Combined
EGFR
/
TGF
‐α Expression and Dynamic Plasma
EBV DNA
Monitoring for Prognostic Stratifica
Junping Liu, Ying Miao, Zhonghao Lin, Jastin Antisdel, Yongqiang Yu ABSTRACT
Background
Risk stratification within anatomically homogeneous stage II nasopharyngeal carcinoma (NPC) remains imprecise. We integrated serial plasma Epstein–Barr virus (EBV) DNA monitoring with pretreatment EGFR/TGF‐α immunohistochemistry to evaluate their combined prognostic value.
Methods
Sixty‐six prospectively enrolled stage II (T2N0M0) NPC patients received cisplatin‐based concurrent chemoradiotherapy (IMRT or VMAT, 66–70 Gy). Plasma EBV DNA was quantified at baseline and at prespecified surveillance intervals (every 2–3 months for the first 2 years, then every 6 months) during 5‐year follow‐up. EGFR and TGF‐α were graded on a four‐tier IHC scale (++/+++ = positive). A parsimonious multivariable Cox model with three biologically prespecified covariates (EGFR, TGF‐α, post‐treatment EBV‐abnormal status) and an exploratory EGFR × TGF‐α interaction were prespecified; a composite three‐tier risk score (0/1/≥ 2 adverse biomarkers) was constructed.
Results
Median potential follow‐up (reverse Kaplan–Meier) was 58.6 months. EGFR was positive in 60.6%, TGF‐α in 53.0%, and pretreatment EBV DNA detectable in 87.9%. Plasma EBV‐DNA crossed the 500 copies/mL detection threshold a median of 3.2 months (range, 1.4–5.8) prior to radiologic recurrence in all six serially monitored patients who developed clinical recurrence. Post‐treatment EBV‐abnormal kinetics (aHR 3.85, 95% CI: 1.60–9.27; p = 0.003) and EGFR positivity (aHR 2.58, 1.08–6.16; p = 0.033) were independent adverse OS prognostic factors; TGF‐α showed a non‐significant trend (aHR 1.98; p = 0.124). The three‐tier composite score discriminated 5‐year OS at 100% (low‐risk, n = 11), 69.2% (intermediate, n = 26), and 26.4% (high‐risk, n = 29; median OS 28.4 months; overall log‐rank p < 0.001).
Conclusion
A parsimonious three‐biomarker risk score integrating EGFR/TGF‐α expression and post‐treatment EBV DNA kinetics provides highly discriminative prognostic stratification in stage II NPC, identifying candidates for both treatment intensification and de‐intensification. External validation is warranted.