Nasopharyngeal Carcinoma Cases Research Articles

Virtual Contrast-Enhanced Magnetic Resonance Images Synthesis for Patients With Nasopharyngeal Carcinoma Using Multimodality-Guided Synergistic Neural Network

To investigate a novel deep-learning network that synthesizes virtual contrast-enhanced T1-weighted (vceT1w) magnetic resonance images (MRI) from multimodality contrast-free MRI for patients with nasopharyngeal carcinoma (NPC). This article presents a retrospective analysis of multiparametric MRI, with and without contrast enhancement by gadolinium-based contrast agents (GBCAs), obtained from 64 biopsy-proven cases of NPC treated at Hong Kong Queen Elizabeth Hospital. A multimodality-guided synergistic neural network (MMgSN-Net) was developed to leverage complementary information between contrast-free T1-weighted and T2-weighted MRI for vceT1w MRI synthesis. Thirty-five patients were randomly selected for model training, whereas 29 patients were selected for model testing. The synthetic images generated from MMgSN-Net were quantitatively evaluated against real GBCA-enhanced T1-weighted MRI using a series of statistical evaluating metrics, which include mean absolute error (MAE), mean squared error (MSE), structural similarity index (SSIM), and peak signal-to-noise ratio (PSNR). Qualitative visual assessment between the real and synthetic MRI was also performed. Effectiveness of our MMgSN-Net was compared with 3 state-of-the-art deep-learning networks, including U-Net, CycleGAN, and Hi-Net, both quantitatively and qualitatively. Furthermore, a Turing test was performed by 7 board-certified radiation oncologists from 4 hospitals for assessing authenticity of the synthesized vceT1w MRI against the real GBCA-enhanced T1-weighted MRI. Results from the quantitative evaluations demonstrated that our MMgSN-Net outperformed U-Net, CycleGAN and Hi-Net, yielding the top-ranked scores in averaged MAE (44.50 ± 13.01), MSE (9193.22 ± 5405.00), SSIM (0.887 ± 0.042), and PSNR (33.17 ± 2.14). Furthermore, the mean accuracy of the 7 readers in the Turing tests was determined to be 49.43%, equivalent to random guessing (ie, 50%) in distinguishing between real GBCA-enhanced T1-weighted and synthetic vceT1w MRI. Qualitative evaluation indicated that MMgSN-Net gave the best approximation to the ground-truth images, particularly in visualization of tumor-to-muscle interface and the intratumor texture information. Our MMgSN-Net was capable of synthesizing highly realistic vceT1w MRI that outperformed the 3 comparable state-of-the-art networks.

Patterns of Local-Regional Relapse Following Intensity-Modulated Radiotherapy for Patients With Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> Despite definite radiotherapy, post-treatment recurrence remains a major challenge for patients with nasopharyngeal carcinoma (NPC). This study aimed to evaluate risk factors for local-regional relapse in patients with non-metastatic NPC treated with intensity-modulated radiation therapy (IMRT). <h3>Materials/Methods</h3> We retrospectively analyzed data from 1040 patients with newly diagnosed, non-metastatic, biopsy-proven NPC from 2013 to 2019 (including 7, 133, 475, and 425 cases of stage I, II, III, and IVA disease, respectively, according to the 8th edition of the American Joint Committee on Cancer staging system). All patients received IMRT at a single institution in China (with or without concurrent chemotherapy). Recurrent sites were delineated on imaging and coregistered with the initial treatment planning computed tomography. The recurrences were classified as "in-field failure" if 95% of GTVr (gross tumor volume of recurrence) was within the 95% isodose; "marginal failure" if 20%–95% of GTVr was within the 95% isodose, or "out-field failure" if less than 20% of GTVr was inside the 95% isodose. Univariate and multivariate analyses with the Cox proportional hazards model were performed to identify the independent risk factors. <h3>Results</h3> With a median follow-up of 44 months, 76 patients (7.3%) developed a recurrence. The median interval of relapse was 20.5 months (range: 7–109 months). The 2-year overall survival, local relapse-free survival and regional relapse-free survival were 95.8%, 96.4% and 98.4%, respectively. Local-alone, regional-alone and synchronous local-regional failures accounted for 57.9% (44/76), 32.9% (25/76), and 9.2% (7/76) of recurrent NPC cases, respectively. In these patients, the male:female ratio was 2.4:1 and the median age was 50 years (range: 21–74 years). Among the 62 local-regional failures with available diagnostic images, 53 cases (85.4%) were "in-field", 5 cases (8.1%) had "marginal", 4 cases (6.5%) were as "out-field". Multivariate analysis showed that the non-keratinizing differentiated subtype and the absence of concurrent chemotherapy (CCT) were independent factors for local recurrence after IMRT (differentiated NPC versus undifferentiated NPC HR = 1.987, 95% CI 1.056–3.738, <i>P</i> = 0.033; non-CCT versus CCT HR = 2.098, 95% CI 1.134–3.884, <i>P</i> = 0.018). The rate of lymph nodes associated with liquefaction was 12.4% by the primary tumors but 46.7% at regional recurrence (liquefaction versus non-liquefaction HR = 11.031, 95% CI 4.992–24.372, <i>P</i><0.001). <h3>Conclusion</h3> The major recurrence patterns were in-field failures. The poor local control rates may be associated with the absence of CCT and differentiated carcinoma of NPC. Lymph node with liquefaction was an independent prognostic factor for regional recurrence.

