Ferrari et al. BMC Cancer 2012, 12:208 http://www.biomedcentral.com/1471-2407/12/208 Page 5 of 7 Figure 1 Kaplan-Meyer curves depicting progression-free survival and overall survival. higher in their patients with distant metastases than in those with long-term disease remission or local relapse. However, in this retrospective study, the post-treatment level was more important than the pre-treatment level in predicting metastases and survival. The same conclu- sion applies to the study of Chan et al. [42], who found that a post-treatment level of >500 copies/mL in patients treated with RT significantly correlated with the poorest outcome, suggesting that this subgroup of patients should be treated more aggressively; on the con- trary, levels of <500 copies/mL were associated with a better prognosis. During the follow-up period in endemic countries, loco-regional recurrence or metastatic disease may be heralded by an increase in plasma EBV DNA levels, which can therefore be considered a useful marker for monitoring NPC patients. In a recent study, Wang et al. Table 2 Recurring patients Patient Initial EBV DNA at No. stage diagnosis (copies/ml) EBV DNA at the EBV DNA at Time to end of treatment recurrence recurrence (copies/ml) (copies/ml) (months) 1 2 3 4 5 6 7 T2N3 T4N2 T3N2 T2N1 T2N3 T3N2 T2N2 290,000 9,600 12,745 3,300 87,425 1,240 7,290 EBV = Epstein-Barr Virus. DNA = Deoxyribonucleic acid. < 350 < 350 < 350 < 350 7,820 < 350 1,560 2,135 900 < 350 < 350 4,398,000 9,185 15,290 14 25 18 26 11 12 12 found that 36 out of 245 NPC patients (14.7%) had ab- normal plasma EBV DNA levels that accurately pre- dicted all of the NPC recurrences, and no disease was found in five patients with clinical signs of recurrence who were negative for EBV DNA. A PET scan helped in identifying the recurring lesions with a sensitivity, speci- ficity and visual accuracy of respectively 81.8%, 77.1%, and 79.2% [43]. In our study on a cohort of patients of Italian origin, we observed three cases of metastatic spread that corre- lated with very high plasma EBV DNA levels, which must be attributed to an enormous load of tumour cells releasing the virus in blood while replicating. We also found that pre-treatment EBV DNA copy numbers sig- nificantly correlate with initial stage (stage IIb vs stage III-IV) and PFS at univariate analysis. Furthermore, the quantification of plasma EBV DNA levels proved to be extremely specific in detecting loco-regional or distant recurrences as none of the disease-free patients showed an increase. Among the relapsing patients, all three with disseminated disease were easily detected by their high EBV DNA loads, whereas the load increased to >350 copies/mL in only two of the four patients with loco- regional recurrences, thus confirming that assaying EBV DNA is less reliable in the case of a limited volume relapse. It has recently been shown that plasma EBV DNA clear- ance rates have predictive and prognostic value during the first month of palliative chemotherapy in patients with me- tastases [44]. However, the study involved a small number of patients (34 treated with old chemotherapeutic drugs), and the unusually high response rate (41.2% CR) and