Survival Of Nasopharyngeal Carcinoma Patients Research Articles

Long-term outcomes of neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (CCRT) vs CCRT alone for nasopharyngeal carcinoma in the era of intensity-modulated radiation therapy using propensity score matching method.

PurposeWhether neoadjuvant chemotherapy (NCT) followed by concurrent chemoradiotherapy (CCRT) could improve survival in nasopharyngeal carcinoma (NPC) remains controversial especially in the era of intensity-modulated radiation therapy (IMRT), and we explored the role of NCT for NPC patients.Patients and methodsA retrospective review was conducted of 255 NPC patients treated with NCT+CCRT (n=67) or CCRT alone (n=188) based on IMRT between December 2006 and December 2012. To control the imbalance, a 1:2 match was performed using propensity score matching (PSM) method based on patient’s heterogeneity and regimens of concurrent chemotherapy (CCT). The long-term treatment outcomes and toxicity between NCT group (n=67) and concurrent chemoradiotherapy (CRT) group (n=134) after PSM were compared.ResultsThe 5-year overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant failure-free survival (DFFS) were 78.8%, 69.1%, 90.0%, 90.0%, 100% and 78.3% for NCT group, while 79.5%, 75.7%, 92.7%, 94.2%, 96.1% and 82.7% for CRT group (P=0.305, 0.448, 0.790, 0.512, 0.104 and 0.671). It indicated that the treatment method (NCT+CCRT vs CCRT) was not the independent prognostic factor for the survival in NPC patients, and only patients who had completed at least two cycles of CCT got better OS, RFS and DFFS (P=0.009, 0.016 and 0.043), whether to receive NCT or not. No difference in the incidences of any acute and most late toxicity between the two groups was shown.ConclusionOur study did not show the exact advantage of NCT followed by CCRT compared with CCRT alone or higher incidences of toxicity in NCT group. It suggests that NCT might not be necessary if two or more cycles of CCT are finished well in the era of IMRT, and when NCT is finished well, less than two cycles of CCT with IMRT could be enough. However, in the era of IMRT, the role of NCT still needs to be further explored.

Low expression of nm23-H1 associates with poor survival of nasopharyngeal carcinoma patients: A prisma-compliant meta-analysis.

Background:Developing a new reliable prognostic marker to predict the prognosis and supply better and more suitable therapy for patients with nasopharyngeal carcinoma (NPC) is urgent. Therefore, we performed this systematic review of the literature with meta-analysis to clarify and explore the associate expression of nm23-H1 with prognosis of NPC patients.Methods:Literature research in Cochrane Library, PubMed, and EMBASE was performed up to July 2016. Eligible case–control studies of associate expression of nm23-H1 with prognosis of NPC patients were included.Results:Nine studies met our inclusion criteria and were finally included for the analysis, involving 861 participants. Our meta-analysis revealed that the low expression of nm23-H1 in NPC was: RR = 2.13, 95% CI 1.15–3.95 and R = 2.56, 95% CI 2.03–3.22; and poorer overall survival (OS) rate was 3-year OS rate: RR: 0.55; 95% CI: 0.45–0.67 and 5-year OS rate: RR: 0.60; 95% CI: 0.52–0.69. Furthermore, the statistical significance was constant irrespective of different NPC subtypes.Conclusion:The low expression of nm23-H1 is associated with poorer prognosis in patients with NPC, suggesting that it is a prognostic factor and potential biomarker for survival in NPC.

Benefits of local tumor excision and pharyngectomy on the survival of nasopharyngeal carcinoma patients: a retrospective observational study based on SEER database

