<p>Supplementary materials including supplementary figures and tables Supplementary Figure S1. Flowchart of randomized controlled trial selection. AC, adjuvant chemotherapy; CCRT, concurrent chemoradiotherapy; GZ, Guangzhou; HeCOG, Hellenic Cooperative Oncology Group; IC, induction chemotherapy; NCCS, National Cancer Centre Singapore; NPC, nasopharyngeal carcinoma; PWH, Prince of Wales Hospital; RCT, randomized controlled trial Supplementary Figure S2. Forest plots for (A) progression-free survival and (B) overall survival. The estimated hazard ratio (HR) for each individual trial is indicated by the center of the square and the horizontal line gives the 95% confidence interval (CI). The closed diamonds show the overall HR and 95% CI. HR < 1 and 95% CI excluding 1 indicate improved survival for the experimental versus control arm. A fixed effect model was used. CCRT, concurrent chemoradiotherapy; GZ, Guangzhou; HeCOG, Hellenic Cooperative Oncology Group; IC, induction chemotherapy; NCCS, National Cancer Centre Singapore; NPC, nasopharyngeal carcinoma; O-E, observed minus expected deaths or events; PWH, Prince of Wales Hospital. Supplementary Figure S3. Multiple treatment comparison network. Each treatment area is proportional to the cumulative number of patients (in parentheses). Solid lines between treatments represent direct comparisons. AC, adjuvant chemotherapy; CCRT, concurrent chemoradiotherapy; CEP, cisplatin, epirubicin and paclitaxel; GCP, gemcitabine, carboplatin and paclitaxel; IC, induction chemotherapy; PF, cisplatin and fluorouracil; PX, cisplatin and capecitabine; TP, docetaxel and cisplatin; TPF, TP and fluorouracil. Supplementary Table S1. Description of the Two Trials Included in the Supplementary Analysis Supplementary Table S2. Description of Patient Characteristics Supplementary Table S3. Disease Status and Pattern of FailureSupplementary Table S4. Compliance with Induction Chemotherapy and Concurrent Chemoradiotherapy Supplementary Table S5. Summary of Major Grade 3-4 Adverse Events*</p>
To determine the incidence and intensity of household impoverishment induced by cancer treatment in China.Average income and daily consumption per capita of the households and out-of-pocket payments for cancer care were estimated. Household impoverishment was determined by comparing per capita daily consumption against the Chinese poverty line (CPL, US$1.2) and the World Bank poverty line (WBPL, US$1.9) for 2015. Both pre-treatment and post-treatment consumptions were calculated assuming that the households would divert daily consumption money to pay for cancer treatment.Cancer patients diagnosed initially from 1 January 2015 to 31 December 2016 who had received cancer treatment subsequently. Those with multiple cancer diagnoses were excluded.A household questionnaire survey was conducted on 2534 cancer patients selected from nine hospitals in seven provinces through two-stage cluster/convenience sampling.5.89% (CPL) to 12.94% (WBPL) households were impoverished after paying for cancer treatment. The adjusted OR (AOR) of post-treatment impoverishment was higher for older patients (AOR=2.666-4.187 for ≥50 years vs <50 years, p<0.001), those resided in central region (AOR=2.619 vs eastern, p<0.01) and those with lower income (AOR=0.024-0.187 in higher income households vs the lowest 20%, p<0.001). The patients without coverage from social health insurance had higher OR (AOR=1.880, p=0.040) of experiencing post-treatment household impoverishment than those enrolled with the insurance for urban employees. Cancer treatment is associated with an increase of 5.79% (CPL) and 12.45% (WBPL) in incidence of household impoverishment. The median annual consumption gap per capita underneath the poverty line accumulated by the impoverished households reached US$128 (CPL) or US$212 (WBPL). US$31 170 395 (CPL) or US$115 238 459 (WBPL) were needed to avoid household impoverishment induced by cancer treatment in China.The financial burden of cancer treatment imposes a significant risk of household impoverishment despite wide coverage of social health insurance in China.
Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. The authors investigated the correlation between the levels of serum VEGF (S-VEGF) in patients with nasopharyngeal carcinoma (NPC) and disease progression.The sera from 65 male patients with nonmetastatic NPC, 22 male patients with metastatic NPC, and 27 healthy male volunteers were obtained. A quantitative enzyme-linked immunosorbent assay was performed to measure the concentrations of S-VEGF in the sera.The mean S-VEGF levels were 371.0 pg/mL(-1) (range, 128.5-691.1 pg/mL(-1)) for healthy controls, 375.6 pg/mL(-1) (range, 72.9-1202.5 pg/mL(-1)) for patients with nonmetastatic NPC, and 958.6 pg/mL(-1) (range, 264.4-3744.9 pg/mL(-1)) for patients with metastatic NPC. The mean S-VEGF level in patients with metastatic NPC was significantly higher than in either patients with nonmetastatic NPC (P < 0.001) or healthy controls (P < 0.001). However, there was no statistical difference between these results for healthy controls and patients with nonmetastatic NPC. At the level of 900 pg/mL(-1), S-VEGF indicated distant dissemination of NPC with a specificity of 95.4%, a sensitivity of 31.8%, a positive predictive value of 70.0%, and a negative predictive value of 80.5%. No significant differences in the levels of S-VEGF were found among various T classifications, N classifications, and clinical stages of nonmetastatic NPC.The levels of S-VEGF were significantly elevated in male patients with metastatic NPC. These levels did not correlate with locoregional progression of NPC. The usefulness of detecting S-VEGF in the early diagnosis of NPC appears to be limited.
