Multidisciplinary Team Meeting in the Core of Nasopharyngeal Cancer Management Improved Quality of Care and Survival of Patients.

Nasopharyngeal cancer (NPC) cases are often diagnosed in advanced stages. The complexity of clinical management for advanced-stage NPC requires thorough communication and shared decisions between medical professionals and allied teams. Incorporating a multidisciplinary team meeting (MDTM) for newly diagnosed NPC patients was chosen to facilitate collaboration and communication between physicians. This retrospective study aimed to compare the quality of care, clinical responses and survival between NPC patients treated with and without MDTM. Data on clinical responses, assessment visits, date of progression and death with progression-free survival (PFS), overall survival (OS), and hazard ratio (HR) were collected and analyzed with 95% confidence interval (CI) and significance set as P < .05. There were 87 of 178 NPC patients treated with MDTM. Revisions of diagnosis and stage occurred in 5.7% and 52.9% of cases during the MDTM. More clinical responses were achieved by patients treated with MDTM (69.0%vs 32.0%, P < .00). NPC patients who received MDTM treatment recommendation had a lower risk for progression (median PFS 59.89 months vs 12.68 months; HR 0.267, 95% CI: 0.17-0.40, P < .00) and mortality (median OS was not reached vs 13.44 months; HR 0.134, 95% CI: 0.08-0.24, P < .00) compared to patients without MDTM. Incorporating the MDTM approach into NPC management improves patients' clinical responses and survival.

Factors associated with time of diagnosis and habilitation of congenital hearing loss in Indonesia: A multicenter study.

OBJECTIVES: To investigate factors associated with time of diagnosis and habilitation of congenital hearing loss in Indonesia. METHOD: A retrospective cohort study was conducted from January to December 2020 by collecting data on patients with congenital hearing loss using validated questionnaires. RESULT: Among 535 children with congenital hearing loss, 2.7% had a family history of congenital hearing loss, 11.2% and 37.4% had a maternal history of ototoxic drugs and herbal medicine use during pregnancy, respectively, and 17.8% had prenatal exposure to TORCH infection. Lower maternal education level was shown to be associated with older age at diagnosis (p = 0.045), while older maternal age (p < 0.001), non-housewife mothers (p = 0.029), and out-of-pocket payment scheme (p = 0.027) were associated with a higher rate of habilitation. CONCLUSION: The present study showed that the presence of family history, the use of certain medications during pregnancy, and prenatal TORCH infection are prevalent in children with congenital hearing loss in Indonesia. Several factors such as maternal education level, age, occupation, and habilitation payment scheme may be associated with time of diagnosis and habilitation of congenital hearing loss.

Survival outcome and prognostic factors of patients with nasopharyngeal cancer in Yogyakarta, Indonesia: A hospital-based retrospective study.

PURPOSE: This study aimed to determine the survival outcome and prognostic factors of patients with nasopharyngeal cancer accessing treatment in Yogyakarta, Indonesia. METHODS: Data on 759 patients with NPC diagnosed from 2007 to 2016 at Dr Sardjito General Hospital were included. Potential prognostic variables included sociodemographic, clinicopathology and treatment parameters. Multivariable analyses were implemented using semi-parametric Cox proportional hazards modelling and fully parametric survival analysis. RESULTS: The median time of observation was 14.39 months. In the whole cohort the median observed survival was 31.08 months. In the univariable analysis, age, education status, insurance type, BMI, ECOG index, stage and treatment strategy had an impact on overall survival (OS) (p values <0.01). Semi-parametric multivariable analyses with stage stratification showed that education status, ECOG index, and treatment modality were independent prognostic factors for OS (p values <0.05). In the fully parametric models age, education status, ECOG index, stage, and treatment modality were independent prognostic factors for OS (p values <0.05). For both multivariable analyses, all treatment strategies were associated with a reduced hazard (semi-parametric models, p values <0.05) and a better OS (parametric models, p values <0.05) compared with no treatment. Furthermore, compared with radiation alone or chemotherapy alone, a combination of chemotherapy and radiation either in a form of concurrent chemoradiotherapy (CCRT), sequential chemotherapy and radiation, or induction chemotherapy followed by CCRT demonstrated a reduced hazard (hazard ratio/HR 0.226, 95% confidence interval/CI 0.089-0.363, and HR 0.390, 95%CI 0.260-0.519) and a better OS (time ratio/TR 3.108, 95%CI 1.274-4.942 and TR 2.531, 95%CI 1.829-3.233) (p values < 0.01). CONCLUSIONS: Median OS for the cohort was low compared to those reported in both endemic and non-endemic regions. By combining the findings of multivariable analyses, we showed that age, education status, ECOG index, stage and first treatment modality were independent predictors for the OS.

Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy.

