Combination of MRI-based temporal tumor response and Epstein-Barr DNA level changes after radiotherapy leads to improved prognostic stratification of patients with nasopharyngeal carcinoma treated with concurrent chemoradiotherapy

AbstractObjectives To investigated the prognostic value of temporal tumor response (TR) and plasma Epstein-Barr virus (EBV) DNA level changes at the end of radiotherapy (pRT0) and 3 months after radiotherapy (pRT3) in nasopharyngeal carcinoma (NPC) patients. Methods A total of 651 patients with biopsy-proven NPC, treated with concurrent chemo-radiotherapy, were retrospectively enrolled. TR and plasma EBV DNA levels were evaluated at pRT0 and pRT3. Progression-free survival (PFS) was the primary endpoint. Results Temporal change of tumor response (TRC) indicated that the refractory-disease group (where TR remained a non-complete response [non-CR] at pRT0 and pRT3) and slow-response group (where TR changed from non-CR to CR at pRT3) had a higher risk than the rapid-response group (where TR remained a CR at pRT0 and pRT3) in the 5-year locoregional relapse-free survival (LRRFS,P < 0.001). Temporal EBV DNA changes (EBV DNAC) indicated that patients with persistently detectable EBV DNA had the lowest 5-year distant metastasis-free survival rate (DMFS,P < 0.001). Our new risk classification (NRC) model combined TRC and EBV DNAC to classify the patients into three risk groups. High-risk and intermediate-risk patients had significantly lower 5-year PFS, overall survival, LRRFS, and DMFS than the low-risk patients. Multivariate analysis indicated that NRC was a significant independent prognostic factor for clinical outcomes, and this was also confirmed by time-dependent receiver operating characteristic analyses. Conclusions TRC was better in predicting locoregional recurrence. EBV DNAC was better in predicting distant metastasis after radiotherapy. NRC greatly improved the risk stratification in NPC patients.