Purpose: To test the hypothesis that prognostication for treatment outcome is feasible by biomarker response at mid-course of radiotherapy, with respect to the model of circulating load of Epstein-Barr viral (EBV) DNA in nasopharyngeal carcinoma (NPC). Method: 108 patients with Stage IIB-IV NPC were prospectively studied. Plasma EBV DNA load was measured by quantitative PCR before commencement of therapy (pre-DNA), at completion of 4 weeks of CRT/RT (wk4-DNA) and within 3 months of completion of therapy (post-DNA). The endpoints are post-DNA load, a recognised powerful prognostic marker of survival, and clinical outcome at 2 years of follow-up. Results: 94% of patients had detectable EBV DNA before therapy (median load = 874 copies/ml). At the end of week 4 of therapy, EBV DNA became undetectable in 58 (54%) patients. Detectable wk4-DNA correlates with detectable residual post-DNA (P=0.028, Chi-Square test) and significantly worse clinical outcome at 2 years of follow-up, in terms of progression-free survival (HR 2.86, P=0.0062) and distant failure (HR 3.6; P=0.0176). Patients with undetectable wk4-DNA and low pre-DNA load constitutes a very good risk group, representing 42% of patients, with an actuarial 2-year recurrence risk of 9%. Conclusion: This is the first model example of biomarker response during mid-course of radiotherapy being capable of predicting clinical outcome at early follow-up. It allows identification of a good risk group among patients with advanced stage disease, and has potential application in modifying treatment decisions for the latter phase of therapy, within the context of individualized therapy.
Third AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development-- Sep 22-25, 2008; Philadelphia, PA