BackgroundThere is ongoing debate about surgery of primary site in nasopharyngeal carcinoma patients.Methods3919 patients with nasopharyngeal carcinoma identified in the SEER registry between 2004 and 2013. The benefit of surgery of primary nasopharynx tumor site on overall and cancer-specific survival was assessed by risk-adjusted multivariate Cox proportional hazard regression and propensity score matching modeling.ResultsSurgery was marginally associated with better overall survival (hazard ratio (HR) = 0.816, 95% CI 0.656–1.015, p = 0.07) and cancer-specific survival (HR = 0.749, 95% CI 0.552–1.018, p = 0.06) in the propensity score model. Among 398 cases who underwent primary site surgery, 282 (70.85%) received local tumor excision and 79 (20.31%) received pharyngectomy. Local tumor excision and pharyngectomy had almost the same effect on survival in propensity score matching analysis. The benefit was significant in subgroups of white, age <60 year, and patients with T3, N1, M0, AJCC stage III, or moderately differentiated tumors. Further survival analysis showed surgery to promote survival in both radiotherapy and non-radiotherapy patients.ConclusionThis is the first population-based analysis using propensity score model to provide evidence of a positive impact of surgery on survival in nasopharyngeal carcinoma. Moreover, surgery demonstrated the significant benefit in subgroups of patients with specific clinical characteristics.

Pretreatment combination of platelet counts and neutrophil-lymphocyte ratio predicts survival of nasopharyngeal cancer patients receiving intensity-modulated radiotherapy.

BackgroundIncreased cancer-related inflammation has been associated with unfavorable clinical outcomes. The combination of platelet count and neutrophil–lymphocyte ratio (COP-NLR) has related outcomes in several cancers, except for nasopharyngeal carcinoma (NPC). This study evaluated the prognostic value of COP-NLR in predicting outcome in NPC patients treated with intensity-modulated radiotherapy (IMRT).Materials and methodsWe analyzed the data collected from 232 NPC patients. Pretreatment total platelet counts, neutrophil–lymphocyte ratio (NLR), and COP-NLR score were evaluated as potential predictors. Optimal cutoff values for NLR and platelets were determined using receiver operating curve. Patients with both elevated NLR (>3) and platelet counts (>300×109/L) were assigned a COP-NLR score of 2; those with one elevated or no elevated value were assigned a COP-NLR a score of 1 or 0. Cox proportional hazards model was used to test the association of these factors and relevant 3-year survivals.ResultsPatients (COP-NLR scores 1 and 2=85; score 0=147) were followed up for 55.19 months. Univariate analysis showed no association between pretreatment NLR >2.23 and platelet counts >290.5×109/L and worse outcomes. Multivariate analysis revealed that those with COP-NLR scores of 0 had better 3-year disease-specific survival (P=0.02), overall survival (P=0.024), locoregional relapse-free survival (P=0.004), and distant metastasis-free survival (P=0.046). Further subgrouping by tumor stage also revealed COP-NLR to be an unfavorable prognostic indicator of 3-year failure-free survival (P=0.001) for locally advanced NPC.ConclusionCOP-NLR score, but not NLR alone or total platelet count alone, predicted survival in NPC patients treated with IMRT-based therapy, especially those with stage III/IVA, B malignancies.

BMP2 promotes proliferation and invasion of nasopharyngeal carcinoma cells via mTORC1 pathway.

Bone morphogenetic protein-2 (BMP2) is a secreted protein that highly expressed in a variety of cancers and contributes to cell proliferation, migration, invasiveness, mobility, metastasis and EMT. However, its clinical significance and biological function in nasopharyngeal carcinoma (NPC) remain unknown up to now. Up-regulation of BMP2 was first observed in NPC cell lines by a genome-wide transcriptome analysis in our previous study. In this study, BMP2 mRNA was detected by qRT-PCR and data showed that it was upregulated in NPC compared with non-cancerous nasopharynx samples. Immunohistochemistry (IHC) analysis in NPC specimens revealed that high BMP2 expression was significantly associated with clinical stage, distant metastasis and shorter survival of NPC patients. Moreover, overexpression of BMP2 in NPC cells promoted cell proliferation, migration, invasiveness and epithelial-mesenchymal transition (EMT). Mechanistically, BMP2 overexpression increase phosphorylated protein level of mTOR, S6K and 4EBP1. Correspondingly, mTORC1 inhibitor rapamycin blocked the effect of BMP2 on NPC cell proliferation and invasion. In conclusion, our results suggest that BMP2 overexpression in NPC enhances proliferation, invasion and EMT of tumor cells through the mTORC1 signaling pathway.

