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Background Nasopharyngeal cancer is endemic to Southeast Asia. However, there is limited clinical evidence of nasopharyngeal cancer in Indonesia, which has the largest population in Southeast Asia. Methods Patterns of care and treatment outcomes in 428 patients with newly-diagnosed and pathologically-confirmed nasopharyngeal cancer were retrospectively analyzed. Results Concurrent chemo-radiotherapy (CCRT) was the first-line treatment for stages I-IVB diseases. The 2-year overall survival (OS) of all patients were 100.0%, 100.0%, 93.8%, 86.2%, 82.9%, and 62.4% for stages I, II, III, IVA, IVB, and IVC, respectively. The 2-year OS of CCRT-treated patients were 100.0%, 100.0%, 92.6%, 82.4%, and 78.3% for stages I, II, III, IVA, and IVB, respectively. Conclusion The patterns of care and treatment outcomes were potentially consistent with world standards, needing future validation. This is the largest study of newly diagnosed nasopharyngeal cancer in Indonesia, a huge disease burden, providing an important basis for the clinical management of this disease.

Introduction EBV infection in nasopharyngeal cancer ensued in latent infection mode. In this latent infection various EBV oncoproteins such as EBNA1 and LMP1 was expressed. EBV oncoproteins could theoretically recruit immune cells, which might help to control cancer. Therefore, this study was aimed to elucidate the association with EBV oncoproteins (EBNA1 and LMP1), immune markers (CD4, CD8, and FOXP3) from nasopharyngeal cancer microenvironment with tumor progression. Method Nasopharyngeal biopsy was obtained from patients suspected to have nasopharyngeal cancer. Those samples with microscopically confirmed nasopharyngeal cancer were tested for EBNA1, LMP1, CD4, CD8, and FOXP3 concentration with ELISA, then verified with IHC. Each patient tumor volume was assessed for primary nasopharyngeal tumor volume (GTVp) and neck nodal metastases tumor volume (GTVn). Correlation test with Spearman correlation and scatterplot were carried out. Result Total 23 samples with nasopharyngeal cancer were analyzed. There was moderate correlation (ρ = 0.45; p value = 0.032) between LMP1 and GTVp. There was strong correlation (ρ = 0.81; p value ρ = 0.6; p value = 0.002) between FOXP3 and GTVp. The CD8 concentration has moderate correlation with both EBNA1 (ρ = 0.46; p value = 0.026) and LMP1 (ρ = 0.47; p value = 0.023). While FOXP3 has moderate correlation with only LMP1 (ρ = 0.58; p value = 0.004). No correlation was found between all the markers tested here with GTVn. Discussion We found larger primary nasopharyngeal tumor was associated with higher CD8 marker. This was thought due to the presence of abundance CD8 T cells in the nasopharynx, but those abundance CD8 T cells were suspected to be dysfunctional. The nasopharyngeal cancer was also known to upregulate chemokines that could recruit T regulatory FOXP3 cells. Furthermore, T regulatory FOXP3 cells differentiation was induced through several pathways which was triggered by EBNA1. The correlation found in this study could guide further study to understand nasopharyngeal carcinogenesis and the relationship with our immune system.

Cell‐free microRNA (miRNA) in biofluids released by tumors in either protein or vesicle‐bound form, represent promising minimally‐invasive cancer biomarkers. However, a highly abundant non‐tumor background in human plasma and serum complicates the discovery and detection of tumor‐selective circulating miRNAs. We performed small RNA sequencing on serum and plasma RNA from Nasopharyngeal Carcinoma (NPC) patients. Collectively, Epstein Barr virus‐encoded miRNAs, more so than endogenous miRNAs, signify presence of NPC. However, RNAseq‐based EBV miRNA profiles differ between NPC patients, suggesting inter‐tumor heterogeneity or divergent secretory characteristics. We determined with sensitive qRT‐PCR assays that EBV miRNAs BART7‐3p, BART9‐3p and BART13‐3p are actively secreted by C666.1 NPC cells bound to extracellular vesicles (EVs) and soluble ribonucleoprotein complexes. Importantly, these miRNAs are expressed in all primary NPC tumor biopsies and readily detected in nasopharyngeal brushings from both early and late‐stage NPC patients. Increased levels of BART7‐3p, BART9‐3p and particularly BART13‐3p, distinguish NPC patient sera from healthy controls. Receiver operating characteristic curve analysis using sera from endemic NPC patients, other head and neck cancers and individuals with asymptomatic EBV‐infections reveals a superior diagnostic performance of EBV miRNAs over anti‐EBNA1 IgA serology and EBV‐DNA load (AUC 0.87–0.96 vs 0.86 and 0.66 respectively). The high specificity of circulating EBV‐BART13‐3p (97%) for NPC detection is in agreement with active secretion from NPC tumor cells. We conclude EV‐bound BART13‐3p in circulation is a promising, NPC‐selective, biomarker that should be considered as part of a screening strategy to identify NPC in endemic regions., What's new? Analysis of DNA from human tumor viruses in patient blood is a non‐invasive screening method for individuals at risk for developing cancer. A drawback is over‐diagnosis as these sensitive methods also detect non‐cancer‐related infections. Here the authors show by RNA sequencing and PCR amplification that a microRNA (BART13‐3p) encoded by the Epstein–Barr Virus (EBV) is associated with circulating vesicles in patients with nasopharyngeal carcinoma, thus distinguishing between cancer and non‐cancer‐related EBV infections.

