Rensheng Wang

Concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: treatment outcomes of a prospective, multicentric clinical study.

BACKGROUND AND PURPOSEnTo evaluate long-term outcome in locoregionally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy.nnnMATERIAL AND METHODSnBetween January 2006 and August 2008, 249 patients with stage III-IVb NPC were treated by IMRT plus concurrent chemotherapy in this multicenter prospective study.nnnRESULTSnWith a mean follow-up of 54.1 months, the 5-year actuarial rates of overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS) were 78.4%, 86.8%, 88.4%, 78.0%, respectively. There were 29 local recurrences, 25 regional recurrences and 52 distant metastases, respectively. Distant metastasis is the main cause of treatment failure. N-stage was an independent prognostic factor for LRFS, RRFS, DMFS and OS. Acute toxicity ⩾grade III mainly consisted of mucositis (34.9%), neutropenia (11.2%), xerostomia (5.6%), and dermatitis (5.2%). The main documented late toxicity was xerostomia, and the severity of xerostomia decreased over time. At 24 months after treatment, 13.2% of patients had grade 2 xerostomia, and none had grade 3 or 4 xerostomia.nnnCONCLUSIONSnIMRT with concurrent cisplatin chemotherapy resulted in encouraging rates of local and distant control and overall survival with acceptable rates of acute and limited rates of late toxicity in patients with locoregionally advanced NPC. Distant metastasis remained the main cause of failure. More effective systemic therapy should be explored for patients with advanced N-stage.

Definitive intensity-modulated radiation therapy for nasopharyngeal carcinoma: long-term outcome of a multicenter prospective study

PurposeTo evaluate long-term outcome in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy.MethodsBetween January 2006 and August 2008, 300 patients with histologically proven NPC were enrolled in this multicenter prospective study. All patients received definitive IMRT. Cisplatin-based concurrent chemotherapy was given to patients with stages III-IVb disease.ResultsMedian follow-up time was 47.1xa0months (range 11–68xa0months). Median survival time was not reached. For all patients, the 4-year local control (LC), regional control (RC), distant metastasis-free survival (DMFS), and overall survival (OS) were 94.0, 95.1, 85.0, and 86.1xa0%, respectively. Thirty-five patients experienced locoregional failures: 18 were local only, 15 were regional only, and 2 were both local and regional. Forty-two patients developed distant metastasis. Of these, 32 patients had single organ metastasis, and 10 patients had multiple organ metastasis. The most common acute toxicities were mucositis, dermatitis, and xerostomia. Grade 0–2 mucositis, dermatitis, and xerostomia occurred in 200 patients (66.7xa0%), 288 patients (96.0xa0%), and 286 patients (95.3xa0%), respectively. Grade 3 mucositis, dermatitis, and xerostomia were seen in 100 patients (33.3xa0%), 12 patients (4.0xa0%), and 14 patients (4.7xa0%), respectively. No Grade 4 acute toxicities were observed. The most common late toxicity for 284 patients who survived for more than 2xa0years was xerostomia. At 3xa0months after treatment, 16.2xa0% of patients had Grade 1, 73.6xa0% had Grade 2, and 10.2xa0% had Grade 3 xerostomia. However, the severity of xerostomia decreased over time. At 24xa0months, only 12.3xa0% of patients had Grade 2 xerostomia, and none had Grade 3 or 4 xerostomia.ConclusionsIMRT for NPC patients achieved excellent long-term locoregional control (LRC) and OS, with acceptable acute and late toxicities. After the treatment, xerostomia was improved over time. Distant metastasis remained the main cause of failure. More effective systemic therapy is demanding for reducing the risk of distant metastasis.

Current Evidence on VEGF+405G/C Polymorphism and Malignancy Susceptibility: A Meta-Analysis Involving 30 Studies

The association of VEGF+405G/C (where VEGF is vascular endothelial growth factor) polymorphism and malignancy susceptibility attracts considerable attention because VEGF is one of the most potent angiogenic factors and plays a critical role in the onset and development of malignancy. However, the published findings remain inconclusive. In order to derive a more precise assessment of the association, we performed a meta-analysis including 30 published case-control studies from PubMed, Embase, and Ovid databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. In the pooled analyses, no significant association was found between VEGF+405G/C polymorphism and malignancy susceptibility in different genetic models (G-allele vs. C-allele: OR=1.00, 95% CI: 0.93-1.07; CC vs. GG: OR=1.01, 95% CI: 0.88-1.15; GC+CC vs. GG: OR=1.00, 95% CI: 0.91-1.10; CC vs. GC+GG: OR=1.01, 95% CI: 0.90-1.13). When stratified by ethnicity, a weak association between this polymorphism and malignancy susceptibility was found in African under allelic frequency comparison (OR=0.65, 95% CI: 0.43-0.98) and dominant genetic model comparison (OR=1.95, 95% CI: 1.09-3.50). In summary, although our meta-analysis indicated a weak association of VEGF+405G/C polymorphism with malignancy susceptibility in African, no persuasive evidence of association between the polymorphism and malignancy susceptibility was detected in the pooled analyses. Therefore, more studies with larger scale of participants, especially Africans, are required to further evaluate gene-environment interaction on this polymorphism and malignancy susceptibility.

