PO.CL01.10 · 临床研究

Dynamic changes in ctDNA methylation predict early response to immunotherapy in advanced esophageal cancer

编号 5310 展板 5 时间 4/21 09:00–12:00 区域 Section 45 主讲 Zhang Hui

分会场 Liquid Biopsies: Circulating Nucleic Acids 4

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作者与单位

Hui Zhang#¹, Yu Lang#¹, Yaping Dong#², Wei Li#³, Jialin Lin⁴, Lu Yang⁵, Jiapeng Kang⁶, Wenqiang Yu*⁷, Changshun Yang*⁸, Jingxun Wu*¹, Qiyuan Li*⁹, Feng Ye*¹, Weiwei Tang*¹

¹Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, The School of Clinical Medicine of Fujian, Medical University, Xiamen, China,²Department of research and development，Shanghai Epiprobe Biotechnology Co.,Ltd, Shanghai, China,³Fudan University Shanghai Cancer Center, Department of Radiotherapy, Shanghai Medical College, Fudan University, Shanghai, China,⁴Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,⁵Department of Medical Oncology,Weifang people's Hospital, Weifang Medical University, Weifang, China,⁶Department of Medical Oncology, Zhangzhou Municipal Hospital, Zhangzhou Municipal Hospital Affiliated of Fujian Medical University, Zhangzhou, China,⁷Shanghai Public Health Clinical Center and Department of General Surgery, Huashan Hospital, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China,⁸Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China,⁹Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, China

摘要 Abstract

Background : Immune checkpoint inhibitors (ICIs) improve the prognosis of advanced esophageal cancer (ESCA), yet accurate response prediction remains challenging. Traditional biomarkers and imaging often lack timely reflection of disease progression. Circulating tumor DNA (ctDNA) methylation offers novel, non-invasive, real-time monitoring. In this study, we evaluated the early dynamic ctDNA methylation changes in advanced ESCA and predicted ICI response and survival. Methods : This observational exploratory study enrolled advanced ESCA patients on ICI treatment.Peripheral blood samples were collected at baseline and regularly throughout treatment.Plasma ctDNA was subjected to methylation sequencing. Patients were stratified into "decreased" (methylation score reduction from baseline) and "non-decreased" (stable or increased scores) groups based on dynamic changes. Kaplan-Meier and log-rank tests assessed methylation score dynamics' association with progression-free survival (PFS) and overall survival (OS). Consistency between ctDNA dynamics and imaging efficacy (RECIST 1.1) was also evaluated. Results : Baseline ctDNA methylation levels did not significantly correlate with outcomes ( p =0.1); however,dynamic changes were strongly prognostic. The "decreased" group demonstrated significantly longer PFS (26.0 vs. 15.85 months; p <0.05) and median OS (35.0 vs. 27.0 months; p =0.01) compared to the "non-decreased" group. CtDNA-defined response occurred significantly earlier than radiological response (1.55 vs. 4.0 months, p <0.05). Median time to ctDNA-defined progression (2.52 vs. 4.0 months) also preceded imaging progression, without statistical significance ( p =0.15). Conclusion : Dynamic ctDNA methylation monitoring presents a promising non-invasive approach for assessing ICI efficacy in advanced ESCA. A reduction in post-treatment ctDNA methylation levels significantly correlated with prolonged survival. ctDNA dynamics enabled earlier prediction of treatment response and progression than radiological assessment, highlighting its potential for timely detection. These findings underscore the value of dynamic ctDNA methylation analysis as a novel early efficacy marker. #These authors contributed equally: Hui Zhang, Yu Lang,Yaping Dong,Wei Li *Correspondence to:Dr. Weiwei Tang, weiweitang008@xmu.edu.cn;Dr. Feng Ye, yefengdoctor@xmu.edu.cn;Dr. Qiyuan Li, qiyuan.li@xmu.edu.cn; Dr.Jingxun Wu,wujingxun@xmu.edu.cn;Dr. Changshun Yang, 282483331@qq.com;Dr. Wenqiang Yu .wenqiangyu@fudan.edu.cn FUNDING: This study was supported by the National Natural Science Foundation of China (Grant No. 81702414), Natural Science Foundation of Fujian Province of China (Grant No. 2020J05306) and Xiamen Medical and Health Guidance Project (Grant No. 3502Z20244ZD1023).

利益披露 Disclosure

H. Zhang#, None.. Y. Lang#, None.. Y. Dong#, None.. W. Li#, None.. J. Lin, None.. L. Yang, None.. J. Kang, None.. W. Yu*, None.. C. Yang*, None.. J. Wu*, None.. Q. Li*, None.. F. Ye*, None.. W. Tang*, None.

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