Survival Of Nasopharyngeal Carcinoma Patients Research Articles

Centromere Protein H Is a Novel Prognostic Marker for Nasopharyngeal Carcinoma Progression and Overall Patient Survival

The aim of the present study was to analyze the expression of Centromere protein H (CENP-H), one of the fundamental components of the human active kinetochore, in nasopharyngeal carcinoma (NPC) and to correlate it with clinicopathologic data, including patient survival. Using reverse transcription-PCR and Western blot, we detected the expression of CENP-H in normal nasopharyngeal epithelial cells, immortalized nasopharyngeal epithelial cell lines, and NPC cell lines. Using immunohistochemistry, we analyzed CENP-H protein expression in 160 clinicopathologically characterized NPC cases. Statistical analyses were applied to test for prognostic and diagnostic associations. Reverse transcription-PCR and Western blot showed that the expression level of CENP-H was higher in NPC cell lines and in immortalized nasopharyngeal epithelial cells than in the normal nasopharyngeal epithelial cell line at both transcriptional and translational levels. By immunohistochemical analysis, we found that 76 of 160 (47.5%) paraffin-embedded archival NPC biopsies showed high expression of CENP-H. Statistical analysis showed that there was a significant difference of CENP-H expression in patients categorized according to clinical stage (P = 0.024) and T classification (P = 0.027). Patients with higher CENP-H expression had shorter overall survival time, whereas patients with lower CENP-H expression had better survival. A prognostic value of CENP-H was also found of the subgroup of N(0)-N(1) tumor classification. Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient's survival. Our results suggest that CENP-H protein is a valuable marker of NPC progression. High CENP-H expression is associated with poor overall survival in NPC patients.

Heparanase expression in nasopharyngeal carcinoma inversely correlates with patient survival

To determine the expression and prognostic significance of heparanase in nasopharyngeal carcinoma (NPC). Immunohistochemistry was performed on formalin-fixed paraffin-embedded sections of 46 patients with NPC. Clinical and immunohistochemical data were correlated with gender, age, histological type, Epstein-Barr virus (EBV) status, stage and survival. Heparanase immunoreactivity was found in 35% (16/46) of specimens. The cumulative survival of patients diagnosed as heparanase negative (n = 30) at 10 years was 70%. In contrast, the cumulative survival of patients diagnosed as heparanase positive (n = 16) at 10 years was 25%, differences that are highly statistically significant (P = 0.03). No significant correlations were found between heparanase immunoreactivity and gender, age, EBV status, tumour histology or tumour stage. Heparanase expression is inversely correlated with survival of NPC patients, clearly indicating that heparanase is a reliable prognostic factor for this malignancy, and further supports the notion that heparanase is a valid target for the development of anti-cancer drugs.

Epidemiology of nasopharyngeal carcinoma (NPC) in California: Survival advantage of Chinese WHO Type 1 NPC patients resulted in Asian ethnicity as an independent and favorable prognostic factor of survival for NPC patients as a whole and for patients with the WHO histologic type 1

5514 Background: We have previously shown that Chinese race is an independent and favorable prognostic factor in NPC survival. We expanded our study to investigate whether Asian ethnicity has the same favorable survival characteristics and if there is a survival difference between Chinese and non-Chinese Asians. Methods: 1,657 newly diagnosed NPC patients from 1992 to 2002 were analysed from the population-based California Cancer Registry. Five year survival rate estimates and Kaplan-Meier curves were calculated. Cox proportional ratios were used to identify independent prognostic factor for survival. Results: The 5-year survival rate of Asian NPC patients was improved compared to non-Asian patients (62% vs 47%; P < .0001). By multivariate analyses, early age of diagnosis, localized stage at presentation (vs distant, HR = 0.41; P < .0001), WHO Type 3 histology (vs Type 1; HR = 0.64; P < .0001), socio-economic status (highest vs lowest quartile; HR = 0.71; P = .0012), use of radiation (vs none; HR = 0.55; P < .0001), and Asian ethnicity (vs Caucasian; HR = 0.82; P = .016) were associated with improved survival. Chinese composed the majority of the Asian ethnicity (49.1%) followed by Filipino (21.2%) and Vietnamese (14.9%). The 5-year survival rate of Chinese was better than non-Chinese Asians (67% vs 56%; P = .0005). When Asian ethnicity was analyzed separately as Chinese and non-Chinese, Chinese retained an overall favorable prognosis (HR = 0.72; P = .0016) whereas non-Chinese Asians did not (HR = 0.91; P = .34). Within each NPC WHO histologic type, early age of diagnosis, localized stage at presentation, and use of radiation were favorable prognostic factors. Chinese (HR = 0.62; P = .0006) but not non-Chinese Asian ethnicity (HR = 0.78; P = .053) was an additional favorable prognostic factor within WHO histologic Type 1. Conclusions: The significant survival advantage of Chinese WHO Type 1 NPC patients resulted in Asian ethnicity being an independent and favorable prognostic factor for survival in NPC. This observation may reflect underlying genetic difference among different racial groups with NPC WHO Type 1. No significant financial relationships to disclose.