Association between MTHFR polymorphisms and acute myeloid leukemia risk: a meta-analysis.

Previous observational studies investigating the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and acute myeloid leukemia risk (AML) have yielded inconsistent results. The aim of this study is to derive a more precise estimation of the association between MTHFR (C677T and A1298C) polymorphisms and acute myeloid leukemia risk. PubMed and Embase databases were systematically searched to identify relevant studies from their inception to August 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were the metric of choice. Thirteen studies were selected for C677T polymorphism (1838 cases and 5318 controls) and 9 studies (1335 patients and 4295 controls) for A1298C polymorphism. Overall, pooled results showed that C677T polymorphism was not significant associated with AML risk(OR, 0.98–1.04; 95% CI, 0.86–0.92 to 1.09–1.25). Similar results were observed for the A1298C polymorphism and in subgroup analysis. All comparisons revealed no substantial heterogeneity nor did we detect evidence of publication bias. In summary, this meta-analysis provides evidence that MTHFR polymorphisms were not associated with AML risk. Further investigations are needed to offer better insight into the role of these polymorphisms in AML carcinogenesis.

Triptolide Combined with Radiotherapy for the Treatment of Nasopharyngeal Carcinoma via NF-κB-Related Mechanism

Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis because of the lack of an effective treatment. Here we explored the efficiency and the molecular mechanisms of combined treatment with triptolide and ionizing radiation for treating NPC. Human nasopharyngeal carcinoma (CNE) cells were treated with triptolide, ionizing radiation, or triptolide plus ionizing radiation in vitro. Tumor potency was examined in an in vivo CNE cell xenograft mouse model, which was treated as above. Our results demonstrated that triptolide caused a significant reduction in cell growth and colony number, and induced a marked apoptosis that was further enhanced with increasing doses of ionizing radiation. Combination treatment synergistically reduced tumor weight and volume without obvious toxicity. Western blot analysis in vitro and in vivo showed that triptolide induced apoptotic protein Bax expression and inhibited phosph-NF-κB p65, Bcl-2 and VEGF proteins without affecting other NF-κB related protein expression. In conclusion, our findings revealed that triptolide plus ionizing radiation had synergistic anti-tumor and anti-angiogenesis effects in NPC via down-regulating NF-κB p65 phosphorylation. The combination therapy may provide novel mechanism insights into inhibit NPC.

A new staging system for nasopharyngeal carcinoma based on intensity-modulated radiation therapy: results of a prospective multicentric clinical study

Purpose To establish a new clinical staging standard for nasopharyngeal carcinoma (NPC), based on intensity-modulated radiotherapy (IMRT), through a prospective multicenter clinical trial. Experiment Design 492 NPC patients were selected from six hospitals in the Guangxi Zhuang Autonomous Region, China from January 2006 to December 2009. Kaplan-Meier method was adopted to calculate survival rates. Log-rank test was used to compare survival differences. Results According to the seventh edition of the UICC/AJCC staging system, the differences between T1, T2 and T3 are not statistically significant, suggesting that T1, T2 and T3 could be combined as new T1. There were significant differences between all N stages except those of N3a and N3b, suggesting that N3a and N3b could be combined as new N3. Additionally, the overall survival (OS) curves of stages I, II, III and IVa were not significantly different. Therefore, we propose a new clinical NPC staging standard based on magnetic resonance imaging (MRI) and IMRT as T stage (including T1 and T2), N stage (including N0, N1, N2 and N3) and clinical staging includes I (T1N0M0), II (T1N1-2M0, T2N0M0), III (T2N1-2M0), IVa (TxN3M0) and IVb (TxNxM1). Recommended staging system performs better in risk difference and distribution balance. Furthermore, the differences in the 5-year curves of local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and OS were all statistically more significant than the seventh edition of the UICC/AJCC staging system. Conclusions Proposed staging system is more adaptable to IMRT and predicts the prognosis of NPC patients more accurately.

Tumor Volume Predicts Survival Rate of Advanced Nasopharyngeal Carcinoma Treated with Concurrent Chemoradiotherapy

Objective To delineate the prognostic value of primary gross tumor volume (GTVp) for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy. Study Design Analysis of prognostic variables in a prospective cohort. Setting Department of Radiotherapy, First Affiliated Hospital of Guangxi Medical University, China. Subjects and Methods Between January 2006 and August 2008, 249 patients with stage III-IVb NPC, all treated by intensity-modulated radiotherapy plus concurrent chemotherapy, were included in this multicenter prospective study. GTVp was measured with treatment-planning computed tomography or magnetic resonance imaging scans. Results GTVp was significantly associated with locoregional control, distant metastasis, and overall survival for patients with advanced NPC. Furthermore, T classification was not an independent prognostic factor. In receiver operator receiver operating characteristic curve analysis, 33 mL was determined as the cutoff points of GTVp for OS and locoregional control. Patients with a GTVp ≥33 mL had poorer OS, worse locoregional control, and more distant metastasis than patients with a GTVp <33 mL (P = .006, .009, .002, and .007, respectively). Conclusions GTVp had significant prognostic value for patients with advanced NPC. The incorporation of GTVp could improve the current TNM classification system.

