Abstract
136 Background: Plasma Epstein-Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma (NPC). However, whether longitudinal on-treatment EBV DNA tracing would inform real-time recurrence risk in NPC remains to be elucidated. To address this issue, we conducted EP-SEASON (NCT03855020), a prospective cohort study of longitudinal on-treatment EBV DNA in EBV-positive NPC patients. Methods: Non-metastatic NPC with detectable pretreatment EBV DNA that received standard sequential chemo-radiotherapy were recruited. Serial EBV DNA in blood specimens were collected across pretreatment, 3-week after each induction chemotherapy (IC), every-week during radiotherapy (RT), within 1-week and 1-3 months upon RT completion. EBV DNA extracted from plasma was quantified by a real-time quantitative polymerase chain reaction assay targeting the BamHI-W region of the EBV genome. Longitudinal changing patterns of EBV DNA and their clinical relevance were analyzed. Results: Between May 2019 and April 2021, a total of 1000 patients underwent per-protocol EBV DNA assessments and treatment; 248 and 752 patients received concurrent chemoradiotherapy (CCRT, subcochortno-IC) and IC plus CCRT (subcochortIC), respectively. Longitudinal changes and clearance rates of EBV DNA displayed unique patterns during IC and RT phases. Throughout IC and RT phases, the rate of EBV DNA clearance decreased with repeated IC cycles; interestingly, the rate re-rose upon the introduction of RT, and then dropped to low levels (<10%/week) after the 4th week of RT (post-RT4w). Patients in subcochortno-IC and subcochortIC also exhibited differential clearance patterns during RT, with the rate of clearance being higher in subcochortno-IC before the 2nd week of RT (post-RT2w). Notably, despite the prognostic significance of EBV DNA at each timepoint ( Pall < 0.05), longitudinal EBV DNA displayed a linkage changing map with dynamic recurrence risks: 3-year disease-free survival (DFS) rate steadily dropped with delayed EBV DNA clearance during IC; it re-rose at the 2nd RT week upon EBV DNA clearance, followed by a sharp decrease at the 4th RT week in subcochortIC. In contrast, 3-year DFS rate continuously decreased with delayed EBV DNA clearance in subcochortno-IC. Finally, we identified different phenotypes of whole-course circulating tumor DNA changing dynamics that showed distinct prognosis ( P < 0.05). Conclusions: Longitudinal on-treatment EBV DNA tracing could forecast real-time risks and facilitate risk-adapted decision-making in NPC.
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