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The aim was to study the expression of Secretory Leukocyte Protease Inhibitor (SLPI) and to explore its correlation with the presence of Epstein-Barr Virus (EBV) among patients with nasopharyngeal carcinoma.The expression levels of SLPI mRNA in NPC cell lines and in ten matched-pairs of NPC and adjacent normal tissue were examined by quantitative real-time Polymerase Chain Reaction (PCR). Furthermore, protein expression of SLPI in 71 paraffin-embedded NPC biopsies was assessed by immunohistochemistry. Finally, the serum level of SLPI in 177 NPC patients and 103 healthy controls was evaluated by enzyme-linked immunosorbent assay (ELISA).The expression of SLPI mRNA in NPC cells was significantly lower than in the adjacent normal epithelium (p0.001). When the expression of SLPI in EBV-positive and -negative NPC cell lines was compared, we found that both mRNA and protein expressions of SLPI were significantly higher in EBV-negative cells. Furthermore, the results of immunohistochemical analysis demonstrated that the frequency of reduced SLPI expression in EBV-positive biopsies was significantly higher than that in EBV-negative biopsies.In this study, we have confirmed that SLPI is significantly down-regulated in NPC tissues. In addition, based on our preliminary results, we propose that the reduction of SLPI in NPC cells is associated with the presence of the EBV genome and/or the expression of EBV-encoded genes. SLPI may play an important role in EBV-mediated NPC tumorigenesis.

Purpose: To investigate the association of pretreatment body mass index (preT BMI) with outcomes of head-and-neck cancer in patients treated with radiotherapy (RT). Methods and Materials: All 1,562 patients diagnosed with head-and-neck cancer and treated with curative-intent RT to a dose of 60 Gy or higher were retrospectively studied. Body weight was measured both at entry and at the end of RT. Cancer-specific survival (CSS), overall survival (OS), locoregional control (LRC), and distant metastasis (DM) were analyzed by preT BMI ( =}25 kg/m{sup 2}). The median follow-up was 8.6 years. Results: Patients with lower preT BMI were statistically significantly associated with poorer CSS and OS than those with higher preT BMI. There was no significant difference between preT BMI groups in terms of LRC and DM. Body weight loss (BWL) during radiation did not influence survival outcomes. However, in the group with higher preT BMI, CSS, OS, and DM-free survival of patients with less BWL during radiation were statistically longer when compared with greater BWL. Conclusion: This study demonstrates that higher preT BMI positively influenced survival outcomes for patients with head-and-neck cancer. Patients with higher preT BMI who were able to maintain their weight during radiation hadmore » significantly better survival than patients with greater BWL.« less

Central nervous system germinoma historically has been treated with radiotherapy alone. Although this regimen provides good tumor control, there are risks of long-term complications; this study used a combination of chemotherapy and low-dose radiotherapy to reduce these risks. Between January 2002 and June 2009, 16 patients (14 male, 2 female) with a median age of 14.7 years (9.2 to 19.6 y), were treated. Thirteen of the tumors had a single focus and 3 were multifocal: 8 were located in the pineal, 8 were suprasellar, and 3 were in the basal ganglion or other periventricular areas. All patients had negative spinal magnetic resonance imaging findings. Treatment consisted of cisplatin-based and etoposide-based chemotherapy, and 2340 cGy of radiotherapy delivered to the whole brain/ventricle. The median time of follow-up was 45 months. None of the patients suffered from treatment failure. Tumors larger than 2.5 cm regressed less completely after upfront chemotherapy than smaller tumors, but overall treatment outcome was not affected by tumor size. One patient developed a new complication (hypopituitarism) 8 months after treatment, and 1 patient developed a second malignancy 3 years after diagnosis. The results confirm that short courses of chemotherapy combined with low-dose whole-brain or whole-ventricular radiotherapy have favorable outcomes.

Tumor necrosis factor alpha (TNFα) is an inflammatory cytokine that is present in the microenvironment of many tumors and is known to promote tumor progression. To examine how TNFα modulates the progression and metastasis of nasopharyngeal carcinoma, we used Affymetrix chips to identify TNFα-inducible genes that are dysregulated in this tumor. Elevated expression of TNFAIP2, which encodes TNFα-inducible protein 2 and not previously known to be associated with cancer, was found and confirmed by quantitative RT-PCR of TNFAIP2 expression in nasopharyngeal carcinoma and adjacent normal tissues. Immunohistochemical analysis showed that the TNFAIP2 protein was highly expressed in tumor cells. Analysis of 95 nasopharyngeal carcinoma biopsy specimens revealed that high TNFAIP2 expression was significantly correlated with high-level intratumoral microvessel density (P=0.005) and low distant metastasis-free survival (P=0.001). A multivariate analysis further confirmed that TNFAIP2 was an independent prognostic factor for nasopharyngeal carcinoma (P=0.002). In vitro, TNFα treatment of nasopharyngeal carcinoma HK1 cells was found to induce TNFAIP2 expression, and siRNA-based knockdown of TNFAIP2 dramatically reduced the migration and invasion of nasopharyngeal carcinoma HK1 cells. These results collectively suggest for the first time that TNFAIP2 is a cell migration-promoting protein and its expression predicts distant metastasis. Our data suggest that TNFAIP2 may serve as an independent prognostic indicator for nasopharyngeal carcinoma.

Current standard treatment of nasopharyngeal carcinoma (NPC) is either radiotherapy alone or combined chemoradiotherapy. Surgery in the form of nasopharyngectomy is usually only offered when there is evidence of local recurrence or persistent disease. Recurrent NPC (rNPC) can be detected earlier with the utilization of Epstein-Barr virus molecular diagnosis. This may result in early management with salvage surgery and hence improved survival. The facial translocation approach enhanced our ability to access the nasopharynx. Through a multidisciplinary approach with the collaboration of neurosurgeons, the surgical indication of salvage surgery is extended. This allowed improved respectability in locally advanced disease and involved the skull base and intracranial extension with reasonable morbidity and mortality. Endoscopic nasopharyngectomy is a choice for recurrent NPC with central roof or floor lesions with minimal lateral extension. Multivariate analysis indicated that gender, parapharyngeal space involvement, surgical margin, and the modality of adjuvant therapy impact significantly on local control. The impact on survival is indicated by the dura or brain involvement, local recurrence and modality of adjuvant therapy. It is apparent that recurrent NPC patients who underwent surgery had a significantly better survival rate than the re-radiation therapy group.