NPC is the most widely found malignant tumor in the head and neck region in Indonesia. Chemoradiation therapy for NPC can induce swallowing disorders (dysphagia) that adversely affects a patients quality of life. This study aimed to assess the swallowing process by flexible endoscopic evaluation of swallowing in patients with nasopharyngeal carcinoma after chemoradiation. Thirty-nine patients with NPC who had chemoradiation therapy more than one month previously underwent flexible endoscopic evaluation of swallowing and were assessed for oral transport time, sensation, standing-secretion, pre-swallowing leakage, residue, penetration, aspiration, and silent aspiration. The most common structural abnormalities were an upright and swollen epiglottis (89.4%), poor oral hygiene, and velopharyngeal closure defects (56.4%). This examination also revealed a mild degree of standing secretion (38.5%) and aspiration (10.3%). No penetration was observed in 64.1% of the patients, and no silent aspiration was observed in any of the patients. A severe degree of residue (45.7%) was observed when administering oatmeal, while the residue was mild to moderate when administering gastric rice, crackers, and milk. The residue changed to a mild degree (32.3%–51.4%) in all food administrations after the watering maneuver. The highest penetration was noted after oatmeal administration (42.8%), and the highest aspiration was found after milk administration (8.6%). Standing secretion in almost all patients was caused by hyposensitivity of the hypopharynx. Persistent residue and hyposensitivity of the hypopharynx led to aspiration. The low percentage of aspiration and silent aspiration might have been caused by the upright and swollen epiglottis that prevented aspiration. Poor oral hygiene and a dry mouth led to prolonged oral transport. Therefore, most patients had hypopharyngeal abnormalities in the form of a swollen and upright epiglottis. Secretion and food residue were also detected. Drinking helps to expedite the swallowing process by facilitating oral phase transport and reducing residues.

Tumor microenvironment have been implicated in many kind of cancers to hold an important role in determining treatment success especially with immunotherapy. In nasopharyngeal cancer, the prognostic role of this immune cells within tumor microenvironment is still doubtful. We conducted a study that included 25 nasopharyngeal cancer biopsy specimens to seek a more direct relationship between tumor infiltrating immune cells and tumor progression. Apart from that, we also checked the PD-L1 protein through immunohistochemistry. The PD-L1 was positively expressed in all our 25 samples with nasopharyngeal cancer WHO type 3 histology. Majority samples have >50% PD-L1 expression in tumor cells. We also found that denser local tumor infiltrating immune cells population have relatively much smaller local tumor volume. The inverse applied, with the mean local tumor volumes were 181.92 cm3 ± 81.45 cm3, 117.13 cm3 ± 88.72 cm3, and 55.13 cm3 ± 25.06 cm3 for mild, moderate, and heavy immune cells infiltration respectively (p = 0.013). Therefore, we concluded that tumor infiltrating immune cells play an important role in tumor progression, hence evaluating this simple and predictive factor may provide us with some valuable prognostic information.

Introduction Nasopharyngeal cancer in Indonesia has a poor survival rate and there is only few studies regarding nasopharyngeal cancer in Indonesia. Therefore, this study was made to present Indonesian nasopharyngeal cancer data with special focus on survival of nasopharyngeal cancer profile that receives radiation therapy. Methods This was a retrospective study conducted in the Department of Radiation Oncology, Dr. Cipto Mangunkusumo Hospital (RSCM). Moreover, survival analysis was done using Kaplan Meier, log rank and cox regression test. Results A total of 398 patients were included with the median follow-up time of 16 (0–65) months. The 3-year survival in patients with stage I–III was >50% while the survival of 5 years was >50% only in early stage patients. The median survival for men was 46 months and for women 42 months. For OTT ≤ 49 days survival of 3 years and 5 years is 67.1%. Stage III–IVB, size N2-N3, and overall treatment time >49 days were the prognostic factors for nasopharyngeal cancer patients. After multivariate analysis, only stage III–IVB was statistically significant as a prognostic factor independent of survival. Conclusion Most of nasopharyngeal cancer patient came in advanced stage. The median time needed for patients to get radiation therapy and median OTT were good. Only stage III–IVB was statistically significant as a prognostic factor independent of survival.

