BACKGROUND:The aim of this phase 2 study was to determine the long-term local control, survival, and late toxicities among patients with locally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiation therapy (SMART) boost technique and concurrent chemotherapy. METHODS: Eighty-one patients with pathologically diagnosed locally advanced NPC were enrolled in this study. IMRT was delivered with the SMART boost technique at prescribed doses of 68 grays (Gy)/30 fraction to the nasopharynx gross target volume. Concurrent cisplatin chemotherapy (80 mg/m 2 /d on Days 1 and 22) was administered. RESULTS: The mean actual physical dose delivered to the nasopharynx gross target volume was 73.8 Gy, and the mean biologically effective dose (BED) for the nasopharynx gross target volume was 84.8 Gy. With a median follow-up of 54 months, 4 (4.9%) patients experienced local recurrence. The 5-year local control rate was 94.9%. Eighteen patients died. Among them, 66.7% died of distant metastasis. The 5-year disease-free and overall survivals were 76.7% and 74.5%, respectively. The most common late toxicities among 68 patients with !4 years follow-up were grade 1-2 xerostomia, hearing loss, skin dystrophy, and subcutaneous fibrosis. No grade 4 late toxicities were noted. CONCLUSIONS: IMRT with SMART to enhance BED and concurrent chemotherapy is feasible in patients with locally advanced NPC. Long-term results showed excellent local control with fewer late toxicities, although no further improvement was noted in overall survival, and the major cause of death was distant metastasis. Exploration of more effective combined chemoradiation strategies is warranted.

Nasopharyngeal carcinoma (NPC) occurs with high frequency in Asian populations, especially among people of Cantonese ancestry. In areas with high incidence, NPC clusters in families, which suggests that both geography and genetics may influence disease risk. Although the HLA-Bw46 locus is associated with increased risk of NPC, no predisposing genes have been identified so far. Here we report the results of a genome-wide search carried out in families at high risk of NPC from Guangdong Province, China. Parametric analyses provide evidence of linkage to the D4S405 marker on chromosome 4 with a logarithm of odds for linkage (lod) score of 3.06 and a heterogeneity-adjusted lod (hlod) score of 3.21. Fine mapping with additional markers flanking D4S405 resulted in a lod score of 3.54 and hlod score of 3.67 for the region 4p15.1-q12. Multipoint nonparametric linkage analysis gives lod scores of 3.54 at D4S405 (P = 5.4 x 10(-5)) and 4.2 at D4S3002 (P = 1.1 x 10(-5)), which is positioned 4.5 cM away from D4S405. When Epstein Barr virus antibody titer was included as a covariate, the lod scores reached 4.70 (P = 2.0 x 10(-5)) and 5.36 (P = 4.36 x 10(-6)) for D4S405 and D4S3002, respectively. Our findings provide evidence of a major susceptibility locus for NPC on chromosome 4 in a subset of families.

Introduction: To assess the role of the 21-gene recurrence score (RS) assay on decision-making of postoperative radiotherapy (RT) following breast-conserving surgery (BCS) in elderly women with early-stage breast cancer.Methods: The 21-gene RS for elderly (≥65 years) women with stage T1–2N0M0 estrogen receptor-positive breast cancer who underwent BCS from 2004 to 2015 was obtained from the Surveillance, Epidemiology, and End Results program. We estimated the association of 21-gene RS and adjuvant RT related to breast cancer-specific survival (BCSS) using propensity score matching (PSM).Results: We identified 18,456 patients, of which 15,326 (83.0%) received postoperative RT. Of identified patients, 58.9, 34.0, and 7.1% of patients had a low-, intermediate-, and high-risk RS, respectively. Receipt of postoperative RT was not related to the year of diagnosis according to the 21-gene RS groups. Multivariate analysis suggested that receipt of postoperative RT was an independent predictor of better BCSS before (hazard ratio [HR] 0.587, 95% confidence interval [CI] 0.426–0.809, P = 0.001) and after (HR 0.613, 95%CI 0.390–0.963, P = 0.034) PSM. However, subgroups analyses indicated that receipt of postoperative RT was related to better BCSS in women with intermediate-risk RS before (HR 0.467, 95%CI 0.283–0.772, P = 0.003) and after (HR 0.389, 95%CI 0.179–0.846, P = 0.017) PSM, but not in women with low- and high-risk RS groups before and after PSM.Conclusions: Although causation cannot be implied, adjuvant RT in elderly women was associated with a greater effect size in patients with an intermediate-risk RS.

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The present study aimed to examine the anti-inflammatory actions of oleoylethanolamide (OEA) in lipopolysaccharide (LPS)-induced THP-1 cells. The cells were stimulated with LPS (1 μg/ml) in the presence or absence of OEA (10, 20 and 40 μM). The pro-inflammatory cytokines were evaluated by qRT-PCR and ELISA. The THP-1 cells were transiently transfected with PPARα small-interfering RNA, and TLR4 activity was determined with a blocking test using anti-TLR4 antibody. Additionally, a special inhibitor was used to analyse the intracellular signaling pathway. OEA exerted a potent anti-inflammatory effect by reducing the production of pro-inflammatory cytokines and TLR4 expression, and by enhancing PPARα expression. The modulatory effects of OEA on LPS-induced inflammation depended on PPARα and TLR4. Importantly, OEA inhibited LPS-induced NF-κB activation, IκBα degradation, expression of AP-1, and the phosphorylation of ERK1/2 and STAT3. In summary, our results demonstrated that OEA exerts anti-inflammatory effects by enhancing PPARα signaling, inhibiting the TLR4-mediated NF-κB signaling pathway, and interfering with the ERK1/2-dependent signaling cascade (TLR4/ERK1/2/AP-1/STAT3), which suggests that OEA may be a therapeutic agent for inflammatory diseases.

AC and ASC subtypes are independent prognostic factors for cervical cancer patients treated with definitive radiotherapy. AC and ASC subtypes are associated with poor survival outcomes than those with SCC.

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