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Background and purposeTo recommend contouring methods and atlas of organs at risk (OARs) for nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy, in order to help reach a consensus on interpretations of OARs delineation.Methods and materialsTwo to four contouring methods for the middle ear, inner ear, temporal lobe, parotid gland and spinal cord were identified via systematic literature review; their volumes and dosimetric parameters were compared in 41 patients. Areas under the receiver operating characteristic curves for temporal lobe contouring were compared in 21 patients with unilateral temporal lobe necrosis (TLN).ResultsVarious contouring methods for the temporal lobe, middle ear, inner ear, parotid gland and spinal cord lead to different volumes and dosimetric parameters (P

BACKGROUND The objective of this study was to evaluate the long-term survival and late toxicities of concurrent-adjuvant chemotherapy in patients with stage III through IVB nasopharyngeal carcinoma (NPC) from endemic regions of China. METHODS Patients with stage III to IVB NPC were assigned randomly to receive radiotherapy (RT) alone (the RT group) or RT plus concurrent adjuvant chemotherapy (the CRT group). CRT patients received concurrent cisplatin (40 mg/m2) weekly during RT followed by cisplatin (80 mg/m2) and fluorouracil (800 mg/m2 daily for 5 days) every 4 weeks for 3 cycles. The primary endpoint was overall survival. RESULTS In total, 316 patients underwent randomization, with 158 to each group. At a median follow-up of 70 months, the 5-year overall survival rate was 72% for the CRT group and 62% for the RT group (hazard ratio, 0.69; 95% confidence interval, 0.48-0.99; P = .043). Failure-free survival was significantly higher in the CRT group (P = .020). Most late toxicities were similar (33% vs 26%; P = .089), except for cranial neuropathy (P = .042), peripheral neuropathy (P = .041), and ear damage (P = .048), which were significantly increased in the CRT group. CONCLUSIONS The addition of concurrent adjuvant chemotherapy to RT provides survival benefits to patients with stage III through IVB NPC in endemic regions of China, and it does not increase most late toxicities apart from cranial neuropathy, peripheral neuropathy, and ear damage. Cancer 2013;119:2230–2238. © 2013 American Cancer Society.

Background Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene. This study aimed to investigate the impact of BRMS1 on metastasis in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic significance of BRMS1 in NPC patients. Methods BRMS1 expression was examined in NPC cell lines using quantitative reverse transcription-polymerase chain reaction and Western blotting. NPC cells stably expressing BRMS1 were used to perform wound healing and invasion assays in vitro and a murine xenograft assay in vivo. Immunohistochemical staining was performed in 274 paraffin-embedded NPC specimens divided into a training set (n = 120) and a testing set (n = 154). Results BRMS1 expression was down-regulated in NPC cell lines. Overexpression of BRMS1 significantly reversed the metastatic phenotype of NPC cells in vitro and in vivo. Importantly, low BRMS1 expression was associated with poor distant metastasis-free survival (DMFS, P P Conclusions Low expression of the metastasis suppressor BRMS1 may be an independent prognostic factor for poor prognosis in NPC patients.

Background Metastasis-associated protein 1 (MTA1) has been associated with poor prognosis in several malignant carcinomas. The purpose of this study was to investigate the expression and prognostic value of MTA1 in nasopharyngeal carcinoma (NPC). Methods MTA1 expression was assessed using immunohistochemistry in paraffin-embedded tumor specimens from 208 untreated NPC patients. Cox regression analysis was used to calculate the hazard ratio (HR), 95% confidence interval (CI) and identify independent prognostic factors, and recursive partitioning analysis was used to create a decision tree. Results Nuclear overexpression of MTA1 was observed in 48.6% (101/208) of the NPC tissues. Nuclear overexpression of MTA1 correlated positively with N classification (P = 0.02), clinical stage (P = 0.04), distant metastasis (P < 0.01) and death (P = 0.01). Additionally, nuclear overexpression of MTA1 correlated significantly with poorer distant metastasis-free survival (DMFS; P P < 0.01). MTA1 had prognostic significance in NPC patients with stage II disease, but not stage III or IV disease. Multivariate analysis demonstrated that nuclear overexpression of MTA1 was independently associated with poorer DMFS (HR, 2.05; 95% CI, 1.13–3.72; P = 0.02) and poorer OS (HR, 1.98; 95% CI, 1.09–3.59; P = 0.03). Using recursive partitioning analysis, the NPC patients could be classified with a low, intermediate or high risk of distant metastasis and death, on the basis of clinical stage, age and MTA1 expression. Conclusion The results of this study suggest that nuclear overexpression of MTA1 correlates significantly with poorer DMFS and poorer OS in NPC. MTA1 has potential as a novel prognostic biomarker in NPC.

