由于治疗相关的肿瘤演变，癌症患者的复发风险可能会在治疗期间发生变化。然而，缺乏可以监测这些变化的生物标志物。在这里，我们研究了通过液体活检追踪循环肿瘤 DNA (ctDNA) 动态是否可以告知实时复发风险。鼻咽癌 (NPC) 提供了一种理想的模型，可以灵敏地检测无细胞 Epstein-Barr 病毒 (EBV) DNA (cfEBV DNA)（一种 ctDNA）。我们开展了 EP-SEASON 研究 (NCT03855020)，前瞻性招募了 1,000 名鼻咽癌患者，在 11 个时间点接受符合方案的 cfEBV DNA 评估，并接受序贯放化疗。在新辅助化疗和放疗期间，纵向 cfEBV DNA 显示出不同的模式。尽管 cfEBV DNA 在每个时间点都具有预后意义，但实时复发风险与 cfEBV DNA 动态同步变化。此外，我们还确定了与不同生存结果相关的全程 ctDNA 变化动态的表型。总之，跟踪治疗中的纵向 ctDNA 可以预测实时复发风险，促进风险适应、个性化的患者管理。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Recurrence risks of cancer patient can change during treatment as a result of treatment-related tumor evolution. However, biomarkers that can monitor these changes are lacking. Here, we investigated whether tracking circulating tumor DNA (ctDNA) dynamics through liquid biopsy can inform real-time recurrence risk. Nasopharyngeal carcinoma (NPC) provides an ideal model where cell-free Epstein-Barr virus (EBV) DNA (cfEBV DNA), a ctDNA, can be sensitively detected. We conducted the EP-SEASON study (NCT03855020) and prospectively recruited 1,000 NPC patients undergoing per-protocol cfEBV DNA assessments at 11 time points and receiving sequential chemo-radiotherapy. Longitudinal cfEBV DNA displayed distinct patterns during neoadjuvant chemotherapy and radiotherapy. Despite the prognostic significance of cfEBV DNA at each time point, real-time recurrence risks changed in sync with cfEBV DNA dynamics. Furthermore, we identified phenotypes of whole-course ctDNA changing dynamics associated with different survival outcomes. In conclusion, tracking longitudinal on-treatment ctDNA can forecast real-time recurrence risk, facilitating risk-adapted, individualized patient management.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.