Wei Xiong Xia

A prognostic model predicts the risk of distant metastasis and death for patients with nasopharyngeal carcinoma based on pre-treatment serum C-reactive protein and N-classification.

PURPOSE Chronic inflammation plays an important role in nasopharyngeal carcinoma (NPC) development and progression. Aim of this study is to determine whether inflammation-related parameters predict distant metastasis in NPC patients. MATERIALS AND METHODS 335 newly diagnosed non-metastatic NPC patients were recruited. The values of the C-reactive protein (CRP), lactate dehydrogenase, albumin, globulin, white blood cell and neutrophil at baseline were measured. RESULTS Among the above six parameters, only CRP was independently associated with distant metastasis-free survival (DMFS). CRP concentration of advanced T-/TNM-classification patients was higher than those with early classification (P = 0.001). Higher-CRP (CRP ⩾ 2.46 mg/L) predicted shorter overall survival, disease-free survival and DMFS than lower-CRP (CRP < 2.46 mg/L). In a multivariable model, higher-CRP and advanced N-classification were independent predictors of distant metastasis. On the basis of these two parameters, a prognostic NC-model was developed as following: (1) low-risk (early N-classification and lower-CRP); (2) intermediate-risk (advanced N-classification or higher-CRP) and (3) the high-risk distant metastasis (advanced N-classification and higher-CRP). When compared with the low-risk group, the hazard ratios (HRs) for distant metastasis and death for the intermediate-/high-risk patients were 3.6/16.1 and 2.26/7.61, respectively (both P < 0.001). CONCLUSION We developed a new prognostic model based on CRP and N-classification for predicting distant metastasis and death of NPC patients, which may facilitate patient counselling and individualised treatment.

Occipital lymph node metastasis from nasopharyngeal carcinoma: a special case report and literature review

Cervical lymph node metastasis is common in patients with nasopharyngeal carcinoma (NPC), but occipital lymph node metastasis in NPC patients has not yet been reported. In this case report, we describe an NPC patient with occipital lymph node metastasis. The clinical presentation, diagnostic procedure, treatment, and outcome of this case were presented, with a review of the related literature.

Favorable prognosis of female patients with nasopharyngeal carcinoma

The female sex is traditionally considered a favorable prognostic factor for nasopharyngeal carcinoma (NPC). However, no particular study has reported this phenomenon. To explore the prognostic impact of gender on patients with NPC after definitive radiotherapy, we reviewed the clinical data of 2063 consecutive patients treated between 1st January 2000 and 31st December 2003 in the Sun Yat-sen University Cancer Center. The median follow-up for the whole series was 81 months. The female and male patients with early stage disease comprised 49.4% and 28.1% of the patient population, respectively. Both the 5-year overall survival (OS) and disease-specific survival (DSS) rates of female patients were significantly higher than those of male patients (OS: 79% vs. 69%, P < 0.001; DSS: 81% vs. 70%, P < 0.001). For patients with locoregionally advanced NPC, the 5-year OS and DSS rates of female vs. male patients were 74% vs. 63% (P < 0.001) and 76% vs. 64%, respectively (P < 0.001). A multivariate analysis showed that gender, age, and TNM stage were independent prognostic factors for the 5-year OS and DSS of NPC patients. The favorable prognosis of female patients is not only attributed to the early diagnosis and treatment but might also be attributed to some intrinsic factors of female patients.

Prospective study of prognostic value of Raf kinase inhibitory protein and pretreatment plasma Epstein-Barr virus DNA for distant metastasis in locoregionally advanced nasopharyngeal carcinoma

The purpose of this prospective study was to investigate the predictive significance of Raf kinase inhibitory protein (RKIP) in locoregionally advanced nasopharyngeal carcinoma (NPC) and its effect on distant metastasis.

Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II–IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised phase 3 trial