To identify the prognostic value and staging categories of masticator space involvement in nasopharyngeal carcinoma (NPC) as determined with anatomic criteria ("anatomic masticator space involvement") to determine whether it is necessary for the masticator space described with criteria of the American Joint Committee on Cancer to exclude the medial and lateral pterygoid muscles.This retrospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. NPC was diagnosed in 924 patients with magnetic resonance (MR) imaging, and medical records and imaging studies were retrospectively analyzed. The overall survival, local relapse-free survival, and distant metastasis-free survival of these patients were analyzed by using the Kaplan-Meier method; differences were compared by using the log-rank test.The frequency of anatomic masticator space involvement was 19.7% (182 of 924 patients). With use of multivariate analysis, anatomic masticator space involvement was identified as an independent prognostic factor for overall survival (P = .02). In addition, anatomic masticator space involvement was associated with a marginally significant decrease in local relapse-free survival (P = .05); however, it had no effect on distant metastasis-free survival. There were no statistically significant differences between different degrees of anatomic masticator space involvement with regard to overall survival and local relapse-free survival in NPC (P = .34 and P = .54, respectively) or between T3 or T4 disease and anatomic masticator space involvement with regard to overall survival and local relapse-free survival (P = .63 and P = .44, respectively).Anatomic masticator space involvement affects the overall survival and local relapse-free survival of patients with NPC. When masticator space involvement includes the medial and lateral pterygoid muscles, the disease should be classified as stage T4.

To investigate the prognostic significance of prevertebral space involvement (PSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT).A retrospective review of data from 506 biopsy-proven, nonmetastatic NPCs was performed. Patients underwent magnetic resonance imaging examinations and received IMRT as their primary treatment.In this series, 161 NPC patients (31.8%) had PSI. Parapharyngeal space (p0.001), skull base (p0.001), and paranasal sinuses (p = 0.009) were associated with PSI after multivariate analysis. The 4-year overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS) for NPC patients with and without PSI was 69.1% and 89.2% (p0.0001), 83.9% and 96.4% (p0.0001), and 71.6% and 89.6% (p0.0001), respectively. Multivariate analysis identified PSI as an independent negative prognostic factor for both OS (HR = 1.478-4.380; p = 0.001) and DMFS (HR = 1.389-4.174; p = 0.002). Patients with PSI had similar survival rates in OS and DMFS (p = 0.241 and p = 0.493, respectively) to that of T4 disease, while the differences between PSI and T3 disease in both OS and DMFS were distinctly significant (p = 0.029 and p = 0.029, respectively).For NPC patients treated with IMRT, PSI was found to be an independent prognostic factor for both OS and DMFS. It seems reasonable that PSI should be classified as a T4 disease on the basis of the current American Joint Committee on Cancer staging classification criteria.

Purpose To evaluate the 7th edition of the International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system for nasopharyngeal carcinoma (NPC) in patients treated with intensity-modulated radiotherapy. Methods and materials We performed a retrospective data review from 512 patients with biopsy-proven, nonmetastatic NPC in our cancer center (South China) between January 2003 and December 2006. Results The local relapse-free survival rates (LRFS) and disease failure-free survival rates (DFS) in the 6th edition system T1 and T2a stages were not significantly different (P = 0.629 and P = 0.820), while the LRFS and DFS of T1 and T2 using the 7th edition system were significantly different (P = 0.019 and P = 0.009). The LRFS and DFS between T2 and T3 in the 7th edition systems were lack of significance (P = 0.874 and P = 0.589). The total difference in distant metastasis-free survival rate and DFS between N0 and N3 was slightly larger using the 7th edition system than the 6th edition. The nodal dimension of a cervical lymph node was not a significant prognostic factor. Conclusions We observed a better segregation of survival curves by using the 7th edition system. It seems reasonable to downstage T3 as T2 and reject nodal greatest dimension from the N-staging system in the future revised edition.