Abstract Background and Objectives: Survivin and Livin are new members from the family of anti‐apoptotic factors. Increased levels of Survivin and Livin have been observed in many malignancies and correlated with poor prognosis. Survivin is expressed almost exclusively in proliferating cells, including various kinds of cancers, but Livin expression is relatively rare in cancer cells. Therefore, the present study examines the expressions of Survivin and Livin in nasopharyngeal carcinoma (NPC) and investigates whether their expression contributes to the prognosis of NPC. Methods: We investigated the expression of Survivin and Livin in 80 NPC samples using immunohistochemistry stain and correlated it with the survival of these patients using log‐rank test and Cox multifactor regression analysis. Results: All the patients were followed up at least for 60 months. During the following period, 21 cases developed distant metastasis, 9 cases developed local‐regional recurrence, and 5 developed both distant metastasis and local‐regional recurrence. Among them, 30 patients died of recurrence of tumor. In addition, the expression of Survivin was related with distant metastasis. Patients with low Survivin expression had better overall survival, disease‐free survival and distant metastasis‐free survival rates than the group with high Survivin expression ( P = .0086, .0097, and .0318, respectively). Cox regression analysis confirmed that high Survivin expression was related to worse prognosis in NPC patients. However Livin expression level was not related with the survival of patients with NPC. Conclusion: NPC expresses high levels of Survivin and Livin, which may play an important role in the oncogenesis and tumor development. Over‐expression of Survivin was related with poor prognosis. We suggest that the determination of Survivin expression may provide predictive information on NPC patients.
Abstract Nasopharyngeal carcinoma is an EB-virus associated malignancy which is highly prevalent in Southeast Asia. If diagnosed early, the 5 year disease-free survival rate is about 90%. However, most patients have already developed local or regional invasion when diagnosed, which results in poor prognosis. So it is essential to develop biomarkers to screen high risk individuals or diagnose the disease at early stages. As nasopharyngeal carcinoma is closely related to EBV infection and microRNAs encoded by BART region (BamHI A Rightward Transcripts) is abundant in NPC, we propose to identify biomarkers from those BART microRNAs. To quantify the copy number of microRNAs in serum samples, we used Taqman Probe-based qPCR. After adding Spiked-in Control (Mixture of Cel-39,Cel-54, Cel-238) to each 100ul serum sample, we extracted total RNA and reverse transcribed microRNA into cDNA with corresponding Taqman primers. Meanwhile, microRNA mimics with known copy number were serial diluted and reverse transcribed along with the samples. qPCR was performed to quantify the level of microRNAs in these samples with diluted cDNA and Taqman Probe. All data was normalized by Spiked-in controls and exact copy number of each microRNA was calculated through the standard curve generated by the serial diluted microRNA mimics. Here, we screened 17 BART microRNAs in discovery stage and found BART 2-5p as a candidate biomarker. In training cohort consisting of 266 patients with nasopharyngeal carcinoma and controls from Hong Kong, the sensitivity, specificity and AUC is 93.2%, 89.8%,0.976 respectively. The results are similar in validation cohort 1 constituted by 376 patients and controls from Guang Zhou. To evaluate the ability of BART 2-5p to distinguish preclinical NPC patients from healthy high risk individuals, we established a nested case-control study with serum samples prospectively collected from 10 NPC patients at least one year prior to their clinical diagnosis and 92 matched healthy high risk controls from a screening scheme conducted in South China. The sensitivity and specificity is 90.0% and 31.5%. Taken together, EBV microRNA BART2-5p is a promising biomarker to improve NPC diagnosis and target preclinical patients more precisely than serologic test. Citation Format: Chen Jiang, Lei Li, Li Jiangchao, Shang-hang Xie, Su-mei Cao, Xin-yuan Guan. Circulating EBV microRNA BART2-5p helps to diagnose nasopharyngeal carcinoma < screen for high risk individuals precisely [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 722. doi:10.1158/1538-7445.AM2017-722
Abstract In the past several decades, declining incidence rates of NPC have been observed in Chinese populations in Hong Kong, Taiwan, Los Angeles, and Singapore.However, the incidents rates in southern China have remained stable.This study describes the incidence trend of nasopharyngeal carcinoma (NPC) using age-period-cohort (APC) analysis from 1987 to 2011 in Sihui County, southern China. Age-standardized incidence rates compared with the world standard population were examined in both males and females. A Joinpoint regression analysis was conducted to quantify the changes in incidence trends. A Poisson regression APC model was used to assess the age, period, and birth cohort effects on incidence. Age-standardized incidence rates during the study period were 30.29 and 13.09 per 100,000 for males and females, respectively. The incidence rates of NPC remained stable with a non statistical significant average annual percentage change of 0.2% for males and -1.6% for females throughout the entire period. A statistically significant increase (estimated annual percentage change, 6.8%; 95% confidence interval, 0.1%-14.0%) was observed from 2003 to 2009 for males. The incidence of NPC increased with advancing age up to ages 50-59 and decreased at ages >60 years. The curves of NPC incidence by period were virtually flat for males and females. The curve for males by birth cohort showed an increase from the 1922 to 1952 cohort and a decrease thereafter. In females, there was an undulating increase in relative risks from the 1922 to 1972 cohort. In conclusion, the incidence trends for NPC remained generally stable in Sihui from 1987 to 2011, with an increase during 2003-2009. The relative risks of NPC increased in younger female cohorts, the underlying reason of which is expected to be further explored. Note: This abstract was not presented at the meeting. Citation Format: Qing Liu, Sumei Cao, Qihong Huang, Lifang Zhang, Yanhua Li, Shanghang Xie. Incidence trend of NPC using age-period-cohort analysis from1987 to 2011 in Sihui County, southern China. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3712. doi:10.1158/1538-7445.AM2015-3712
Associations between trace elements and nasopharyngeal carcinoma (NPC) have been speculated but not thoroughly examined.This study registered a total of 225 newly diagnosed patients with NPC and 225 healthy controls matched by sex and age from three municipal hospitals in Guangdong Province, southern China between 2011 and 2015. Information was collected by questionnaire on the demographic characteristics and other possibly confounding lifestyle factors. Eight trace elements and the level of Epstein-Barr virus (EBV) antibody were measured in casual (spot) serum specimens by inductively coupled plasma-mass spectrometry (ICP-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. Restricted cubic splines and conditional logistic regression were applied to assess the relationship between trace elements and NPC risk through single-and multiple-elements models.Serum levels of chromium (Cr), cobalt (Co), nickel (Ni), arsenic (As), strontium (Sr) and molybdenum (Mo) were not associated with NPC risk. Manganese (Mn) and cadmium (Cd) were positively associated with NPC risk in both single-and multiple-element models, with ORs of the highest tertile compared with the reference categories 3.90 (95% CI, 1.27 to 7.34) for Mn and 2.30 (95% CI, 1.26 to 3.38) for Cd. Restricted cubic splines showed that there was a linear increasing trend between Mn and NPC risk, while for Cd there was a J-type correlation.Serum levels of Cd and Mn was positively related with NPC risk. Prospective researches on the associations of the two trace elements with NPC ought to be taken into account within the future.
Abstract Epstein-Barr virus (EBV) is associated with a range of epithelial and B cell malignancies as well as autoimmune disorders, for which there are still no specific treatments or effective vaccines. Here, we isolate EBV gH/gL-specific antibodies from an EBV-infected individual. One antibody, 1D8, efficiently neutralizes EBV infection of two major target cell types, B cells and epithelial cells. In humanized mice, 1D8 provides protection against a high-dose EBV challenge by substantially reducing viral loads and associated tumor burden. Crystal structure analysis reveals that 1D8 binds to a key vulnerable interface between the D-I/D-II domains of the viral gH/gL protein, especially the D-II of the gH, thereby interfering with the gH/gL-mediated membrane fusion and binding to target cells. Overall, we identify a potent and protective neutralizing antibody capable of reducing the EBV load. The novel vulnerable site represents an attractive target that is potentially important for antibody and vaccine intervention against EBV infection.
The potential effect of alcohol or tea intake on the risk of nasopharyngeal carcinoma (NPC) remains controversial.In a population-based case-control study in southern China, we assessed alcohol or tea intake from 2,441 histopathologically confirmed NPC cases and 2,546 controls. We calculated mean daily ethanol (g/day) and tea intake (mL/day). Fully adjusted ORs with 95% confidence intervals (CI) were estimated using logistic regression; potential dose-response trends were evaluated using restricted cubic spline analysis.Compared with nondrinkers, no significantly increased NPC risk in men was observed among current alcohol drinkers overall (OR, 1.08; 95% CI, 0.93-1.25), nor among current heavy drinkers (OR for ≥90 g/day ethanol vs. none, 1.32; 95% CI, 0.95-1.84) or former alcohol drinkers. Current tea drinking was associated with a decreased NPC risk (OR, 0.73; 95% CI, 0.64-0.84). Compared with never drinkers, those with the low first three quintiles of mean daily current intake of tea were at significantly lower NPC risk (OR, 0.53, 0.68, and 0.65, respectively), but not significant for the next two quintiles. Current daily tea intake had a significant nonlinear dose-response relation with NPC risk.Our study suggests no significant association between alcohol and NPC risk. Tea drinking may moderately reduce NPC risk, but the lack of a monotonic dose-response association complicates causal inference.Tea drinking might be a healthy habit for preventing NPC. More studies on biological mechanisms that may link tea with NPC risk are needed.
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