Minimal residual disease profiling predicts pathological complete response in esophageal squamous cell carcinoma

作者：Pinli Yue, Fenglong Bie, Jiarun Zhu, Linrui Gao, Zhendiao Zhou, Guangyu Bai, Xiaobing Wang, Ziyi Zhao, Zefen Xiao, Yong Li, Aiping Zhou, Wenyang Liu, Yuchen Jiao, Shugeng Gao · 发表于：Molecular Cancer · 年份：2024 · DOI：10.1186/s12943-024-02006-x · 被引用次数：21 · 研究领域：Cancer Genomics and Diagnostics、Pancreatic and Hepatic Oncology Research、Lung Cancer Treatments and Mutations

Accurate presurgical prediction of pathological complete response (pCR) can guide treatment decisions, potentially avoiding unnecessary surgeries and improving the quality of life for cancer patients. We developed a minimal residual disease (MRD) profiling approach with enhanced sensitivity and specificity for detecting minimal tumor DNA from cell-free DNA (cfDNA). The approach was validated in two independent esophageal squamous cell carcinoma (ESCC) cohorts. In a cohort undergoing neoadjuvant, surgical, and adjuvant therapy (NAT cohort), presurgical MRD status precisely predicted pCR. All MRD-negative cases (10/10) were confirmed as pCR by pathological evaluation on the resected tissues. In contrast, MRD-positive cases included all the 27 non-pCR cases and only one pCR case (10/10 vs 1/28, P < 0.0001, Fisher's exact test). In a definitive radiotherapy cohort (dRT cohort), post-dRT MRD status was closely correlated with patient prognosis. All MRD-negative patients (25/25) remained progression-free during the follow-up period, while 23 of the 26 MRD-positive patients experienced disease progression (25/25 vs 3/26, P < 0.0001, Fisher's exact test; progression-free survival, P < 0.0001, log-rank test). The MRD profiling approach effectively predicted the ESCC patients who would achieve pCR with surgery and those likely to remain progression-free without surgery. This suggests that the cancer cells in these MRD-negative patients have been effectively eliminated and they could be...