The 8 edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage classification (TNM) for nasopharyngeal carcinoma (NPC) was launched. It remains unknown if incorporation of non-anatomic factors into the stage classification would better predict survival. We prospectively recruited 518 patients with non-metastatic NPC treated with radical IMRT +/- chemotherapy based on the 8 edition TNM. Recursive partitioning analysis (RPA) incorporating pretreatment plasma EBV DNA derived new stage groups. Multivariable analyses to calculate adjusted hazard ratios (AHRs) derived another set of stage groups. 5-year progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS) were: stage I (PFS 100%, OS 90%, CSS 100%), II (PFS 88%, OS 84%, CSS 95%), III (PFS 84%, OS 84%, CSS 90%) and IVA (PFS 71%, OS 75%, CSS 80%) (p < 0.001, p = 0.066, and p = 0.002 respectively). RPA derived 4 new stages: RPA-I (T1-T4N0-N2 & EBV DNA <500 copies/ml) (PFS 94%, OS 89%, CSS 96%), RPA-II (T1-T4N0-N2 & EBV DNA ≥500 copies/ml) (PFS 80%, OS 83%, CSS 89%), RPA-III (T1-T2N3) (PFS 64%, OS 83%, CSS 83%) and RPA-IVA (T3-T4N3) (PFS 63%, OS 60% and CSS 68%) (all with p < 0.001). AHR using covariate adjustment also yielded a valid classification (I: T1-T2N0-N2; II: T3-T4N0-N2 or T1-T2N3, and III: T3-T4N3) (all with p < 0.001). However, RPA stages better predicted survival for PS and CSS after bootstrapping replications. Our RPA-based stage groups revealed better survival prediction compared to the 8 edition TNM and the AHR stage groups. This article is protected by copyright. All rights reserved.

The hair growth cycle consists of three stages known as the anagen (growing), catagen (involution), and telogen (resting) phases. This cyclical growth of hair is regulated by a diversity of growth factors. Although normal expression of both epidermal growth factor and its receptor (EGFR) in the outer root sheath is down-regulated with the completion of follicular growth, here we show that continuous expression of epidermal growth factor in hair follicles of transgenic mice arrested follicular development at the final stage of morphogenesis. Data from immunoprecipitation and immunoblotting showed that epidermal growth factor signals through EGFR/ErbB2 heterodimers in skin. Furthermore, topical application of tyrphostin AG1478 or AG825, specific inhibitors of EGFR and ErbB2, respectively, completely inhibited new hair growth in wild type mice but not in transgenic mice. When the transgenic mice were crossed with waved-2 mice, which possess a lower kinase activity of EGFR, the hair phenotype was rescued in the offspring. Taken together, these data suggest that EGFR signaling is indispensable for the initiation of hair growth. On the other hand, continuous expression of epidermal growth factor prevents entry into the catagen phase. We propose that epidermal growth factor functions as a biologic switch that is turned on and off in hair follicles at the beginning and end of the anagen phase of the hair cycle, guarding the entry to and exit from the anagen phase.

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