Epstein-Barr virus infection mediated TP53 and Bcl-2 expression in nasopharyngeal carcinoma pathogenesis.

Epstein Barr virus (EBV) stimulates neoplastic transformation of nasopharyngeal epithelial cells through various molecular mechanisms, predominantly affecting inactivation of tumor-suppressor genes and activation of oncogenes. EBV infection is a major risk factor for nasopharyngeal carcinoma (NPC), yet its role in the carcinogenesis is not clear. EBV infection alters the expression of antiapoptotic proteins and tumor suppressor proteins. Therefore, this study investigated the correlation between EBV infection status with B cell lymphoma-2 (Bcl-2) and TP53 protein expression amongst laryngeal and nasopharyngeal cancer cases. This study was performed using 22 nasopharyngeal and 11 laryngeal cancer cases. EBV infection status, TP53 and Bcl-2 protein expression was studied using immunohistochemistry. The majority of the laryngeal cancer cases exhibited a poor prognosis and presented low Bcl-2 expression. A total of 22.7% cases were infected with EBV in the NPC cases. Upregulated TP53 expression was associated with EBV infection in the NPC cohort, and EBV infection was correlated with TP53 upregulation in the patients with NPC, suggesting mutual regulation between TP53 and EBV.

Geraniin inhibits cell growth and promoted autophagy-mediated cell death in the nasopharyngeal cancer C666-1 cells.

BackgroundNasopharyngeal carcinoma (NPC) is a rare malignant tumor developing from epithelial linings of nasopharynx, and 10–50 out of 100,000 NPC cases were recorded globally particularly in the Asian countries.MethodologyThe cytotoxicity of geraniin against the NPC C666-1 cells were analyzed using MTT assay. The influences of geraniin on the C666-1 cell viability with the presence of ROS and apoptosis inhibitors were also studied. The expressions of PI3K, Akt, mTOR, and autophagic markers LC3, ATG7, P62/SQSTM1 expressions in the C666-1 cells were studied by western blotting analysis. The ROS production was assayed using DCFH-DA staining. The immunofluorescence assay was performed to detect the NF-κB and β-catenin expressions in the C666-1 cells.ResultsThe cell viability of C666-1 cells were appreciably prevented by the geraniin. The geraniin treatment also inhibited the C666-1 cell growth with the presence of apoptotic inhibitor Z-VAD-FMK. The geraniin-treatment effectively improved the ROS production and inhibited the NF-κB and β-catenin expressions in the C666-1 cells. Geraniin appreciably modulated the PI3K/Akt/mTOR signaling axis and improved the autophagy-mediated cell death via improving the autophagic markers LC3 and ATG7 expressions in the C666-1 cells.ConclusionIn conclusion, our results proved that geraniin inhibits C666-1 cell growth and initiated autophagy-mediated cell death via modulating PI3K/Akt/mTOR cascade and improving LC3 and ATG7 expressions in the C666-1. Geraniin and it could be a hopeful and efficient candidate to treat the human NPC in the future.

Vision Impairment: An Unusual Initial Presentation of Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a rare malignancy worldwide. It is the fifth most common cancer among the Malaysian male. NPC is complex and unique in terms of its initial presentation. The patient usually presents late when the NPC is already in its advanced stage due to unusual and confusing nature of its manifestation which often misleads the clinician. Initial presentation of vision loss or impairment is rare in NPC. Up to date, there are only 9 reports of NPC cases presenting initially with impaired vision. We report a case of NPC with an uncommon initial presentation of bilateral visual impairment.