Nasopharyngeal carcinoma (NPC) is usually diagnosed at advanced clinical stages, resulting in poor outcomes. To discover serum biomarkers for improved NPC diagnosis and/or management, we simultaneously analyzed the NPC cell secretome and tissue transcriptome to identify candidate genes/proteins that are highly upregulated in NPC tissues and also secreted/released from NPC cells. Among the 30 candidates identified, 11 proteins were chosen for further validation using the serum samples from NPC patients and healthy controls, including cystatin A, cathepsin B, manganese superoxide dismutase and matrix metalloproteinase 2. The results showed that serum levels of all the four proteins were indeed higher in NPC patients versus healthy controls and that the use of a three-marker panel (cystatin A, manganese superoxide dismutase and matrix metalloproteinase 2) can contribute to a better NPC detection than each marker alone. In addition, a higher pretreated serum level of cystatin A was found to be associated with a higher nodal stage and poorer prognosis of NPC patients and cystatin A could modulate the migration and invasion of NPC cells in vitro. Altogether, our results indicate that analysis of both the cancer cell secretome and tissue transcriptome is a feasible strategy for efficient identification of novel NPC serum marker panel.

Heterogeneous nuclear ribonucleoprotein K (hnRNP K) mediates antiapoptotic activity in part by inducing downstream antiapoptotic genes. To systematically identify hnRNP K targets in nasopharyngeal carcinoma (NPC), affymetrix chips were used to identify genes that were both overexpressed in primary NPC and downregulated by hnRNP K knockdown in NPC-TW02 cells. The resulting gene set included the antiapoptotic gene, FLIP, which was selected for further study. In cells treated with hnRNP K siRNA, TRAIL-induced apoptosis was enhanced and the FLIP protein level was reduced. Promoter, DNA pull-down and chromatin-immunoprecipitation assays revealed that hnRNP K directly interacts with the poly(C) element on the FLIP promoter, resulting in transcriptional activation. Through iTRAQ-mass spectrometric identification of proteins differentially associated with the poly(C) element or its mutant, nucleolin was determined to be a cofactor of hnRNP K for FLIP activation. Furthermore, FLIP was highly expressed in tumor cells, and this high-level expression was significantly correlated with high-level hnRNP K expression (P=0.002) and poor overall survival (P=0.015) as examined in 67 NPC tissues. A multivariate analysis confirmed that FLIP was an independent prognostic factor for NPC. Taken together, these findings indicate that FLIP expression is transcriptionally regulated by hnRNP K and nucleolin, and may be a potential prognostic and therapeutic marker for NPC.

Glioblastoma and astrocytoma are the most common brain tumors affecting adults 45-60 years of age. The poor prognosis for glioblastoma patients results from recurrence after treatment. There is therefore an urgent need to develop diagnostic and prognostic markers as well as new therapies.Microarray analyses of clinical specimens from glioblastoma patients were used to identify potential tumor markers. Expression of candidate genes was analyzed by real-time reverse transcription-polymerase chain reaction and by immunoblotting and immunohistochemistry.Five potential markers (CD44 antigen (CD44), growth arrest and DNA-damage-inducible, alpha (GADD45A), fibronectin 1 (FN1), CD63 antigen (CD63) and secreted phosphoprotein 1 (SPP1)) showed expression patterns that correlated significantly with malignant glioma. In particular, expression of the CD44 antigen was elevated in more severe tumor types, and higher in tumor cores than in peripheral regions. However, lower levels of CD44 expression surprisingly correlated with lower survival.The CD44 antigen is a promising candidate for further development as a prognostic and therapeutic tool.

This study evaluated associations between the histological differentiation of oral squamous cell carcinoma and additional clinicopathological manifestations, adverse events after treatment, and the outcomes of patients in a region prevalent for betel quid chewing.Case series with chart review.Tertiary referral center.A total of 150 patients with primary oral squamous cell carcinomas who underwent surgery with or without adjuvant therapy were enrolled.Well, moderate, and poorly differentiated oral squamous cell carcinomas were reported in 54 (36%), 84 (56%), and 12 (8%) patients, respectively. There were no significant differences among different histological differentiations in age, sex, tumor, node, metastasis stage, bone invasion, depth of invasion, and history of carcinogen exposure. However, we found significant associations between tumor histological differentiation and nodal metastasis (P0.0001), extracapsular spread (P = 0.002), and perineural invasion (P0.0001). In the analysis of adverse events for survival during patient follow-up, oral squamous cell carcinomas with poor differentiation had a higher probability of developing neck recurrence (P = 0.001) and distant metastasis (P = 0.019), but not local recurrence or a second primary cancer. For survival analysis, univariate analysis showed that patient age, tumor stage, extracapsular spread, presence of perineural invasion, and tumor differentiation were significant factors. Multivariate analysis further demonstrated that poor differentiation (P = 0.007) was still a statistically significant factor.The current study demonstrates that poorer tumor histological classifications of oral squamous cell carcinoma are significantly associated with positive nodal status, extracapsular spread, perineural invasion of primary tumors, and the probability of developing neck recurrence and distant metastasis after treatment.

Nasopharyngeal carcinoma (NPC), one of the most common cancers in Southeast Asia, is commonly diagnosed late due to its deep location and vague symptoms. To identify biomarkers for improving NPC diagnosis, we established a proteomic platform for detecting aberrant serum proteins in nude mice bearing NPC xenografts. We first removed the three most abundant proteins from serum samples of tumor-bearing and control mice, and then labeled the samples with different fluorescent cyanine (Cy) dyes. The labeled serum proteins were then mixed equally and fractionated with ion-exchange chromatography followed by SDS-PAGE. Differentially expressed proteins were identified by in-gel tryptic digestion and MALDI-TOF MS. We identified peroxiredoxin 2 (Prx-II) and carbonic anhydrase 2 (CA-II) as being elevated in the xenograft mouse model compared to controls. Western blot analysis confirmed up-regulation of Prx-II and CA-II in plasma from five NPC patients, and ELISA showed that plasma Prx-II levels were significantly higher in NPC patients (n = 84) versus healthy controls (n = 90) (3.03 +/- 4.47 versus 1.90 +/- 2.74 microg/mL, p = 0.047). In conclusion, Cy dye labeling combined with three-dimensional fractionation is a feasible strategy for identifying differentially expressed serum proteins in an NPC xenograft model, and Prx-II may represent a potential NPC biomarker.

