Different Stages Of Nasopharyngeal Carcinoma Research Articles

Low-Dose Aspirin Use Significantly Improves the Survival of Late-stage NPC: A Propensity Score-Matched Cohort Study in Taiwan.

Background: Aspirin use has been associated with improved survival rates in various cancers. However, it remains unclear if aspirin confers a survival benefit on patients with nasopharyngeal carcinoma (NPC). The aim of this study was to assess the associations between aspirin use and survival in different stages of NPC. Methods: This is a 10-year retrospective cohort study of NPC patients. A total of 565 NPC patients were recruited after we performed a 1:4 propensity score match between aspirin users and non–users. Cox regression models with adjusted covariates were employed to evaluate factors that influence the survival rate of NPC patients. Results: The Kaplan-Meier analysis revealed that the overall survival (p < 0.0001) and disease-specific survival (p < 0.0001) rates of 180-day aspirin users increased. Increased survival rates were also observed in 180-day aspirin users with Stages III and IV, T, N1 and 2, and N3 categories. Cox regression models indicated that factors, including aspirin use (univariate: HR = 0.28, 95% CI = 0.14–0.55, p < 0.001; multivariate: HR = 0.23, 95% CI = 0.12–0.46, p < 0.001), were independent prognostic factors for survival. Conclusions: Aspirin use for more than 180 days is associated with an increased survival rate and is a positive independent prognostic factor in NPC.

Dosimetric comparison between three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) in the treatment of different stages of nasopharyngeal carcinoma

AbstractBackgroundThis work aims to compare the dosimetric performance of three-dimensional conformal radiotherapy (3D-CRT), a relatively available technique in developing countries, to intensity-modulated radiotherapy (IMRT) in the treatment of different stages of nasopharyngeal carcinoma (NPC).Materials and MethodsAccording to the diagnostic stages, 40 NPC patients were divided into two equal groups. Three planning techniques such as 3D-CRT, seven-field IMRT (7F-IMRT) and nine-field IMRT (9F-IMRT) were compared. Dose prescriptions of 70 and 66 Gy were delivered in 35 fractions to gross planning target volume (PTV1) and bilateral retropharyngeal carcinoma (PTV2), respectively.ResultsStage I dose data for almost all of the three investigated planning techniques obey the international recommendations. The dose delivered to PTV1 and PTV2 for 3D-CRT and 7F-IMRT are statistically similar, whereas 9F-IMRT is significantly better than 3D-CRT. For organs at risk (OARs), the delivered dose is significantly better for 9F-IMRT compared with the other two techniques, whereas 7F-IMRT is significantly better than 3D-CRT.Conclusions3D-CRT is an acceptable alternative treatment technique for stage I NPC patients in developing countries suffering from the lack of advanced radiotherapy treatment techniques. 3D-CRT and 7F-IMRT have comparable performance in PTVs, while 9F-IMRT is superior in PTVs and OARs.

Establishment of EA-D-IgA antibody detection method and its diagnostic efficacy for nasopharyngeal carcinoma in different clinical stage

Objective To establish a serological detection method for EA-D-IgA antibody, and to evaluate its diagnostic efficacy for nasopharyngeal carcinoma in different clinical stage. Methods EA-D-IgA antibody serological detection method was established by using the polypropylene microplate with eukaryotic expression product of BMRF1 whole gene fragment of EB virus. Fifteen early stage (stage Ⅰ and Ⅱ) and 48 advanced (stage Ⅲ and Ⅳ) patients with nasopharyngeal carcinoma in Shanxi Provincial Cancer Hospital and Shanxi Dayi Hospital from April 2012 to August 2017, and serum samples from 40 patients with rhinitis who were treated at Shanxi Dayi Hospital from October 2016 to October 2017 were examined respectively by using the constructed EA-D-IgA antibody detection method. The positive detection rate of EA-D-IgA antibodies in different groups was calculated. When the patients with rhinitis were used as the differential control, the diagnostic efficacy of this index for different stages of nasopharyngeal carcinoma was evaluated. Results EA-D-IgA antibody serological method was successfully established. The positive detection rate of EA-D-IgA antibody in early nasopharyngeal carcinoma, advanced nasopharyngeal carcinoma and rhinitis control was 60.0 % (10/15), 68.3 % (33/48) and 5.0 % (2/40) respectively. The differences between early stage nasopharyngeal carcinoma and the rhinitis control, advanced nasopharyngeal carcinoma and the rhinitis control were statistically significant (χ 2 = 20.625, P = 0.000; χ2 = 37.017, P = 0.000). The difference between early nasopharyngeal carcinoma and advanced nasopharyngeal carcinoma was not statistically significant (χ 2 = 0.394, P = 0.530). When compared with the patients with rhinitis, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value was 60.0 % and 68.3 %, 95.0 % and 95.0 %, 81.8 % and 94.3 %, 86.4 % and 71.7 % respectively in early nasopharyngeal carcinoma and advanced nasopharyngeal carcinoma. Conclusion The method constructed in this study effectively improves the efficacy of EA-D-IgA antibody detection in serological diagnosis of nasopharyngeal carcinoma, which can be used as an adjunct for early diagnosis of nasopharyngeal carcinoma, yet not as a reference for clinical staging. Key words: Nasopharyngeal neoplasms; BMRF1; Eukaryotic expression; Clinical staging; Diagnostic efficiency