Influence of MRI abnormality in skull base bone on prognosis of nasopharyngeal carcinoma.

To evaluate the influence of skull base bone (SBB) abnormality showed by MRI on prognosis of nasopharyngeal carcinoma (NPC). From March 1993 to December 1998, 122 NPC patients received prime radiotherapy treatment. All of them were proved pathologically and checked by magnetic resonance imaging (MRI). Every patient received radiation through conjoint facio-cervical field and conventional dose-fractionation schedules. The total dose to the primary tumor was 60-75 Gy (median, 70 Gy). The Kaplan-Meier method, the Log-rank test and the Cox regression model were used to evaluate the significance of prognostic factors on NPC patient survival. The overall median survival period was 50 (6-92) months, and the 1, 3 and 5 year-survival rates were, respectively, 99.2%, 87.9%, and 73.3%. The 1, 3, and 5 year-survival rates of abnormality and normality of the SBB on MRI were 98.9%, 87.2%, 71.9%, and 100.0%, 89.8%, 77.0%, respectively (P = 0.4233). Gender, age, head pain, SBB abnormality, cranial nerve palsy, cervical lymphadenopathy and primary tumor extent were analyzed with the Cox regression model and SBB abnormality on MRI did not prove to have statistical significance (P = 0.6934). According to the analysis of regrouping, patients with SBB abnormalities > or =2 sites have a worse prognosis (P = 0.0427). Then, the above seven factors are analyzed by Cox regression model and the result had statistical significance (P = 0.0385). The SBB abnormality on MRI is of no obvious influence on prognosis of NPC. However, when SBB abnormality sites were > or =2, there is obvious statistical significance on the prognosis.

A prospective study of pre-treatment cell kinetics and clinical outcome in nasopharyngeal carcinoma

Background and purpose: To study pre-treatment cell kinetics and their clinical correlations in nasopharyngeal carcinoma (NPC).Materials and methods: Ninety newly diagnosed NPC patients were studied using in vivo Bromodeoxyuridine (BrdU) labeling and flow cytometric analysis. Immunohistochemical staining for BrdU and Ki 67 was also performed.Results: The median S-phase duration (Ts) was 6.2 h (range 3.5–18.7 h), median flow cytometric labeling index (FCM-LI) was 7.4% (1.3–37.6%), and median potential doubling time (Tpot) was 3.6 days (0.5–19.9 days). The median histologic labeling index (H-LI) was 12.4% (1.2–43.3%), and median histologic Tpot (H-Tpot) was 2.1 days (0.5–33.3 days). FCM-LI and H-LI were both positively correlated with Ki67 whereas Tpot and H-Tpot were both negatively correlated with Ki67 and N-stage. In univariate analysis, Tpot and H-Tpot showed a trend for progression free survival. Tpot was significantly associated with local relapse free survival, but lost its significance in multivariate analysis. N-stage was the only significant prognostic factor for all radiotherapy outcomes in both univariate and multivariate analyses.Conclusions: Tpot was the only pre-treatment cell kinetic parameter for which some evidence was found for an association with survival in NPC patients. Future studies should aim to combine cell kinetic parameters together with other biological markers and clinical parameters to provide more useful prognostic information to guide individual patient's therapy.

Long-term survival of nasopharyngeal carcinoma patients treated with adjuvant chemotherapy subsequent to conventional radical radiotherapy

Purpose : To assess the long-term survival of patients with nasopharyngeal carcinoma (NPC) who were treated with conventional radical radiotherapy (RT) followed by adjuvant chemotherapy. Methods and Materials : Ninety-one newly diagnosed patients with Stage III and IV (American Joint Committee on Cancer, 1988) NPC, seen at the University of Malaya Medical Center, Kuala Lumpur, Malaysia between January 1992 and May 1997, were treated with RT followed by adjuvant chemotherapy. The tumor dose was 70 Gy delivered in 35 fractions, 5 fractions weekly. Three cycles of chemotherapy, each consisting of 5-fluorouracil, 1 g/m 2/d on Days 1–4 and cisplatin 100 mg/m 2 on Day 1, were administered 3 weeks after RT completion. Thirty-six patients had Stage II, 10 had Stage III, and 45 had Stage IV disease (AJCC 1997 staging system). Results : After a median follow-up of 61 months, the 5-year overall survival rate for all 91 patients was 80.1%, the disease-free survival rate was 76%, and the locoregional control rate was 85%. The 3-year overall survival rate for Stage II was 94.3%; it was 80% for Stage III and 79.8% for Stage IV ( p = 0.0108). The 3-year DFS rate for Stage II was 90%; it was 80% for Stage II and 65% for Stage IV. The rate of distant failure for Stage IV was 8.9%. Conclusion : Radical RT followed by adjuvant chemotherapy was effective in our patients with locoregionally advanced NPC. The long-term results appear encouraging, even for patients with Stage IV disease. This single institution experience deserves further investigation in prospective trials.

