• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7097-7101
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• 2015

Background: Nasopharyngeal carcinoma (NPC) is linked to Epstein Barr virus infection and is particularly common in the Far East, particularly among some Chinese groups. Certain ethnicities have been reported to have low incidence of NPC. This study looked at NPC in Brunei Darussalam over a three decade period. Materials and Methods: The cancer registry from 1986 to 2014 maintained by the State Laboratory was retrospectively reviewed. The age standardized rates (ASR) and the age specific incidence rates (ASIR) were calculated. Non NPC tumors were excluded from the study. Results: Altogether, there were a total of 450 NPC cases diagnosed accounting for 4.4% of all total cancer cases over the study period, declining from 10.3% in 1986-1990 to 2.3% in 2011-2014. The most common tumor type was the undifferentiated carcinoma (96.4%). The case characteristics were mean age $50.4{\pm}14.4$ years old, male 69%, and predominately Malays 74.4%, followed by Chinese 16.7%. The mean age of diagnosis increased over the study period from $45.6{\pm}17.1$ years (1986-1989) to $54.1{\pm}12.5$ years (ANOVA, p<0.01 for trend). There were no differences in the mean age of diagnosis between the ethnic groups or genders. The ASR showed a declining trend from 11.1 per 100,000 in 1986-1990 to 5.95 per 100,000 in 2011-2014, similar trends been observedfor both genders. Among the age groups, declining trends were seen in all the other age groups apart from the >70 years group. The overall ASRs for the Malays and Chinese were 7.92/100,000 and 8.83/100,000 respectively, both showing declining trends. Conclusions: The incidence of NPC in Brunei Darussalam is comparable to rates reported from Singapore and Malaysia, but higher than rates reported from the other Southeast Asian nations. Unlike higher rates reported for Chinese compared to the Malays in other countries, the rates between the Malays and Chinese in our study was comparable. Importantly, the ASR is declining overall and for both genders and ethnic groups.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.75-79
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• 2012

Purpose: the study aimed to compare the quality of life (QOL) and radiotherapy complications among Chinese nasopharyngeal carcinoma (NPC) patients at different 3-dimensional conformal radiotherapy (3DCRT) stages adjusting for other variables. Methods: 511 NPC patients at different 3DCRT stages were enrolled. They were interviewed regarding SF-36, complications and socio-demographic variables and cancer- or treatment-related variables. Analysis of covariance (ANCOVA) based on SF-36, complications scores as dependent variables, 3DCRT stages as independent variables, and other variables as covariate were established. Results: The influencing factors of PCS included 3DCRT stages and age group. The influencing factors of MCS included 3DCRT stages and income. Most QOL scores of NPC patients were significantly associated with 3DCRT stage, after accounting for other variables. QOL scores of the patients receiving 3DCRT were the lowest, QOL scores of people after 3DCRT gradually increased. PCS scores of people greater than 5 years after 3DCRT was improved to or even better than the level before 3DCRT. The complications with significantly different scores of patients at different 3DCRT status included xerostomia, throat ache, hypogeusia, caries, hearing loss, snuffles. Conclusions: Clinicians should pay more attention to older NPC patients and patients with lower income. When patients receive 3DCRT, measures should be taken to reduce radiation injury to improve the patients' QOL.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.65-72
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• 1991

One hundred and thirty five patients with carcinoma of the nasopharyx were treated by radiation therapy in the Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University between August 1977 and July 1987. Of the 30 patients omitted: 8 had distant metastases at initial diagnosis or during radiotherapy; 18 Patients refused or did not receive a full course of radiation therapy, and four had not been confirmed histologically. The remaining 105 patients were analysed to determine the incidence and pattern of distant metastases. Diagnosis of distant metastases was made based on clinical signs and radiography, even though histologic confirmation was not made. Twenty-six patients developed distant metastases after definite irradiation of nasopharyx and neck, an incidence rate of $24.8\%$ . The common sites of distant metastases were, in descending order, bone, lung, liver, and brain. There was a strong correlation between Ho's N stage and distant metastases rate. But sex, age, histologic subtype (squamous cell and undifferentiated cell), AJC T and N stage, treatment modalities (radiotherapy alone and radiotherapy combined with chemotherapy) were not significant. Of those patients who developed distant metastases, $80.8\%$ were discovered within 2 years of their radical radiotherapy. The prognosis for nasopharyngeal carcinoma patients developing distant metastases was poor: median survival was nine months and $80\%$ of those patients died within two years of the initial diagnosis of distant metastasis.

