Long-Term Prognostic Effects of Plasma EBV DNA Load after Induction Chemotherapy in Advanced Nasopharyngeal Carcinoma

Abstract

Induction chemotherapy (IndCT) has become an option of initial treatment for advanced nasopharyngeal carcinoma (NPC) patients. We hypothesized that plasma EBV DNA (pEBV DNA) status afterIndCT could predict long-term treatment outcome. This retrospective study included 206 previously untreated, pathologically-proven NPC patients with stage II-IVB diseases and available pEBV DNA data after IndCT before radiotherapy (RT). All patients received a uniform protocol of ten weekly IndCT consisting of cisplatin 60 mg/m2 on day 1 and 5- fluorouracil 2500 mg/m2 + leucovorin 250 mg/m2 on day 8, repeated every 2 weeks for 5 cycles, followed by RT 70-74 Gy. After a median follow-up of 90 months, there were 71 recurrences and 85 deaths. Pretreatment pEBV DNA (median, 1550 copies/ml; interquantile range, 375-5688) was detectable in 95.1% (196/206) patients. Only 40.8% (84/206) patients had detectable pEBV DNA (> 0 copy/ml) after IndCT with very lower copy numbers (median, 18 copies/ml; interquantile range, 7-153, for these 84 patients). Patients with a higher N-classification (N3 vs. N0-2, P<0.0001) and overall stage (IV vs. II-III, P=0.0400) had a higher detectable pEBV DNA after IndCT. Forty-twor of 84 (50.0%) patients with detectable pEBV DNA (> 0 copy/ml) developed tumor relapse, whereas 23.8% (29/122) patients with undetectable pEBV DNA (= 0 copy/ml) had tumor relapse (P<0.0001). The patterns of failure revealed that patients with detectable post-IndCT pEBV DNA had more distant (39.3% vs. 17.2%, P=0.0004) and neck (7.1% vs. 1.6%, P=0.0650) failures but not local recurrence (11.9% vs. 9.8%, P=0.6366), compared with those of undetectable EBV DNA.The 5-year overall survival rates were 63.1% and 70.4% for patients with post-IndCT viral load > and = 0 copies/ml (P=0.0010). The corresponding figures of relapse-free survival rates were 54.4% and 78.4% (P<0.0001). Post-IndCT pEBV DNA status can predict long-term outcome for NPC patients. More intensive treatment strategy for these high-risk patients with persistently detectable pEBV DNA after IndCT should be studied further.