The detection and significance of T cells in nasopharyngeal carcinoma patients.

Nasopharyngeal carcinoma (NPC) is by far the most common malignant tumor of the nasopharynx and is suggested to be related to immune system dysfunction. T cells play a central role in the cell-mediated immunity. However, how the T cells vary during the NPC treatment is still unclear. We divided the NPC patients into previously untreated, partial remission, complete remission, and relapse groups. Healthy controls were those without any autoimmune diseases, cancer, or recent infection. We used flow cytometry to detect the changes in T cell subsets. We found the quantity (%) of CD4+ CD25+ CD127low/- Treg regulatory T cells and CD8+ CD28- T cells were obviously increased in NPC previously untreated, partial remission, and relapse groups. There was no difference in these two subsets between complete remission groups and healthy controls. In addition, the quantity (%) of CD3+ CD4+ and CD8+ CD28+ effector T cells were reduced in NPC previously untreated, partial remission, and relapse groups. There was no difference in these two subsets between complete remission groups and healthy controls. Our research determines the changes of T cell subsets in different stages of NPC.

Label-Free Classification of a Nasopharyngeal Carcinoma Tissue Test at Different Stages Based on Raman Spectroscopy.

Raman spectroscopy (RS) of nasopharyngeal carcinoma (NPC) tissue provides substantial biomolecular information and various biomedicine features for tissue at different stages of cancer development. This study suggested an automatic and quick method for the classification of Raman spectra at different stages of NPC by multivariate statistical analysis. During RS measurement, Raman spectra were acquired from all NPC tissues in two groups of samples: 30 early-stage NPC patients (stages I and II) and 46 advanced-stage NPC patients (stages III and IV). In addition, a tentative diagnostic algorithm comprising principal components analysis and support vector machine was used to effectively classify multivariate data from the Raman spectra to yield sensitivities (70%; 21 of 30 samples) and specificities (91%; 42 of 46 samples) by the leave-one-out cross-validation method. Meaningful chemical compositions in the classification process were then deduced by analyzing the classified mathematical model. This beneficial work provides a great potential clinical method for the automatic classification of NPC stages and the speculation of the chemical compositions for NPC staging.

Distinctive microRNA expression in early stage nasopharyngeal carcinoma patients

The goal of this study was to investigate microRNAs (miRs) expression at different stages of nasopharyngeal carcinoma (NPC). MiR expression profiling at various stages of NPC was performed by miR array and further verified using quantitative real‐time RT‐PCR. Pathway enrichment analysis was carried out to identify the functional pathways regulated by the miRs. The expression of a selected group of identified miRs was verified in stage I NPC by in situ hybridization (ISH). A total of 449 miRs were identified with significantly different expressions between NPC tissues and normal pharyngeal tissues. Eighty‐four miRs were dysregulated only in stage I NPC, among which 45 miRs were up‐regulated and the other 39 were down‐regulated. Pathway enrichment assay revleaed that three significantly down‐regulated and three significantly up‐regulated miRs involved in 12 pathways associating with tumour formation and progression. Quantitative RT‐PCR confirmed the miR array result. In addition, the low expression levels of hsa‐miR‐4324, hsa‐miR‐203a and hsa‐miR‐199b‐5p were further validated in stage I NPC by ISH. This present study identifed the miR signature in stage I NPC, providing the basis for early detection and treatment of NPC.