Identifying pretreatment baseline factors predictive of distant metastasis in patients with nasopharyngeal carcinoma after radiotherapy.

This retrospective study was performed to identify pretreatment baseline factors that could predict the development of distant metastasis (DM) in patients with nasopharyngeal carcinoma (NPC).A cohort of 119 NPC patients undergoing radiotherapy (RT) or chemoradiotherapy (CRT) were recruited into the study. Among them, 51 developed DM (DM group) within 3 years after treatment and 68 did not (DM-free group). Various clinicopathological factors were measured before the treatment and analyzed by univariate as well as multivariate analyses for the potential correlation with DM development.Univariate analysis revealed that increased peripheral lactate dehydrogenase (LDH) level, lower lymphocyte–monocyte ratio (LMR), higher neutrophil–lymphocyte ratio (NLR), advanced American Joint Committee on Cancer (AJCC) stage, advanced T stage, and advanced N stage were significantly correlated with the presence of DM. Multivariate analysis identified advanced AJCC stage and high LDH level were independent predictive factors for DM.Routinely measured pretreatment clinical factors, including AJCC state and serum LDH level, could independently predict DM. These factors will benefit the selection of appropriate treatment options and improve the overall survival of NPC patients.

Prognostic Significance of Standardized Uptake Value on 18Fluorine-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients with Nasopharyngeal Carcinoma.

The aim of this study was to investigate the prognostic significance of standardized uptake value (SUV) on 18 fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in patients with nasopharyngeal carcinoma (NPC). Thirty-four patients who have histologically proven NPC and underwent 18F-FDG PET/CT were included in this study. After 18F-FDG PET/CT, all the patients received radiation therapy and 32 of them received concomitant weekly chemotherapy. The maximum SUV (SUVmax) at the primary tumor and the SUVmaxof the highest neck nodes were determined. The SUVmax-T ranged from 5.00 to 30.80 (mean: 15.37 ± 6.10) and there was no difference between SUVmax-T values for early and late stages (P = 0.99). The SUVmax-N ranged from 3.10 to 23.80 (mean: 13.23 ± 5.76). There was no correlation between SUVmax-T and SUVmax-N (r = 0.111, P = 0.532). There was no difference between the SUVmax-T and the positivity of neck lymph nodes (P = 0.169). The ability of SUVmaks-N to predict stage was obtained by a receiver operating characteristic (ROC) analysis. The area under the curve is 0.856 and the best cut-off value is 7.88. There was a good correlation between SUVmax-N and stage. While the mean SUVmax-T for the alive patients was slightly lower than that for the dead (14.65 ± 5.58 vs. 20.30 ± 7.92, P = 0.061), the difference between the groups was not statistically significant. Furthermore, there was no statistically significant difference for SUVmax-N between these two groups (P: 0.494). Cox-regression analysis showed that an increase in SUVmax-T and SUVmax-N was associated with death risk (relative risk [RR]: 1.13, P = 0.078 and RR: 1.052, P = 0.456, respectively). SUVmax-T and SUVmax-N were independent prognostic factors for survival in NPC patients. This will help the clinicians in choosing suitable candidates for more aggressive treatment modalities.

Radiation therapy for nasopharyngeal carcinoma: the predictive value of interim survival assessment.

Pretreatment characteristics are suggested as predictive and/or prognostic factors for nasopharyngeal carcinoma (NPC); however, individual tumor radiosensitivities have previously not been considered. As boost planning is recommended for NPC, we performed interim assessments of magnetic resonance (MR) images for boost planning and retrospectively evaluated their predictive value for the survival of NPC patients. Radiation therapy via elective nodal irradiation (median dose: 39.6 Gy) with/without chemotherapy was used to treat 63 NPC patients. Boost irradiation (median total dose: 70 Gy) was performed based on the interim assessment. The largest lymph node (LN) was measured on MR images acquired at the time of interim assessment. The site of first failure was local in 8 (12.7%), regional in 7 (11.1%), and distant in 12 patients (19.0%). All 7 patients with regional failure harbored LNs ≥15 mm at interim assessment. We divided the 63 patients into two groups based on LN size [large (≥15 mm), n = 10 and small (<15 mm), n = 53]. Univariate analysis showed that 5-year overall survival (OS) and cause-specific survival (CSS) rates for large LNs were significantly lower than for small LNs (OS: 12.5% vs 70.5%, P < 0.001 and CSS: 25.0% vs 80.0%, P < 0.001). Multivariate analysis showed that large LNs were a significantly unfavorable factor for both OS (hazard ratio = 4.543, P = 0.002) and CSS (hazard ratio = 6.020, P = 0.001). The results suggest that LN size at interim assessment could predict survival in NPC patients.