Background and objective The Chinese 2008 staging system for nasopharyngeal carcinoma (NPC) was a common set of recommendations by initial revision of the previous'92 staging system. This study was to verify the Chinese 2008 staging system and to provide evidence for its further revision. Methods Between January 2003 and December 2004, 924 consecutive patients with newly diagnosed, nondisseminated biopsy-proven NPC, presented at the Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, were entered into our study. All patients received magnetic resonance imaging examination of the neck and nasopharynx before treatment. According to the principle of the staging system, the indices of hazard consistency, hazard discrimination, prognostic value, and distribution were used to evaluate the Chinese 2008 staging system. Results According to the Chinese 2008 staging system, the distribution of stage group for the whole series was 4.9% for the stage I, 22.6% stage II, 38.0% stage III, and 34.5% stage IVA. As for hazard discrimination, the 4-year local relapse-free survival (LRFS) rates for T1-T4 patients were 95.4%, 93.7%, 90.5% and 79.1%, respectively. Although the separation of LRFS for all subclassifications of T-stage showed reasonable, the differences among the subgroups T1, T2, and T3 were still lack of significant statistically. The 4-year distant metastasis failure-free survival (DMFS) rates for N0-N3 patients were 89.4%, 84.3%, 73.6, and 59.2%, respectively. The 4-year overall survival (OS) rates for stage I-IV patients were 96.7%, 94.1%, 82.6% and 67.1%, respectively. As for hazard consistency, the distinctions between T3 with skull base involvement and T3 with medial pterygoid muscle in the hazard ratios of local failure (1.628 vs. 3.905) and disease failure (1.630 vs. 3.288) were large. Multivariate analyses showed that cervical nodal level, extranodal neoplastic spread, and laterality were independent prognostic factors for OS and DMFS, but maximal axial diameter was not. Conclusion Using the Chinese 2008 staging system for NPC produces an acceptable distribution of patient numbers. Stage group, T classification, and N classification represent independent prognosis factors for major endpoints. However, our study reveals several deficiencies in the current system yet.

The aim of this study was to investigate the outcome in 556 patients with locally advanced nasopharyngeal carcinomas treated by radiation therapy alone. We observed 556 patients with stage T3-4 and N0-3 carcinoma who were treated by conventional radiotherapy alone between January and December 1999. The total dose delivered to the nasopharynx was 66-80 Gy over 6.5-8 weeks and to the neck lymph nodes 60-70 Gy over 6-7 weeks. The 5-year actuarial overall survival rate (OS) reached 66.41%. The OS was higher among stage T3 patients than among stage T4 patients (69.12% vs 58.96%, p = 0.0359). Among patients with stage N0, N1, N2 and N3 disease, the OS was 73.98%, 65.96%, 57.58% and 29.39%, respectively (p = 0.0009). Differences in disease-free survival, locoregional control rate and metastasis-free survival rate among each N stage were statistically significant, although this was not true of differences between stage T3 and T4 disease. Multivariate analysis showed that gender, age, T stage and N stage were significant prognostic factors for 5-year overall survival, disease-free survival, locoregional control and metastasis-free survival. We found that N stage is the dominant prognostic indicator for patients with locally advanced nasopharyngeal carcinoma receiving conventional radiation therapy alone, and that T stage was only a secondary correlative factor.

