysis focuses on feasibility and safety outcomes.
RESULTS: Between February 2023 and September 2024, 349 patients were randomized and 316 included in analysis (experimental: 210; control: 106). Among the experimental group, 115 were ctDNA-high-risk and 89 ctDNA-low-risk. High-risk patients were significantly older and more often male, with larger tumors, longer tumor-to-anal verge distance, greater circumferential involvement, and higher EMVI rates (all p ＜0.05). Serious adverse events (SAEs, CTCAE v5.0, grade 3-4) occurred in 10.0 % vs. 6.6 % of patients in the experimental and control groups (p = 0.316). Notably, 15.7 % of TNT-treated patients discontinued chemotherapy due to SAEs, whereas all nCRT recipients completed treatment.
CONCLUSION: This interim analysis demonstrates the feasibility and safety of a ctDNA-guided, risk-adapted neoadjuvant strategy for LARC. Final outcomes will further clarify its clinical efficacy.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05601505.