Overexpression of the DNA methyltransferase 3B (DNMT3B) gene and its effect on carcinogenesis has been demonstrated for various types of cancer. Recently, three single nucleotide polymorphisms (SNPs) of the DNMT3B promoter region, C46359T (-149C>T), -283T>C, and -579G>T have also been reported to be stratification markers that can predict an individual's susceptibility to cancers. In this study, we analyzed expression of DNMT3B in nasopharyngeal carcinoma (NPC) specimens and did not find elevated levels of DNMT3B in tumors using cDNA microarray analysis and RT-PCR. Meanwhile, 259 NPC patients and 250 controls were genotyped for the above three SNPs using a MALDI-TOF based mini-sequencing method. For C46359T (-149C>T), only the T/T genotype was found to be present in both patient and control groups (100% frequency). The frequency of the genotypes, -283CC, -283CT and -283TT, amongst NPC patients versus controls was, respectively, 86.1% versus 84.0%, 13.5% versus 15.6%, and 0.4% versus 0.4% (P=0.589). The allele frequency, -597TT, -597GT and -597GG, for patients versus controls was, respectively, 87.3% versus 84.8%, 12.0% versus 15.2%, and 0.8% versus 0 (P=0.501). The distribution of SNPs among cancer patients either featuring or not featuring cervical metastasis also did not reveal any significant difference. In conclusion, our data indicate that neither overexpression of DNMT3B nor the presence of three DNMT3B SNPs are associated with NPC, which suggests that DNMT3B might not play a role in hypermethylation of many tumor suppressor genes during carcinogenesis of NPC.

This hospital-based cohort study evaluated the efficacy of three Epstein-Barr virus (EBV) - associated assays for nasopharyngeal carcinoma (NPC) primary screening and monitoring treatment outcome. Five hundred and seventeen consecutive subjects, including 156 NPC patients, 264 healthy volunteers and 97 patients with head and neck squamous cell carcinoma (HNSCC) were enrolled. The sensitivity and specificity of EBV IgAs to viral capsid antigen (VCA), complementary EBV IgAs to early antigen and nuclear antigen-1 (EA+EBNA-1), and EBV DNA load were examined by immunofluorescent assays, enzyme-linked immunosorbent assays, and quantitative real-time PCR, respectively. After constructing the receiver operating characteristics to demonstrate screening efficacy, EBV EA+EBNA-1 IgA (AUC: 0.952; 95% CI, 0.930-0.974) was proved superior to EBV VCA IgA (AUC: 0.888; 95% CI, 0.854-0.922) or EBV DNA load (AUC: 0.893; 95% CI, 0.854-0.932) in differentiating NPC patients from controls. Comparison of screening efficacy between NPC patients and HNSCC patients revealed EBV EA+EBNA-1 IgA (AUC: 0.964; 95% CI, 0.943-0.985) still outperformed EBV VCA IgA (AUC: 0.884; 95% CI, 0.845-0.923). In subjects with higher serum titer or level equal to or above 1:80 and 6 EU/ml for EBV VCA IgA and EA+EBNA-1 IgA, the specificity reached as high as 99.2% and 95.1%, respectively, in the control groups. However, correlation of these three assays with clinicopathological manifestations of NPC, revealed only EBV DNA load significantly associated with N stage and overall stage in NPC patients. Additionally, EBV DNA load could be used to further raise the specificity of EBV EA+EBNA-1 IgA assays and was also the only assay to be consistently predictive of tumor relapse in post-treatment patients according to serial test results by time frame. Consequently, an EBV EA+EBNA-1 IgA-based protocol is recommended for mass screening, but EBV DNA load should be used solely for post-treatment monitoring for NPC in endemic areas.

Osteoradionecrosis (ORN) is one of the most serious complications of radiotherapy of nasopharyngeal carcinoma (NPC). ORN rarely occurs in the external auditory canal.This is a retrospective review of 11 NPC patients who had ORN in the external auditory canal. Exposed necrotic bone over the external auditory canal was the diagnostic hallmark. Three patients wore hearing aids and 2 had had previous otological surgery. ORN was detected between 2 and 15 years after radiation therapy (mean 8 years). The radiation dose ranged from 6480 to 8460 rads in 8 patients.The symptoms of external auditory canal ORN were crust (100%), otorrhea (91%), otalgia (91%), hearing impairment (73%), foul odor (45%) and retroauricular discharging fistula (9%), all of which mimicked those of chronic otitis media. After treatment, the diagnoses of 2 patients were rectified to external auditory canal malignancy and external auditory canal cholesteatoma, and the other 9 (82%) patients' diagnoses remained as ORN. After combined treatment with local cleansing, hyperbaric oxygen therapy, sequestrectomy and ear drops, resolution of symptoms was achieved in all the patients. Three patients who underwent sequestrectomy were free of disease.External auditory canal ORN is rare in NPC patients. The clinical presentation mimics that of chronic otitis media and differentiation is difficult. The disease is prone to occur in patients who wear hearing aids or have had previous surgery. A high index of suspicion is mandatory for early diagnosis. The disease may lead to disastrous complications and should never be neglected by clinicians.

Background: Epstein-Barr virus latent membrane protein 1 (LMP1) is known to be involved in the carcinogenesis of numerous cancers, including nasopharyngeal carcinoma and lymphoma. The C-terminus of LMP1 can recruit a spectrum of host cell cytosolic signaling molecules to exert its effects on downstream pathways. However, the function of the cytosolic N-terminus of LMP1 is not clear. Methods: Partial deletion or point mutation of the N-terminus of LMP1 were made. Results: Sequence analysis showed that not only were the lengths of LMP1 N- and C-termini different, so too were their distributions of charged amino acid side chains, with negatively charged amino acids being abundant in the C-terminus and positively charged amino acids dominating in the N-terminus. We found that deletion or mutation of N-terminal positively charged amino acids weakened the effects of LMP1 on nuclear factor NF-κB transcriptional activity. Furthermore, co-expressing a short N-terminal peptide of LMP1 enhanced the effect of full-length LMP1 on NF-κB transcriptional activity. We further demonstrated that the LMP1 N- and C-termini interact, which facilitated downstream signal transduction. Mutation of N-termial positively charged side chain amino acid could weaken LMP1 effect on cell motility. Conclusion: LMP1 N- and C-termini could interact and facilitate NF-κB transcriptional activity and cell motility. Citation Format: Cheng-Lung Hsu, Hsin-Pai Li, Yung-Chia Kuo, Ngan-Ming Tsang, Yu-Sun Chang. Latent membrane protein 1 N-C interaction of EBV facilitates (nuclear factor kappa-light-chain-enhancer of activated B cells transcriptional activity. [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 1020. doi:10.1158/1538-7445.AM2015-1020