BACKGROUND: For this report, the authors analyzed the spread pattern of lymph node (LN) metastases in patients with nasopharyngeal carcinoma (NPC) by using magnetic resonance imaging (MRI). In addition, the efficacy of selective neck irradiation was assessed based on the volume irradiated. METHODS: This was a retrospective review of data from 924 patients with newly diagnosed and nondisseminated NPC who underwent MRI and treatment between January 2003 and December 2004. RESULTS: According to the criteria for involved LNs detected by MRI, the incidence of LN metastases was 85.1% (786 of 924 patients). An analysis of the distribution of LN metastases in these 786 patients demonstrated that the retropharyngeal LNs (RLN) and Level II LNs were the most frequently involved regions, followed in order by Level III and Level V LNs, Level IV LNs, and supraclavicular fossa (SCF) LNs. In only 4 of 786 patients (0.5%) did metastasis skip LNs in their progression. In addition, 5 of 354 patients (1.4%) who had unilateral, higher level LN metastases (including RLNs and Level II LNs) had contralateral or bilateral, lower level LN involvement (including Level III, Level IV, Level V, and SCF LNs). In patients who had LN-negative (N0) disease, the risks of regional recurrence and distant metastasis did not differ statistically between patients with inferior border of the neck irradiation field either at the cricoid cartilage or below the cricoid cartilage. CONCLUSIONS: By using MRI, LN metastases spread in an orderly fashion from higher level LNs to lower level LNs. The current results did not support prophylactic irradiation of Level IV and SCF LNs in patients who were negative for LN metastases, and these concepts need to be tested clinically before they may be recommended generally. Cancer 2009. © 2008 American Cancer Society.

Purpose: To evaluate the prognostic value of variables including nodal size, level, laterality, extranodal neoplastic spread (ENS), and necrosis in patients with nasopharyngeal carcinoma (NPC) and further explore the feasibility of an N-staging system using Radiation Therapy Oncology Group (RTOG) guidelines for lymph node levels based on magnetic resonance imaging (MRI). Experimental Design: The MRI scans of 924 patients with histologically diagnosed nondisseminated NPC were reviewed retrospectively. The distribution of the tumors was mapped using RTOG guidelines and laterality. The multiplicity of each tumor was calculated, as well as the size and status of ENS and the necrosis of individual nodes. Results: Nodal level, cervical lymph node laterality, and ENS were independent prognostic factors for disease failure and distant failure in multivariate analyses. There was no significant difference in the hazard ratios (HR) for distant failure between level II and retropharyngeal, level Ib, level V, or level III involvement, whereas patients with level IV and supraclavicular fossa involvement had a significant increase in HRs. The subsets that made up a given N stage group had similar HRs for distant failure. Both the HRs for disease failure and distant failure by the proposed N staging system between one stage and the next were statistically significant (P < 0.05). The survival curves of disease-free survival and distant metastasis-free survival for all subclassifications of N stage showed significant difference from the adjacent stage (P < 0.05). The overall distribution pattern of the proposed N staging was more equitable than that of the 6th American Joint Committee on Cancer N staging. Conclusions: Nodal variables including level, cervical lymph node laterality, and ENS are independent prognostic factors for NPC. The proposed N staging system of NPC using RTOG guidelines based on MRI is highly predictive and may provide a more objective method for staging NPCs.

To define by MRI the local extension patterns in patients presenting with nasopharyngeal carcinoma (NPC) and to improve clinical target volume delineation.Consecutive patients (N = 943) with newly diagnosed and untreated NPC were included in this study. All patients underwent MRI of the nasopharynx and neck, which was reviewed by two radiologists.According to the incidence rates of tumor invasion, the anatomic sites surrounding the nasopharynx were initially classified into three risk grades: high risk (or = 35%), medium risk (or = 5-35%), and low risk (5%). Incidence rates of tumor invasion into anatomic sites at medium risk were increased, reaching 55.2%, when adjacent high-risk anatomic sites were involved. However, the rates were substantially lower, mostly10%, when adjacent high-risk sites were not involved. The incidence rates of concurrent tumor invasion into bilateral sites were10%, except in the case of prevertebral muscle involvement (13.1%). Among the 178 incidences of cavernous sinus invasion, there were often two or more simultaneous infiltration routes (60.6%); when only one route was involved, the foramen ovale was the most common (26.4%).In patients presenting with NPC, local disease spreads stepwise from proximal sites to more distal sites. Tumors extend quickly through privileged pathways such as neural foramina. The anatomic sites surrounding the nasopharynx are at low risk of concurrent bilateral tumor invasion. Selective radiotherapy of the local disease in NPC may be feasible.

