Combining EBV DNA dynamics with RECIST-based radiographic response to improve prognostic stratification of recurrent/metastatic nasopharyngeal carcinoma in the era of immunotherapy

BACKGROUND: This study assessed the prognostic value of early Epsteinâ€"Barr virus (EBV) DNA dynamics combined with Response Evaluation Criteria in Solid Tumours (RECIST)-based radiographic response in patients with recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) receiving immunotherapy, to refine risk stratification. METHODOLOGY: A real-world cohort of 306 patients with R/M NPC and detectable EBV DNA at baseline received PD-1 monoclonal antibodies (PD-1 mAbs), alone or with chemotherapy. EBV DNA and radiological assessments were performed at baseline and after two therapy cycles. Biological responses based on EBV DNA were compared with RECIST evaluations. Survival outcomes were analysed using inverse probability treatment weighting, and a Cox regression model was developed incorporating baseline features and early responses. RESULTS: Among 306 patients, 174 achieved complete biological response (cBR), and 203 achieved complete or partial radiological response (CR/PR). Patients achieving both cBR and CR/PR had the most favourable progression-free survival. Early cBR was the dominant prognostic factor for overall survival, whereas radiological response did not affect overall survival within biological response strata. A prediction model integrating baseline features, radiological, and biological responses achieved an optimismcorrected C-index, surpassing models with baseline features alone, baseline plus radiological response, and baseline with biological response. CONCLUSIONS: Early biological response by EBV DNA was a stronger prognosticator than radiological response in PD-1 mAbs-treated R/M NPC. Combining baseline clinical features with biological and radiological responses improved survival prediction.