Intensity-modulated radiotherapy controls nasopharyngeal carcinoma distant metastasis and improves survival of patients.

BackgroundThis study evaluated the distant metastatic outcomes in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT) plus chemotherapy.Methods530 Non-metastatic NPC patients were retrospectively collected and reviewed after receiving IMRT with or without chemotherapy between June 2006 and December 2011. Patients were treated with one fraction of IMRT daily for 5 days a week for 69.96–74.09 Gy, while 473 (89.2 %) of patients also received chemotherapy.ResultsPatients were followed up for a median follow-up duration of 49 months (range from 5 to 98 months). After treatment, 91 (17.3 %) patients developed distant metastasis. Distant metastasis after treatment was significantly associated with advanced 2010 Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) T staging (p = 0.034), N stage (p < 0.001), 2010 UICC/AJCC stage (p < 0.001), and tumor recurrence (p = 0.029). However, chemotherapy failed to reduce cancer distant metastasis in early stage patients, the distant metastasis rate was 17.5 % in stage III and 24.2 % in stage IVA–B diseases, after IMRT and chemotherapy. The multivariate analysis showed that cancer remission duration, treatment modality, and metastatic site (p < 0.001, p = 0.027 and p = 0.022, respectively) were all independent predictors for overall survival of NPC patients after IMRT and chemotherapy.ConclusionsThis study provided insight into the effects of IMRT plus chemotherapy in the treatment of NPC. Future studies will explore the efficacy of more aggressive systemic therapies for high-risk patients with distant metastasis.

Expression of EIF5A2 associates with poor survival of nasopharyngeal carcinoma patients treated with induction chemotherapy.

BackgroundNasopharyngeal carcinoma (NPC) is a type of head-neck cancer with a distinguishable geographic and racial distribution worldwide. Increasing evidence supports that the accumulation of additional genetic and epigenetic abnormalities is important in driving the NPC tumorigenic process. In this study, we aim to investigate the association between EIF5A2 (Eukaryotic translation initiation factor 5A2) expression status and NPC clinical outcomes.MethodsThe expression status of EIF5A2 was investigated in the NPC tissue microarray. Tissues were from 166 NPC patients staging II-IV, collected between 1999 and 2005. All patients were administered 2–3 cycles of DDP (cisplatin) + 5-Fu (5-fluorouracil) induction therapy and then treated with a uniform conventional two-dimensional radiotherapy. Cell motility assay, tumor growth assay and cytotoxicity assay were performed on the EIF5A2 overexpressed cells and control cells. siRNA was also used in the in vitro studies.ResultsPositive staining of EIF5A2 was observed in 85.4 % (105/123) informative tumor cases. Multivariate analyses demonstrated that EIF5A2 was an independent prognostic marker of poor overall survival (OS) (P = 0.041), failure-free survival (FFS) (P = 0.029), and distant failure-free survival (D-FFS) (P = 0.043) in patients with locoregionally advanced NPC patients treated with cisplatin + 5-Fu chemoradiotherapy. The forced expression of EIF5A2 in NPC cells enhanced the cells’ motility and growth ability. Knock-down of EIF5A2 in NPC cells decreased the cell’s motility and growth ability. Our results also demonstrated that EIF5A2 overexpression induced chemoresistance of NPC cells to 5-Fu.ConclusionsOur findings suggested that EIF5A2 expression, as examined by immunohistochemistry, could function as an independent prognostic factor of outcomes in NPC patients with cisplatin + 5-Fu chemoradiotherapy. EIF5A2 might be a novel therapeutic target for the inhibition of NPC progress.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2714-2) contains supplementary material, which is available to authorized users.

