Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma.
BACKGROUND
Epstein-Barr virus (EBV) DNA can be detected and quantified in the plasma of patients with EBV-related tumors, such as nasopharyngeal carcinoma (NPC). Although NPC at early stages can be cured by radical radiotherapy, there is a high recurrence rate in patients with advanced NPC. The pretreatment level of circulating EBV DNA is a prognostic factor for NPC, but the prognostic value of post-treatment EBV DNA has not been studied. We designed a prospective study in Hong Kong, China, to investigate the value of plasma EBV DNA as a prognostic factor for NPC.


METHODS
One hundred seventy NPC patients, without metastatic disease at presentation, were treated with a uniform radiotherapy protocol. Circulating EBV DNA was measured by real-time quantitative polymerase chain reaction before treatment and 6-8 weeks after radiotherapy was completed. Risk ratios (RRs) were determined with a Cox regression model, and associations of various factors with progression-free and overall survival and recurrence rates were determined with a stepwise Cox proportional hazards model. All statistical tests were two-sided.


RESULTS
Ninety-nine percent of patients achieved complete clinical remission. Levels of post-treatment EBV DNA dominated the effect of levels of pretreatment EBV DNA for progression-free survival. The RR for NPC recurrence was 11.9 (95% confidence interval [CI] = 5.53 to 25.43) for patients with higher post-treatment EBV DNA and 2.5 (95% CI = 1.14 to 5.70) for patients with higher pretreatment EBV DNA. Higher levels of post-treatment EBV DNA were statistically significantly associated with overall survival (P<.001; RR for NPC recurrence = 8.6, 95% CI = 3.69 to 19.97). The positive and negative predictive values for NPC recurrence for a higher level of post-treatment EBV DNA were 87% (95% CI = 58% to 98%) and 83% (95% CI = 76% to 89%), respectively.


CONCLUSIONS
Levels of post-treatment plasma EBV DNA in patients with NPC appear to strongly predict progression-free and overall survival and to accurately reflect the post-treatment residual tumor load.
Chan
Anthony T C
AT
Department of Clinical Oncology, Sir Y. K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
Lo
Y M Dennis
YM
Zee
Benny
B
Chan
Lisa Y S
LY
Ma
Brigette B Y
BB
Leung
Sing-Fai
SF
Mo
Frankie
F
Lai
Maria
M
Ho
Stephen
S
Huang
Dolly P
DP
Johnson
Philip J
PJ
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000532:radiotherapy*; D004279:DNA, Viral / Q000097:blood* / Q000302:isolation & purification; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000401:mortality / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction / Q000379:methods; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors
D004279:DNA, Viral