Thymic lymphoepitheliomalike carcinoma (LELC) in children is extremely rare and we report 2 such cases with molecular analysis of Epstein-Barr virus (EBV) and its encoded latent membrane protein-1 as well as a literature review. Both of our patients were male, presented with a huge anterior mediastinal mass, expired within a year after diagnosis despite treatment. There were altogether 9 cases of thymic LELC in children. Their common clinical features include a male predominance, large tumor size, advanced clinical stage, and poor clinical outcome. All cases were associated with EBV and nearly half developed concurrent hypertrophic osteoarthropathy (HOA). Thymic LELC in children is an aggressive EBV-associated malignant tumor frequently accompanied by HOA. We proposed that EBV might play a role in the development of HOA through the interactions of latent membrane protein-1, vascular endothelial growth factor, and cyclooxygenases-2.

Background. The C-terminal activation region 2 (CTAR2) of Epstein-Barr virus latent membrane protein 1 is the major site that correlates with metastasis-related signaling path- way. The variation of CTAR2 sequence may affect the incidence of distant metastasis in patients with nasopharyngeal carcinoma (NPC). Methods. Two hundred forty-nine specimens from consecu- tive patients with nonmetastatic NPC were collected. Amplifica- tion by polymerase chain reaction and sequence analysis of CTAR2 were performed. DNA sequence identical to the Cao strain was grouped as Cao CTAR2, whereas sequences differ- ing from Cao made up non-Cao CTAR2. Clinical characteristics and CTAR2 status were subjected to statistical analysis for dis- tant metastasis. Results. Non-Cao CTAR2 was associated with a statistically significant lower distance metastasis and superior survival rate. A combination of clinical stage and CTAR2 expression provided an accurate method of identifying high risk of metastasis. Conclusion. NPC patients with non-Cao CTAR2 were less likely to have metastasis develop than those characterized by Cao CTAR2. V C 2006 Wiley Periodicals, Inc. Head Neck 29: 109-119

Objectives: Retromolar trigone (RMT) squamous cell carcinoma is uncommon but notorious for poor prognosis. We reviewed our experience in the management of RMT cancer to determine survival rates and to identify prognostic factors. Methods: Fifty patients with RMT squamous cell carcinoma were treated with surgery and/or radiation or chemoradiation therapy between July 1993 and June 2004 at Chang Gung Memorial Hospital, Taiwan. Patients were followed up for 3 to 106 months (mean, 36 months). There were 6 stage I, 13 stage II, 4 stage II, and 27 stage N patients. Results: The 5-year actuarial survival rate for stage I to N and all stages were 100%, 74.1%, 75%, 43.6%, and 60.6%, respectively. Seventeen (34%) patients had maxilla bone (11 [22%]) or mandible bone (9 [18%]) invasion. Eleven (22%) patients had masticator space involvement. Cervical metastasis rate was 26%. Multivariate analysis revealed that masticator space involvement, neck recurrence, and cervical metastasis were poor prognosticators of survival by order. The maxilla bone was more apt to be involved by RMT cancer than the mandible. Patients with masticator space involvement had a 5-year actuarial survival rate of 22.5% and the mean survival time was only 37.8 months. Conclusions: RMT squamous cell carcinomas are aggressive tumors. The maxilla is more apt to be involved than the mandible. Deep infiltration of the masticator space and invasion of the maxilla and mandible worsen the prognosis.

Objective: The specific 30-bp deletion of the Epstein-Barr virus (EBV)-derived latent membrane protein-1 gene has been suggested to be associated with the pathogenesis of nasopharyngeal carcinoma (NPC) and a more aggressive phenotype of some EBV-associated malignancies. Methods: The authors conducted a retrospective cohort study. Between 1995 and 2001, 542 patients who had received complete courses of radiotherapy followed by at least 3 years of follow up were enrolled. Patients were divided into two groups according to the presence or absence of the 30-bp deletion in their tumor samples. Results: A total of 446 (82.3%) patients were found to feature the 30-bp deletion, whereas 88 (16.2%) did not. Interestingly, dual infection was found in eight (1.5%) patients. No statistical significance was found in age, gender, NPC-presenting stage, radiosensitivity, and pathologic classification between the two groups. The actuarial 5-year overall survival rate and the distant metastasis-free rate for the 30-bp deletion and nondeletion group were not statistically different (61.3% vs. 65.4% and 68.1% vs. 73.1%; P = .132 and .135, respectively). In multivariate analysis, older age, nasopharyngeal recurrence, advanced tumor stage, and the development of distant metastasis were shown to be poorer prognosticators for overall survival, whereas the presence of 30-bp deletion was not. For distant metastasis, only advanced tumor stage was shown to be a poor prognosticator, whereas other variables, including the presence of 30-bp deletion, had no statistical significance. Conclusions: In this retrospective cohort, we have demonstrated that this specific 30-bp sequence deletion might be only the predominant variant rather than an NPC phenotype-associated polymorphism. Additionally, dual infection is a rare but possible phenomenon in the endemic NPC tumors.

Purpose: The presence of Epstein-Barr virus latent membrane protein-1 (LMP-1) gene in nasopharyngeal swabs indicates the presence of nasopharyngeal carcinoma (NPC) mucosal tumor cells. This study was undertaken to investigate whether the time taken for LMP-1 to disappear after initiation of primary radiotherapy (RT) was inversely associated with NPC local control. Methods and Materials: During July 1999 and October 2002, there were 127 nondisseminated NPC patients receiving serial examinations of nasopharyngeal swabbing with detection of LMP-1 during the RT course. The time for LMP-1 regression was defined as the number of days after initiation of RT for LMP-1 results to turn negative. The primary outcome was local control, which was represented by freedom from local recurrence. Results: The time for LMP-1 regression showed a statistically significant influence on NPC local control both univariately ( p p = 0.004). In multivariate analysis, the administration of chemotherapy conferred a significantly more favorable local control ( p = 0.03). Advanced T status (≥ T2b), overall treatment time of external photon radiotherapy longer than 55 days, and older age showed trends toward being poor prognosticators. The time for LMP-1 regression was very heterogeneous. According to the quartiles of the time for LMP-1 regression, we defined the pattern of LMP-1 regression as late regression if it required 40 days or more. Kaplan-Meier plots indicated that the patients with late regression had a significantly worse local control than those with intermediate or early regression ( p = 0.0129). Conclusion: Among the potential prognostic factors examined in this study, the time for LMP-1 regression was the most independently significant factor that was inversely associated with NPC local control.