MRI-based radiomics nomogram for predicting temporal lobe injury after radiotherapy in nasopharyngeal carcinoma.

To develop and validate a magnetic resonance imaging (MRI)-based radiomics nomogram model combining radiomic features and clinical factors for the prediction of radiotherapy-induced temporal lobe injury (RTLI) in patients with nasopharyngeal carcinoma (NPC). From 203 NPC cases receiving radiotherapy, 128 RTLI-positive and 278 RTLI-negative lobes were retrospectively analyzed. They were randomly divided into training (n = 285) and validation (n = 121) sets. Three hundred ninety-six texture features based on T2WI images were extracted from each temporal lobe. The minimum redundancy maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to reduce the dimension of the features and establish a radiomics signature model. Clinical risk factors and the radiomics signature were combined by multivariable logistic regression analysis to construct a radiomics nomogram model. We assessed the performance of the radiomics nomogram on discrimination, calibration, and clinical utility. The radiomics signature consisted of 14 selected features that were significantly associated with RTLI. In the training set, the radiomics nomogram model demonstrated a better predictive performance (AUC, 0.87; 95% CI, 0.82-0.91) than the radiomics model (AUC, 0.71; 95% CI, 0.65-0.78) and clinical model (AUC, 0.73; 95% CI, 0.67-0.79). These results were confirmed in the validation set. The radiomics nomogram model demonstrated good calibration and was clinically useful by decision curve analysis. The radiomics nomogram model combining radiomics signatures and clinical factors is an effective method for the noninvasive prediction of RTLI in NPC patients after radiotherapy. • The radiomics model based on T2WI images at the end of intensity-modulated radiotherapy can predict radiotherapy-induced temporal lobe injury in patients with NPC. • Dosimetric factors can improve the prediction performance of the radiomics model in predicting radiotherapy-induced temporal lobe injury. • An MRI-based radiomics nomogram combining radiomics signatures and clinical factors had better prediction performance than both radiomics and clinical model for the prediction of radiotherapy-induced temporal lobe injury in patients with NPC.

Influence of Epstein\u2013Barr virus and human papillomavirus infection on macrophage migration inhibitory factor and macrophage polarization in nasopharyngeal carcinoma

BackgroundTo assess the effects of Epstein–Barr virus (EBV) and human papillomavirus (HPV) infection on the tumor microenvironment, we examined the relationship between viral infection status, macrophage migration inhibitory factor (MIF), and tumor-associated macrophages in nasopharyngeal carcinoma (NPC).MethodsA tissue microarray containing 150 cores from 90 patients with NPC and six with chronic inflammation was used. EBV and HPV status were detected using in situ hybridization with commercial EBER1 and HPV16/18 probes. Immunofluorescence double staining of MIF, pan-macrophage marker CD68, M1 macrophage marker CD11c, and M2 macrophage marker CD163 were analyzed using the same tissue microarray. The levels of these markers between NPC and inflammation cases and between tumor nests and stroma were compared. Correlations among these markers were analyzed.ResultsWe found EBER1(+) cases in 90% of NPC patients, including 10% EBV/HPV co-infection. M1 macrophages mainly infiltrated the tumor nest, while M2 macrophages infiltrated the tumor stroma. We found a significant positive correlation between EBER1 levels and MIF levels in tumor nests and a significant positive correlation between HPV16/18 and CD11c(+) cell levels in NPC tissues.ConclusionsIt is suggested that MIF is associated with EBV, and M1 macrophage infiltration is affected by HPV status in NPC.

NASOPHARYNGEAL CARCINOMA IN AN ADOLESCENT AFRICAN AMERICAN MAN PRESENTING AS TEMPOROMANDIBULAR JOINT DISORDER: A CASE REPORT WITH MULTIDETECTOR COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING

<h3>BACKGROUND</h3> Nasopharyngeal carcinoma (NPC) has unique demographic characteristics, risk factors, and clinical presentation. Epstein-Barr virus (EBV) infection and exposure to nitrosamines are the main known contributing risk factors for NPC. The highest risk demographic for NPC, however, is young men of Chinese and Southeast Asian descent. In this case report, we discuss a rare case of NPC in an adolescent African American male patient presenting with symptoms of temporomandibular disorder and with no known predisposing risk factors. <h3>CASE REPORT</h3> A 16-year-old African American male patient presented with initial symptoms of pain in the left temporomandibular joint (TMJ) and left angle of the mandible for 2 months. Lateral neck swelling and one episode of epistaxis were also reported. After a clinical exam and ultrasound examination, the diagnoses of temporomandibular disorder and peritonsillar abscess were considered. Antibiotics were prescribed and a month later multidetector computed tomography (CT) was ordered. The CT findings were significant for an infiltrative malignant nasopharyngeal mass with early skull base involvement and cervical lymphadenopathy. Subsequent magnetic resonance findings were significant for invasion of palatal, paraspinal, and masticatory muscles as well as the carotid sheath and V3 encasement with V3 perineural spread. Tissue sampling of the lesion was definitive for EBV-positive squamous cell carcinoma. The definitive diagnosis was NPC with TNM staging T4 N2c M0. Radiation and chemotherapy were then administered to the patient. Magnetic resonance imaging surveillance studies at 2 and 7 months showed continued tumor involution and lymphadenitis improvement with no evidence of progressive disease. <h3>DISCUSSION/CONCLUSIONS</h3> NPC in young African American patients is exceedingly rare. Nasopharyngeal soft tissue masses in young patients can be misinterpreted as hypertrophic adenoid tissue in cone beam computed tomography images. However, in the presence of unexplained symptoms such as TMJ pain, hearing loss, and epistaxis, a malignancy must be considered and investigated. Careful attention should be paid to skull base bony morphology and foramina for possible perineural spread when nasopharyngeal masses are present.

Low vitamin D exposure and risk of nasopharyngeal carcinoma: Observational and genetic evidence from a multicenter case–control study

Little is known about the risk of nasopharyngeal carcinoma (NPC) in relation to vitamin D exposure. The aim of this study was to examine the associations of NPC risk with serum level of 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD, and potential effect modification by several putative risk factors of NPC. Our multicenter case-control study in Hong Kong recruited 815 NPC cases and 1502 frequency-matched (by sex and age) hospital controls from five major regional hospitals, and recruited 299 healthy subjects from blood donation centers (2014-2017). Circulating level of 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD (rs12785878, rs11234027, rs12794714, rs4588 and rs6013897) were measured by validated enzyme immunoassay and the iPLEX assay on the MassARRAY System, respectively. Data were also collected on demographics, lifestyle factors, ultraviolet radiation exposure, and potential confounders using a computer-assisted, self-administered questionnaire with satisfactory test-retest reliability. Unconditional logistic regression models were used to estimate ORs and 95% CIs. Despite no significant association of NPC risk with circulating 25OHD and genetic predicted 25OHD, there was evidence for an inverse association in participants with normal body mass index (between 18.5 and 27.5) across categories of 25OHD (Ptrend=0.003), and a positive association in those with low socioeconomic status across categories based on the genetic score (Ptrend=0.005). In addition, risk of NPC diagnosed at an early stage was higher for genetically lower 25OHD level (adjusted OR=3.09, 95% CI=1.04-9.21, Ptrend=0.022). Findings of this first comprehensive study to investigate the positive association of NPC risk with vitamin D deficiency need to be confirmed and be best interpreted with results of further similar studies. Our findings may inform possible etiological mechanisms of the associations with several putative risk/protective factors of NPC.

Cancer patterns in nasopharyngeal carcinoma multiplex families over 15 years.

Genetic and environmental factors are important determinants of nasopharyngeal carcinoma (NPC). NPC is associated with Epstein-Barr virus (EBV) infection. Studies have reported familial aggregation of NPC, but evidence has been mixed for elevated rates of cancers other than NPC. The authors reassessed their previous evaluation of familial aggregation of cancer in 348 high-risk Taiwanese multiplex families with 2 or more NPC cases enrolled between 1980 and 2003. Participants were linked to the Taiwan National Cancer Registry and National Death Registry to identify cancers. In all, 2590 individuals contributed 37,959 person-years over an average of 15 years of follow-up; 314 incident cancers were identified. The authors computed multiple primary standardized incidence ratios (MP-SIRs) to evaluate the overall risk and the risk of infection-associated, EBV-associated, and individual cancers. The overall MP-SIR was 1.24 (95% confidence interval [CI], 1.10-1.38). The exclusion of excess NPC risk led to an overall MP-SIR of 1.11 (95% CI, 0.98-1.25). Similarly, the risk of cancers associated with infectious agents was driven by the excess in NPC, and its exclusion led to an MP-SIR of 1.22 (95% CI, 0.99-1.48) for infection-associated cancers and to an MP-SIR of 1.18 (95% CI, 0.72-1.82) for EBV-associated cancers. The authors observed a significant excess of second cancers among NPC cases (oral cancer, mouth cancer, tongue cancer, gum cancer, nasal cavity cancer, bone cancer, and non-Hodgkin lymphoma). This reassessment of the largest NPC multiplex family study confirms the presence of NPC coaggregation within families in Taiwan but does not provide evidence for a broader familial syndrome involving NPC and other tumors. Among NPC cases, elevated rates of secondary cancers, mostly at the, head and neck and hematopoietic cancers suggest radiation treatment effects on subsequent cancer risk.

