• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6513-6518
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• 2013

Background: To evaluate the treatment outcome and major late complications of all patients with recurrent nasopharyngeal carcinoma (NPC) treated with intracavitary brachytherapy (ICBT) in Hospital Kuala Lumpur. Materials and Methods: This retrospective study was conducted at the Department of Radiotherapy and Oncology, Hospital Kuala Lumpur, Malaysia. All patients with histologically confirmed recurrent NPC in the absence of distant metastasis treated in the period 1997-2010 were included in this study. These patients were treated with ICBT alone or in combination with external beam radiotherapy (EBRT). Treatment outcomes measured were local recurrence free survival (LRFS), disease free survival (DFS) and overall survival (OS). Results: Thirty three patients were eligible for this study. The median age at recurrence was 56 years with a median time to initial local recurrence of 27 months. Majority of patients were staged as rT1-2 (94%) or rN0 (82%). The proportion of patients categorised as stage III-IV at first local recurrence was only 9%. Twenty one patients received a combination of ICBT and external beam radiotherapy while 12 patients were treated with ICBT alone. Median interval of recurrence post re-irradiation was 32 months (range: 4-110 months). The median LRFS, DFS and OS were 30 months, 29 months and 36 months respectively. The 5 year LRFS, DFS and OS were 44.7%, 38.8% and 28.1% respectively. The N stage at recurrence was found to be a significant prognostic factor for LRFS and DFS after multivariate analysis. Major late complications occurred in 34.9% of our patients. Conclusions: Our study shows ICBT was associated with a reasonable long term outcome in salvaging recurrent NPC although major complications remained a significant problem. The N stage at recurrence was a significant prognostic factor for both LRFS and DFS.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3411-3416
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• 2016

Background: Nasopharyngeal carcinoma (NPC), a malignancy arising from the epithelial lining of the nasopharynx, is distinct from others cancers in terms of its epidemiologic features. It is rare in most parts of the world except for a few regions with populations of Mongoloid origin. Objectives: To study the expression pattern of Epstein Barr virus (EBV) encoded oncoproteins EBNA1 and LMP1 in different histological types of NPC and to correlate expression patterns with sex, age and histological types. Materials and Methods: A total of 40 formalin-fixed, paraffin-embedded NPC biopsy samples and tissues from 20 healthy controls were collected to study the expression level of EBNA1 and LMP1 using immunohistochemistry. Results: EBNA1 and LMP1 expression was found in 92.5% and 90% respectively, of the cases and none of the control specimens. The expression patterns of EBNA1 and LMP1 were determined to be statistically significant (p<0.05) when correlated with sex, age and histological distributions. Also immunohistochemistry was found to be a sensitive technique in the detection of EBV. Conclusions: The study reveals that the potent oncoproteins EBNA1 and LMP1 were over expressed in our population cohort. Our findings are to some extent inconsistent with earlier reports as our population showed a higher expression of both EBNA1 and LMP1 compared to other studies.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.383-398
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• 2023

Dihydroaustrasulfone alcohol (DA), the synthetic precursor of a natural compound (austrasulfone) isolated from the coral species Cladiella australis, has shown cytotoxic effects against cancer cells. However, it is unknown whether DA has antitumor effects on nasopharyngeal carcinoma (NPC). In this study, we determined the antitumor effects of DA and investigated its mechanism of action on human NPC cells. The MTT assay was used to determine the cytotoxic effect of DA. Subsequently, apoptosis and reactive oxygen species (ROS) analyses were performed by using flow cytometry. Apoptotic and PI3K/AKT pathway-related protein expression was determined using Western blotting. We found that DA significantly reduced the viability of NPC-39 cells and determined that apoptosis was involved in DA-induced cell death. The activity of caspase-9, caspase-8, caspase-3, and PARP induced by DA suggested caspase-mediated apoptosis in DA-treated NPC-39 cells. Apoptosis-associated proteins (DR4, DR5, FAS) in extrinsic pathways were also elevated by DA. The enhanced expression of proapoptotic Bax and decreased expression of antiapoptotic BCL-2 suggested that DA mediated mitochondrial apoptosis. DA reduced the expression of pPI3K and p-AKT in NPC-39 cells. DA also reduced apoptosis after introducing an active AKT cDNA, indicating that DA could block the PI3K/AKT pathway from being activated. DA increased intracellular ROS, but N-acetylcysteine (NAC), a ROS scavenger, reduced DA-induced cytotoxicity. NAC also reversed the chances in pPI3K/AKT expression and reduced DA-induced apoptosis. These findings suggest that ROS-mediates DA-induced apoptosis and PI3K/AKT signaling inactivation in human NPC cells.

