Percent change in apparent diffusion coefficient and plasma EBV DNA after induction chemotherapy identifies distinct prognostic response phenotypes in advanced nasopharyngeal carcinoma

Background To evaluate the prognostic value of the apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (MRI) and monitor the early treatment response to induction chemotherapy (IC) with plasma EBV DNA in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Results A total of 307 stage III-IVb NPC patients were prospectively enrolled. All patients underwent MRI examinations to calculate ADC and plasma EBV DNA measurements pretreatment and post-IC. The participants’ ADC value of 92.5% (284/307) increased post-IC. A higher percent change in ADC value (ΔADC% high group) post-IC was associated with a higher 5-year OS rate (90.7% vs 74.9%, p < 0.001) than those in the ΔADC% low group. Interestingly, ΔADC% was closely related to the response measured by RECIST 1.1 ( p < 0.001) and plasma EBV DNA level ( p = 0.037). The AUC significantly increased when post-IC plasma EBV DNA was added to ΔADC% to predict treatment failure. Thus, based on ΔADC% and plasma EBV DNA, we further divided the participants into three new prognostic response phenotypes (early response, intermediate response, and no response) that correlated with disparate risks of death ( p = 0.001), disease progression ( p < 0.001), distant metastasis ( p < 0.001), and locoregional relapse ( p < 0.001). Conclusion The percentage change in ADC post-IC is indicative of treatment response and clinical outcome. ΔADC% and plasma EBV DNA-based response phenotypes may provide potential utility for early termination of treatment and allow guiding risk-adapted therapeutic strategies for LA-NPC.