Improvement of local control of T3 and T4 nasopharyngeal carcinoma by hyperfractionated radiotherapy and concomitant chemotherapy

Purpose: When the primary tumor of nasopharyngeal carcinoma (NPC) is treated at the base of skull and intracranium with conventional radiotherapy, the result is generally poor. In this report, we investigated whether hyperfractionated radiotherapy (HFRT) and concomitant chemotherapy (CCT) could achieve better local control and survival in NPC patients with T3 and T4 lesions.Patients and Methods: Forty-eight patients (11 T3 and 37 T4 NPC) were treated with HFRT and CCT. HFRT was administered at 1.2 Gy per fraction, two fractions per day, Monday–Friday for 62 fractions for a total dose of 74.4 Gy. Concomitant chemotherapy consisting of cis-diamino-dichloroplatinum (CDDP) alone or CDDP and 5-fluorouracil was delivered simultaneously with radiotherapy during Weeks 1 and 6. Adjuvant chemotherapy consisted of CDDP and 5-fluorouracil for 2 to 3 cycles and was given monthly beginning 1 month after completion of radiation.Results: With a median follow-up of 57 months (range: 28–94 months), the 3-year locoregional control rate was 93%, the disease-free survival rate was 71%, and the overall survival rate was 72%. For T4 patients, the 3-year locoregional control rate was 91%, disease-free survival was 62%, and overall survival was 63%. The major acute toxicity was Grade 3 mucositis in 73% and Grade 2 weight loss in 31% of patients. Fifty percent of patients were tube fed. Most patients tolerated the combined modality treatments relatively well; 88% of patients completed their radiation treatment within 8 weeks.Conclusion: HFRT and CCT for T3 and T4 NPC were associated with excellent local control and improved survival. The treatment-related toxicity was acceptable and reversible. We would recommend using HFRT with CCT for advanced T-stage NPC if the three-dimensional conformal radiation planning shows a significant portion of the brainstem to be inside the treatment field.

Downregulation and abnormal expression of E-cadherin and β-catenin in nasopharyngeal carcinoma: Close association with advanced disease stage and lymph node metastasis

Nasopharyngeal carcinoma (NPC) is predominantly of the undifferentiated histological subtype. Histological differentiation is of limited prognostic significance in NPC. Recent studies have suggested that downregulation of the cadherin-catenin cell adhesion complex may play a crucial role in the initial stage of cancer invasion and metastasis and is associated with poor prognosis in human cancers. Expression of E-cadherin has not been reported previously in NPC, and its prognostic value in NPC is unknown. The purpose of this study was to examine the expression pattern of E-cadherin and its associated partner, β-catenin, in NPC and their possible applications as prognostic markers to predict the clinical outcome of NPC. Expression of the E-cadherin and β-catenin was examined by immunohistochemical methods in 74 cases of primary NPC and 17 of their corresponding lymph node metastases. Normal nasopharyngeal epithelium showed strong and homogeneous immunocytochemical staining of E-cadherin and β-catenin at the cell membranes and intercellular junctions. In contrast, primary NPC showed variable and heterogeneous staining patterns of E-cadherin and β-catenin. Loss of membranous E-cadherin expression was significantly associated with advanced stages of diseases ( P < .001). Eighty percent to ninety percent of NPC in stages IV and V (Ho's staging), respectively, showed a reduced (<35%) membranous staining of E-cadherin compared with normal nasopharyngeal epithelium. Expression of β-catenin also was downregulated in advanced NPC. Ninety percent to one hundred percent of NPC in stages IV and V (Ho's staging) expressed a reduction (<35%) of immunocytochemical staining of β-catenin. The expression pattern of β-catenin staining was strongly associated with the expression of E-cadherin ( P < .001). Unlike E-cadherin, nuclear staining of β-catenin expression was observed in some of the primary NPC and lymph node metastasis. Reduced expression of E-cadherin and β-catenin expression was associated with a shorter survival of NPC patients ( P < .001). In advanced NPC patients (stages IV and V), a significant difference in survival was observed in tumors with higher or lower levels of E-cadherin expression ( P = .0224, log-rank test). These observations suggests that expression of E-cadherin and β-catenin may have prognostic values in NPC patients.

Eustachian Tube Function of Patients with Nasopharyngeal Carcinoma

Prolonged observations of the eustachian tube (ET) function were made on 40 ears of 20 patients with nasopharyngeal carcinoma (NPC) who survived more than 5 years after radiotherapy in a state of remission. The ET function tests included passive opening, inflation-deflation, and clearance, and were performed before, at 6 months, and at 5 years after radiotherapy. The test results were found to be worst at 6 months after radiotherapy and improved at 5 years after radiotherapy. Tubal obstruction and inflammation are the main causes of the ET malfunction that results in otitis media with effusion (OME) in NPC patients after radiotherapy. Insertion of a ventilation tube into the ear with OME can relieve tubal obstruction but can aggravate inflammation. Thus, myringotomy and aspiration of effusion and local treatment may be preferable to insertion of a ventilation tube in NPC patients with OME. When hearing improvement in prolonged survival of NPC patients with OME is needed, the use of amplification is recommended.