Influence of change in anatomical volume on dose distribution during intensity-modulated radiotherapy for different stages of nasopharyngeal carcinoma

Objective To explore the change in anatomical volume during intensity-modulated radiotherapy (IMRT) for different stages of nasopharyngeal carcinoma (NPC) and its influence on dose distribution, and to assess the necessity to modify the IMRT plan. Methods Twenty-four patients with newly diagnosed NPC who received IMRT and chemotherapy were enrolled in the study, and were divided into early-intermediate group (12 cases) and locally advanced group (12 cases) according to the 2008 staging system for NPC. Each patient had a repeated CT scan at week 5 of radiotherapy, and target volume and organs at risk (OAR) were contoured. The dose distribution of the original plan shown on CT was calculated. Changes in target volume, OAR anatomical volume, and dose distribution were analyzed, and paired t-test and Spearman correlation analysis were performed. Results In the early-intermediate group, gross target volume of neck positive lymph nodes (GTVnd) was reduced during radiotherapy (P=0.059), and gross target volume of nasopharynx (GTVnx), high-risk clinical target volume (CTV1), and parotid volume were reduced significantly during radiotherapy (P=0.001, 0.012, 0.002, and 0.000, respectively). In locally advanced group, GTVnx, GTVnd, CTV1, and parotid volume were significantly reduced during IMRT (P=0.000, 0.000, 0.003, 0.003, and 0.000, respectively). Compared with the values before radiotherapy, the parotid dose increased significantly in the two groups during IMRT (P=0.044, 0.026, 0.033, and 0.026, respectively; P=0.024, 0.016, 0.030, and 0.015, respectively), and the increase in GTVnd dose was observed in the locally advanced group (P=0.029 and 0.049). Conclusions It is recommended to perform another CT scan for patients with locally advanced NPC at week 5 of radiotherapy and formulate a new IMRT plan to maintain target volume dose and guarantee a safe parotid dose. Key words: Nasopharyngeal neoplasms/intensity-modulated radiotherapy; Volumetric changes; Dosimetric changes

Anti-angiogenic pathway associations of the 3p21.3 mapped BLU gene in nasopharyngeal carcinoma.

Zinc-finger, MYND-type containing 10 (ZMYND10), or more commonly called BLU, expression is frequently downregulated in nasopharyngeal carcinoma (NPC) and many other tumors due to promoter hypermethylation. Functional evidence shows that the BLU gene inhibits tumor growth in animal assays, but the detailed molecular mechanism responsible for this is still not well understood. In current studies, we find that 93.5% of early-stage primary NPC tumors show downregulated BLU expression. Using a PCR array, overexpression of the BLU gene was correlated to the angiogenesis network in NPC cells. Moreover, expression changes of the MMP family, VEGF and TSP1, were often detected in different stages of NPC, suggesting the possibility that BLU may be directly involved in the microenvironment and anti-angiogenic activity in NPC development. Compared with vector-alone control cells, BLU stable transfectants, derived from poorly-differentiated NPC HONE1 cells, suppress VEGF165, VEGF189 and TSP1 expression at both the RNA and protein levels, and significantly reduce the secreted VEGF protein in these cells, reflecting an unknown regulatory mechanism mediated by the BLU gene in NPC. Cells expressing BLU inhibited cellular invasion, migration and tube formation. These in vitro results were further confirmed by in vivo tumor suppression and a matrigel plug angiogenesis assay in nude mice. Tube-forming ability was clearly inhibited, when the BLU gene is expressed in these cells. Up to 70–90% of injected tumor cells expressing increased exogenous BLU underwent cell death in animal assays. Overexpressed BLU only inhibited VEGF165 expression in differentiated squamous NPC HK1 cells, but also showed an anti-angiogenic effect in the animal assay, revealing a complicated mechanism regulating angiogenesis and the microenvironment in different NPC cell lines. Results of these studies indicate that alteration of BLU gene expression influences anti-angiogenesis pathways and is important for the development of NPC.