Background. Lhermitte's sign (LS) is a side effect of radiotherapy (RT) on the spinal cord and typically occurs shortly after the procedure has been conducted. When treating patients with cancer of the head and neck region with irradiation, it remains difficult to avoid exposing the cervical spinal cord to unintended radiation. In this study, we focused on nasopharyngeal cancer (NPC) alone and looked for various parameters that might influence the occurrence of LS associated with this disease after RT. Methods. From 1979 through 1990, 1171 patients with NPC completed RT either with or without chemotherapy at the Lin-Kou Medical Center, Chang Gung Memorial Hospital (CGMH), Tao-Yuan, Taiwan; the RT regimens for these treated patients were very similar. The nasopharyngeal tumor was treated to 75 Gy by photon teletherapy and after-loading brachytherapy. The neck lymphatics were irradiated with photon irradiation to 46.8 Gy and then boosted with electron beams to 10 to 30 Gy, in accordance with the patient's nodal status, either unilaterally or bilaterally. Every patient was followed monthly for the first 3 months after therapy and subsequently every 2 to 3 months for the next 2 years and, finally, every 6 months thereafter. At follow-up, a neurologic checkup of each patient was performed to determine whether any injury to the spinal cord or brain stem had arisen. Results. LS was observed for 121 patients (10.3%). The median development time for such signs was 3.0 months after the completion of RT (range, 0.2–72 months), and the appearance of such a sign lasted 1 to 82 weeks (median, 17 weeks). No statistically significant differences between the sexes were noted in the development of such a sign (p = .5263),or among various T classifications (p = .0757) and N classifications (p = .4412). The incidence of LS was significantly lower for those patients who had also received chemotherapy than it was for those who had not (p = .003), and it was also lower for patients older than 60 years than for those younger than 60 years (p = .0061). Of the subjects who did not undergo neck-lymphatic boosting or who had undergone only unilateral neck-lymphatic boosting, 7.2% had LS develop, whereas 11.5% of patients who had been boosted bilaterally had LS develop (p = .0285). Conclusions. The incidence of LS associated with NPC and after RT was higher in patients who underwent bilateral neck-lymphatic boosting by electron beams than for those who underwent unilateral boosting or who did not undergo boosting. A correlation between increased incidence of LS and RT dose on the cervical spinal cord was noted when the cord dose exceeded 48.9 Gy. Therefore, wherever possible, a CT simulator and a three-dimensional treatment-planning system should necessarily be used to verify the dose distribution of electron-beam RT to diminish the chance of radiation overdose on the cervical cord. © 2004 Wiley Periodicals, Inc. Head Neck27: 187–194, 2005

Objectives The aim of this study was to investigate the feasibility of molecular diagnosis of nasopharyngeal carcinoma (NPC) by combining nasopharyngeal swab and polymerase chain reaction (PCR) to detect Epstein-Barr virus (EBV) derived latent membrane protein-1 gene (LMP-1) and Epstein-Barr nuclear antigen gene (EBNA). Methods 437 adults underwent nasopharyngoscopy, possible biopsy, and nasopharyngeal swab to obtain nasopharyngeal cells for the detection of LMP-1 and EBNA by PCR. Results By detecting LMP-1 and EBNA in the nasopharyngeal swabs, NPC could be diagnosed with a false-positive rate of 1.7% (6/354), a false-negative rate of 8.6% (6/70), a sensitivity of 91.4% (64/70), a specificity of 98.3% (348/354), positive predictive value of 91.4% (64/70), and negative predictive value of 98.3% (348/354). Conclusion Detecting EBV genomic LMP-1 and EBNA by nasopharyngeal swab verifies NPC with a sensitivity of 91.4% and specificity of 98.3%. The nasopharyngeal swab coupled with PCR based EBV LMP-1 and EBNA detection could serve as a good supplement to pathological diagnosis of NPC.

Objectives: Epstein-Barr virus (EBV) is closely related to nasopharyngeal carcinoma (NPC). Detection of EBV genomic DNA in a nasopharyngeal swab specimen may indicate the presence of NPC, and the EBV genomic DNA is only detected in patients with NPC and not in other head and neck cancers. This study aims to prove that detection of EBV genomic DNA by means of the latent membrane protein (LMP)-1 gene and the Epstein-Barr nuclear antigen (EBNA)-1 gene in the nasopharynx in NPC patients after radiation therapy indicates local recurrence of NPC. Study Design: Prospective. Methods: Nasopharyngeal swab with polymerase chain reaction (PCR)-based LMP-1 and EBNA-1 gene detection was used to monitor local recurrence in 84 NPC patients who completed radiation therapy. Results: Of the 12 patients demonstrating positive LMP-1 and EBNA-1 gene, 11 had local recurrence, and 10 of them had early rT1 mucosal recurrence. Subsequent salvage nasopharyngectomy controlled local disease in nine. Only one local recurrence in the skull base failed to show LMP-1 gene initially. Detection of LMP-1 gene and later verification with EBNA-1 gene from nasopharyngeal swabs in NPC patients after radiation therapy predicted local recurrence with a sensitivity of 91.7% and a specificity of 98.6%. Conclusions: Nasopharyngeal swab with LMP-1 and EBNA-1 gene detection is a useful and reliable method to monitor local recurrence in NPC patients. It helps to detect recurrence early and may improve local control and enhance survival.

