Individualizing treatment for patients with nasopharyngeal cancer

Individualizing Treatment for Patients With Nasopharyngeal Cancer The treatment for endemic Epstein-Barr virus (EBV)-positive, locally advanced nasopharyngeal carcinoma (NPC) has been slowly advancing with the improvement in conformal radiotherapy techniques like intensity-modulated radiotherapy (IMRT), modern imaging, and the addition of systemic therapy. Currently, the standard of care for patients with locally advanced NPC in the United States is concomitant chemoradiotherapy followed by 5fluorouracil (5FU), as in the Intergroup trial 0099 protocol. However, the benefit of adjuvant cisplatin(II) (CDDP) and 5FU has been questioned by a randomized noninferiority trial from China. Chen et al compared radiotherapy (RT) with weekly CDDP followed by either adjuvant systemic therapy or observation and reported no statistically significant improvement in progression-free survival (PFS) or overall survival (OS) with adjuvant therapy. In that trial, only 63% of patients were able to complete the adjuvant chemotherapy, and the inability to tolerate more treatment after chemoradiotherapy was an issue. Our ability to obtain locoregional control in patients with EBV-positive NPC has improved to approximately 90% or better with IMRT. Unfortunately, many patients will fail at distant sites, demonstrating a need for better systemic therapy. Analyses of trials in Asia indicate that adjuvant chemotherapy reduces distant metastasis, particularly in high-risk patients. Phase 3 trials from Hong Kong, Singapore, and the Groupe d’Oncologie Radioth erapie Tête Et Cou are investigating induction chemotherapy for the treatment of patients with NPC. The current challenge is to determine the best way to identify high-risk patients who may benefit from additional therapy and low-risk patients who can be spared from the added toxicity. A well known prognostic biomarker for EBV-positive NPC is circulating EBV DNA, which can be quantitatively measured in the plasma in>95% of patients. The level of plasma EBV DNA at diagnosis has been associated with tumor stage and survival, and detectable or rising levels after treatment have been linked to tumor recurrence. In this issue of Cancer, Dr. Hui and colleagues report the largest multi-institutional prospective trial to date validating circulating EBV DNA as a prognostic biomarker for NPC after chemoradiotherapy. Of the 576 patients with stage IIB through IVB NPC who were enrolled in the study, 403 patients had undetectable EBV DNA levels after definitive radiotherapy or chemoradiotherapy, whereas 173 patients still demonstrated detectable levels (>0 copies/mL). At a median follow-up of 3.82 years (range, 3.53-4.02 years), the 3-year relapse-free survival (RFS) rates for the EBV-negative and EBV-positive groups were 85.8% versus 48.6%, respectively (hazard ratio [HR], 4.37; 95% confidence interval [CI], 3.16-6.04; P< .0001), and the OS rates were 94.5% versus 69.9%, respectively (HR, 4.55; 95% CI, 3.04-6.82; P< .0001). These results confirm previous single-institution reports demonstrating that post-treatment EBV DNA levels are highly prognostic for RFS and OS—more so than pretreatment levels. They also validate the prognostic importance of post-treatment EBV DNA in the modern era with improved imaging and radiation delivery. The generalizability of a biomarker depends not only on the robustness of the marker but also on its sensitivity, specificity, and the ability to reproduce measurements across different clinical laboratories. The same applies to circulating EBV DNA. Although several polymerase chain reaction (PCR) assays can be used to quantify circulating EBV DNA levels, Le et al demonstrated that the assay using the BamHI-W primer/probe set was the most sensitive in detecting EBV DNA in NPC plasma samples. In addition, they found that the measurements of plasma EBV DNA using the same