Search

Background To evaluate the expression of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) by using immunohistochemistry analysis in locoregionally advanced nasopharyngeal carcinoma (NPC) patients receiving cisplatin, fluorouracil, and docetaxel followed by concurrent chemoradiotherapy. Methods As part of a previously reported trial, 108 patients were enrolled in this study. Results We observed that Epstein-Barr Virus (EBV) antibody levels were associated with PD-1 positive staining in NPC and PD-1 positive staining was identified as an independent prognostic factor for progression-free survival (hazard ratio 0.363, 95% confidence interval 0.134-0.987, P = .047). By contrast, the correlation between the PD-L1 level and hemoglobin, lactate dehydrogenase and high-sensitivity C-reactive protein was not identified. Moreover, high levels of PD-L1 staining were not significantly associated with clinical outcomes. Conclusion NPC patients with negative PD-1 staining had a significantly reduced survival outcome. Furthermore, patients with positive PD-1 staining had significantly higher EBV antibody levels.

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that has been demonstrated to be clinically useful for the treatment of patients with non-small cell lung cancer (NSCLC). However, ~50% of patients do not respond to EGFR TKI treatment through the emergence of mutations, such as T790M. Therefore, it is important to determine which patients are eligible for treatment with gefitinib. As a preferred dimerization partner for EGFR, the role of EGFR 2 (HER2) in mediating sensitivity to gefitinib is poorly understood. In the present study, full-length human HER2 cDNA was introduced to the NSCLC cell lines H1975 and H1299, which have a low endogenous expression level of HER2. In addition, it was observed in the present study that the H1975 cell line harbored the L858R and T790M mutations in the EGFR kinase domain. Western blot analysis and MTT assay were used to evaluate the TKI sensitivity of HER2 expression status, and the activation of HER3 and HER2 downstream effectors. The results indicated that the sensitivity of H1975 cells to gefitinib was restored by the overexpression of HER2, which stimulated HER2-driven signaling cascades accompanied by the activation of protein kinase B. By contrast, ectopic HER2 overexpression in H1299 cells did not significantly alter the sensitivity to gefitinib treatment. In conclusion, the current study results suggested that the relatively resistance of the H1975 cell line to gefitinib could be reversed by the overexpression of HER2. Therefore, the expression of HER2 could also be considered when evaluate the patients' potential response to gefitinib, particularly in the subgroup of lung cancer patients who harbor an EGFR mutation.

// Ting Jin 1,2,* , Wei-feng Qin 1,2,* , Feng Jiang 1,2 , Qi-feng Jin 1,2 , Qi-chun Wei 3 , Xiu-wen Tang 4 , Yong-shi Jia 5 , Xiao-nan Sun 6 , Wen-feng Li 7 , Xing-lai Feng 1,2 and Xiao-zhong Chen 1,2 1 Key Laboratory of Radiation Oncology in Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China 2 Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China 3 Department of Radiation Oncology, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The SecondAffiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China 4 Department of Biochemistry and Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China 5 Department of Radiation Oncology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China 6 Department of Radiation Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China 7 Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China * These authors have contributed equally to this study Correspondence to: Xiao-zhong Chen, email: // Keywords : nasopharyngeal carcinoma, chemotherapy, concurrent chemoradiation, radiotherapy, docetaxel Received : May 18, 2016 Accepted : June 15, 2016 Published : July 28, 2016 Abstract In this study, we aim to compare the progression-free survival (PFS) rates and side effects of induction chemotherapy based on docetaxel, cisplatin and fluorouracil (TPF) versus cisplatin and fluorouracil (PF) in patients with locoregionally-advanced nasopharyngeal carcinoma who received subsequent chemoradiotherapy. We randomly assigned 276 patients with stage III or IV NPC (without distant metastases) to receive either TPF or PF induction chemotherapy, followed by cisplatin-based chemoradiotherapy every 3 weeks and intensity-modulated radiation therapy for 5 days per week. After a minimum of 2 years follow-up, a PFS benefit was observed for TPF compared to PF, though this difference was not statistically significant (84.5% vs. 77.9%, P = 0.380). Due to increased frequencies of grade 3 or 4 neutropenia and diarrhea, significantly more patients in the TPF group required treatment delays and dose modifications. Our findings suggest that PF induction chemotherapy has substantially better tolerance and compliance rates than TPF induction chemotherapy. However, the treatment efficacy of PF is not superior to TPF induction chemotherapy in patients with locoregionally-advanced NPC (ClinicalTrials.gov number, NCT01536223).