Nasal NK/T cell lymphoma is a distinctive type of extranodal lymphoma with an unique immunophenotype and a strong association with Epstein-Barr virus (EBV). It is one of the common extranodal lymphomas in Taiwan. We studied 22 cases of nasal NK/T cell lymphoma to characterize their clinicopathologic features and to explore the possible differences between histologic subtypes and their clinical behavior as well as the prevalence of 30-base pair (bp) deleted latent membrane protein-1 ( LMP-1) gene of the EBV. They consisted of 5 cases of small cell type (SC), 6 cases of medium-sized cell type (MC), 6 cases of large cell type (LC), and 5 cases of pleomorphic cell type (PC). Twelve patients were men and 10 were women (1.2 to 1), and their ages ranged from 34 to 75 years with a median age of 55.5 years. The median ages of the LC type and PC type were older than the other 2 types. No other clinical features differed significantly among the 4 subtypes. Nasal obstruction was the most common initial presenting symptom. All but 1 case had stage IE disease at the time of diagnosis. Five cases developed extranasal involvement and skin was the most common site. No bone marrow involvement was detected. The majority of patients received local radiotherapy and chemotherapy. Local irradiation was more effective than chemotherapy alone. We achieved an overall survival of 63.6% at 5 years as estimated by the Kaplan-Meier analysis, which was better than other series. All cases displayed an immunophenotypic profile of CD3ε+, CD20-, CD56+, and TIA-1+ except that 1 case was CD3ε-. Fourteen of 22 cases (64%) expressed LMP-1. Nine cases of various cell types (41%) were also CD30+. Among the 4 histologic subtypes, the SC type differed from the other types by the absence of angiodestruction and necrosis, although angioinvasive growth was seen in 2 of them. Pseudoepitheliomatous hyperplasia was seen in only 3 cases of the SC type, and all 5 cases of the SC type were CD30-. No statistical difference in survival was found among the 4 histologic subtypes or between CD30+ and CD30-cases. All 22 cases were positive for EBV by polymerase chain reaction and Epstein-Barr virus early RNA (EBER) in-situ hybridization. A high prevalence rate of 86% (19/22) of the 30-base pair (bp) deleted LMP-1 gene was found, but 81.5% (22/27) of the EBV-positive control reactive lymphoid tissues also had the 30-bp deleted LMP-1 gene. Therefore, the high prevalence of the 30-bp deleted LMP-1 gene found in NK/T cell lymphoma could be due to the high prevalence of the deleted variant in this geographic region. However, it remains possible that the high prevalence of the deleted LMP-1 gene contributed to the increased incidence of EBV-associated nasal NK/T cell lymphoma in Taiwan.

Problem: The 30-bp deletion in the carboxy-terminal region of the Epstein-Barr virus-derived latent membrane protein-1 gene has been proved to be associated with carcinogenesis of nasopharyngeal carcinoma (NPC), a common head and neck cancer in Taiwan. We conducted a retrospectively prospective cohort study to investigate whether this sequence deletion did play any role in the clinicopathological manifestation of NPC Methods: Between 1994 and 2003, 242 NPC patients who received the complete course of radiotherapy followed by at least 2-year follow-up were enrolled. Patients were divided into 2 groups according to the presence or absence of the 30-bp deletion. Patients’ initial clinicopathological manifestations, radiosensitivity, distant metastasis status, and overall survival were analyzed. Results: A total of 197 (81.4%) patients were found to have the 30-bp deletion and 42 (17.4%) did not. Surprisingly, 3 (1.2%) patients had the dual infection. Age, sex, presenting stage, locoregional radiosensitivity, and pathological classification all lack statistical difference between 2 groups. In survival analysis, the actuarial 5-year overall survival, distant metastasis-free rate, and disease-free survival of nondeletion group tend to be better than those of the 30-bp deletion group (71.6% vs 59.0%, 87.4% vs 70.2%, and 43.2% vs 39.5%). In multivariate analysis, we discovered that older NPC patients with the 30-bp deletion and the patients presenting with advaced tumor stages have worse prognosis in the overall survival. Conclusion: 81.4% of Taiwanese NPC patients had the 30-bp deletion. Our findings indicate that this sequence deletion has no effect on clinicopathological manifestations but tends to be a worse prognostic factor in the overall survival and distant metastasis. Our study also demonstrated that dual infection is a rare but possible phenomenon in NPC tumors. Significance: Our studies indicate that this 30-bp deletion has no effect on the NPC’s various clinicopathological manifestations, but the negative impact of the 30-bp deletion to overall survival will be enlarged as patient’s age increases. Support: This study was supported by grants from the Taiwan National Science Council (NSC88-2314-B-182A-010, NSC92-2314-B-182A-207) and Chang Gung University (CMRPG32077, CMRPG32090).

Background. The purpose of this study was to investigate the frequency of Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) in tonsils and non-neoplastic nasopharynxes in Taiwan. Methods. Nest-polymerase chain reaction (nest-PCR) was used to examine the presence of LMP-1 gene in lymphoid hyperplasia from non-neoplastic tonsillar and nasopharyngeal tissues and in tonsillar cancers. Results. In 152 cases, 64 biopsy tissues were obtained from lymphoid hyperplasia of nasopharynxes, 57 from tonsillectomy of non-neoplastic tonsils, and 31 from tonsillar cancers. LMP-1 was detected in 43.4% of the study group. Nineteen (29.7%) and 29 (50.9%) lymphoid hyperplasias from normal nasopharynxes and tonsils, respectively, and 18 (58.1%) biopsies from tonsillar cancers had positive LMP-1. The 30–base pair (bp) deleted variant was detected in 89.5% and 82.8% of normal nasopharynxes and tonsils, respectively, and in 66.7% of biopsies from tonsillar cancers (p = .198). Conclusion. This study found that the 30-bp variant was the predominant type of LMP-1 from a healthy population in Taiwan. © 2004 Wiley Periodicals, Inc. Head Neck26: 619–624, 2004

From May 1994 to December 1999, 43 patients with meningiomas in the base of the skull underwent linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) at Chung Gung Memorial Hospital. SRS was performed as a primary treatment in 14 patients, and after resection in 29 patients. The mean tumor volume was 5.68 cc, and the mean target surface dose was 16 Gy, delivered with an average of three isocenters. The median follow-up was 74.5 months. The 7-year local control rate and 7-year overall survival rate were 89.7% and 80.2%, respectively. The 7-year local control was 100% and 84.4% in SRS alone group and surgical excision with SRS group (p = 0.21), respectively. A stationary tumor following SRS was seen in 23 (53.5%) patients, partial shrinkage was seen in 16 (37.2%) patients, and complete disappearance in one patient was seen (2.3%). Furthermore, disease progression was noted in three (7%) patients, one of whom died of disease. The median time to tumor response was 15.4 months (range 5.8-52.8 months). Cases remained stable or had improved neurological statuses without any deterioration in 37.9% and 78.7% of the groups treated with surgery and SRS and SRS alone, retrospectively. In summary, LINAC-based SRS is an effective and safe modality of treating unresectable or partially resected meningiomas in the base of the skull. For tumors with diameters of 3 cm or less, particularly in patients without or with minimal clinical neurological symptom, SRS alone can provide a good local control without causing cranial neuropathy.

