BackgroundTalin-1 is a cytoskeletal protein that plays an important role in tumourgenesis, migration and metastasis in several malignant tumors. The aim of this study was to evaluate the expression and prognostic value of Talin-1 in nasopharyngeal carcinoma (NPC).MethodsTalin-1 mRNA and protein expression were examined in NPC cell lines and clinical nasopharyngeal tissues by quantitative RT-PCR, agarose gel electrophoresis and western blotting. The expression of Talin-1 was analyzed by immunohistochemical staining in 233 paraffin-embedded NPC specimens with clinical follow-up data and cox regression analysis was used to identify independent prognostic factors. The functional role of Talin-1 in NPC cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by the wound healing and transwell invasion assays.ResultsThe expression of Talin-1 was significantly upregulated in most NPC cell lines and clinical tissues at both the mRNA and protein levels. High expression of Talin-1 was significantly associated with distant metastasis (P = 0.001) and patient death (P = 0.001). In addition, high expression of Talin-1 was associated with significantly poorer overall survival (OS: HR, 2.15; 95% CI, 1.28-3.63; P = 0.003) and poorer distant metastasis-free survival (DMFS: HR, 2.39; 95% CI, 1.38-4.15; P = 0.001). Cox regression analysis indicated that high expression of Talin-1 and TNM stage were independent prognostic indicators (both P < 0.05). Stratified analysis demonstrated that high expression of Talin-1 was associated with significantly poorer survival in patients with advanced stage disease (stage III-IV, HR, 1.91; 95% CI, 1.09-3.35; P = 0.02 for OS and HR, 2.22; 95% CI, 1.24-3.99; P = 0.006 for DMFS). Furthermore, the depletion of Talin-1 suppressed the migratory and invasive ability of NPC cells in vitro.ConclusionsOur data demonstrate that high expression of Talin-1 is associated with significantly poorer OS and poorer DMFS in NPC and depletion of Talin-1 expression inhibited NPC cell migration and invasion. Talin-1 may serve as novel prognostic biomarker in NPC.

BackgroundTo assess the feasibility of elective neck irradiation to level Ib in nasopharyngeal carcinoma (NPC) using intensity-modulated radiation therapy (IMRT).MethodsWe retrospectively analyzed 1438 patients with newly-diagnosed, non-metastatic and biopsy-proven NPC treated with IMRT.ResultsGreatest dimension of level IIa LNs (DLN-IIa) ≥ 20 mm and/or level IIa LNs with extracapsular spread (ES), oropharynx involvement and positive bilateral cervical lymph nodes (CLNs) were independently significantly associated with metastasis to level Ib LN at diagnosis. No recurrence at level Ib was observed in the 904 patients without these characteristics (median follow-up, 38.7 months; range, 1.3–57.8 months), these patients were classified as low risk. Level Ib irradiation was not an independent risk factor for locoregional failure-free survival, distant failure-free survival, failure-free survival or overall survival in low risk patients. The frequency of grade ≥ 2 subjective xerostomia at 12 months after radiotherapy was not significantly different between low risk patients who received level Ib-sparing, unilateral level Ib-covering or bilateral level Ib-covering IMRT.ConclusionLevel Ib-sparing IMRT should be safe and feasible for patients without a DLN-IIa ≥ 20 mm and/or level IIa LNs with ES, positive bilateral CLNs or oropharynx involvement at diagnosis. Further investigations based on specific criteria for dose constraints for the submandibular glands are warranted to confirm the benefit of elective level Ib irradiation.

BackgroundTo assess the feasibility of elective neck irradiation to level Ib in nasopharyngeal carcinoma (NPC) using intensity-modulated radiation therapy (IMRT).MethodsWe retrospectively analyzed 1438 patients with newly-diagnosed, non-metastatic and biopsy-proven NPC treated with IMRT.ResultsGreatest dimension of level IIa LNs (DLN-IIa) ≥ 20 mm and/or level IIa LNs with extracapsular spread (ES), oropharynx involvement and positive bilateral cervical lymph nodes (CLNs) were independently significantly associated with metastasis to level Ib LN at diagnosis. No recurrence at level Ib was observed in the 904 patients without these characteristics (median follow-up, 38.7 months; range, 1.3–57.8 months), these patients were classified as low risk. Level Ib irradiation was not an independent risk factor for locoregional failure-free survival, distant failure-free survival, failure-free survival or overall survival in low risk patients. The frequency of grade ≥ 2 subjective xerostomia at 12 months after radiotherapy was not significantly different between low risk patients who received level Ib-sparing, unilateral level Ib-covering or bilateral level Ib-covering IMRT.ConclusionLevel Ib-sparing IMRT should be safe and feasible for patients without a DLN-IIa ≥ 20 mm and/or level IIa LNs with ES, positive bilateral CLNs or oropharynx involvement at diagnosis. Further investigations based on specific criteria for dose constraints for the submandibular glands are warranted to confirm the benefit of elective level Ib irradiation.