• Korean Journal of Head & Neck Oncology
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• v.22 no.2
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• pp.123-129
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• 2006

Objective ： This retrospective study was designed to evaluate the anti-tumor efficacy and toxicities of the radiation therapy(RT) combined with cisplatin-based chemotherapy in locally advanced nasopharyngeal cancer(NPC). Materials and Methods ： Fifty three patients with locally advanced NPCs(AJCC stage II, III, IV) received curative RT and cisplatin-based chemotherapy. Duration of follow-up ranged from 5.5 to 201 months(median 50.8 months). Nineteen patients(35.8%) were treated with induction chemotherapy including cisplatin $100mg/m^2$ for 1 day and 5-fluorouracil $1g/m^2$ for 5 days followed by RT(Induction CTx-RT). Another 34 patients (64.2%) were treated with concurrent chemoradiation(CCRT) using cisplatin $100mg/m^2$(D1, 22, 43). Results ： Thirty-six(67.9%) and 11(20.8%) patients achieved clinical complete response and partial response, respectively. The pattern of failure was as follows：14 locoregional recurrence(26.4%) and 7 distant metastasis(13.2%). Among them, two patients(3.8%) had both locoregional and distant failure. Median overall survival(OS) and progression-free survival(PFS) were 85.5 months and 87.5 months, respectively. Five-year OS rate was 57.1%. The stage(AJCC), tumor response to chemoradiation and T stage were significant prognostic factors for OS(p=0.0113, p=0.0362 and p=0.0469). The stage(AJCC), tumor response to chemoradiation were also significant prognostic factors for PFS(p=0.0329, p=0.0424). Compared to each treatment group(Induction CTx-RT vs. CCRT), there were no significant differences in OS and PFS(p=0.7000, p=0.8261). Grade 3-4 mucositis, nausea/vomiting and hematological toxicities were noticed in 35.8%, 11.3% and 13.2%, respectively. Delayed RT over 2 weeks was inevitable in 26.5%. Seventeen patients(50%) successfully completed planned 3 courses of cisplatin in CCRT group. Conclusions ： RT combined with cisplatin-based chemotherapy in locally advanced NPC showed high response rate, good locoregional control, and survival rate. As expected, frequency of acute toxicities increased, and the patient's compliance to treatment was need to be improved. Although our data could not show additional survival benefit of CCRT compare to that of induction chemotherapy followed by RT, patients' accrual and further follow-up are required due to limitation of retrospective study.

• Molecules and Cells
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• v.43 no.10
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• pp.856-869
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• 2020

To elucidate the mechanism of action of HOXA11-AS in modulating the cisplatin resistance of nasopharyngeal carcinoma (NPC) cells. HOXA11-AS and miR-454-3p expression in NPC tissue and cisplatin-resistant NPC cells were measured via quantitative reverse transcriptase polymerase chain reaction. NPC parental cells (C666-1 and HNE1) and cisplatin-resistant cells (C666-1/DDP and HNE1/DDP) were transfected and divided into different groups, after which the MTT method was used to determine the inhibitory concentration 50 (IC₅₀) of cells treated with different concentrations of cisplatin. Additionally, a clone formation assay, flow cytometry and Western blotting were used to detect DDP-induced changes. Thereafter, xenograft mouse models were constructed to verify the in vitro results. Obviously elevated HOXA11-AS and reduced miR-454-3p were found in NPC tissue and cisplatin-resistant NPC cells. Compared to the control cells, cells in the si-HOXA11-AS group showed sharp decreases in cell viability and IC₅₀, and these results were reversed in the miR-454-3p inhibitor group. Furthermore, HOXA11-AS targeted miR-454-3p, which further targeted c-Met. In comparison with cells in the control group, HNE1/DDP and C666-1/DDP cells in the si-HOXA11-AS group demonstrated fewer colonies, with an increase in the apoptotic rate, while the expression levels of c-Met, p-Akt/Akt and p-mTOR/mTOR decreased. Moreover, the si-HOXA11-AS-induced enhancement in sensitivity to cisplatin was abolished by miR-454-3p inhibitor transfection. The in vivo experiment showed that DDP in combination with si-HOXA11-AS treatment could inhibit the growth of xenograft tumors. Silencing HOXA11-AS can inhibit the c-Met/AKT/mTOR pathway by specifically upregulating miR-454-3p, thus promoting cell apoptosis and enhancing the sensitivity of cisplatin-resistant NPC cells to cisplatin.