WNT8B as an Independent Prognostic Marker for Nasopharyngeal Carcinoma.

Background: Members of the Wnt signaling pathway have been shown to play a role in nasopharyngeal carcinoma (NPC) progression. Aim: The purpose of this study was to investigate WNT8B protein expression in NPC patients using tissue microarray (TMA) analysis and to evaluate its correlation with patient survival and clinical parameters. Methods: A total of 82 NPC cases, together with six normal nasopharyngeal tissue samples, were targeted to construct the TMA blocks. The WNT8B protein expression was evaluated by immunohistochemistry and its correlation to the clinicopathological features was investigated. Results: Sixty-two of 82 (75.6%) cases exhibited high WNT8B protein expression while 20/82 (24.4%) cases appeared to have low WNT8B expression. The univariate analysis revealed that systemic metastasis was associated with patient 5-year survival. The multivariate Cox proportional hazard regression analysis showed that WNT8B expression and systemic metastasis were significantly associated with the survival of NPC patients. Furthermore, there was no correlation found between the WNT8B protein expression and other clinicopathological parameters. Conclusion: Our results suggest that the expression of WNT8B is associated with NPC patients’ survival and could serve as an independent prognostic factor for NPC patients.

Comparison of new magnetic resonance imaging grading system with conventional endoscopy for the early detection of nasopharyngeal carcinoma

Although stratifying individuals with respect to nasopharyngeal carcinoma (NPC) risk with Epstein-Barr virus-based markers is possible, the performance of diagnostic methods for detecting lesions among screen-positive individuals is poorly understood. The authors prospectively evaluated 882 participants aged 30 to 70 years who were enrolled between October 2014 and November 2018 in an ongoing, population-based NPC screening program and had an elevated NPC risk. Participants were offered endoscopy and magnetic resonance imaging (MRI), and lesions were identified either by biopsy at a follow-up endoscopy or further contact and linkage to the local cancer registry through December 31, 2019. The diagnostic performance characteristics of endoscopy and MRI for NPC detection were investigated. Eighteen of 28 identified NPC cases were detected by both methods, 1 was detected by endoscopy alone, and 9 were detected by MRI alone. MRI had significantly higher sensitivity than endoscopy for NPC detection overall (96.4% vs 67.9%; Pdifference = .021) and for early-stage NPC (95.2% vs 57.1%; P = .021). The sensitivity of endoscopy was suggestively lower among participants who had previously been screened in comparison with those undergoing an initial screening (50.0% vs 81.2%; P = .11). The authors observed a higher overall referral rate by MRI versus endoscopy (17.3% vs 9.1%; P < .001). Cases missed by endoscopy had early-stage disease and were more commonly observed for tumors originating from the pharyngeal recess. MRI was more sensitive than endoscopy for NPC detection in the context of population screening but required the referral of a higher proportion of screen-positive individuals. The sensitivity of endoscopy was particularly low for individuals who had previously been screened.

