ctDNA detects residual disease after neoadjuvant chemoradiotherapy and guides adjuvant therapy in esophageal squamous cell carcinoma
The diagnostic accuracy of circulating tumor DNA (ctDNA) for detecting molecular residual disease (MRD) after multimodal treatment remains unclear. In a prospective cohort of 132 patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT) followed by clinical response evaluation and surgery, tumor-informed personalized-panel and fixed-panel ctDNA assays are applied to serial blood samples. Personalized ctDNA assay demonstrates a superior baseline detection rate (99.2%) and outperforms fixed panels in diagnosing post-nCRT residual disease. Integrating personalized ctDNA with conventional clinical diagnostic methods increases sensitivity for predicting non-pathological complete response (non-pCR) from 78.4%-80.7% to 92.0%-93.2%. Patients with detectable MRD post-nCRT and/or post-surgery exhibit worse survival outcomes. In non-pCR patients, adjuvant immunotherapy improves disease-free survival in post-surgery MRD-positive cases, whereas MRD-negative patients derive no benefit. These findings support incorporating ctDNA into response assessment to guide organ-sparing strategies and adjuvant therapy decisions in ESCC. This study is registered at ClinicalTrials.gov (NCT03937362).
Authors
- Bianca Mostert (ORCID: https://orcid.org/0000-0001-5193-0820)
- Yin‐Kai Chao (ORCID: https://orcid.org/0000-0001-8649-8783)
- Xuning Fan
- Zhigang Li (ORCID: https://orcid.org/0000-0001-5086-5334)
- Simon Law (ORCID: https://orcid.org/0000-0002-6518-5806)
- Guoqiang Wang (ORCID: https://orcid.org/0000-0002-5736-9568)
- Jun Liu (ORCID: https://orcid.org/0000-0003-4800-7749)
- Yang Yang (ORCID: https://orcid.org/0000-0002-1290-6665)
- Zhihong Zhang (ORCID: https://orcid.org/0000-0002-1454-1604)
- Hong Zhang (ORCID: https://orcid.org/0000-0002-6191-0046)
- Zhichao Liu (ORCID: https://orcid.org/0000-0003-3542-0905)
- Chunguang Li (ORCID: https://orcid.org/0000-0003-3249-4087)
- Peng Cui (ORCID: https://orcid.org/0000-0001-8465-4164)
- Yuchen Su (ORCID: https://orcid.org/0009-0009-4034-5883)
- Jinyu Yang
- Xing Gao (ORCID: https://orcid.org/0000-0002-5035-3600)
- Bas P. L. Wijnhoven
- J.J.B. van Lanschot
- Shangli Cai
Institutions
- Shanghai Jiao Tong University (CN)
- Queen Mary Hospital (CN)
- Shanghai Chest Hospital (CN)
- Chang Gung Memorial Hospital (TW)
- Burning Rock Biotech (China) (CN)
- Linkou Chang Gung Memorial Hospital (TW)
- Erasmus MC Cancer Institute (NL)
- University of Hong Kong (HK)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102334
- Citations
- 4
- Primary Topic
- Esophageal Cancer Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 8.03
Funders
- National Natural Science Foundation of China
- Shanghai Hospital Development Center
- National Key Research and Development Program of China
- Program of Shanghai Academic Research Leader