Purpose: Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) and highly prevalent in Indonesia. EBV-DNA load can be used for early diagnosis and may have prognostic value. In this study, EBV-DNA load was evaluated in minimal invasive nasopharyngeal (NP) brushings and whole blood for initial diagnosis and therapy assessment against the standard-of-care diagnosis by biopsy with EBV-RISH and standard EBV-IgA serology. Experimental Design: NP brushings and blood samples were collected from 289 consecutive ENT patients suspected of NPCs and 53 local healthy controls. EBV-DNA load was quantified by real-time PCR and serology by peptide-based EBV-IgA ELISA. Tissue biopsies were examined by routine histochemistry and by EBER RNA in situ hybridization. Results: Repeated NP brushing was well tolerated by patients and revealed high viral load in the 228 NPC cases at diagnosis than 61 non-NPC cancer cases and healthy controls (P < 0.001). The diagnostic value of EBV-DNA load in blood and EBV-IgA serology was inferior to the NP brush results. The level of EBV-DNA load in brushes of patients with NPC was not related to T, N, or M stage, whereas elevated EBV-DNA load in blood correlated with N and M stage. EBV-DNA levels in brushings and whole blood showed a significant reduction at 2 months after treatment (P = 0.001 and P = 0.005, respectively), which was not reflected in EBV-IgA serology. Conclusions: NP brush sampling combined with EBV-DNA load analysis is a minimal invasive and well-tolerated diagnostic procedure, suited for initial diagnosis and follow-up monitoring of NPCs. Clin Cancer Res; 19(8); 2175–86. ©2013 AACR.

Objective: To evaluate the effectiveness of a nasopharyngeal carcinoma (NPC) awareness programme on the short-term and long-term improvement of knowledge and referral of patients with NPC by primary healthcare centres (PHCCs) staff in Indonesia. Design: The NPC awareness programme consisted of 12 symposia including a Train-The-Trainer component, containing lectures about early symptoms and risk factors of NPC, practical examination and the referral system for NPC suspects. Before and after training participants completed a questionnaire. The Indonesian Doctors Association accredited all activities. Participants: 1 representative general practitioner (GP) from each PHCC attended an NPC awareness symposium. On the basis of the Train-The-Trainer principle, GPs received training material and were obligated to train their colleagues in the PHCC. Results: 703 GPs attended the symposia and trained 1349 staff members: 314 other GPs, 685 nurses and 350 midwives. After the training, respondents’ average score regarding the knowledge of NPC symptoms increased from 47 points (of the 100) to 74 points (p

Undifferentiated nasopharyngeal carcinoma (NPC) is 100% associated with Epstein‐Barr virus (EBV) as oncogenic driver. NPC is often diagnosed late due to initial vague complaints and obscured location. Prior studies suggest that measurement of EBV DNA load and RNA transcripts in nasopharyngeal (NP) brushings is useful for minimally invasive NPC diagnosis. However, whether these EBV markers relate to local virus replication or reflect tumor origin remains to be demonstrated. To resolve this, we analysed EBV‐DNA characteristics and quantified latent and lytic viral RNA transcripts in NP brushings and matching frozen NP‐biopsy specimens from patients suspected of having NPC. We observed non‐fragmented and Cp‐promotor methylated EBV‐DNA in both NP brushings and biopsies suggestive of tumor origin. Using quantitative RT‐PCR we determined expression levels of 7 critical latent (EBER1, Qp‐EBNA1, EBNA2, BART, LMP1, LMP2, BARF1) and 5 lytic (Zta, Rta, TK, PK and VCA‐p18) RNA transcripts. Although latent and early lytic RNA transcripts were frequently detected in conjunction with high EBV viral load, in both brushings and biopsies the latent transcripts prevailed and reflected a typical NPC‐associated latency‐II transcription profile without EBNA2. Late lytic RNA transcripts were rare and detected at low levels mainly in NP brushings, suggestive of abortive viral reactivation rather than complete virus replication. EBV‐IgA serology (EBNA1, VCA, Zta) did not correlate to the level of viral reactivation in situ. Overall, viral RNA profiling, DNA fragmentation and methylation analysis in NP brushings and parallel biopsies indicate that NP brush sampling provides a true and robust indicator of NPC tumor presence., What's new? Nasopharyngeal carcinoma (NPC) often is diagnosed at late stages, in part because physical examination of the nasopharyngeal (NP) space is difficult. Moreover, despite a strong association with Epstein‐Barr virus (EBV) infection, optimal EBV‐based diagnostic modalities for NPC are lacking. Here, EBV DNA load, methylation status and EBV latent and lytic RNA profiles obtained from NP brush biopsy were found to be robustly indicative of tumor presence at the site of initiation. EBV (immediate) early mRNAs were frequently detected, suggesting local abortive viral reactivation. Using the described EBV markers, NP brushing may be a practical minimally invasive approach for NPC diagnosis.