BACKGROUND. Retropharyngeal lymph node (RLN) metastasis was not included in the current American Joint Committee on Cancer (AJCC) staging system (6th edition) for nasopharyngeal carcinoma (NPC).The object of the current study was to investigate the prognostic value and staging categories of RLN metastasis in NPC detected by magnetic resonance imaging (MRI). METHODS. All 924 consecutive patients with newly diagnosed NPC were examined with MRI before treatment with definitive intent radiotherapy. RESULTS. The incidence of RLN metastasis was 73.5%. On multivariate analysis, RLN metastasis was found to be an independent prognostic factor for distant metastasis-free survival (DMFS) in all patients (P = .040). In patients with N0 disease, significant differences were observed between patients with and those without RLN metastasis after adjusting for T classification (P = .046). With regard to laterality, no significant differences were observed in DMFS between patients with unilateral and bilateral RLN metastasis in N0 disease (P = .734). No significant difference in the hazards ratios for either DMFS or disease-free survival (DFS) was found between patients with N0 disease with RLN metastasis and patients with N1 disease (P = .092 and P = .149, respectively). When RLN was classified as N1 disease, there was a better segregation of different N classifications in terms of DFS and DMFS curves, whereas the difference in hazards ratios for N0 and N1 disease was more obvious in DMFS (from 0.461 vs 0.785 to 0.317 vs 0.690). CONCLUSIONS. The results of the current MRI-based study demonstrate that RLN metastasis affects the DMFS rates of NPC. The authors propose that RLN metastasis be classified as N1 disease, regardless of its laterality. Cancer 2008. ©2008 American Cancer Society.

Purpose To use magnetic resonance imaging to re-evaluate and improve the 6th edition of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma. Methods and Materials We performed a retrospective review of the data from 924 biopsy-proven nonmetastatic nasopharyngeal carcinoma cases. All patients had undergone magnetic resonance imaging examinations and received radiotherapy as their primary treatment. Results The T classification, N classification, and stage group were independent predictors. No significant differences in the local failure hazards between adjacent T categories were observed between Stage T2b and T1, Stage T2b and T2a, and Stage T2b and T3. Although the disease failure hazards for Stage T1 were similar to those for Stage T2a, those for Stage T2b were similar to those for Stage T3. Survival curves of the different T/N subsets showed a better segregation when Stage T2a was downstaged to T1, T2b and T3 were incorporated into T2, and the nodal greatest dimension was rejected. The disease failure hazard for T3N0-N1 subsets were similar to those of the T1-T2N1 subsets belonging to Stage II; the same result was found for the T4N0-N2 subsets in the sixth American Joint Committee on Cancer staging system. However, the staging system we propose shows more consistent hazards within the same stage group and better survival discrimination among T categories, N categories, and overall stages. Conclusion Using the 6th American Joint Committee on Cancer staging system produces an acceptable distribution of patient numbers and segregation of survival curves among the different stage groups. The prognostic accuracy of the staging system could be improved by recategorizing the T, N, and group stage criteria.