Direct quantification of circulating miRNAs in different stages of nasopharyngeal cancerous serum samples in single molecule level with total internal reflection fluorescence microscopy.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate human gene expression at the post-transcriptional level. Growing evidence indicates that the expression profile of miRNAs is highly correlated with the occurrence of human diseases including cancers. Playing important roles in complex gene regulation processes, the aberrant expression pattern of various miRNAs is implicated in different types and even stages of cancer. Besides localizing in cells, many of these miRNAs are found circulating around the body in a wide variety of fluids such as urine, serum and saliva. Surprisingly, these extracellular circulating miRNAs are highly stable and resistant to degradation, and therefore, are considered as promising biomarkers for early cancer diagnostic via noninvasive extraction from body fluids. Unfortunately, the abundance of these small RNAs is ultralow in the body fluids, making it challenging to quantify them in complex sample matrixes. Establishing a sensitive, specific yet simple assay for an accurate quantification of circulating miRNAs is therefore desirable. Our group previously reported a sensitive and specific detection assay of miRNAs in single molecule level with the aid of total internal reflection fluorescence microscopy. In this work, we advanced the assay to differentiate the expression of a nasopharyngeal carcinoma (NPC) up-regulator hsa-mir-205 (mir-205) in serum collected from patients of different stages of NPC. To overcome the background matrix interference in serum, a locked nucleic acid-modified molecular beacon (LNA/MB) was applied as the detection probe to hybridize, capture and detect target mir-205 in serum matrix with enhanced sensitivity and specificity. A detection limit of 500 fM was achieved. The as-developed method was capable of differentiating NPC stages by the level of mir-205 quantified in serum with only 10 μL of serum and the whole assay can be completed in 1 h. The experimental results agreed well with those previously reported whereas the quantity of miR-205 determined by our assay was found comparable to that of quantitative reverse transcription polymerase chain reaction (qRT-PCR), supporting that this assay can be served as a promising noninvasive detection tool for early NPC diagnosis, monitoring and staging.

Retrospective analysis of results of treatment for nasopharyngeal carcinoma in Macao.

Nasopharyngeal carcinoma (NPC) is a common malignancy in Southeast Asia, however, a full consensus has not yet been reached as to the value of comprehensive treatment for NPC. This study was designed to evaluate the epidemiological characteristics of NPC and their prognostic value, as well as the long-term efficacy of NPC treatment. A total of 248 patients, with different stages of NPC, were included in this study. The 5-year overall survival (OS) rates for patients in stages I, II, III and IV were 90.48%, 76.71%, 76.89% and 33.87%, respectively (P=0.000), while the respective 5-year progression-free survival (PFS) rates were 85.15%, 72.36%, 63.88% and 26.26% (P=0.000). The respective 5-year OS rates, according to stage, for the group that received radiotherapy combined with chemotherapy and for the group that received radiotherapy only were as follows: stages I and II, 81.67% and 79.59% (P=0.753); stage III, 79.91% and 70.38% (P=0.143); stage IV, 35.22% and 0% (P=0.000). The respective 5-year PFS rates in these groups were as follows: stages I and II, 75.83% and 74.98% (P=0.814); stage III, 74.08% and 42.25% (P=0.027); stage IV, 27.31% and 0% (P=0.000). Clinical staging appears to be the most important prognostic factor for NPC. As the stage number increases, both the 5-year OS and PFS significantly decrease. Adding chemotherapy to radiotherapy was not advantageous for patients with stage I or II NPC, however the addition of chemotherapy to radiotherapy significantly improved OS and PFS in patients with stage IV NPC. The addition of chemotherapy improved PFS, but not OS in patients with stage III NPC.

Signaling Transduction Network Mediated by Tumor Suppressor/Susceptibility Genes in NPC

Nasopharyngeal carcinoma (NPC) is a polygenetic disease. SPLUNC1, UBAP1, BRD7, NAG7, NOR1, NGX6 and LTF genes were found to be tumor suppressor/susceptibility genes in different stages of NPC. SPLUNC1, an early warning molecular diagnosis marker, inhibits the bacteria clone formation, and is an innated immune molecule. SPLUNC1 can negatively regulate the ERK/MAPK signaling transduction pathway to inhibit NPC cell proliferation and induce apoptosis. BRD7, a transcript regulation factor, interacts with BRD2, and promotes apoptosis induced by BRD2. Its promoter is regulated by c-Myc and SP1. BRD7 inhibits NPC cell cycle progression, preventing passage through G0/G1 by suppressing ras/MEK/ERK, Rb/E2F and Wnt signaling pathways. Abnormal activation of BRD7 is crucial to cell cycle turbulence in NPC. NGX6, a metastasis-associated protein, can negative-regulate the EGF/Ras/MAPK signaling transduction pathway, and interacts with ezrin protein to inhibit NPC cell invasion and metastasis. LTF, also a metastasis-associated protein, can negatively regulate MAPK signal transduction pathways, such as JNK2 and ERK, to inhibit NPC cell proliferation and growth. Taken together, it was found that these tumor suppressor/susceptibility genes can regulate key molecules involved in cell signal pathways such as ras/MEK/ERK, Rb/E2F and EGFR ras/MEK/MAPK, and can regulate the expression of some adhesion molecules such as ezrin, nm23 and α-catenin. According to functional genomics and signaling transduction pathways, we have described a signaling cross-talk network between the tumor suppressor/susceptibility genes involved in NPC. These tumor suppressor/susceptibility genes may be potential treatment targets for NPC in the future.