BackgroundNasopharyngeal carcinoma (NPC) is endemic in Indonesia and 20% of the patients are diagnosed before the age of 31. This study evaluates presentation and treatment outcome of young patients in Jakarta, in a tertiary referral centre.MethodsForty-nine patients under the age of 31, diagnosed with NPC between July 2004 and January 2007, were evaluated. Baseline data included histological type, stage of disease and presenting symptoms. We intended to follow all patients after diagnosis to reveal treatment outcome and overall survival (OS).ResultsAll but two patients had advanced stage disease (94%), 7 (14%) had distant metastasis. The median interval between start of complaints and diagnosis was 9 months. Forty-two patients were planned for curative intent treatment. Eleven patients (26%) never started treatment, 2 patients did not complete treatment and 3 patients did not return after finishing treatment. Four patients died before radiation could start. Three patients died within 4 months after treatment. Nine patients (21%) had a complete response. Due to the high number of patients who were lost to follow-up (LFU), OS was analyzed as follows: a best-case (patients censored at last contact) and a worst-case scenario (assuming that patients who did not finish treatment or had disease at last contact would have died). The 2-year OS for patients without distant metastases was 39-71%.ConclusionTreatment outcome for young patients with NPC in this institute was poor. Improvement can be achieved when NPC is diagnosed at an earlier stage and when there is better treatment compliance.

UNLABELLED:In Indonesia, Nasopharyngeal Carcinoma (NPC) is the most frequent cancer of the head and neck region. At first presentation in the hospital most patients already have advanced NPC. Our previous study showed that general practitioners (GPs) working in Yogyakarta, Indonesia lack the knowledge necessary for early detection of NPC. By providing training on early symptoms of NPC we hope that the diagnosis and referral will occur at an earlier stage. Here we assess the current NPC knowledge levels of GPs in Jakarta, evaluate improvement after training, compare the effectiveness of two training formats, and estimate the loss of recall over a two week period. METHODS:Two Indonesian GPs visited 31 Primary Health Care Centres (PHCCs) and provided a lecture on NPC. The alternative format consisted of a symposium at the Universitas Indonesia, Jakarta, presented by local head and neck surgeons, with all GPs in the region being invited. To evaluate the effect of both formats a questionnaire was conducted before and after. RESULTS:The lecture in the PHCCs was attended by 130 GPs. Sixty-six GPs attended the training in the university hospital and 40 GPs attended both. Pre training the NPC knowledge level was poor with an average of 1.6 symptoms being correctly identified out of a potential maximum of 12, this was increased to 4.9 post training (p

Background: The treatment of persistent and recurrent nasopharyngeal carcinoma (NPC) remains a challenge, especially in Indonesia. We investigated the safety and efficacy of temoporfin mediated photodynamic therapy (PDT) for patients with local persistent and recurrent NPC. Material and methods: Twenty-two patients with persistent and recurrent NPC (maximum tumor depth

Nasopharyngeal carcinoma (NPC) is the most prevalent ENT-tumour in Indonesia. We investigated the primary diagnostic value of Epstein-Barr virus (EBV) DNA load and mRNA detection in noninvasive nasopharyngeal (NP) brushings, obtained prospectively from consecutive Indonesian ENT-patients with suspected NPC (N=106) and controls. A subsequent routine NP biopsy was taken for pathological examination and EBER-RISH, yielding 85 confirmed NPC and 21 non-NPC tumour patients. EBV DNA and human DNA load were quantified by real-time PCR. NP brushings from NPC patients contained extremely high EBV DNA loads compared to the 88 non-NPC controls (p