Plasma EBV DNA Clearance Rate as a Novel Prognostic Marker for Metastatic/Recurrent Nasopharyngeal Carcinoma

Abstract

Purpose: To investigate the prognostic effect of the concentrations and clearance rates of plasma EBV DNA in metastatic/recurrent nasopharyngeal carcinoma (NPC).Experimental Design: Thirty relapsed and four previously nontreated metastatic NPC patients were treated according to the consensus guidelines of the head and neck cancer team in our hospital (i.v. chemotherapy first, followed by local irradiation boost and oral maintenance chemotherapy where applicable). Multiple plasma samples were collected during the first month of chemotherapy. Circulating EBV DNA concentrations were measured by a real-time quantitative PCR. The half-life values (t 1/2 ) of plasma EBV DNA clearance were calculated. The associations between clinical outcome and plasma EBV DNA assays were analyzed.Results: Tumor response evaluated after 12 weeks of treatment showed 14 complete responses (41.2%), 12 partial responses (35.3%), 7 stable diseases (20.6%), and 1 progression disease (2.9%). The plasma EBV DNA concentrations have no significant effects on outcome prediction. The t 1/2 of plasma EBV DNA clearance ranged from 1.85 to 28.29 days (median, 3.99). Patients with a short t 1/2 of plasma EBV DNA clearance have significantly higher complete response rate and overall survival than those with long t 1/2 . Multivariate analysis revealed a significant effect of the t 1/2 of plasma EBV DNA clearance on survival.Conclusions: The clearance rates of plasma EBV DNA during the first month of chemotherapy can predict tumor response and patient survival. Early change of chemotherapy regimen may be considered for patients with slow plasma EBV DNA clearance rate. Clin Cancer Res; 16(3); 1016-24. ©2010 AACR.Nasopharyngeal carcinoma (NPC) is distinct from other cancers of the head and neck by its epidemiology, histopathology, clinical characteristics, methods of treatment, and patterns of failure. Because of the inherent anatomic constraints and a high degree of radiosensitivity, radiotherapy has been the primary treatment for NPC patients without distant metastasis. Treatment failure in the past was due to a high rate of local recurrence and/or distant metastasis. However, advances in radiation oncology have improved the locoregional control, and treatment failure is now due mainly to distant metastasis. To date, the outcome of salvage treatment for relapse is still very poor, with the 5-year survival rates after local recurrence and distant metastasis being 9.4% to 30% and <5%, respectively (1-6). Because most metastatic/recurrent patients will succumb rapidly to the disease, the development of a quick and precise marker to predict treatment response is urgently needed.NPC has been proven as an EBV-associated cancer. EBV genome is present in the cells from almost every primary and metastatic NPC, regardless of the degree of tumor differentiation or the geographic origin of the patients. Recently, the quantification of plasma EBV DNA by the real-time quantitative PCR has been shown as a useful marker in the detection, monitoring, and prognos...

Plasma Epstein-Barr virus DNA level strongly predicts survival in metastatic/recurrent nasopharyngeal carcinoma treated with palliative chemotherapy

“…These results were inconsistent with the most recently published study by Wang et al, 14 which showed that the clearance rates of plasma EBV DNA during the first month of chemotherapy rather than baseline plasma EBV DNA level could predict tumor response and patient survival. However, as we mentioned above, a rather high CR rate (41.25%) and long median survival (28 months) were reported in his cohort, which suggested a patient selection bias and relatively small sample size, because most of previous studies in the same setting reported a CR rate of 3% to 6% and a median survival of 12 to 18 months.…”

“…To our knowledge, only 1 study has demonstrated the predictive and prognostic value of the clearance rates of plasma EBV DNA during the first month in metastatic/recurrent NPC. 14 However, only 34 patients were included in that study, and a rather high complete response rate (41.2%) and long median survival (28 months) were achieved, although most patients were just treated with old chemotherapy agents such as mitomycin-C, epirubicin, cisplatin, or 5-fluorouracil, which might suggest a patient selection bias. Moreover, multiple plasma samples were needed during the first month of chemotherapy, which further limits the utility of plasma EBV DNA clearance rate in clinical practice.…”

Levels of plasma Epstein-Barr virus DNA prior and subsequent to treatment predicts the prognosis of nasopharyngeal carcinoma

“…Although specificity is approximately identical in the two sample types, it has been established that the detection of EBV-DNA is more sensitive in plasma than in serum (23). Plasma EBV-DNA has become a well-known prognostic factor for the relapse and survival of NPC patients (11)(12)(13)19). Similarly, the presence of serum immunoglobulin (Ig)A antibodies against the EBV capsid antigen (VCA-IgA) has also been identified to be associated with an increased risk of NPC (24,25).…”

“…EBV-DNA may be detected in NPC cells (5,6), and cell-free EBV-DNA may be detected in the plasma of patients with NPC (7)(8)(9)(10)(11)(12)(13). Furthermore, the levels of plasma EBV-DNA in recently diagnosed NPC patients have been significantly correlated with tumor volume (14,15), response to treatment (16), tumor clearance (17,18) and tumor recurrence (19)(20)(21).…”

Beating 'Guangdong cancer': a review and update on nasopharyngeal cancer

“…Following the observation that EBV DNA was rapidly cleared from the circulation after surgical resection of NPC, 39 subsequent studies demonstrated that patients with more rapid clearance of plasma EBV DNA responded better to chemotherapy or CRT compared with patients with a slower clearance. 40,41 A prospective trial evaluating the response to chemotherapy by measuring plasma EBV DNA half-life together with tumour metabolic response (via fluorodeoxyglucose positron emission tomographic scan) is currently underway.…”