• Korean Journal of Head & Neck Oncology
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• v.12 no.1
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• pp.3-7
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• 1996

Nasopharyngeal carcinoma(NPC) is a disease whose primary initial treatment is radiation. Results of radiation therapy in early stage disease is promising; however, in stage IV disease, the best reported five-year survival is only about 30%. In patients with post-radiation recurrent disease, radiation controls only a small portion of patients, as well as being associated with significant radiation injury. In this paper we discuss the use of salvage treatment modalities for post-radiation recurrence. A retrospective chart review and analysis of salvage treatment results were performed for 39 patients with recurrent post-radiation NPC and positive cervical lymph nodes during the period beginning 1985 until 1995. Mean age of these patients was 52.3$\pm$10.37 years and male: female ratio was 1.8 : 1. Twenty patients were treated with salvage treatment, and ten patients were treated by salvage chemotherapy. A total of nine patients underwent surgical salvage treatment, including neck dissection(6), transnasal laser surgery and booster radiotherapy(2), and primary surgery(1). Salvage treatment were effective in reducing patients' pain in twenty patients (51.3%) and prolonging life in nine patients(23.1%); however, recurrence of disease within six months and/or residual disease by clinical or radiologic exam was noted in all patients receiving salvage radiotherapy, chemotherapy, laser surgery with radiotherapy, and primary site surgery. In the group undergoing salvage neck dissection, three patients(50%) were disease free for at least two years. Of the different modalities, radiotherapy was associated with the best quality of life while catastrophic salvage surgery resulting in insignificant prolongation of life was associated with the poorest quality of life. We conclude that salvage surgery is the optimal choice of treatment for regional recurrence such as nodal failure, however palliative salvage therapy could be preferred in other cases with recurrent post-radiation NPC.

• Journal of Korean Neurosurgical Society
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• v.63 no.3
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• pp.397-405
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• 2020

Objective : We retrospectively evaluated the efficacy of Gamma Knife radiosurgery (GKS) for recurrent nasopharyngeal carcinoma (NPC) in patients who previously underwent radiotherapy, and analyzed the treatment outcomes over 14 years. Methods : Ten patients with recurrent NPC who had previously received radiotherapy underwent stereotactic radiosurgery using a Gamma Knife^® (Elekta Inc, Atlanta, GA, USA) between 2005 and 2018. The median target volume was 8.2 ㎤ (range, 1.7-17.8), and the median radiation dose to the target was 18 Gy (range, 12-30). The median follow-up period was 18 months (range, 6-76 months). Overall and local failure-free survival rates were determined using the Kaplan-Meier method. Results : The NPCs recurred at the primary cancer site in seven patients (70%), as distant brain metastasis in two (20%), and as an extension into brain in one (10%). The recurrent tumors in seven of the 10 patients (70%) were found on the routine follow-up imaging studies. Two patients presented with headache and one with facial pain. Local failure after GKS occurred in five patients (50%) : two of whom died eight and 6 months after GKS, respectively. No adverse radiation effects were noted after GKS. The 1- and 3-year overall survival rates after GKS were 90% and 77%, respectively. The local failure-free survival rates at 6 months, 1 year, and 3 years after GKS were 80%, 48%, and 32%, respectively. The median interval from GKS to local failure was 8 months (range, 6-12). Univariate analysis revealed that using co-registration with positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) was associated with a lower local failure rate of recurrent NPC (p=0.027). Conclusion : GKS is an acceptable salvage treatment option for patients with recurrent NPC who previously received radiation therapy. PET-CT and MRI co-registration for dose planning can help achieve local control of recurrent NPC.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.177-182
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• 1990

