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Although the benefits of concurrent chemotherapy (CC) in the treatment of locally advanced nasopharyngeal carcinoma (NPC) had been proven in the era of two-dimensional radiotherapy, long-term efficacy and safety of using CC combined with intensity-modulated radiotherapy (IMRT) remain unclear. A retrospective analysis of 1,182 patients who underwent IMRT for clinical II-Iva NPC was performed. Propensity score matching algorithm was used to identify two matched cohorts with or without CC (264 patients per cohort). Median follow-up time was 45.6 and 43.6 months for the two cohorts. The estimated 5-year overall survival rate was 81.8% (95% CI 76.6-87.4) in patients treated with CC and 73.7% (95% CI 67.8-80.0) in those treated without CC, respectively (hazard ratio 0.64, 95% CI 0.44-0.93; p = 0.018). The benefit of CC was mainly observed in those patients with good performance status, male, age > 48 years, T4 and N2 classification. Grade 3/4 acute toxicities were more common in those patients administrated with CC. The grade and incidence of late salivary glands damage were also increased by CC (p = 0.003). These findings indicated that the addition of CC significantly improved treatment outcomes of NPC patients treated with IMRT, but accompanied increased toxicities. Tailored CC and optimizing schedule of IMRT and systemic therapy were needed, provided that distant metastasis was the predominant pattern of failure in patients treated with IMRT.

Growing evidence has demonstrated that human epidermal growth factor receptor 2 (HER2) is involved in the radiation response to breast cancer. However, the underlying mechanism remains elusive. Therefore, we investigated if HER2 overexpression is associated with radiosensitivity of breast cancer. We constructed breast cancer cell lines differing in HER2 expression by transducing HER2 cDNA or short hairpin RNA against HER2. We then assessed the radiosensitivity and investigated the potential mechanism by using cell proliferation assay, cell adhesion assays, anoikis assays, colony formation assays, and western blotting analyses. We found that HER2 introduction in breast cancer cell lines MCF-7 (low HER2 expression) and MDA-MB-231 (HER2 is not expressed) promoted cell proliferation and invasion and enhanced cell adhesion and resistance to anoikis. Moreover, HER2 reduced radiosensitivity in these two cells compared with the corresponding control. The opposite results were observed when HER2 was silenced in breast cancer cell lines ZR-7530 and SK-BR-3 (both cells with high expression of HER2) using HER2 shRNA. In addition, animal experiment results showed HER2 could enhance the radioresistance of xenograft tumors. Further studies showed HER2 promoted the phosphorylation of focal adhesion kinase (Fak) and thereby up-regulated the expression of proteins associated with the epithelial-to-mesenchymal transition such as Claudin-1, ZO-1, and ZEB-1. The inhibition of Fak activity using the Fak inhibitor (PF-562281) restored the radiosensitivity in HER2-overexpressing cells. In conclusion, HER2 reduces the radiosensitivity of breast cancer by activating Fak in vitro and in vivo. Fak might be a potential target for the radiosensitization of HER2-overexpressed breast cancer., Competing Interests: The authors declare no conflicts of interest.