Plasma Epstein-Barr virus DNA and risk of nasopharyngeal carcinoma in a prospective seropositive population

ObjectivePlasma Epstein-Barr virus (EBV) DNA is considered a biomarker for nasopharyngeal carcinoma (NPC). However, its long-term role in NPC development is unclear.Materials and methodsA total of 1363 participants seropositive for EBV VCA-IgA and EBNA1-IgA in a community-based NPC screening program in southern China were tested for plasma EBV DNA levels by real-time qPCR between 2008 and 2015. New NPC cases were confirmed by active follow-up approach and linkage to local cancer registry through the end of 2016. Cox proportional hazards regression analysis was performed to calculate the hazard ratios (HRs) for NPC risk with plasma EBV DNA.ResultsThirty patients were newly diagnosed during a median 7.5 years follow-up. NPC incidence increased with the plasma EBV DNA load ranging from 281.46 to 10,074.47 per 100,000 person-years in participants with undetectable and ≥ 1000 copies/ml levels; the corresponding cumulative incidence rates were 1.73 and 50%. Furthermore, plasma EBV DNA loads conferred an independent risk for NPC development after adjustment for other risk factors, with HRs of 7.63 for > 3–999 copies/ml and 39.79 for ≥1000 copies/ml. However, the HRs decreased gradually after excluding NPC cases detected in the first 2 to 3 years and became statistically nonsignificant by excluding cases detected during the first 4 years.ConclusionElevated plasma EBV DNA can predict NPC risk over 3 years. Monitoring plasma EBV DNA can be used as a complementary approach to EBV serological antibody-based screening for NPC.

High miR-3650 expression in nasopharyngeal carcinoma and its clinical prognostic values

BackgroundA recent study has reported that miR-3650 expression was significant reduced in hepatocellular carcinoma and predicted poor prognosis. However, the role of miR-3650 in nasopharyngeal carcinoma (NPC) remains indefinite. MethodsTotal 140 cases of NPCs were included in this study. The expression of miR-3650 was determined in NPC tissues and adjacent nontumor tissues using qRT-PCR. Then the relationship between miR-3650 expression and clinicopathological features as well as survival were analyzed. ResultsThe expression of miR-3650 was significant higher in NPC tissues than that in adjacent nontumor tissues (P < 0.001). High expression of miR-3650 was significant correlated with tumor progression and distant metastasis of NPC patients. And patients with high miR-3650 expression have much worse 5-year overall survival (OS) and 5-year progression-free survival (PFS) than those with low expression (all P < 0.0001). Furthermore, Cox regression analysis showed that miR-3650 was an independent risk predictor for OS and PFS in NPC patients (all P = 0.000). ConclusionOur results demonstrated for the first time that miR-3650 was markedly upregulated in NPC tissues and positively associated with tumor progression and poor survival, suggesting that miR-3650 may be a potential novel prognostic biomarker and therapeutic target for NPC patients.

Correlation analysis of neck node levels in 960 cases of Nasopharyngeal carcinoma (NPC)

PurposeThe delineation of intermediate risk nodal regions (CTVn2) and low-risk nodal regions (CTVn3) base on the correlation analysis between neck node levels of NPC has not been reported. We aim to analyze the correlations between different neck node levels in 960 cases of NPC, and to provide preliminary suggestions for clinical target volume (CTV) delineation of NPC base on the correlation analysis. Methods and materialsWe retrospectively analyzed the records of 960 NPCs in our institution from 2011 to 2019. Diagnostic head and neck CTs and MRIs were reviewed. The involvements of nodal levels were evaluated according to the 2013 updated guidelines. The correlations between different levels were studied using Chi-square test and logistic regression model. ResultsThe top four levels with the highest rate of lymph node metastasis were VIIa(86.35%), IIb(84.06%), IIa(62.29%), and III(47.29%). Correlation analysis showed that lymph node metastasis in level Ib was correlated with levels IIa and III. Level IIa was correlated with levels Ib, IIb, III, and Va. Level IIb was correlated with levels IIa, III, Va, and VIIa. Level III was correlated with levels IIa, IIb, IVa, Va, Vb, VIIa, and T stage. Level IVa was correlated with levels III, IVb, and Va. Level IVb was only correlated with level IVa. Level Va was correlated with levels IIb, III, IVa, Vb, and posterior to level V (PLV region). Level Vb was correlated with levels III, Va, Vc, and PLV region. Level Vc was correlated with levels IVb, Vb, and PLV region. Level VIIa was correlated with levels IIb and III. Level VIIb had no correlations with other levels. Level VIII was correlated with levels Ib and IVb. The PLV region was correlated with levels Va, Vb, and Vc. All the above P values were <0.05. ConclusionsThis study recommends setting the related levels as CTVn2 and the unrelated levels as CTVn3. The levels of nodal spread are different in NPC patients, this study reflects the principle of individualized CTV delineation.