This study is a retrospective analysis of 134 patients treated with radiotherapy at our hospital. The sample included 88 stage T1 and 46 stage T2 patients. Sixty-two patients had anterior commissure involvement, 37 patients had impaired vocal cord mobility, and 24 patients had supraglottic or subglottic extension. Irradiation was given, with the dose ranging from 60 to 72 Gy. Laryngectomy was the main salvage treatment for local recurrence. The 5-year initial and final local control rates were 71% and 83%, and the 10-year initial and final local control rates were 69% and 80%, comparable to the results of other series. The 5-year rate of overall survival with final larynx preservation was 77%. Multivariate analysis revealed that anterior commissure involvement is prognostic of a poor outcome in patients with T1 glottic cancer. Further subgroup analysis revealed that a fraction size of >200 cGy could overcome the negative impact of anterior commissure involvement and significantly improve the 5-year local control rate in T1 patients (100% at >200 cGy versus 45% at ≤200 cGy; p = .04). Subglottic extension of the glottic cancer predicted poor outcome in T2 patients. The 5-year local control rates of patients with and without subglottic extension were 9% and 77%, respectively (p < .001). According to our results, radiotherapy with a fraction size of >200 cGy is recommended for T1 disease with anterior commissure involvement. For patients with T2 disease and subglottic extension, radiotherapy alone produces poor results. Further improvement of outcomes by other treatment strategies needs to be investigated.

Objective The object of this study was to determine the incidence of p53 mutation in recurrent nasopharyngeal carcinoma refractory to radiotherapy. Study Design Prospective study. Methods There were 31 patients enrolled in this study between 1995 and 1998. All patients had received radiotherapy but none of them had undergone chemotherapy or local salvage surgery previously. Results The p53 status of each tumor was analyzed by polymerase chain reaction and by sequencing of exons 5 to 8 (codons 126–306). Five (16.1%) of 31 patients had mutations in the p53 gene, of which 2 were non-sense mutations, 2 were transition mutations, and 1 was a frameshift deletion mutation. The majority of the p53 mutations were found in exon 5. There is no significant difference in the incidence of p53 mutation compared with that of the previous reports for the primary disease. Based on the clinicopathologic data, there was no specific difference found between these 5 patients and the others. Conclusions This study shows that p53 mutation is an infrequent event and may have no essential role in recurrent nasopharyngeal carcinomas.

Background: To investigate the relationship between pretreatment plasma EBV DNA copy number and sites and numbers of metastases in patients with nasopharyngeal carcinoma (NPC). Methods: One hundred and thirty-three patients with metastatic NPC were treated at outpatient department. Their plasma EBV DNA concentrations were determined by real-time quantitative PCR. Results: The overall patient response rate after 3-6 months of treatment was 48.1%. Pretreatment plasma EBV DNA concentrations were lower in patients with solitary nodule (≤5,000 copies/mL, 18/25 [72%] vs. multiple nodules, 49/128 [45.4%], P=0.025) or pure lung metastases (≤5,000 copies/mL, 19/21 [90.5%] vs. not lung metastases alone 48/112 [42.9%], P5,000 copies/mL, median OS, 26 vs. 10 months; HR, 2.852; P Conclusions: Pretreatment plasma EBV DNA copy number correlated with number and sites of metastases and with OS in patients with metastatic NPC. Citation Format: Hung-Ming Wang, Kai-Ping Chang, Tung-Liang Lin, Shiang-Fu Huang, Ngan-Ming Tsang, Sheng-Chieh Chan, Cheng-Lung Hsu. Correlation between number and sites of metastases and differential pretreated EBV DNA load profiles and their effects on outcomes in patients with metastatic nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2871. doi:10.1158/1538-7445.AM2014-2871

Objectives In patients with nasopharyngeal carcinoma (NPC), the differentiation between recurrent primary cancer and osteoradionecrosis (ORN) is clinically difficult. Epstein-Barr virus (EBV)-derived latent membrane protein-1 (LMP-1) has been demonstrated to be highly associated with NPC. The objective of this study is to define the role of the LMP-1 gene in the differential diagnosis of recurrent NPC and ORN. Study Design Prospective. Methods From July 1998 to June 2000, 15 postirradiated patients with NPC who were initially diagnosed to have skull base ORN underwent endoscopic sequestrectomy. The sequestra were examined for the presence of the LMP-1 gene and cancer. Results Two of 15 patients had recurrent cancer and only these two patients demonstrated a positive LMP-1 gene in their surgically removed sequestra. The presence of the LMP-1 gene in the sequestrum coincided with biopsy-proven local recurrence. Conclusions The LMP-1 gene is a potential marker to differentiate between recurrent NPC and ORN. The presence of the LMP-1 gene in patients with ORN may indicate local recurrence.

Purpose : To assess the outcome of and determine prognostic factors for locally recurrent nasopharyngeal carcinoma (NPC) in patients treated with a second course of radiotherapy (RT). Materials and methods : From 1982 to 1995, 186 NPC patients, who had initially been treated in the Department of Radiation Oncology, Chang Gung Memorial Hospital-Linkou, developed local recurrence in the nasopharynx and were re-treated with RT (≥20 Gy). The time from the initial RT to re-treatment ranged from 8 to 136 months (median: 23 months). All patients were treated with external RT and conformal radiotherapy was used in 35 patients after 1993. Fifteen received radiosurgery as a boost treatment. The RT dose at the nasopharyngeal tumor area ranged from 20 to 67.2 Gy (median 50 Gy). Eighty-two patients received one to eight courses of cisplatin-based chemotherapy in addition to RT. Results : The 1-, 3- and 5-year survival was 54.9, 22.1 and 12.4%, respectively. Patients whose tumor relapsed later than 2 years after the first treatment had a better survival than those with earlier relapse (3-year survival: 30.1 vs. 10.8%; P =0.015), but the difference became insignificant in patients who received ≥50 Gy. Patients without evidence of intracranial invasion or cranial nerve palsy had better survival than those with such lesions (3-year survival: 30.9 vs. 3.7%; P =0.006). A re-treatment dose ≥50 Gy yielded better survival (3-year survival: 22.8 vs. 18.5%; P =0.003). Addition use of radiosurgery may improve survival. The use of chemotherapy did not improve survival. Conformal radiotherapy resulted in significantly fewer severe complications than conventional RT. Conclusions : A repeat course of RT for locally recurrent NPC successfully prolongs survival in a significant number of patients. Intracranial invasion and/or cranial nerve palsy and re-treatment dose affect the prognosis, with a dose of ≥50 Gy significantly improving survival. Radiosurgery boost may also improve survival. Our preliminary data indicates that conformal radiotherapy may decrease the severity of radiation-induced complications. However; longer follow-up and larger sample size is necessary to document the findings.