A new staging system for nasopharyngeal carcinoma based on intensity-modulated radiation therapy (IMRT)

Objective This study is to establish a new staging system for nasopharyngeal carcinoma (NPC) based on the magnetic resonance imaging (MRI) and intensity-modulated radiation therapy (IMRT). Methods Totally 492 patients with nasopharyngeal carcinoma were included in this study. These patients were diagnosed by pathological detection (without distant metastasis) and underwent the initial treatment of IMRT. These patients were subjected to the staging with the International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system. Survival rates were calculated by the Kaplan-Meier method. Log-rank test was used to calculate the single factor prognosis, and the COX risk model was used to analyze the multivariate prognosis. Results In these 492 patients, according to our recommended new T and N staging criteria, there were 290 cases of T1 and 202 cases of T2; there were 64 cases of N0, 159 cases of N1, 226 cases of N2, and 43 cases of N3. Univariate and multivariate analyses showed that the T and N staging combination parameters were independent prognostic factors, which affected the overall survival rates and tumor-free survival rates. According to risk difference and survival curve distribution, the following new clinical staging criteria were established: stage I (T1N0M0), stage II (T1N1M0 and T2N0M0), stage III (T1N2M0 and T2N1-2M0), stage IVa (T1-2N3M0), and stage IVb (TxNxM1). Conclusion A new staging system for NPC based on MRI and IMRT has been recommended, which provides valuable evidence for disease treatment and prognosis prediction.

Validation of the 8th edition of the UICC/AJCC staging system for nasopharyngeal carcinoma treated with intensity-modulated radiotherapy

An accurate TNM staging system is crucial for treatment guidance and prognosis prediction in nasopharyngeal carcinoma (NPC) patients. In this retrospective study, we evaluated the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system for NPC treated with intensity-modulated radiotherapy (IMRT). A total of 608 patients with biopsy-proven, non-metastatic NPC, treated with IMRT between January 2008 and March 2010, were enrolled. The 5-year overall survival (OS), disease-free survival (DFS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 81.5%, 80.1%, 86.0%, and 81.1%, respectively. The LRFS rates of patients with stages T1 vs. T2, T2 vs. T3, and T1 vs. T3 did not differ between the 7th and 8th editions. By contrast, the DMFS rates of patients with N0 vs. N1, N1 vs. N2, and N2 vs. N3 differed between the 8th and the 7th editions, though no difference was observed between N3a and N3b, according to the 7th edition. The difference in OS between stages II and III, and between stages III and IVa, was larger according to the 8th edition than the 7th edition. There was no difference in the OS between stages I and II. These data indicate that in the IMRT era, the 8th edition staging system can predict the prognosis of NPC patients more accurately than the 7th edition.

A novel N staging system for NPC based on IMRT and RTOG guidelines for lymph node levels: Results of a prospective multicentric clinical study

The present study aimed to investigate the cervical lymph node metastasis of nasopharyngeal carcinoma (NPC) and to establish a novel N staging standard for NPC, based on intensity modulated radiation therapy (IMRT) via a prospective multicenter clinical trial. Between January 2006 and December 2009, a total of 492 patients with NPC without distant metastasis were included in the present study. All patients were treated with IMRT. According to Radiation Therapy Oncology Group division standards, the present study proposed a novel N staging system following the review of magnetic resonance images in comparison with the 7th edition of Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system. Retropharyngeal lymph nodes, cervical lymph node level and cervical lymph node laterality were independent prognostic factors used in multivariate analyses. According to the results of the risk variety, the present study suggested that the novel N staging system included: N0 (no lymph node metastasis), N1 [retropharyngeal or/and unilateral upper cervical (I, II, III, Va, VIIb, VIII, IX and X regions) lymph node metastasis], N2 [bilateral upper cervical (I, II, III, Va, VIIb, VIII, IX and X regions) lymph node metastasis] and N3 (lymph node metastasis in IVa and Vb regions and their lower regions). The novel N staging system proposed in the present study performs better in risk difference and distribution balance. Furthermore, the differences of 5-year curves of distant metastasis-free survival and overall survival had greater statistically significant differences compared with the 7th edition of the UICC/AJCC staging system. The present study suggested a novel N staging system for cervical lymph node metastasis of NPC, which may predict the prognosis of patients with NPC in a more objective and accurate way.