To analyze the degree and pattern of influence of magnetic resonance imaging (MRI) on staging according to the 6th edition of the American Joint Committee on Cancer staging system compared with computed tomography (CT).The MRI and CT scans and medical records of 420 consecutive patients with newly diagnosed nasopharyngeal carcinoma (NPC) were analyzed retrospectively. The tumors of all patients were staged according to the 6th edition of the American Joint Committee on Cancer staging system.A significant difference (p0.05) was found between CT and MRI in demonstrating involvement in the oropharynx (CT, 25.0% vs. MRI, 14.5%), prevertebral muscle (CT, 18.4% vs. MRI, 36.0%), parapharyngeal space (CT, 82.6% vs. MRI, 68.8%), skull base (CT, 31.0% vs. MRI, 52.6%), sphenoid sinus (CT, 13.6% vs. MRI, 16.7%), ethmoid sinus (CT, 7.1% vs. MRI, 3.3%), intracranial area (CT, 4.8% vs. MRI, 16.0%), and retropharyngeal lymph nodes (CT, 52.1% vs. MRI, 69.0%). The incidence of cervical lymph node metastasis and lymph node metastasis at each level was similar according to CT and MRI. MRI resulted in changes in 49.8% of T stage cases, 10.7% of N stage cases, and 38.6% of clinical stage cases.MRI demonstrated early primary tumor involvement more precisely and deep primary tumor infiltration more easily. The use of MRI caused dramatic changes in the results of the T stage and clinical staging and should be preferred to CT in staging NPC. Patients would benefit from changes in treatment strategies resulting from the use of MRI.

We investigated the prognostic value and gradation of the T category in N0 nasopharyngeal carcinoma (NPC) patients undergoing magnetic resonance imaging (MRI) and intensity-modulated radiotherapy (IMRT). A total of 749 patients were retrospectively reviewed, and a total of 181 N0 NPC patients were included in this retrospective study. All patients were restaged according to the 7th edition of the American Joint Committee on Cancer staging system. The following endpoints were estimated: overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS). The 5-year survival rates for T1 to T4 were: OS (97.3%, 100.0%, 86.1%, and 82.8%; P = 0.007), PFS (94.6%, 96.9%, 76.5%, and 76.7%; P = 0.002), LRFS (98.5%, 100.0%, 92.2%, and 86.7%; P

Ruiwan Chen,1,* Yafei Xu,2,* Xiaojing Du,2,* Na Liu,2 Yingqin Li,2 Qingmei He,2 Linglong Tang,2 Yanping Mao,2 Ying Sun,2 Lei Chen,2,* Jun Ma2,* 1Department of Radiotherapy, The First Affiliated Hospital, Sun Yat-sen University, 2Department of Radiation Oncology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic ofChina *These authors contributed equally tothis work Abstract: The chemokine receptor 4/chemokine ligand 12 (CXCR4/CXCL12) axis plays an important role in tumorigenesis, metastasis, and recurrence of tumors. Its single nucleotide polymorphisms (SNPs) are associated with patient survival in several types of cancer. However, the prognostic value of SNPs in nasopharyngeal carcinoma (NPC) has not been fully investigated. This retrospective study assessed the relationships between CXCR4 rs2228014 and CXCL12 rs1801157 polymorphisms and patient outcome in 222 patients newly diagnosed with NPC. The analysis found no significant correlation between the presence of both SNPs and clinicopathological factors. However, univariate analysis showed that N classification, clinical stage, and the CXCL12 rs1801157 polymorphism were significantly associated with distant metastasis-free survival (P=0.018, 0.028, and 0.013, respectively) and progression-free survival (P=0.007, 0.046, and 0.021, respectively). After adjusting clinicopathological factors, multivariate analysis identified CXCL12 rs1801157 as an independent prognostic factor for distant metastasis-free survival and progression-free survival (hazard ratio: 3.332; 95% confidence interval: 1.597–6.949; P=0.001 and hazard ratio: 2.665 95% confidence interval: 1.387–5.119; P=0.003, respectively). Our results suggest that CXCL12 rs1801157 AA genotype might serve as a potential prognostic factor in patients with NPC. Keywords: nasopharyngeal carcinoma, CXCR4, CXCL12, polymorphism, prognosis

Background The development of intensity-modulated radiotherapy (IMRT) has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the prognostic value and classification of TNM stage system for retropharyngeal lymph node (RLN) metastasis in NPC in the IMRT era. Material and Methods We retrospectively reviewed data from 749 patients with biopsy-proven, non-metastatic NPC. All patients received IMRT as the primary treatment. Chemotherapy was administered to 86.2% (424/492) of the patients with stage III or IV disease. Results The incidence of RLN metastasis was 64.2% (481/749). Significant differences were observed in the 5-year disease-free survival (DFS; 70.6% vs. 85.4%, P