From 1984 to 1988, fourty two patients with nasopharyngeal cancer were treated at the Department of Radiation Oncology in Kyungpook National University Hospital. Thirteen patients refused treatment and the median survival time was 7.8 months. Twenty nine patients received a full course of radiation at least 70 Gy to the primary site and 60 Gy to the nodal sites. These patients were all belonged to stage III or IV, The local control rate was $75\% in squamous cell carcinomas, and all the patients with lymphoepithelioma showed a complete response. Overall locoregional failure was $27.6\%. Distant metastasis was the predominant pattern of failures; 4/6 in lymphoepithelioma, 4/10 En squamous cell carcinoma. The Three-year-survival rate for squamous cell carcinoma was $40.5\%$, and for lymphoepithelioma $25.9\%, respectively. This may be due to the more frequent distant metastases in lymphoepithelioma and ineffective chemotherapy. No survival correlation was found with the level of neck node involvement. Though adjuvant chemotherapy was found to be of no benefit in overall survival, more prudent and aggressive chemotherapy would be necessary.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.183-188
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• 1990

Between January 197l and December 1987, 113 patients with nasopharyngeal cancer (NPC) were treated by radiation therapy with or without chemotherapy in the department of Radiation Oncology, Yonsei University Hospital. There were 19 patients under thirty years of age. The histology was undifferentiated carcinoma in $68\%$ of the younger patients as compared to $47\%$ of the older patients. Sex, stage, initial symptoms and treatment modalities differed little from those of older patients. In younger patients, the initial complete response rate was $79\%$ as compared to older patients with $54\%$, distant metastases were more common and the overall five year survival rate was not significantly different between the two age groups ($33.7\%$ for the young vs. $37.4\%$ for the old). The five year survival rates for stage III and IV were $60.0\%$ and $24.5\%$, respectively. Histologic subtype was not correlated with survival. The best survival was found only in patients who obtained a complete clearance of disease after radiation therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2747-2751
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• 2014

Background: DNA repair pathways play a crucial role in maintaining the human genome. Previous studies associated DNA repair gene polymorphisms (XPD Lys751Gln, XRCC1 Arg280His and XRCC1 Arg399Gln) with nasopharyngeal carcinoma. These non-synonymous polymorphisms may alter DNA repair capacity and thus increase or decrease susceptibility. The present study aimed to determine the genotype distribution of XPD codon 751, XRCC1 codon 280 and codon 399 polymorphisms and haplotype associations among NPC cases and controls in the Malaysian population. Materials and Methods: We selected 157 NPC cases and 136 controls from two hospitals in Kuala Lumpur, Malaysia for this study. The polymorphisms studied were genotyped by PCR-RFLP assay and allele and genotype frequenci es, haplotype and linkage disequilibrium were determined using SNPstat software. Results: For the XPD Lys751Gln polymorphism, the frequency of the Lys allele was higher in cases than in controls (94.5% versus 85.0%). For the XRCC1 Arg280His polymorphism, the frequency of Arg allele was 90.0% and 89.0% in cases and controls, respectively and for XRCC1 Arg399Gln the frequency of the Arg allele was 72.0% and 72.8% in cases and controls respectively. All three polymorphisms were in linkage disequilibrium. The odds ratio from haplotype analysis for these three polymorphisms and their association with NPC was 1.93 (95%CI: 0.90-4.16) for haplotype CGC vs AGC allele combinations. The global haplotypte association with NPC gave a p-value of 0.054. Conclusions: Our study provides an estimate of allele and genotype frequencies of XRCC1Arg280His, XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms in the Malaysian population and showed no association with nasopharyngeal cancer.