Longitudinal on-treatment circulating tumor DNA as a biomarker for real-time dynamic risk monitoring in cancer patients: The EP-SEASON study
Jia‐Wei Lv, Ling-Xin Xu, Zhi‐Xuan Li, Li Lin, Chen‐Fei Wu, Ting-Qiu Quan, Zi-Cheng Zhen, Wen‐Fei Li, Ling‐Long Tang, Yan‐Ping Mao, Lei Chen, Rui Guo, Lulu Zhang, XinLei Ai, Shi-Yue Wu, Meng-Yu Hao, Denghui Wei, Jibin Li, Jun Ma, Yu‐Pei Chen, Guan‐Qun Zhou, Ying Sun
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.