No abstract

The outcomes for patients with metastatic or locally recurrent Epstein–Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) remain poor. Adoptive immunotherapy with EBV-specific cytotoxic T lymphocytes (EBV-CTLs) has proven clinical efficacy, but it has never been evaluated in the first-line treatment setting in combination with chemotherapy. To evaluate the safety and efficacy of a chemotherapy in combination with adoptive EBV-CTL transfer, we conducted a phase 2 clinical trial consisting of four cycles of gemcitabine and carboplatin (GC) followed by up to six doses of EBV-CTL. Thirty-eight patients were enrolled, and 35 received GC and EBV-CTL. GC-CTL therapy resulted in a response rate of 71.4% with 3 complete responses and 22 partial responses. With a median follow up of 29.9 months, the 2-year and 3-year overall survival (OS) rate was 62.9 and 37.1%, respectively. Five patients did not require further chemotherapy for more than 34 months since initiation of CTL. Infusion of CTL products containing T cells specific for LMP2 positively correlated with OS (hazard ratio: 0.35; 95% confidence interval: 0.14–0.84; P = 0.014). Our study achieved one of the best survival outcomes in patients with advanced NPC, setting the stage for a future randomized study of chemotherapy with and without EBV-CTL.

Because of the uneven geographic distribution and small number of randomized trials available, the value of additional induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) remains controversial. This study performed an individual patient data (IPD) pooled analysis to better assess the precise role of IC + CCRT in locoregionally advanced NPC. Four randomized trials in endemic areas were identified, representing 1,193 patients; updated IPD were obtained. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively. Median follow-up was 5.0 years. The HR for PFS was 0.70 [95% confidence interval (CI), 0.56-0.86; = 0.0009; 9.3% absolute benefit at 5 years] in favor of IC + CCRT versus CCRT alone. IC + CCRT also improved OS (HR = 0.75; 95% CI, 0.57-0.99; = 0.04) and reduced distant failure (HR = 0.68; 95% CI, 0.51-0.90; = 0.008). IC + CCRT had a tendency to improve locoregional control compared with CCRT alone (HR = 0.70; 95% CI, 0.48-1.01; = 0.06). There was no heterogeneity between trials in any analysis. No interactions between patient characteristics and treatment effects on PFS or OS were found. After adding two supplementary trials to provide a more comprehensive overview, the conclusions remained valid and were strengthened. In a supplementary Bayesian network analysis, no statistically significant differences in survival between different IC regimens were detected. This IPD pooled analysis demonstrates the superiority of additional IC over CCRT alone in locoregionally advanced NPC, with the survival benefit mainly associated with improved distant control. .

Our data suggest that lymph node density is a reliable and applicable predictor of prognosis in patients with tongue SCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E859-E866, 2016.