Nasopharyngeal cancer (NPC), endemic in Southeast Asia, lacks effective diagnostic and therapeutic strategies. Even in high-income countries the 5-year survival rate for stage IV NPC is less than 40%. Here we report high somatostatin receptor 2 (SSTR2) expression in multiple clinical cohorts comprising 402 primary, locally recurrent and metastatic NPCs. We show that SSTR2 expression is induced by the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) via the NF-κB pathway. Using cell-based and preclinical rodent models, we demonstrate the therapeutic potential of SSTR2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved SSTR2-binding cytostatic agents. Furthermore, we reveal significant correlation of SSTR expression with increased rates of survival and report in vivo uptake of the SSTR2-binding 68Ga-DOTA-peptide radioconjugate in PET-CT scanning in a clinical trial of NPC patients (NCT03670342). These findings reveal a key role in EBV-associated NPC for SSTR2 in infection, imaging, targeted therapy and survival.

Transcriptome Profile of Next-Generation Sequencing Data Relate to Proliferation Aberration of Nasopharyngeal Carcinoma Patients in Indonesia.

OBJECTIVE: Nasopharyngeal carcinoma (NPC) is the most common cancer arising from epithelial cells of the nasopharynx in  Indonesia. This study aims to determine the differential level of gene expression in NPC patients when compared with normal individuals. Transcriptome profiling analysis was performed using RNA-Seq technology to determine the differential gene expression relate to proliferation aberration that occurs in NPC patients compared with normal individuals. So we get the transcriptomic profile of Indonesia NPC patients. METHODS: In this study, we used 9 samples, 7 NPC samples and 2 normal samples as control.  Fresh tissue of tumor samples was collected from biopsy, and normal samples were collected brushing technique. The total RNA was isolated from fresh tissue samples and brushing samples using the Rneasy® RNA Extraction Mini Kit. The cDNA library was generated using TruSeq® RNA Library Preparation Kit V2, and its concentration was determined using qPCR. The library was sequenced using the Next-Generation Sequencing (NGS) Illumina Next Seq 550 platform. The raw sequence data quality was analyzed using FastQC and interpreted using HISAT2, HTSeq, edgeR, and PANTHER. RESULTS: From the analysis, 25493 gene transcripts were expressed, with 1956 genes were significantly upregulated, 90 genes were significantly downregulated in NPC samples, and 23897 genes didn't change the expression level significantly (p <0.05), 10 of which genes were associated with cell proliferation. These genes are involved in the regulation of cancer cell proliferation through several signaling pathways, which are the apoptosis signaling pathway, IGF signaling pathway, Notch signaling pathway, and P13K signaling pathway. CONCLUSION: There were significant differences in gene expression levels between NPC patients and normal individuals. Each gene that has changed the expression level plays a role in regulating various pathways that lead to cell proliferation aberration in NPC cases.

Transcriptome Related to Avoiding Immune Destruction in Nasopharyngeal Cancer in Indonesian Patients Using Next-Generation Sequencing.

OBJECTIVE: This study aims to obtain the transcriptomes profile associated with avoiding immune destruction from nasopharyngeal cancer patients in Indonesia using next-generation sequencing. METHODS: The samples are divided into two types of samples; 1) biopsy of nasopharyngeal cancer tissue samples, 2) brushing tissue of people without nasopharyngeal cancer as control samples. The sequencing results were mapped (HISAT2) and quantified (HTSeq) for differential expression analysis using edgeR software. Transcripts data analyzed with Pantherdb and DAVID software to find genes related to the immune system and pathways related to immune destruction by cancer. RESULTS: The differential expression results show that 2,046 genes that have a significant differential expression. The 90 genes expression has down-regulated and 1,956 genes expression up-regulated, there are 20 genes related to the immune system. The 20 genes related to the immune system by analyzing lionproject.net that directly related to hallmark avoiding immune destruction that genes are CXCL9/10/11. The gene expression of CXCL9/10/11 regulates PD-L1 expressions via the Jak/STAT signaling pathway. The interaction between the extracellular domain PD-1 and PD-L1 in cancer cells have avoiding immune destruction. CONCLUSION: The results of this study suggest that the gene expression of CXCL9/10/11 have up-regulated is related to avoiding immune destruction that can use as an early detection biomarker of nasopharyngeal cancer in Indonesian patients.

Transcriptome Profile of Next Generation Sequence Data Related to Inflammation on Nasopharyngeal Carcinoma Cases in Indonesia.