Second malignancies in children with head and neck primary tumors.

e22014 Background: Children with primaries in the head and neck region, especially those who recieve radiotherapy (RT) are at increased risk for second malignancies (SM). This study aims to assess the incidence and outcome of SM in children with head and neck primary tumors. Methods: During 1990-2017, 3214 children with cancer were treated in theIstanbul University, Oncology Institute. The primary tumor was in the head and neck region in 1414 (651 brain tumors,289 retinoblastoma,474 other). Survivors followed up for at least 3 years from diagnosis were evaluated for second malignancies. Results: 30 SM were identified in 28 survivors (18 male,10 female) at a median of 12 years (2-26) from diagnosis. The primary diagnosis was nasopharyngeal carcinoma (NPC) in 8, bilateral retinoblastoma (RBS) in 7, embryonal brain tumors (CNST) in 8, Hodgkin lymphoma (HD) in 3, rhabdomyosarcoma(RMS) in 2. Two RBS patients who did not recieve radiotherapy developed pilocytic astrocytoma (at 2 years) and osteosarcoma of the extremity (at 4 years) each, both are alive with no evidence of disease (NED) for 3.5 and 10 years. 26 patients recieved RT: one with CNST developed MDS (at 8 years) and died due to complications after stem cell transplantation (SCT). One with NPC developed PNET of the bladder (at 5 years) and died of disease (DOD). One with relapse HD developed Langerhans cell histiocytosis 2 years after SCTand is with NED for 10 years. The other 23 developed SM in the/proximity of the RT field. These SM were 7 sarcomas (in 4 retinoblastoma,2 NPC, 1 RMS), 6 thyroid cancer (in 2 CNST, 1 RMS, 1 HD, 1 NPC), 3 meningiomas (in 2 CNST, 1 RBS), 5 carcinomas (in 4 NPC, 1 RBS), 1 basal cell carcinoma (in a recurrent re-irradiated CNST, is with NED), 1 peripheral nerve sheath tumor (in 1 HD, DOD), glioblastoma multiforme and non Hodgkin's lymphoma (in the same CNST case, DOD at 6 months). One of the NPC case developed both sarcoma (at 18 years) and carcinoma (at 25 years, NED). The RT dose (20-70 Gy) differed according to diagnosis. All survivors of thyroid cancer are with NED except one who died in an accident; of 3 meningiomas, the one with retinoblastoma who developed malignant meningioma died. Of five carciinomas as SM, two with NPC who developed carcinomas died. Of sarcomas as SM, two with fibrosarcomas are with NED at 10 years each (1NPC, 1 RMS). All patients survived for a median of 3 (0.5-16) years after SM; 16/28 (57%) are with NED at a median of 8 (1-16) years; 12 died at a median of 1.8 (0.5-4.75) years after SM. (1 CNST due to accident, 1 NPC due to infectious complications after a reconstructive surgery, 10 DOD). All SM were detected early during regular surveillance. Conclusions: Children with head and neck primaries are at risk for SM which may occur many years later, especially in RT sites. RT should be avoided when possible such as currently in RBS. Patients need regular surveillance lifelong, for early detection of SM. SM should be treated with curative intent, to achieve long term survival.

Descriptive epidemiology of nasopharyngeal carcinoma at Tikur Anbessa Hospital, Ethiopia

BackgroundNasopharyngeal cancer is distinguished from other cancers of the head and neck in its epidemiology, histopathology, clinical characteristics, and therapeutic outcome. Its unique clinico-epidemiologic pattern of the disease is an area focus for this investigation. Accordingly, the study investigated the demographic and histologic characteristics, as well as the clinical stage at presentation of nasopharyngeal carcinoma patients at Tikur Anbessa Specialized hospital.MethodsHospital based retrospective descriptive study was conducted from September 2017 – October 2020. All biopsy proven incidental cases during the study period are included. SPSS version 26 is used for data entry and analysis.ResultA total of 318 patients with histologically confirmed nasopharyngeal carcinoma cases during the study period were included. There were 218 males and 90 females, with a male: female ratio of 2.5:1. The age of patients ranges from 13 to 81 years with a mean age of 37.8 ± 15 years. The median age at diagnosis was 38 years. Age distribution has two peaks for males, first between 30 to 39 and second 50 to 59 years of age. While the peak age of occurrence for females is in the 20–39 age range. Juvenile cases constituted 34% of the study group. The study revealed, nonkeratinizing carcinoma as the most prevalent histology at 94.3% (undifferentiated type 85.9% and differentiated keratinizing squamous cell carcinoma 8.4%) and 5.7% of the cases showed keratinizing squamous cell carcinoma. Majority of the patients, 86%, presented late with stage III and IV disease.ConclusionNasopharyngeal cancer is commonly found among the young and productive age group, under the age 30. Nonkeratinizing carcinoma is the predominant histopathologic variant resembling that seen in endemic areas of the world. Thus, genetic and early life environmental exposures should be well studied to identify possible risk factors in the region. Late-stage presentation at diagnosis impacts the treatment outcome of patients, thereby indicating the need for a raised index of suspicion among health professionals for early diagnosis and better prognosis of patients.

