Disparity of sensitivities in detection of radiation-naïve and postirradiation recurrent nasopharyngeal carcinoma of the undifferentiated type by quantitative analysis of circulating Epstein-Barr virus DNA1,2.

PURPOSE: The purpose of this research was to compare the sensitivities of plasma EBV DNA in detection of postirradiation locally recurrent nasopharyngeal carcinoma (NPC), postirradiation distant metastatic NPC, and radiation-naïve NPC. EXPERIMENTAL DESIGN: Twenty-four patients with postirradiation local recurrence of NPC were assessed for plasma EBV DNA levels by a real-time quantitative PCR system. The results were compared with those of a cohort of 140 patients with newly diagnosed NPC and with those of 25 patients with distant metastatic relapse. EBV-encoded RNA positivity was also assessed in locally recurrent tumors and newly diagnosed tumors with undetectable plasma EBV DNA levels. RESULTS: Postirradiation locally recurrent tumors were associated with a significantly lower rate of detectable plasma EBV DNA compared with radiation-naïve tumors of comparable stage [stage I-II tumors: 5 of 12 (42%) versus 47 of 51 (92%), P = 0.0002; stage III-IV tumors: 10 of 12 (83%) versus 88 of 89 (99%), P = 0.01; Fisher's exact test], and compared with distant metastatic recurrences [15 of 24 (63%) versus 24 of 25 (96%), P < 0.02; Fisher's exact test]. The median EBV DNA level in patients with detectable EBV DNA was also significantly lower in locally recurrent tumors than in radiation-naïve tumors. All of the tissue samples of tumors associated with undetectable EBV DNA levels, where available, were EBV-encoded RNA positive. CONCLUSIONS: The sensitivity of EBV DNA in the detection of tumors regrowing from an irradiated site is much lower than that from a radiation-naïve site. Although plasma EBV DNA is very effective in detecting distant metastatic relapse of NPC, it cannot be relied on as the sole surveillance tool for detection of local relapse.