This study is the first to use genome-wide association study (GWAS) data to evaluate the multidimensional genetic architecture underlying nasopharyngeal cancer. Since analysis of data from GWAS confirms a close and consistent association between elevated risk for nasopharyngeal carcinoma (NPC) and major histocompatibility complex class 1 genes, our goal here was to explore lesser effects of gene-gene interactions. We conducted an exhaustive genome-wide analysis of GWAS data of NPC, revealing two-locus interactions occurring between single nucleotide polymorphisms (SNPs), and identified a number of suggestive interaction loci which were missed by traditional GWAS analyses. Although none of the interaction pairs we identified passed the genome-wide Bonferroni-adjusted threshold for significance, using independent GWAS data from the same population (Stage 2), we selected 66 SNP pairs in 39 clusters with P

Background: This prospective phase II clinical trial evaluated the efficacy and toxicity of cisplatin, oral tegafur-uracil, leucovorin, and mitomycin C in patients with recurrent or metastatic nasopharyngeal carcinoma. Methods: Patients with histologically proven non-keratinizing or undifferentiated nasopharyngeal carcinoma were prospectively enrolled from April 2002 to June 2005. Cisplatin 50 mg/m 2 on day 1, 22 and mitomycin C 6 mg/m 2 on day 1 were administered. Oral tegafur-uracil 300 mg/m 2 /day and oral leucovorin 60 mg/day were given on day 1-14 and day 22-35, respectively. Each cycle was repeated every 6 weeks. Primary and secondary endpoints are response rate and toxic profiles with survivals, respectively. Results: Twenty-two patients with the median age of 47 (35-69) years were enrolled in the study. Sixteen (72.7%) patients had undifferentiated nasopharyngeal carcinoma. The regimen was well-tolerated by all patients with the exception of one patient (4.6%) who experienced grade IV anorexia, and two patients (9.1%) who had grade IV vomiting. There was no treatment-related death. The overall response rate was 59.1%, including 3 (13.6%) complete remissions. The median duration of response was 15.9 months, the median time to tumor progression was 10.0 months, and the median overall survival was 16.0 months. Conclusion: This outpatient chemotherapy regimen is acceptably effective and toxic among patients with recurrent or metastatic nasopharyngeal carcinoma.

Purpose: Radiation therapy (RT) may lead to difficulty in swallowing and subsequently weight loss in patients with head and neck cancer. We investigated the association of pre-treatment body mass index (preT BMI) with outcomes of head and neck cancer in patients treated with radiation. Methods: All 1562 patients diagnosed with head and neck cancer and treated with curative-intent RT to a dose of 60Gy or higher between 1994 and 2004 were retrospectively studied. Body weight was measured both at entry and at the end of RT. cancer-specific survival (CSS), overall survival (OS), locoregional control (LRC) and distant metastasis (DM) were analyzed by preT BMI (< 25 Kg/m2 vs ≤ 25Kg/m2). The median follow-up was 8.6 years. Results: Patients with higher preT BMI appeared to have earlier T and N stage. Patients with lower preT BMI were statistically significantly associated with poor CSS (p = 0.023) and OS (p < 0.0001) than those with higher preT BMI. There is no significant difference between high and low preT BMI in LRC and DM. Body weight loss (BWL) during radiation did not influence survival outcomes. However, in the group of higher preT BMI, CSS, OS and DM-free survival of patients with less BWL during radiation was statistically longer when compared with greater BWL (p = 0.002, < 0.0001, and 0.033). Conclusion: This study demonstrates preT BMI greater than or equal to 25 Kg/m2 positively influenced survival outcomes for patients with head and neck cancer. Patients with higher preT BMI who were able to maintain their weight during radiation had significantly better survival and distant outcomes than patients experiencing greater BWL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1689. doi:1538-7445.AM2012-1689

PURPOSE: The presence of EBV latent membrane protein-1 (LMP-1) gene in nasopharyngeal swabs indicates the presence of nasopharyngeal carcinoma (NPC) tumor cells. This study was undertaken to investigate whether the viral load in nasopharyngeal (NP) swabs after a cumulative dose of 4,000 cGy during radiotherapy (RT) was inversely associated with NPC local control. METHODS AND MATERIALS: During April 2000 and June 2007, there were 77 non-disseminated NPC patients receiving serial examinations of NP swabbing with the detection of LMP-1 during the course of RT. The median number of NP swabs performed was 5 among the studied patients. EBV DNA in NP swabs was quantified using real-time quantitative PCR. LMP-1 regression was defined as minimal viral load which was represented by being lower than 1,000 copies per 200 μg DNA in the specimen obtained via NP swab. The primary outcome was freedom from local recurrence, which represented local tumor control. In addition, 36 cases had at least 2 serum stocks during the course of RT as well. The median number of serum stocks obtained was 4 in this patient subgroup. If available, serial serum EBV viral loads were also checked to evaluate whether they were correlated with the viral loads in NP swabs. RESULTS: At the time of analyzing the data, there were 18 cases (23%) developing local recurrence after completion of RT. Reviewing the viral load in NP swabs after a cumulative dose of 4,000 cGy during RT, there were 14 locally recurrent cases whose viral loads were greater than 1,000 copies/200 μg DNA in the specimens of NP swabs. On the other hand, among the 59 patients who have not experienced local recurrence at the time of current analysis, 28 non-recurrent NPC patients had a viral load greater than 1,000 copies/200 μg DNA during the corresponding period. The NPC patients would have a significantly higher likelihood of experiencing local recurrence if the viral loads in their NP swabs are still greater than 1,000 copies/200 μg DNA after a cumulative dose of 4,000 cGy during the course of definitive RT (chi-square test, p = 0.031). Paradoxically, it was observed in our study that serum EBV viral loads failed to decline rapidly during the course of RT as the viral loads in NP swabs did. In the majority of the studied patients, the serum viral loads tended to be stationary during RT. Focusing on the patients with an increasing level of viral load during primary RT, neither distant metastases nor local recurrence have occurred among them by the time of current analysis. CONCLUSION: After a cumulative total dose of 4,000 cGy during RT, the NPC patients have a statistically greater risk of developing local recurrence if the viral loads in NP swabs were greater than 1,000 copies/200 μg DNA. Conversely, the alteration of serum viral loads during RT fails to predict the probability of local recurrence after definitive RT. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5641.