Overexpression of Mitochondria Mediator Gene TRIAP1 by miR-320b Loss Is Associated with Progression in Nasopharyngeal Carcinoma.

The therapeutic strategy for advanced nasopharyngeal carcinoma (NPC) is still challenging. It is an urgent need to uncover novel treatment targets for NPC. Therefore, understanding the mechanisms underlying NPC tumorigenesis and progression is essential for the development of new therapeutic strategies. Here, we showed that TP53-regulated inhibitor of apoptosis (TRIAP1) was aberrantly overexpressed and associated with poor survival in NPC patients. TRIAP1 overexpression promoted NPC cell proliferation and suppressed cell death in vitro and in vivo, whereas TRIAP1 knockdown inhibited cell tumorigenesis and enhanced apoptosis through the induction of mitochondrial fragmentation, membrane potential alteration and release of cytochrome c from mitochondria into the cytosol. Intersecting with our previous miRNA data and available bioinformatic algorithms, miR-320b was identified and validated as a negative regulator of TRIAP1. Further studies showed that overexpression of miR-320b suppressed NPC cell proliferation and enhanced mitochondrial fragmentation and apoptosis both in vitro and in vivo, while silencing of miR-320b promoted tumor growth and suppressed apoptosis. Additionally, TRIAP1 restoration abrogated the proliferation inhibition and apoptosis induced by miR-320b. Moreover, the loss of miR-320b expression was inversely correlated with TRIAP1 overexpression in NPC patients. This newly identified miR-320b/TRIAP1 pathway provides insights into the mechanisms leading to NPC tumorigenesis and unfavorable clinical outcomes, which may represent prognostic markers and potential therapeutic targets for NPC treatment.

Abstract 3515: MiR-320b-regulated TRIAP1 prevents mitochondria fragmentation and apoptosis by controlling cytochrome c release in nasopharyngeal carcinoma

Abstract Mitochondria play critical roles in apoptosis. Imbalance of mitochondria fusion/fission leads to mitochondrial fragmentation and initiates intrinsic apoptosis, but the regulation of mitochondrial fragmentation in nasopharyngeal carcinoma (NPC) remains undefined. Here we show that TRIAP1 is aberrantly overexpressed and associated with poor survival in NPC patients. TRIAP1 overexpression promotes cell growth and suppresses NPC cell death in vitro and in vivo, whereas TRIAP1 knockdown inhibits cell tumorigenesis and enhances apoptosis through induction of mitochondrial fragmentation, membrane potential alteration and release of cytochrome c from mitochondria to cytosol. In intersection with our previous miRNA data and available bioinformatics algorithms, we identified miR-320b as a negative regulator of TRIAP1 expression. Further studies show that miR-320b suppresses NPC cell proliferation and enhances mitochondrial fragmentation and apoptosis by targeting TRIAP1. Moreover, loss of miRA-320b expression is conversely correlated with TRIAP1 overexpression and poor prognosis in NPC patients. This study reveals the regulation of miR-320b/TRIAP1 in mitochondrial fragmentation and apoptosis, and suggests potential therapeutic targets for NPC treatment. Citation Format: Ying-Qin Li, Na Liu, Jun Ma. MiR-320b-regulated TRIAP1 prevents mitochondria fragmentation and apoptosis by controlling cytochrome c release in nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3515.

Combined CT-guided radiofrequency ablation with systemic chemotherapy improves the survival for nasopharyngeal carcinoma with oligometastasis in liver: Propensity score matching analysis.