Prevalence of Nasopharyngeal Carcinoma in Patients with Dermatomyositis: A Systematic Review and Meta-Analysis.

For more than 50 years, nasopharyngeal carcinoma (NPC) has been associated with dermatomyositis (DM), a rare idiopathic inflammatory disorder that mainly affects the skin and muscles. Although the association between these rare diseases is well-documented, the actual prevalence of NPC in DM patients remains unknown. Here, a systematic review and meta-analysis of published data was conducted in accordance with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Electronic databases including PubMed, Scopus, ScienceDirect, and Google Scholar were searched without year or language restrictions for studies reporting the occurrence of NPC in DM patients. The study protocol was lodged with PROSPERO (CRD42021225335). A total of 95 studies covering 303 cases of NPC among 16,010 DM patients was included. Summary estimates were calculated using the random-effects model. The pooled prevalence of NPC in DM was 3.3% (95% CI, 2.5-4.3). When stratified according to study location, higher prevalence estimates were obtained for Hong Kong (36.5%), Malaysia (27.7%), and Singapore (11.9%). There was a predominance of cases among male DM patients compared with females, and most patients were aged 40 and above. Many of the NPC cases were found to be diagnosed after the diagnosis of DM. It is therefore pertinent to screen for NPC in DM patients, especially among older DM patients in the Asian region.

Roles of Inflammasomes in Epstein-Barr Virus-Associated Nasopharyngeal Cancer.

Simple SummaryInflammasomes play a key role in mediating innate immunity by regulating the processing and production of pro-inflammatory cytokines and eliminating foreign pathogens via pyroptosis. The expression of Epstein–Barr virus (EBV) viral antigens during EBV infection, a known causative agent of nasopharyngeal carcinoma (NPC), can trigger host’s antiviral immune response through activation of the inflammasomes and subsequent production of pro-inflammatory cytokines. This review explores the roles of inflammasomes during viral infection, the possible impact of inflammasomes on oncogenesis in EBV-associated NPC, and current developments in targeting inflammasomes for cancer treatment. With the contrasting roles of inflammasomes reported in different types of cancers, this paper aims to inspire further investigations into the exact role and mechanism of inflammasomes in EBV-associated NPC, as well as the therapeutic potentials of targeting inflammasomes in NPC.Epstein–Barr virus (EBV) infection is recognised as one of the causative agents in most nasopharyngeal carcinoma (NPC) cases. Expression of EBV viral antigens can induce host’s antiviral immune response by activating the inflammasomes to produce pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18. These cytokines are known to be detrimental to a wide range of virus-infected cells, in which they can activate an inflammatory cell death program, called pyroptosis. However, aberrant inflammasome activation and production of its downstream cytokines lead to chronic inflammation that may contribute to various diseases, including NPC. In this review, we summarise the roles of inflammasomes during viral infection, how EBV evades inflammasome-mediated immune response, and progress into tumourigenesis. The contrasting roles of inflammasomes in cancer, as well as the current therapeutic approaches used in targeting inflammasomes, are also discussed in this review. While the inflammasomes appear to have dual roles in carcinogenesis, there are still many questions that remain unanswered. In particular, the exact molecular mechanism responsible for the regulation of the inflammasomes during carcinogenesis of EBV-associated NPC has not been explored thoroughly. Furthermore, the current practical application of inflammasome inhibitors is limited to specific tumour types, hence, further studies are warranted to discover the potential of targeting the inflammasomes for the treatment of NPC.

Occupational exposures and risk of nasopharyngeal carcinoma in a high‐risk area: A population‐based case‐control study

The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based case-control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self-reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration-response relations. Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26-1.68), chemical vapors (OR, 1.37; 95% CI, 1.17-1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25-1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30-1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia. Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas. The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration-response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high-incidence region.