BACKGROUND Cisplatin-based concurrent chemoradiotherapy is currently considered to be the standard treatment regimen for patients with advanced nasopharyngeal carcinoma, but has well known side-effects such as gastrointestinal reactions, nephrotoxicity, and ototoxicity. Nedaplatin was developed to decrease the toxic effects induced by cisplatin, and in this trial we assessed whether a nedaplatin-based concurrent chemoradiotherapy regimen was non-inferior to a cisplatin-based regimen in patients with locoregional, stage II-IVB nasopharyngeal carcinoma. METHODS We did an open-label, non-inferiority, phase 3, randomised, controlled trial at two centres in China. Patients aged 18-65 years with non-keratinising stage II-IVB (T1-4N1-3 or T3-4N0) nasopharyngeal carcinoma, a Karnofsky score of at least 70, and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either nedaplatin 100 mg/m2 or cisplatin 100 mg/m2 on days 1, 22, and 43 for three cycles concurrently with intensity-modulated radiotherapy. Randomisation was done manually using a computer-generated random number code and patients were stratified by treatment centre and clinical stage. Patients and clinicians were not masked to treatment allocation. The primary endpoint was progression-free survival at 2 years; non-inferiority was shown if the upper limit of the 95% CI for the difference in 2-year progression-free survival between the two groups did not exceed 10%. Analyses were by both intention to treat and per protocol, including all patients who received at least one complete cycle of chemotherapy. This trial is registered with ClinicalTrials.gov, number NCT01540136, and is currently in follow-up. FINDINGS Between Jan 16, 2012, and July 16, 2014, we randomly assigned 402 patients to nedaplatin-based (n=201) or cisplatin-based (n=201) concurrent chemoradiotherapy. In the intention-to-treat population, 2-year progression-free survival was 89·9% (95% CI 85·8-94·0) in the cisplatin group and 88·0% (83·5-94·5) in the nedaplatin group, with a difference of 1·9% (95% CI -4·2 to 8·0; pnon-inferiority=0·0048). In the per-protocol analysis (cisplatin group, n=197; nedaplatin group, n=196), 2-year progression-free survival was 89·7% (95% CI 85·4-94·0) in the cisplatin group and 88·7% (84·2-94·5) in the nedaplatin group, with a difference of 1·0% (95% CI -5·2 to 7·0; pnon-inferiority=0·0020). A significantly higher frequency of grade 3 or 4 vomiting (35 [18%] of 198 in the cisplatin group vs 12 [6%] of 200 in the nedaplatin group, p<0·0001), nausea (18 [9%] vs four [2%], p=0·0021), and anorexia (53 [27%] vs 26 [13%], p=0·00070) was observed in the cisplatin group compared with the nedaplatin group. 11 (6%) patients in the nedaplatin group had grade 3 or 4 thrombocytopenia compared with four (2%) in the cisplatin group (p=0·065). Patients in the cisplatin group had a higher frequency of any grade or grade 3 or 4 late auditory or hearing toxicities than did patients in the nedaplatin group (grade 3 or 4: three [2%] in the nedaplatin group vs 11 [6%] in the cisplatin group, p=0·030). No patients died from treatment-related causes. INTERPRETATION Our findings show that nedaplatin-based concurrent chemoradiotherapy represents an alternative doublet treatment strategy to cisplatin-based concurrent chemoradiotherapy for patients with locoregional, advanced nasopharyngeal carcinoma. Further investigations are needed to explore the potential use of this treatment as induction or adjuvant chemotherapy or in combination with other agents. FUNDING National Key R&D Program of China, National Natural Science Foundation of China, Sun Yat-sen University Clinical Research 5010 Program, Sci-Tech Project Foundation of Guangzhou City, National Key Basic Research Program of China, Special Support Plan of Guangdong Province, Sci-Tech Project Foundation of Guangdong Province, Health & Medical Collaborative Innovation Project of Guangzhou City, National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, PhD Start-up Fund of Natural Science Foundation of Guangdong Province, Cultivation Foundation for the Junior Teachers in Sun Yat-sen University, and Fundamental Research Funds for the Central Universities.

Combining cetuximab with chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma: A propensity score analysis

OBJECTIVE To compare the effectiveness of concurrent cisplatin chemoradiotherapy plus cetuximab with that of concurrent chemoradiotherapy (CCRT) alone in locoregionally advanced nasopharyngeal carcinoma (LRANPC) patients. MATERIALS AND METHODS A total of 3257 LRANPC patients from a prospectively maintained database were included in this observational study to examine the effectiveness of adding cetuximab to CCRT. We compared overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) using the propensity score method. RESULTS In this cohort, 131 patients received CCRT plus cetuximab. Cetuximab-treated patients were more likely to receive intensity-modulated radiation therapy and were less likely to receive induction chemotherapy or adjuvant chemotherapy. The addition of cetuximab was associated with increased DMFS compared with CCRT alone based on univariable and multivariable analyses (5-year OS, 94.1% vs. 87.3%; P=0.044), but not with increased OS, DFS, or LRRFS. Propensity score matching identified 96 patients in each cohort and confirmed that a DMFS benefit was associated with the addition of cetuximab (HR, 0.38; 95% CI, 0.15-0.99, P=0.044). Subgroup analyses demonstrated a significant DMFS benefit with CCRT plus cetuximab in patients with N2-N3 stage disease compared with N2-N3 patients receiving CCRT alone (87.9% and 66.2%, respectively; P=0.045). CONCLUSIONS In conclusion, the addition of cetuximab to first-line chemoradiotherapy is associated with an improvement in DMFS in patients with LRANPC. A prospective randomized clinical trial will be necessary to validate this result.

The CXCL5/CXCR2 axis contributes to the epithelial-mesenchymal transition of nasopharyngeal carcinoma cells by activating ERK/GSK-3β/snail signalling

BackgroundDistant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear.MethodsQuantitative RT-PCR (qRT-PCR), western blotting, cell growth, foci formation, migration and invasion assays, and xenograft mouse models were utilized to examine the expression levels and functions of the CXCL5/CXCR2 axis in NPC. A luciferase reporter assay, western blotting, immunofluorescence, and migration and invasion assays were used to identify and verify the ERK/GSK-3β/Snail signalling pathway.ResultsCXCL5 was significantly increased in the sera of NPC patients, and high expression levels of CXCL5/CXCR2 in NPC primary tissues indicated poor survival. CXCL5 and CXCR2 were upregulated in NPC cell lines. Ectopic expression of the CXCL5/CXCR2 axis promoted NPC cell migration and invasion in vitro and the formation of lung metastases in vivo. Mechanistically, the dual overexpression of CXCL5 and CXCR2 promoted cell spreading by inducing the epithelial-mesenchymal transition (EMT) through the activation of the ERK/GSK-3β/Snail signalling pathway.ConclusionThe CXCL5/CXCR2 axis contributes to the EMT of NPC cells by activating ERK/GSK-3β/Snail signalling, and this axis may be a potential diagnostic marker and therapeutic target for patients with NPC.