Background Intensity-modulated radiation therapy (IMRT) provides excellent locoregional control for nasopharyngeal carcinoma (NPC), and has gradually replaced two-dimensional conventional radiotherapy as the first-line radiotherapy technique. Furthermore, in the new seventh edition of the American Joint Committee on Cancer (AJCC) staging system, retropharyngeal lymph nodes were upgraded from N0 to N1 disease as a result of their negative impact on the distant metastasis-free survival (DMFS) rates of NPC. This retrospective study was conducted in order to review the treatment outcomes and patterns of failure in NPC patients with N0 disease after IMRT in order to effectively guide treatment in the future. Methods We retrospectively reviewed data from 506 biopsy-proven nonmetastatic NPC patients. There were 191 patients with negative cervical lymph node involvement. According to the seventh edition of the American Joint Committee on Cancer (AJCC) staging system, 110 patients (21.7%) were staged with N0 disease, and 81 patients (16.0%) were reclassified with N1 disease due to the presence of RLN metastasis. All patients received IMRT as the primary treatment. Results In patients with negative cervical lymph node involvement, distant metastasis-free survival (DMFS) was significantly higher in patients without retropharyngeal lymph node (RLN) metastasis than those with RLN metastasis (95.9% vs. 88.1% respectively, P = 0.04). For N0 disease, the 5-year overall survival (OS), local relapse-free survival (LRFS), nodal relapse-free survival (NRFS) and DMFS rates were 93.8%, 97.1%, 99.1% and 95.9%, respectively. For T1N0, T2N0, T3N0 and T4N0, OS was 97.8%, 100%, 93.8% and 76.9%, LRFS was 100%, 92.9%, 100% and 88.9% and DMFS was 96.6%, 90.9%, 100% and 93.3%, respectively. OS and LRFS were higher in T1-3 N0 patients than T4N0 patients (P < 0.01 and P = 0.01, respectively). Conclusions The seventh edition of the AJCC N-staging system improves prognostic accuracy by upgrading RLN metastasis to N1 disease. IMRT produces excellent survival rates in T1-3 N0 disease; however, T4N0 disease remains a challenge and additional improvements are required to achieve a favorable prognosis for these NPC patients.

Background Talin-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). Methods Talin-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. Results The 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

Introduction It is important to decrease the radiation exposure of normal tissue in intensity-modulated radiation therapy (IMRT). Minimizing planning target volume (PTV) margins with more precise target localization techniques can achieve this goal. This study aimed to quantify the extent to which organs at risk (OARs) are spared when using reduced margins in the treatment of nasopharyngeal carcinoma (NPC). Methods Two IMRT plans were regenerated for 40 patients with NPC based on two PTV margins, which were reduced or unchanged following cone beam computed tomography online correction. The reduced-margin plan was optimized based on maximal dose reduction to OARs without compromising target coverage. Dosimetric comparisons were evaluated in terms of target coverage and OAR sparing. Results Improvements in target coverage occurred with margin reduction, and significant improvements in dosimetric parameters were observed for all OARs (P

Background Metastasis remains the major cause of death in nasopharyngeal carcinoma (NPC). Yippee-like 3 (YPEL3) plays an important role in tumorigenesis. However, its function and mechanism in NPC has not been systematically explored. Methods We evaluated YPEL3 expression in NPC cell lines and tissues using real-time PCR and western blotting. Then, we established NPC cell lines that stably overexpressed YPEL3 and knocked down YPEL3 expression to explore its function in NPC in vitro and in vivo. Additionally, we investigated the potential mechanism of YPEL3 action by identifying the Wnt/β-catenin signaling pathway downstream genes using western blotting. Results YPEL3 was downregulated in NPC cell lines and tissue samples. Ectopic expression of YPEL3 inhibited NPC cell migration and invasion in vitro; while silencing of YPEL3 promoted NPC cell migration and invasion. Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial–mesenchymal transition (EMT) and that silencing it enhanced EMT. Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo. The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/β-catenin signaling pathway downstream genes and the nuclear translocation of β-catenin. Conclusions YPEL3 suppresses NPC EMT and metastasis by suppressing the Wnt/β-catenin signaling pathway, which would help better understanding the molecular mechanisms of NPC metastasis and provide novel therapeutic targets for NPC treatment.