• 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.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.221-225
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• 2000

Purpose : This study was designed to examine the reliability of the new version of the AJCC staging system (1997) of nasopharyngeal carcinoma in comparison with the AJCC staging system of 1992. Materials and Methods :Between 1983 and 1996, 185 patients with histologically proven nasopnaryngeal carcinoma were treated with radiation therapy at the Department of Therapeutic Radiology Seoul National University Hospital. For these patients, AJCC staging system of 1992 was compared with the 1997 version by reviewing hospital records, computed tomography (CT) and/or magnetic resonance imaging (MRI). Results :5-year overall suwival rates according to the 1992 and 1997 AJCC staging systems were 100$\%$, and 100$\%$ at stage 1: 100$\%$, and 68.8$\%$ at stage 11; 61.4$\%$, and 63.8$\%$ at stage 111; 61.1$\%$, and 63.2$\%$ at stage IV. S-year overall survival rates of each classification showed significant differences between stages (p=0.0049 for the old version, p=0.01 for the new), but no significant difference was found between the staging systems except at stage 11. Conclusion : The new AJCC staging system allows staging as reliably as the 1992 version, but the adequacy of the newly modified staging classification should be confirmed by further clinical examination.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.269-275
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• 2003

Purpose: To evaluate the results of radiation management on recurrence, survival and prognostic factors of patients with nasopharyngeal cancer Materials and Methods: Forty-nine patients, treated for nasopharyngeal cancer by radiotherapy between January 1984 and June 2000, were retrospectively studied. All patients were followed up for at least 2.5 years. Their median age was 52 years (range 17$\~$78). The histological types were 21 squamous cell carcinoma, 25 undifferentiated carcinoma, and 3 adenoid cystic carcinoma. The tumor stages were as follows: T1 in 14 patients, T2 in 24, T3 in 3, and T4 in 8, and N0 in 17 patients, Nl in 15, N2 in 4 and N3 in 13. Stages I, IIa, IIb ,III, IV and IVb were 4, 7, 12, 5, 8, and 13 patients respectively. Radiation doses of 58$\~$70 Gy (median 68.7 Gy) were given to the nasopahryngeal and involved lymphatic areas and of 46 $\~$ 50 Gy to the uninvolved neck areas. Results: The overall 5 and 10-year actuarial and disease free survival rates were 54.53$\%$ and 47$\%$ and 55.7$\%$ and 45.3$\%$, respectively The overall five-year survival rates were 100$\%$ in stage I , 80$\%$ in stage IIa, 59.5$\%$ in stage IIIb, 40$\%$ in stage III, and 42.2$\%$ in stage IV tumors. Twenty-three patients fatted either loco-regionally or distantly. Incidences of local failure, regional failure and distant metastasis for the first failure were 20.4$\%$, 8.2$\%$ and 20.4$\%$, respectively. Local recurrences were 4.3$\%$ in T1, 12.5$\%$ in T2, 0$\%$ in T3, and 62.5$\%$ in T4 lesions. Distant metastasis was seen in 41.2$\%$ of N2-3 lesions. Fifty percent of local recurrence appeared within 2 years of treatment at the primary lesion, whereas 70$\%$ of distant metastasis appeared within 2 years following treatment. Young age, female, early T stage, N0 stage; and poorly differentiated carcinoma were all related with good survival. However only stage showed statistically significance. Conclusionn: Based on the results of this study, radiation therapy to nasopharyngeal cancer showed high local recurrence in T4 and increased metastasis in N2-3 lesions. To improve local failure, further radiation doses, such as stereotactic radiation or IMRT radiation, are necessary especially in T4 lesions. The high incidence of distant metastasis in positive lymph node patients, indicates that combined radiation and effective chemotherapeutic agents with appropriated schedule are necessary.

• Radiation Oncology Journal
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• v.13 no.3
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• pp.215-223
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• 1995

