SCI

12 August 2024

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

（Cancer Cell；IF：48.8）

  • Lv J, Xu LX, Li ZX, Lin L, Wu CF, Quan TQ, Zhen ZC, Li WF, Tang LL, Mao YP et al: Longitudinal on-treatment circulating tumor DNA as a biomarker for real-time dynamic risk monitoring in cancer patients: The EP-SEASON study. Cancer Cell 2024.

  • Correspondence to: majun@sysucc.org.cn (J.M.), chenyup1@sysucc.org.cn (Y.-P.C.), zhougq@sysucc.org.cn (G.-Q.Z.), sunying@sysucc.org.cn (Y.S.)

SUMMARY摘要

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.

肿瘤患者的复发风险在治疗过程中会因治疗相关的肿瘤演变而改变。然而，目前缺乏可监测这些变化的生物标志物。在本研究中，我们研究了通过液体活检追踪循环肿瘤DNA (ctDNA)动力学能否实时告知复发风险。鼻咽癌(NPC)提供了一个理想的模型，其中无细胞EB病毒(EBV)DNA (cfEBV DNA)，一种ctDNA，可以敏感地检测。我们进行了EP-SEASON研究(NCT03855020)，前瞻性招募了1,000例鼻咽癌患者，在11个时间点接受了符合方案的cfEBV DNA评估，并接受了序贯放化疗。纵向cfEBV DNA在新辅助化疗和放疗期间表现出不同的模式。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动态变化同步。此外，我们确定了与不同生存结局相关的ctDNA全程变化动力学表型。总之，追踪治疗期间的纵向ctDNA可实时预测复发风险，从而促进根据风险调整的个体化患者管理。