Background To evaluate the influence of the progonistic nutritional index (PNI) and weight loss on metastasis and long-term mortality in nasopharyngeal carcinoma (NPC). Methods We retrospectively reviewed 694 newly diagnosed patients with non-disseminated, biopsy-proven NPC. Survival analysis was used to evaluate the predictive value of PNI and weight loss. Results Multivariate analysis demonstrated that a low pre-therapy PNI (

Background Nasopharyngeal carcinoma (NPC) shows a high proportion of lymph node metastasis, and treatment guidelines have been developed for positive nodes. However, no irradiation guidelines have been proposed for patients with enlarged neck lymph nodes (ENLNs) that do not meet the radiological criteria of 10 mm in diameter for positive lymph nodes. This study aimed to determine the prognostic value and radiation dose for ENLNs in N0-category NPC patients treated with intensity-modulated radiotherapy (IMRT). Methods We reviewed the medical data of 251 patients with non-metastatic, N0-category NPC treated with IMRT. Receiver operating characteristic curves were used to calculate the cut-off value of the ENLN diameter for the prediction of disease failure. The biological equivalent dose (BED) for ENLNs was calculated. Patient survival was compared between the small and large ENLN groups. Independent prognostic factors were identified using the Cox proportional hazards model. Results The estimated 4-year regional relapse-free survival rate was higher in patients with ENLNs ≥5.5 mm than in those with ENLNs 0.05 for all survival rates). In the subgroup analysis, patients receiving BED ≥72 Gy had a similar prognosis as patients receiving BED

Background To identify the radiation volume effect and significant dosimetric parameters for temporal lobe injury (TLI) and determine the radiation dose tolerance of the temporal lobe (TL) in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT). Methods Twenty NPC patients with magnetic resonance imaging (MRI)-diagnosed unilateral TLI were reviewed. Dose-volume data was retrospectively analyzed. Results Paired samples t-tests showed all dosimetric parameters significantly correlated with TLI, except the TL volume (TLV) and V75 (the TLV that received ≥75 Gy, P = 0.73 and 0.22, respectively). Receiver operating characteristic (ROC) curves showed V10 and V20 (P = 0.552 and 0.11, respectively) were the only non-significant predictors from V10 to V70 for TLI. D0.5cc (dose to 0.5 ml of the TLV) was an independent predictor for TLI (P 0.5cc was 0.843 (P Conclusions A D0.5cc of 69 Gy may be the dose tolerance of the TL. The risk of TLI was highly dependent on high dose ‘hot spots’ in the TL; physicians should be cautious of such ‘hot spots’ in the TL during IMRT treatment plan optimization, review and approval.

Background MiRNAs play important roles in diverse biological processes including tumorigenesis. However, little is known about the function and mechanism of miR-451 in nasopharyngeal carcinoma (NPC). Methods Quantitative RT-PCR was used to quantify miR-451 expression in NPC cell lines and clinical tissues. Kaplan-Meier curves were used to estimate the association between miR-451 expression and survival. The MTT, colony formation, Transwell migration and invasion assays, and a xenograft model were performed. A miR-451 target was confirmed using luciferase reporter assays, quantitative RT-PCR, and Western blotting. Results MiR-451 was significantly downregulated in NPC cell lines and clinical tissues (P P = 0.01) and disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) than patients with high expression. MiR-451 was an independent prognostic factor in NPC in multivariate Cox regression analysis. Ectopic expression of miR-451 suppressed cell viability, colony formation, and cell migration and invasion in vitro, and inhibited xenograft tumor growth in vivo. MIF was verified as a direct target of miR-451, and MIF regulated NPC cell growth and invasion. Conclusions The newly identified miR-451/MIF pathway provides insight into NPC initiation and progression, and may represent a novel therapeutic target.