中山大学孙颖小组的一项最新研究发现了动态ctDNA指导鼻咽癌风险适应性治疗。相关论文于2026年3月11日发表在《自然》杂志上。

在此，研究组报告了EP-STAR试验的结果——一项多中心、ctDNA驱动、风险适应、非随机II期研究（NCT04072107; ClinicalTrials.gov），该试验以鼻咽癌为模型，测试了以治疗中ctDNA动力学为指导的风险适应治疗（RAT）策略是否能显著提高生存率。纳入符合条件的患者，并开始接受标准治疗的吉西他滨-顺铂新辅助化疗（GP-NAC，缩写中的P代表铂），然后在GP-NAC期间进行RAT或ctDNA清除轨迹指导的标准治疗放化疗。从前瞻性注册的ctDNA生物标志物队列（NCT03855020）中抽取符合方案要求的未接受RAT治疗的患者，作为非随机、同期无RAT的外部对照组。RAT组的主要终点为无衰竭生存期（FFS）。

中位随访47.3个月后，RAT组（n=110）的3年FFS为89.1%（83.2–95.0%）。与无RAT外部对照组相比，接受RAT治疗的患者FFS显著改善（对数秩检验P=0.003；风险比=0.41 [0.23–0.75]；Cox回归模型P=0.004）。RAT策略耐受性良好，无治疗相关死亡事件。总的来说，这些数据表明，ctDNA驱动的大鼠模式可能是一种有希望提高生存率的策略，挑战传统的固定细胞、静态治疗方法。

据悉，尽管有令人鼓舞的数据显示，治疗期间循环肿瘤DNA （ctDNA）动态可以实时告知肿瘤的反应和复发风险，但如何最好地将这些见解转化为可操作的临床决策仍不清楚。

附：英文原文

Title: Risk-adaptive therapy guided by dynamic ctDNA in nasopharyngeal carcinoma

Author: Lv, Jiawei, Zheng, Dan-Xue, Liang, Jin-Hui, Zhang, Ning, Ye, Zu-Lu, Xu, Xu-Dong, Chua, Melvin. L. K., Zhang, Lu-Lu, Du, Zi-Ming, Zhang, Zi-Chen, Li, Wen-Fei, Tang, Ling-Long, Chen, Lei, Mao, Yan-Ping, Guo, Rui, Chen, Yu-Pei, Lin, Li, Zhang, Yuan, Liu, Xu, Xu, Cheng, Li, Zhi-Xuan, Xu, Ling-Xin, Yang, Pan-Yang, Chen, Kun, Bin, Deng, Gao, Tian-Sheng, Yan, Jian-Ye, Chen, Lu-Si, Huang, Shao Hui, Zhao, Hong-Yun, Hong, Shu-Bin, Jie, Yu-Sheng, Huang, Hui-Ling, Tang, Xu-Hua, Yun, Jing-Ping, Liu, Li-Zhi, Tian, Li, Li, Hao-Jiang, Li, Ji-Bin, Zhou, Guan-Qun, Ma, Jun, Sun, Ying

Issue&Volume: 2026-03-11

Abstract: Despite promising data showing that circulating tumour DNA (ctDNA) dynamics during treatment can inform real-time tumour response and recurrence risk1, how best to translate these insights into actionable clinical decision-making remains unclear. Here we report results from the EP-STAR trial—a multi-centre, ctDNA-driven, risk-adapted, non-randomized phase II study (NCT04072107; ClinicalTrials.gov) testing whether a risk-adaptive treatment (RAT) strategy guided by on-treatment ctDNA dynamics can meaningfully improve survival, using nasopharyngeal carcinoma as a model. Eligible patients were enrolled and began treatment with standard-of-care gemcitabine–cisplatin neoadjuvant chemotherapy (GP-NAC; the P in this abbreviation stands for platinum)2, followed by RAT or standard-of-care chemoradiotherapy guided by ctDNA clearance trajectory during GP-NAC. Protocol-eligible patients who did not receive RAT, drawn from a prospectively registered ctDNA biomarker cohort (NCT03855020)3, served as a non-randomized, contemporaneous no-RAT external cohort. The primary end-point was failure-free survival (FFS) in the RAT group. After a median follow-up of 47.3months, the 3-year FFS was 89.1% (83.2–95.0%) in the RAT group (n=110). Patients who received RAT showed significantly improved FFS (P = 0.003, log–rank test) compared with the no-RAT external cohort (hazard ratio=0.41 [0.23–0.75]; P=0.004, Cox regression model). The RAT strategy was well-tolerated with no treatment-related deaths. Collectively, these data show that a ctDNA-driven RAT paradigm could be a promising strategy to improve survival, challenging the conventional fixed-course, static treatment approach.

DOI: 10.1038/s41586-026-10244-w

Source: https://www.nature.com/articles/s41586-026-10244-w