BackgroundThe impact of cumulative dose of cisplatin on clinical outcomes of nasopharyngeal carcinoma (NPC) patients who received intensity-modulated radiotherapy (IMRT) was evaluated.MethodsThis study included 491 consecutive patients with histologically confirmed NPC who were treated with concurrent chemoradiotherapy with IMRT. The patients were divided into three groups: low- (cumulative dose ≤100 mg/m2), medium- (cumulative dose >100 mg/m2 and ≤200 mg/m2), and high- (cumulative dose >200 mg/m2) dose groups. Subgroups of patients included pre-treatment levels of Epstein–Barr Virus DNA (EBV DNA) <4000 copies/ml and pre-treatment EBV DNA ≥4000 copies/ml. To test for independent significance, the Kaplan–Meier with the log–rank test and the Cox proportional hazards model were used.ResultsThe 5-year overall survival (OS) rates of the low-, medium-, and high-dose groups were 64.1 %, 91.1 %, and 89.4 %, respectively (P = 0.002). Based on multivariate analysis, patients who were in the medium- and high-dose groups had compared with the low-dose group, with an odds ratio of 0.135 (95 % CI 0.045–0.405, P < 0.001) and 0.225 (95 % CI 0.069–0.734, P = 0.013), respectively. For the low-risk patients, the cumulative dose of cisplatin significantly associated with a lower OS (P < 0.001). The medium-dose group had reduced odds of death compared with the low-dose group, with an odds ratio of 0.062 (95 % CI 0.001–0.347, P = 0.002), according to multivariate analysis.ConclusionsThe cumulative dose of cisplatin is associated with OS and distant metastasis-free survival (DMFS) among NPC patients who received IMRT.

BackgroundTalin-1 is a cytoskeletal protein that plays an important role in tumourgenesis, migration and metastasis in several malignant tumors. The aim of this study was to evaluate the expression and prognostic value of Talin-1 in nasopharyngeal carcinoma (NPC).MethodsTalin-1 mRNA and protein expression were examined in NPC cell lines and clinical nasopharyngeal tissues by quantitative RT-PCR, agarose gel electrophoresis and western blotting. The expression of Talin-1 was analyzed by immunohistochemical staining in 233 paraffin-embedded NPC specimens with clinical follow-up data and cox regression analysis was used to identify independent prognostic factors. The functional role of Talin-1 in NPC cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by the wound healing and transwell invasion assays.ResultsThe expression of Talin-1 was significantly upregulated in most NPC cell lines and clinical tissues at both the mRNA and protein levels. High expression of Talin-1 was significantly associated with distant metastasis (P = 0.001) and patient death (P = 0.001). In addition, high expression of Talin-1 was associated with significantly poorer overall survival (OS: HR, 2.15; 95% CI, 1.28-3.63; P = 0.003) and poorer distant metastasis-free survival (DMFS: HR, 2.39; 95% CI, 1.38-4.15; P = 0.001). Cox regression analysis indicated that high expression of Talin-1 and TNM stage were independent prognostic indicators (both P < 0.05). Stratified analysis demonstrated that high expression of Talin-1 was associated with significantly poorer survival in patients with advanced stage disease (stage III-IV, HR, 1.91; 95% CI, 1.09-3.35; P = 0.02 for OS and HR, 2.22; 95% CI, 1.24-3.99; P = 0.006 for DMFS). Furthermore, the depletion of Talin-1 suppressed the migratory and invasive ability of NPC cells in vitro.ConclusionsOur data demonstrate that high expression of Talin-1 is associated with significantly poorer OS and poorer DMFS in NPC and depletion of Talin-1 expression inhibited NPC cell migration and invasion. Talin-1 may serve as novel prognostic biomarker in NPC.

BackgroundTo compare the survival outcomes and acute toxicities of concurrent chemoradiotherapy (CCRT), induction chemotherapy (IC) plus radiotherapy (RT), and IC plus CCRT in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated using intensity-modulated radiotherapy (IMRT).MethodsPatients with stage III–IVB NPC who were treated with IMRT between 2009 and 2012 at a single institution were retrospectively reviewed. The induction regimens included PF (cisplatin and fluorouracil) and TP (docetaxel and cisplatin) every 3 weeks for 2–3 cycles; the concurrent regimen was cisplatin every three weeks for 2–3 cycles. A propensity score matching method was used to match patients from each group in a 1:1:1 ratio.ResultsIn total, 147 eligible patients were propensity-matched, with 49 patients in each treatment group. The median follow-up duration was 38.5 months (range, 4.5 – 56 months). The 3-year disease-free survival, overall survival, distant metastasis-free survival, and locoregional relapse-free survival rates were 82.1 %, 92.8 %, 87 %, and 90.4 % in the CCRT group; 86.3 %, 91.0 %, 91.6 %, and 94.4 % in the IC plus RT group; and 87.8 %, 95.8 %, 93.8 %, and 93.9 % in the IC plus CCRT group, respectively. No statistically significant survival differences were observed between the three treatment groups in either univariate or multivariate analyses. The incidence of grade 3–4 acute toxicities was similar among groups.ConclusionsThis study suggests that CCRT, IC plus RT, and IC plus CCRT are similarly efficacious treatment strategies for patients with locoregionally advanced NPC treated using IMRT; however, long-term, large-scale randomized trials are required to confirm these findings.