动态监测循环游离 EBV-DNA 用于早期自然杀伤/T 细胞淋巴瘤的风险评估

Although circulating tumor DNA has shown promise in real-time monitoring of recurrence risk in various solid tumors, the clinical relevance of cell-free Epstein-Barr virus (EBV) DNA (cfEBV-DNA) in natural killer/T-cell lymphoma (NKTCL) remains unclear. In this study, 710 consecutive patients with early-stage NKTCL were included from 5 hospitals between January 2014 and December 2022, all of whom underwent longitudinal monitoring of cfEBV-DNA. All patients received asparaginase-based induction chemotherapy (IC) followed by radiation therapy (RT). The pretreatment cfEBV-DNA was positive in 487 patients (68. 6%), 258 of whom became negative after the first cycles of IC. During chemotherapy, the percentage of patients becoming cfEBV-DNA-negative increased, whereas the velocity of cfEBV-DNA clearance decreased.

Achieving cfEBV-DNA negativity during different treatment phases (post-IC cycle 1 [post-IC1] to post-IC6, and post-RT) was significantly associated with better progression-free survival (PFS) and overall survival (OS) compared with those who remained positive (all P< . 01). Subsequently, using unsupervised clustering analysis, patients were classified into 4 cfEBV-DNA response phenotypes: (1) consistently negative, (2) early response, (3) late response, and (4) no response.

These cohorts had significantly different 5-year PFS (94%, 83%, 57%, and 18%, respectively; P value for trend < . 001) and OS (98%, 91%, 70%, and 33%, respectively; P value for trend < . 001). In the Cox multivariable analyses, cfEBV-DNA response phenotype was still independently correlated with PFS and OS.

In conclusion, dynamic monitoring of on-treatment cfEBV-DNA provides longitudinally prognostic information in patients with early-stage NKTCL and may have therapy implications.