Purpose : The aim of this study was to assess the effectiveness, survival rate and complication of radiation in nasopharyngeal cancer. Materials and Methods : From January 1980 to May 1989. Fifty patients who had nasopharyngeal carcinoma treated with curative radiation therapy at Kosin Medical Center were retrospectively studied. Thirty seven patients($74{\%}$) were treated with radiation therapy alone(Group I) and 13 patients ($26{\%}$) treated with combination of chemotherapy and radiation (Group II). Age distribution was 16-75 years(median : 45.8 years). In histologic type, squamous cell carcinoma was in 30 patients($60{\%}$), undifferentiated carcinoma in 17 patients($34{\%}$), and lymphoepithelioma in 3 patients($6{\%}$). According t AJCC staging system. 4 patients($8{\%}$) were in $T_1$, 13 patients($26{\%}$) in $T_2$. 20 patients($40{\%}$) in $T_3$, 13 patients($26{\%}$) in $T_4$ and 7 patients($14{\%}$) in $N_0$, 6 patients($12{\%}$) $N_1$, 23 patients($46{\%}$) in $N_2$, 14 patients($28{\%}$) in $N_3$. Total radiation dose ranges were 5250-9200cGy(median : 7355 cGy) in Group I and 5360-8400cGy(median : 6758cGy) in Group II Radiotherapy on 4-6MV linear accelerator and/or 6-12MeV electron in boost radiation was given with conventional technique to 26 patients($52{\%}$), with hyperfractionation(115-120cGy/fr., 2times/day) to 16 patients($32{\%}$), with accelerated fractionation(160cGy/fr., 2 times/day) to 8 patients($16{\%}$). In chemotherapy, 5 FU 1000mg daily for 5 consecutive days, pepleomycin 10mg on days 1 and 3, and cisplatin 100mg on day 1 were administered with 3weeks interval, total 1 to 3 cycles(average 1.8cycles) prior to radiation therapy. Follow up duration was 6-140 months(mean : 58 months). Statistics was calculated with Chi-square and Fisher's exact test. Results : Complete local control rates in Group I and II were $75.7{\%},\;69.2{\%} Overall 5 year survival rates in Group I and II were $56.8{\%},\;30.8{\%}$. Five year survival rates by histologic type in Group I and II were $52.2{\%},\;14.3{\%}$ is squamous cell carcinoma and $54.5{\%},\;50{\%}$ in undifferentiated carcinoma. Survival rates in Group I were superior to those of Group II though there were not statistically significant. In both group, survival rates seem to be increased according to increasing total dose of radiation up to 7500cGy, but not increased beyond it. There were not statistically significant differences in survival rates by age, stage, and radiation techniques in both group. Twenty four patients($48{\%}$) experienced treatment failures. Complications were found in 12 patients($24{\%}$). The most common one was osteomyelitis(4 patients, $33.3{\%}$) involving mandible (3 patients) and maxilla(1 patient). Conclusion : Chemotherapy in combination with radiotherapy was found to be not effective to nasopharyngeal cancer and the survival rate was also inferior to that of radiation alone group though it was statistically not significant due to small population in chemotherapy combined group.

• Korean Journal of Head & Neck Oncology
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• v.7 no.1
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• pp.40-44
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• 1991

Cystic metastasis in the neck from pharyngeal cancer has often been mistaken for either primary squamous cell carcinoma of branchiogenic origin or branchial cleft cyst. The distinctive histological and clinical features of cystic metastasis reviewed after its correct indentification can lead to the discovery of an unsuspected primary lesion and result in specific treatment options. Recendy, the authors experienced three cases of cystic metastasis in the neck from pharyngeal cancer ; one was from nasopharyngeal squamous cell carcinoma and the other two were from tonsillar squamous cell carcinomas. This report summarizes our experiences and review of the literatures.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4663-4670
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• 2014

Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor. We here investigated its effects on proliferation and apoptosis of the CNE2 carcinoma cell line, and attempted to establish genome-wide DNA methylation alteration due to differentially histone acetylation status. After cells were treated by TSA, the inhibitory rate of cell proliferation was examined with a CCK8 kit, and cell apoptosis was determined by flow cytometry. Compared to control, TSA inhibited CNE2 cell growth and induced apoptosis. Furthermore, TSA was found to induce genome-wide methylation alteration as assessed by genome-wide methylation array. Overall DNA methylation level of cells treated with TSA was higher than in controls. Function and pathway analysis revealed that many genes with methylation alteration were involved in key biological roles, such as apoptosis and cell proliferation. Three genes (DAP3, HSPB1 and CLDN) were independently confirmed by quantitative real-time PCR. Finally, we conclude that TSA inhibits CNE2 cell growth and induces apoptosis in vitro involving genome-wide DNA methylation alteration, so that it has promising application prospects in treatment of NPC in vivo. Although many unreported hypermethylated/hypomethylated genes should be further analyzed and validated, the pointers to new biomarkers and therapeutic strategies in the treatment of NPC should be stressed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4393-4399
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• 2015

Background: To explore the independent prognostic factors for the recurrence/metastasis of patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and Methods: A total of 604 patients initially diagnosed as LANPC by pathohistology in Fujian Provincial Cancer Hospital were selected to analyze the relationship between the clinical pathological patterns, therapeutic protocols and clinical stages with the recurrence/metastasis of LANPC. Results: The 1-, 3- and 5-year locoregionally recurrent rates of LANPC patients were 2.0%, 9.5% and 12.9% respectively, with average recurrent period being 78 months. Univariate analysis results indicated that clinical stages had certain influence on the recurrent period of LANPC patients. However, COX regression models showed that ages, genders and clinical stages were not the independent prognostic factors influencing the recurrence. The 1-, 3- and 5-year metastatic rates of LANPC patients were 6.6%, 17.5% and 18.8% respectively, with average metastatic period of 73 months. Univariate analysis results demonstrated that ages, N stages, clinical stages, locations of lymph node, retropharyngeal lymph node and extracapsular invasion of lymph node had certain influence on the metastatic period of LANPC patients. Additionally, further COX regression analysis results suggested that T stages, reduction protocols and extracapsular invasion of lymph node were the independent prognostic factors influencing the metastasis of patients with LANPC, in which T stages and extracapsular invasion of lymph node were the pestilent factors while reduction protocols the protective factor. Conclusions: Induction chemotherapy is beneficial to LANPC patients with initial treatment, and the metastatic rate decreases greatly after the application of reduction chemotherapy.