Plasma Epstein-Barr Virus DNA Temporal Clearance Pattern During Induction-Concurrent (Chemo)Radiation Therapy for Risk Stratification in Nasopharyngeal Carcinoma.

Abstract

Plasma Epstein-Barr virus (EBV) DNA is a widely used biomarker for nasopharyngeal carcinoma (NPC). Prior investigations predominantly assessed EBV DNA at a single time point, thus neglecting the differential prognostic implications of the temporal clearance pattern of EBV DNA during induction-concurrent (chemo)radiation therapy (RT). We retrospectively reviewed EBV DNA clearance patterns during induction-concurrent chemoRT in newly diagnosed patients with nonmetastatic NPC. EBV DNA was tested at 3 time points (baseline [T0], end of induction chemotherapy [T1], and end of RT [T2]) and recorded as detectable (D) and undetectable (U). The association between EBV DNA pattern and progression-free survival was analyzed. A total of 2203 NPCs were included. Five distinct EBV DNA trajectory patterns were identified: type Ⅰ (negative-stable, U-U-U, 7.3%), type Ⅱ (induction chemotherapy-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%]). The median follow-up was 53.5 months (IQR, 43.1-66.9). Type Ⅱ patients displayed superior 5-year progression-free survival (82.9% [95% CI, 80.4%-85.5%]) versus type Ⅲ (75.9% [72.8%-79.1%], P < .001), type Ⅳ (52.5% [46.4%-59.5%], P < .001), and type Ⅴ (72.5% [62.2%-84.6%], P = .028). The 5-year progression-free survival for type V patients with "D-U-D," "U-D-U," "U-D-D," and "U-U-D" patterns was 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. Temporal EBV DNA clearance patterns during induction-concurrent chemoRT provide valuable prognostic insights, enabling the identification of patients with high-risk NPC 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 U after induction chemotherapy.