Frequency of skeletal metastases in nasopharyngeal carcinoma after initiation of therapy: should bone scans be used for follow-up?

Previous reports have indicated a relatively high incidence of distant metastases in patients with nasopharyngeal carcinoma (NPC), one of the most common sites being the skeleton. Although bone scintigraphy offers the advantage of whole-body imaging in patients with cancer by providing useful information about disease spread, its value in patients with NPC is not well defined because of cost-effectiveness considerations. In this study, we assessed the value of follow-up bone scintigraphy for the evaluation of skeletal metastases in patients with different stages of NPC. Between 1994 and 2001, 230 patients with histologically proven NPC were admitted to the Department of Radiation Oncology. Out of 230 patients, 171 were examined for skeletal metastases with bone scintigraphy prior to therapy and at 1 year intervals. Bone scintigraphy detected increased uptake in 29 patients, which was reported as suggestive of metastases or equivocal. Twenty-six of these were true-positive, confirmed by radiography or clinical follow-up. Bone pain was present in 67% of these patients and serum lactate dehydrogenase and alkaline phosphatase were elevated in 35% and 37%, respectively. The incidence of bone metastases correlated with the extent of lymph node involvement, which were detected after a median time of 10.5 months following the diagnosis of the primary disease. No correlation was observed between the metastatic status and local T stage, histological differentiation age or gender of the patient. We can therefore recommend that bone scintigraphy be used in determining the presence of bone metastases, but its utilization should be preserved for those with nodal involvement.

Intensity-modulated radiotherapy in nasopharyngeal carcinoma: dosimetric advantage over conventional plans and feasibility of dose escalation

Purpose To compare intensity-modulated radiotherapy (IMRT) with two-dimensional RT (2D-RT) and three-dimensional conformal radiotherapy (3D-CRT) treatment plans in different stages of nasopharyngeal carcinoma and to explore the feasibility of dose escalation in locally advanced disease. Methods and materials Three patients with different stages (T1N0M0, T2bN2M0 with retrostyloid extension, and T4N2M0) were selected, and 2D-RT, 3D-CRT, and IMRT treatment plans (66 Gy) were made for each of them and compared with respect to target coverage, normal tissue sparing, and tumor control probability/normal tissue complication probability values. In the Stage T2b and T4 patients, the IMRT 66-Gy plan was combined with a 3D-CRT 14-Gy boost plan using a 3-mm micromultileaf collimator, and the dose–volume histograms of the summed plans were compared with their corresponding 66-Gy 2D-RT plans. Results In the dosimetric comparison of 2D-RT, 3D-CRT, and IMRT treatment plans, the T1N0M0 patient had better sparing of the parotid glands and temporomandibular joints with IMRT (dose to 50% parotid volume, 57 Gy, 50 Gy, and 31 Gy, respectively). In the T2bN2M0 patient, the dose to 95% volume of the planning target volume improved from 57.5 Gy in 2D-RT to 64.8 Gy in 3D-CRT and 68 Gy in IMRT. In the T4N2M0 patient, improvement in both target coverage and brainstem/temporal lobe sparing was seen with IMRT planning. In the dose-escalation study for locally advanced disease, IMRT 66 Gy plus 14 Gy 3D-CRT boost achieved an improvement in the therapeutic ratio by delivering a higher dose to the target while keeping the normal organs below the maximal tolerance dose. Conclusion IMRT is useful in treating all stages of nonmetastatic nasopharyngeal carcinoma because of its dosimetric advantages. In early-stage disease, it provides better parotid gland sparing. In locally advanced disease, IMRT offers better tumor coverage and normal organ sparing and allows room for dose escalation.

Expression of beta-2-microglobulin by nasopharyngeal carcinoma.

Serum beta-2-microglobulin (beta 2M) levels of 274 Chinese patients with different stages of nasopharyngeal carcinoma at presentation and that of 35 patients who developed distant metastases post-treatment were assayed. beta 2M level was found to increase with advancing stage of disease, with statistically significant differences among early-stage, advanced-stage, and metastatic disease. Elevated pre-treatment beta 2M levels were expressed more frequently by tumours with lower degree of histological differentiation. The sensitivity of serum beta 2M for diagnosis of nasopharyngeal carcinoma, however, is low.