The aim of this study was to retrospectively compare the treatment efficacy of systemic chemotherapy combined with sequential CT-guided radiofrequency ablation (Chemo-RFA) to chemotherapy alone (Chemo-only) in the management of nasopharyngeal carcinoma (NPC) with liver metastasis. Between 2003 and 2011, 328 NPC patients diagnosed with liver metastasis at Sun Yat-sen University Cancer Center were enrolled. One-to-one matched pairs between Chemo-RFA group with the Chemo-only group were generated using propensity score matching. The associations of treatment modality with overall survival (OS) and progression-free survival (PFS) were determined by Cox regression. Of the patients enrolled, 37 patients (11.8 %) received combined treatment, 291 (82.2) received chemotherapy alone. The patients in Chemo-RFA group were more frequently classified as lower number (≤3) of liver metastatic lesions (P<0.001), had lower rates of bi-lobar liver metastasis (P<0.001) and extra-hepatic metastasis (P<0.001) than patients in Chemo-only group. After propensity score matching, 37 pairs of well-matched liver metastatic NPC patients were selected from different treatment groups. The adjusted hazard ratio in OS and PFS of the choice for Chemo-RFA approach to Chemo-only was 0.53 (95%CI, 0.30-0.93) and 0.60 (95%CI, 0.36-0.97), respectively. In conclusion, combined CT-guided RFA and chemotherapy approach offer the chance of improved survival for NPC patients with oligometastasis in liver, and should be considered if the ablation is technically feasible.

Impact of X-linked inhibitor of apoptosis protein on survival of nasopharyngeal carcinoma patients following radiotherapy.

This study aims to investigate CNE1 and CNE2 cell proliferation and apoptosis of nasopharyngeal cancer (NPC) and X-linked inhibitor of apoptosis protein (XIAP) expression in NPC patients after radiotherapy. Quantitative real-time quantitative polymerase chain reaction (qRT-PCR) and Western Blot detected XIAP and XIAP-associated factor1 (XAF1) messenger RNA (mRNA) and protein expression of CNE1 and CNE2 in NPC cells irradiated by γ-ray; MTT and flow cytometry assays detected CNE2 cells proliferation and apoptotic rate, respectively. With a retrospective analysis of 109 NPC patients in Xinxiang Central Hospital, immunohistochemistry (IHC) method detected XIAP expression, followed by a 5-year clinical analysis of the prognosis relevance after radiotherapy. In vitro, the inhibition and apoptotic rates of cells increased with the growth of radiation dose. qRT-PCR and Western blot detection declared that XIAP mRNA and protein expression increased, whereas XAF1 mRNA and protein expression decreased with the growth of radiation dose and exposure time. And XIAP mRNA and protein expression were negatively correlated with proliferation and apoptotic rates of the cells. In vivo, positive XIAP expression rate was negatively correlated with pathological tumor-node-metastasis (p-TNM) staging and tumor differentiation. Further, high XIAP expression, high p-TNM staging, and lower degree of differentiation were significantly correlated with the decrease of NPC patients' survival rate. Additionally, XIAP expression, p-TNM staging, and degrees of differentiation were independent risk factors for the survival of the NPC patients after radiotherapy. Increased XIAP expression and decreased XAF1 expression may be one reason for the apoptosis delays of CNE1 and CNE2 cells after irradiation, and the XIAP expression or the p-TNM staging and degree of differentiation are independent risk factors for NPC patients' survival after radiotherapy, providing a molecular rationale for radiotherapy and prognosis of NPC.

Critical weight loss predicts poor prognosis in nasopharyngeal carcinoma.

BackgroundThe impacts of weight loss on prognosis in nasopharyngeal carcinoma (NPC) remain unclear. The present study was therefore undertaken to investigate the association between critical weight loss and long-term survival in NPC patients.MethodsThe eligible 2399 NPC patients were reviewed. Weight change was categorized into critical weight loss (CWL) and non-critical weight loss (Non-CWL). The associations of CWL with long-term survival were analyzed by Cox regression in the entire patient and two subsets. Propensity score matching was performed to reduce the effects of confounding factors.ResultsCWL was defined as body weight loss of ≥4.6 %. Compared with patients without CWL, patients with CWL had significantly lower 5-year OS (72.4 vs. 79.3 %, P < 0.001), FFS (71.1 vs. 78.4 %, P <0.001), and LR-FFS (78.1 vs. 84.8 %, P <0.001), respectively. After adjustment for potential confounders, CWL remained an independence prognostic factor for OS (HR = 1.352; 95 % CI 1.160–1.576; P < 0.001), FFS (HR = 3.275; 95 % CI 1.101–9.740; P = 0.033), and LR-FFS (HR = 6.620; 95 % CI 2.990–14.658; P < 0.001), respectively. Furthermore, subgroup analysis in the cohort of patients received concurrent chemoradiotherapy or radiotherapy alone confirmed the results in the entire patient even after the propensity-score matching. In IMRT cohort, CWL was also significantly associated with a lower OS (P = 0.04) and FFS (P = 0.04).ConclusionsCWL has a significant and independent impact on long-term survival in nasopharyngeal carcinoma patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2214-4) contains supplementary material, which is available to authorized users.

