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Patients with locally advanced head and neck squamous cell carcinoma (LA‐HNSCC) have poor survival outcomes. The real‐world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)‐based chemoradiotherapy in patients with LA‐HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3‐year overall survival (OS) rate. Log‐rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow‐up time was 54.2 (95% confidence interval [CI]: 52.7–55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57–0.99, p = 0.038) and progression‐free survival (PFS) (HR = 0.74, 95% CI: 0.58–0.96, p = 0.021). Subgroup analysis revealed that aged 50–60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab‐related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA‐HNSCC patients in an IMRT era. [ABSTRACT FROM AUTHOR]

Objective To explore the correlation between EBV DNA load and peripheral immune cells (including lymphocyte supsets and natural killer cells) before treatment in patients with NPC, and analyze the influence of circulating immune cell supsets related to EBV on the prognosis of NPC patients. Methods We retrospectively analyzed the general data of 203 NPC patients without distant metastasis at the first treatment, as well as the data of peripheral blood EBV DNA and circulating immune cell supset. The ROC curve analysis was used to determine the cutoff value of each circulating immune cell supset. Kaplan-Meier method was used for survival analysis, and Cox regression model was used for multi-factor prognostic correlation analysis. Results The 3-year OS, PFS, DMFS and LRFS of EBV DNA < 400 copies/ml group and EBV DNA≥400 copies/ml group were 99.2% vs. 90.1% (P=0.001), 96.7% vs. 90.1% (P=0.028), 98.4% vs. 90.1% (P=0.005) and 98.4% vs. 100% (P > 0.05), respectively. EBV DNA is negatively correlated with the ratio of CD19+ B cells before treatment (r=-0.138, P=0.040), and there was no significant correlation between EBV DNA and other circulating immune supgroups (P > 0.05). ROC analysis showed that the cut-off value of CD19+B cell ratio before treatment related to the 3-year OS was 8.33% (P=0.02). The 3-year OS, PFS, DMFS and LRFS of patients with CD19+B cells ratio ≤8.33% and CD19+B cells ratio > 8.33% were respectively 90.4% vs. 99.2% (P=0.003), 89.2% vs. 97.5% (P=0.008), 90.4% vs. 98.3% (P=0.008) and 98.8% vs. 99.2% (P > 0.05). However, ROC analysis showed that there was no significant correlation between OS and other peripheral immune cells (including the proportion of CD3+T, CD3+CD4+T, CD3+CD8+T and CD56+NK cells and CD4+/CD8+ ratio). Multivariate analysis showed that EBV DNA load was an independent prognostic factor of 3-year PFS of NPC patients, and the ratio of CD19+B cells was an independent prognostic factor of 3-year PFS, MFS and OS of NPC patients. Conclusion Before treatment, there is a negative correlation between plasma EBV DNA and the proportion of CD19+B cells in peripheral blood. Both can be used as the predictors of 3-year OS, PFS and DMFS of NPC patients.

Objective To investigate whether the inhibition of EGFR nuclear transport could reduce the radioresistance of human cervical cancer cells. Methods Human cervical cancer CaSki and HeLa cells were exposed to radiation treated with or without Thr654 inhibitory peptide, cetuximab and gefitinib. The expression levels of pEGFR-T654 and pDNA-PK-T2609 were determined using Western blot. The survival fraction (SF2) was determined by colony formation and the dose-survival curve was fitted with a singlehit multi-target model to calculate the radiosensitization ratio (SER). Results After 4 Gy irradiation, EGFR expression in the nuclear of CaSki and HeLa cells were up-regulated in a time-dependent manner. Compared with the control peptide, Thr654 inhibitory peptide significantly reduced the expression levels of pEGFR-T654, DNA-PK and pDNA-PK-T2609 in the nucleus of CaSki and HeLa cells; compared with irradiation alone, cetuximab combined with irradiation significantly reduced the expression levels of EGFR, pEGFR-T654 and DNA-PK-T2609 in the nucleus of CaSki cells, as well as clone formation rate and survival fraction (SF2=31.030), and increased the radiosensitivity (SER=2.34). Conclusion Radiationinduced pEGFR-T654 nuclear translocation mediates the activation of pDNA-PK-T2609, and the inhibition of pEGFR-T654 nuclear transport by cetuximab reduces DNA-PK-mediated radiation resistance of cervical squamous cell carcinoma.

Objective To investigate the effects of high-energy X-rays irradiation at different dose rates on the plating efficiency, survival fraction and radiobiological parameters of cervical cancer HeLa cell line. Methods Human cervical cancer Hela cell line in exponential growth phase were treated with 0, 1, 2, 4, 6, 8Gy at 2, 6, 10Gy/min dose rates. After irradiation for 12 days in the incubator, 0.5% crystal violet staining was fixed, and the number of clones larger than 50 cells was counted. The data was analyzed and dose-survival curves were plotted following the standard linear-quadratic model using GraphPad Prism 5.0 software to get the values of radiobiological parameters. Differences of survival fraction with different dose rates were tested with analysis of variance by SPSS19.0 software. Results After 2, 6, 10 Gy/min of high-energy X-rays irradiation, the differences between the plating efficiency and survival fraction of HeLa cells were statistically significant (P=0.03 and 0.04). The average α/β values were 3.28Gy, 3.35Gy, 3.93Gy, SF2 were 0.79, 0.78, 0.75. Three dose rates showed no statistically significant difference in the biological parameters, α/β, D0, Dq or SF2 (P > 0.05). Conclusion With the increasing dose rate of high-energy X-rays (2, 6, 10Gy/min), the survival rate of HeLa cells gradually decreases while the biological effect gradually increases.