OBJECTIVE: Transcriptomic Profile Analysis Related to Inflammation in Nasopharyngeal Carcinoma Cases. METHODS: This study used 2 control samples taken using the brushing technique and 7 cancer samples with tissue biopsy. Isolate total RNA using Rneasy® RNA Extraction Mini Kit. Measurement of total RNA concentration and purity using a fluorometer and nanodrop Qubit. Synthesis of cDNA library uses TruSeq® RNA Library Preparation Kit V2 and concentration is measured using qPCR. Sequencing samples using NGS Illumina NextSeq 550 platform engine. Quality control results of sequencing using FASTQC, and raw data processing using HISAT2. Differential analysis of gene expression (DEGs) using edgeR and pathway analysis using DAVID and PANTHER. RESULTS: From the 25,493 genes that experienced a significant change in expression level (P <0.05) from DEG analysis there were 13 genes that play a role in the inflammatory process. Based on DAVID pathway analysis software, there are 8 genes detected based on the KEGG pathway database found in 2 pathways, namely Inflammatory Mediator Regulation of TRP Channels pathway with genes that play HTR2A, NGF, TRPA1, PRKCG, and ADCY8. CXCL9, CXCL10, and CXCL11 genes are found in the Toll-Like Receptor Signaling pathway. Based on PANTHER pathway analysis software, 6 genes were found, namely CXCL10, MYLK2, COL20A1, MYH2, ACTC1, and ALOX15 in the Inflammation Mediated by Chemokine and Cytokine Signaling pathways. Almost all genes found from DEGs are upregulated, except the ALOX15 gene that is downregulated. CONCLUSION: There are 13 genes that play a role in the inflammatory process in Nasopharyngeal Carcinomafrom a sample of the Indonesian population. Genes CXCL9, CXCL10, CXCL11, MYLK2, COL20A1, MYH2, ACTC1, HTR2A, NGF, TRPA1, PRKCG, and ADCY8 have been upregulated and ALOX15 has been downregulated. These genes play a role in the Inflammation Mediated by Chemokine and Cytokine Signaling pathways, Inflammatory Mediator Regulation of TRP Channels, and Toll-Like Receptor Signaling.

Seroprevalence of IgA anti Epstein-Barr virus is high among family members of nasopharyngeal cancer patients and individuals presenting with chronic complaints in head and neck area.

Epstein-Barr (EBV) infection and presence of a nasopharyngeal cancer (NPC) case in the family increases the risk of developing NPC. Aberrant anti-EBV immunoglobulin A (IgA) antibodies (EBV-IgA) may be present in the sera of non-cancer individuals and predict NPC. Limited studies report the presence of EBV-IgA antibodies within non-cancer individuals in Indonesia where the disease is prevalent. This study aimed at exploring whether EBV-IgA was found more frequently among first degree relatives of NPC patients and individuals presenting with chronic symptoms in the head and neck area compared to healthy controls. A total of 967 non-cancer subjects were recruited, including 509 family members of NPC cases, 196 individuals having chronic complaints in the head and neck region, and 262 healthy donors of the local blood bank. Sera were analyzed using a standardized peptide-based EBV-IgA ELISA. Overall, 61.6% of all individuals had anti-EBV IgA reactivity equal to or below cut off value (CoV). Seroreactivity above CoV was significantly higher in females (38.7%) compared to males (28.7%) (p = 0.001). Older individuals had more seroreactivity above CoV (42.5%) than the younger ones (26.4%) (p< 0.001). Seroprevalence was significantly higher in family members of NPC patients (41.7%), compared to 32.7% of individuals with chronic head and neck problems (p = 0.028) and 16.4% healthy blood donors (p< 0.001). As conclusion, this study showed a significant higher seroprevalence in healthy family members of NPC cases and subjects presenting with chronic symptoms in the head and neck area compared to healthy individuals from the general community. This finding indicates that both groups have elevated risk of developing NPC and may serve as targets for a regional NPC screening program.

Hypoxia-Inducible Factor-1α Expression in Indonesian Laryngeal Squamous Cell Carcinoma Patients.

Objectives. This research aimed to determine the association between hypoxia-inducible factor-1α (HIF-1α) expression and laryngeal squamous cell carcinoma clinical stage. Methods. We retrospectively analyzed paraffin-embedded tissue from 47 laryngeal squamous cell carcinoma (LSCC) patients from 2011 to 2014. HIF-1α expression was analyzed by immunohistochemistry using an anti-HIF-1α mouse monoclonal antibody. The association between HIF-1α expression and clinical stage was analyzed using the chi square test. Results. The glottis was the predominant site of laryngeal squamous cell carcinoma occurrence, and 43/47 (91.5%) patients presented at an advanced stage. Of the advanced stage patients, 27/43 stained positive for HIF-1α expression and 16/43 stained negative. Of the early stage patients, 2/4 stained positive for HIF-1α expression and 2/4 stained negative. Statistical analysis did not demonstrate significant association of HIF-1α expression. Conclusion. There was no statistically significant association between HIF-1α expression and the clinical stage or histological differentiation of LSCC.