The effects of hemoglobin levels and their interactions with cigarette smoking on survival in nasopharyngeal carcinoma patients.

There is very little published information regarding the prognostic value of hemoglobin (Hb) levels combined with smoking on the survival of patients with nasopharyngeal carcinoma (NPC), and the interactions between them remain unclear. A total of 2440 NPC patients were confirmed, and multivariate analysis was performed to identify valuable prognostic Hb levels in the entire population and in the cohort of smokers. The survival differences were compared using log‐rank tests. The multiplicative and additive interactions were assessed using Cox regression and a Microsoft Word Excel spreadsheet. Postradiotherapy (RT) Hb was an independent prognostic factor for overall survival (OS) (HR = 0.797; P = 0.006), failure‐free survival (FFS) (HR=0.811; P = 0.010), and loco‐regional failure‐free survival (LR‐FFS) (HR = 0.725; P = 0.000). In the cohort of smokers, pack‐years was also an independent predictor of OS (HR = 0.673; P < 0.001) and FFS (HR = 0.681; P < 0.001), LR‐FFS (HR = 0.663; P = 0.001). A significant positive additive effect was found for the interaction between low post‐RT Hb and high SI on OS, with RERI = 5.616, AP = 0.665, and S = 4.078. Stratified analyses demonstrated that heavy smokers with low post‐RT Hb had HRs of 2.295 (P < 0.001) for death, 2.222 (P < 0.001) for disease failure, and 2.267 (P < 0.001) loco‐regional recurrence compared with light smokers with high post‐RT Hb levels, and post‐RT Hb level is an important predictor of survival in patients with NPC. The positive interaction between post‐RT Hb level and pack‐years contributes to the elevated risk of poor survival. Oncologists should devote particular attention to heavy smokers with low post‐RT Hb levels in the future.

Long-term survival of nasopharyngeal carcinoma patients with Stage II in intensity-modulated radiation therapy era.

To evaluate the long-term survival and the role of chemotherapy in nasopharyngeal carcinoma (NPC) patients in Stage II treated by intensity-modulated radiation therapy (IMRT). Three hundred and eleven NPC patients in Stage II were reviewed. All were treated with IMRT with or without chemotherapy, with 191, 20 and 100 patients being defined as T1N1M0, T2N0M0 and T2N1M0 stage, respectively. At a median follow-up of 57 months, the 5-year overall survival, disease-specific survival, distant metastasis-free survival, loco-regional relapse-free survival (LRRFS) and progression-free survival were 91.1, 93.5, 90.6, 95.9 and 87.6%, respectively. T2N1 patients had significant poorer survival outcomes than T1N1 patients, with T2N0 patients in between. Further analysis showed that the addition of chemotherapy could only improve LRRFS [hazard ratio (HR) 0.263, 95% confidence interval (CI) 0.083-0.839, P = 0.024], especially for T1N1 patients (HR 0.209, 95% CI 0.046-0.954, P = 0.043). For those in the T2N1M0 group, chemotherapy, as used in our series, added no benefit to any endpoint. IMRT in NPC patients in Stage II was quite therapeutic; however, different subgroups have distinct survival outcomes. Distant metastasis was the main failure pattern, especially for those with T2N1 disease, and the chemotherapy currently in use failed to treat subclinical metastatic foci effectively. Further prospective study is warranted to find out the role and the optimal schedule of chemotherapy in this subgroup of patients.

Axl Is a Potential Cancer Prognostic Marker for the Migration and Invasion of Nasopharyngeal Carcinoma.

