Huang Z, Li Y, Wu W, Wu L, Chen Z, Xu S, Li Y, Lai J, Qiu S, Lu J.

Int J Radiat Oncol Biol Phys. 2025

Background: Plasma Epstein-Barr virus (EBV) DNA is a widely utilized biomarker for nasopharyngeal carcinoma (NPC). Prior investigations predominantly assessed EBV DNA at a single time point, thus neglecting the differential prognostic implications of temporal clearance pattern of EBV DNA during induction-concurrent (chemo)radiotherapy.

Methods: We retrospectively reviewed EBV DNA clearance pattern during induction-concurrent (chemo)radiotherapy in newly diagnosed non-metastatic NPC patients. EBV DNA was tested in 3 timepoints (baseline [T0], end of induction chemotherapy [T1], and end of radiotherapy [T2]), and recorded as detectable (D) and undetectable (U). The association of EBV DNA pattern and progression-free survival (PFS) were analyzed.

Results: A total of 2203 NPC were included. Five distinct EBV DNA trajectory patterns were identified: Type-Ⅰ (Negative-stable, U-U-U, 7.3%), Type-Ⅱ (IC-elimination, D-U-U, 42.8%), Type-Ⅲ (RT-elimination, D-D-U, 35.0%), Type-Ⅳ (Persistent-positive, D-D-D, 11.7%), and Type-Ⅴ (Resurgence, D-U-D [1.5%], U-D-U [1.2%], U-D-D [0.4%], or U-U-D [0.2%]). Median follow-up was 53.5 months (interquartile range [IQR]: 43.1-66.9). Type-Ⅱ patients displayed superior 5-year PFS (82.9% [95% CI, 80.4%-85.5%] versus Type-Ⅲ (75.9% [72.8%-79.1%], P < 0.001), Type-Ⅳ (52.5% [46.4%-59.5%], P < 0.001), and Type-Ⅴ (72.5% [62.2%-84.6%], P = 0.028). The 5-year PFS for Type-V patients with "D-U-D", "U-D-U", "U-D-D", and "U-U-D" pattern were 62.4% (46.2%-84.3%), 78.6% (63.1%-97.8%), 85.7% (63.3%-100.0%), and 75.0% (42.6%-100.0%), respectively. All 33 patients with the "D-U-D" pattern had stage Ⅲ-Ⅳ disease at diagnosis.

Conclusions: Temporal EBV DNA clearance patterns during induction-concurrent (chemo)radiotherapy provide valuable prognostic insights, enabling the identification of high-risk NPC patients and informing personalized treatment strategies. Resurgence of EBV DNA may occur occasionally (3.3%). Caution is required when considering reduced-intensity therapy in patients with locoeregionally advanced disease when EBV DNA becomes undetectable after induction chemotherapy.