Longitudinal on-treatment circulating tumor DNA as a biomarker for real-time dynamic risk monitoring in cancer patients: The EP-SEASON study

IF 48.8 1区医学 Q1 CELL BIOLOGY

Cancer Cell Pub Date : 2024-07-25 DOI:10.1016/j.ccell.2024.07.001

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引用次数: 0

Abstract

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.

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将纵向治疗循环肿瘤 DNA 作为生物标记物，对癌症患者进行实时动态风险监测：EP-SEASON研究

癌症患者的复发风险会在治疗过程中因与治疗相关的肿瘤演变而发生变化。然而，目前还缺乏能监测这些变化的生物标记物。在此，我们研究了通过液体活检跟踪循环肿瘤DNA（ctDNA）动态是否能为实时复发风险提供信息。鼻咽癌（NPC）提供了一个理想的模型，可以灵敏地检测细胞游离爱泼斯坦-巴氏病毒（EBV）DNA（cfEBV DNA）（一种ctDNA）。我们开展了EP-SEASON研究（NCT03855020），前瞻性地招募了1000名鼻咽癌患者，在11个时间点按协议进行cfEBV DNA评估，并接受连续化疗和放疗。在新辅助化疗和放疗期间，纵向cfEBV DNA显示出不同的模式。尽管每个时间点的cfEBV DNA都具有预后意义，但实时复发风险与cfEBV DNA的动态变化同步。此外，我们还发现了与不同生存结果相关的全病程ctDNA动态变化表型。总之，追踪治疗过程中的纵向ctDNA可以预测实时复发风险，从而促进适应风险的个体化患者管理。

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来源期刊

Cancer Cell 医学-肿瘤学

CiteScore

55.20

自引率

1.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.