The Axl receptor tyrosine kinase has been demonstrated to be elevated and activated in many human cancers including liver, lung, breast, and pancreatic cancer. Its high expression has been considered as a cancer biomarker for predicting poor prognosis and increased invasiveness/metastasis. The aim of the study was to investigate the clinical significance of Axl in nasopharyngeal carcinoma (NPC) and its role in cell migration and invasion. We detected Axl expression in 86 collected NPC tissues and 20 collected normal nasopharyngeal epithelial tissues using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical staining. Axl was knocked down by a specific shRNA in NPC cell lines, 5-8F and 6-10B. Transwell assays were used to determine NPC cell migration and invasion. The expressions of Axl mRNA and protein in NPC tissues were significantly higher than those in normal nasopharyngeal epithelial tissues (p < 0.05, respectively). The positive expression of Axl was significantly correlated with distant metastasis and high TNM stage in NPC (p < 0.05, respectively). Furthermore, Axl positive expression was correlated with a worse overall survival of NPC patients (p < 0.05). Multivariate Cox repression analysis indicated that Axl was an independent factor for predicting overall survival of NPC patients (p < 0.05). In vitro studies found that Axl knockdown significantly reduced the number of migrated and invaded 5-8F and 6-10B cells (p < 0.05, respectively). The positive expression of Axl is correlated with the poor clinicopathological features in NPC. Furthermore, Axl is an independent prognostic marker for predicting overall survival of NPC patients. Functionally, Axl may facilitate tumour progression by promoting NPC cell migration and invasion.

Development and External Validation of Nomograms for Predicting Survival in Nasopharyngeal Carcinoma Patients after Definitive Radiotherapy.

The distant metastasis free survival (DMFS) and overall survival (OS) differ significantly among individuals even within the same clinical stages. The purpose of this retrospective study was to build nomograms incorporating plasma EBV DNA for predicting DMFS and OS of nasopharyngeal carcinoma (NPC) patients after definitive radiotherapy. A total of 1168 non-metastatic NPC patients from two institutions were included to develop the nomograms. Seven and six independent prognostic factors were identified to build the nomograms for OS and DMFS, respectively. The models were externally validated by a separate cohort of 756 NPC patients from the third institutions. For predicting OS, the c-index of the nomogram was significantly better than that of the TNM staging system (Training cohort, P = 0.005; validation cohort, P = 0.03). The c-index of nomogram for DMFS in the training and validation set were both higher than that of TNM classification with marginal significance (P = 0.048 and P = 0.057, respectively). The probability of 1-, 3-, and 5-year OS and DMFS showed optimal agreement between nomogram prediction and actual observation. The proposed stratification of risk groups based on the nomograms allowed significant distinction between Kaplan-Meier curves for survival outcomes. The prognostic nomograms could better stratify patients into different risk groups.

Prognostic score models for survival of nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy and chemotherapy.

To establish accurate prognostic score models to predict survival for patients with nasopharyngeal carcinoma (NPC), treated with intensity-modulated radiotherapy (IMRT) and chemotherapy. Six hundred and seventy-five patients with newly diagnosed, nonmetastatic and histologically proven NPC who were treated with IMRT and chemotherapy were analyzed retrospectively. Samples were split randomly into a training set (n = 338) and a test set (n = 337) to analyze. All data from the training set were used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from the test set was used as an external validation set. Risk group stratification was proposed for the nomograms. The nomograms are able to predict survival with a C-index for external validation of local recurrence-free survival (LRFS; 0.66, 95% CI: 0.58-0.74), distant metastasis-free survival (DMFS; 0.73, 95% CI: 0.66-0.79), and disease-specific survival (DSS; 0.73, 95% CI: 0.67-0.79). The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation. The C-index of the nomogram for LRFS, DMFS and DSS were statistically higher than the C-index values of the AJCC seventh edition (P < 0.001). In the test set, the nomogram discrimination was also superior to the AJCC Staging systems (P < 0.001). The stratification in risk groups allows significant distinction between Kaplan-Meier curves for outcome. Prognostic score models were successfully established and validated to predict LRFS, DMFS, and DSS over a 5-year period after IMRT and chemotherapy, which will be useful for individual treatment.