The serological diagnostic value of EBV-related IgA antibody panels for nasopharyngeal carcinoma: a diagnostic test accuracy meta-analysis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is diagnosed relatively late and has a poor prognosis, requiring early detection to reduce the disease burden. This diagnostic test accuracy meta-analysis evaluated the serological diagnostic value of nine EBV-related IgA antibody panels (EBNA1-IgA, VCA-IgA, EA-IgA, Zta-IgA, EBNA1-IgA + VCA-IgA, VCA-IgA + EA-IgA, VCA-IgA + Rta-IgG, EBNA1-IgA + VCA-IgA + Zta-IgA and VCA-IgA + EA-IgA + Rta-IgG), aiming to identify suitable serological detection biomarkers for NPC screening. METHODS: PubMed, Embase, China National Knowledge Infrastructure and Chinese BioMedical Literature Database were searched from January 1st, 2000 to September 30th, 2023, with keywords nasopharyngeal carcinoma, IgA, screening, early detection, early diagnosis, sensitivity and specificity. Articles on the diagnostic value of serum EBV-related IgA antibody panels for NPC were included. Study selection, data extraction, and quality assessment were performed independently by two researchers, and a third researcher was consulted in the case of disagreement. Bivariate models were used for statistical analysis. The quality of included studies was evaluated through Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). RESULTS: A total of 70 articles were included, involving 11 863 NPC cases and 34 995 controls. Among the nine EBV-related IgA antibody panels, EBNA1-IgA + VCA-IgA [0.928 (0.898, 0.950)], VCA-IgA + Rta-IgG [0.925 (0.890, 0.949)], EBNA1-IgA + VCA-IgA + Zta-IgA [0.962 (0.909, 0.985)] and VCA-IgA + EA-IgA + Rta-IgG [0.945 (0.918, 0.964)] demonstrated higher pooled sensitivity (95%CI). In terms of diagnostic odds ratio (DOR) (95%CI), EBNA1-IgA + VCA-IgA [107.647 (61.173, 189.430)], VCA-IgA + Rta-IgG [105.988 (60.118, 186.857)] and EBNA1-IgA + VCA-IgA + Zta-IgA [344.450 (136.351, 870.153)] showed superior performance. Additionally, the SROC curves for EBNA1-IgA + VCA-IgA and VCA-IgA + Rta-IgG were more favorable. However, publication bias was detected for VCA-IgA (P = 0.005) and EBNA1-IgA + VCA-IgA (P = 0.042). CONCLUSIONS: In general, parallel detection of serum EBNA1-IgA, VCA-IgA and Zta-IgA antibodies using ELISA demonstrates better pooled sensitivity and DOR among the studied panels. In the cases where fewer indicators are used, serum VCA-IgA and EBNA1-IgA/Rta-IgG antibody panel exhibits a comparable performance. TRIAL REGISTRATION: The International Prospective Register of Systematic Reviews registration number: CRD42023426984, registered on May 28, 2023.

68Ga-DOTATATE PET/CT Imaging of a Solitary Nasopharyngeal Metastasis of Merkel Cell Carcinoma.

ABSTRACT: Merkel cell carcinoma (MCC) is an uncommon highly aggressive cutaneous neuroendocrine neoplasm with high mortality. Rarer still is nasopharyngeal metastasis of MCC. Herein, we report the 68Ga-DOTATATE PET/CT findings of MCC with metastasis to the nasopharynx in a 53-year-old man who underwent surgery for MCC in his thigh 2 years ago.

B7-H3 promotes nasopharyngeal carcinoma progression by regulating CD8+ T cell exhaustion.

BACKGROUND: B7-H3 protein is an important regulator of the adaptive immune response in human tumorigenesis. 4-1BB is a co-stimulatory receptor expressed on activated CD8+ T cells, and regulates T cell immunity. Here, we investigated the role of B7-H3 in the growth and invasion of nasopharyngeal carcinoma (NPC) and the effect of its interaction with 4-1BB on tumor immunity. METHODS: Short hairpin (sh) RNA was designed to knock down B7-H3 expression in NPC cells. NPC cells with stable knockdown of B7-H3 were established and injected into nude mice. The effects of B7-H3 on cell proliferation, apoptosis, and epithelial-to-mesenchymal transition (EMT) were detected by the CCK8 assay, flow cytometry, TUNEL assay, and western blot analysis. The migration and invasion abilities were determined using the Transwell assay and scratch assay. Co-immunoprecipitation (Co-IP) assays were performed to study the interaction between B7-H3 and 4-1BB. Anti-4-1BB antibody was used in a co-culture system and xenograft mice to study the effect of 4-1BB on NPC development. RESULTS: NPC cells transfected with sh-B7-H3 showed a higher rate of apoptosis, slower growth rate, impaired migration, and less EMT in vitro. Xenograft mice with stable knockout of B7-H3 had lower tumor burdens, and the stripped tumors had lower rates of cell proliferation, higher rates of apoptosis, and less EMT in vivo. Additionally, decreased B7-H3 expression was positively correlated with interferon-γ, tumor necrosis factor-α, and 4-1BB+CD8+ tumor-infiltrating lymphocytes. Co-IP studies showed that B7-H3 interacts with 4-1BB. Also, the inhibitory effects of sh-B7-H3 on NPC tumor growth, invasion, and tumor immunity could be alleviated by the anti-4-1BB antibody both in vivo and in vitro. CONCLUSION: Our findings suggest that B7-H3 may accelerate tumor growth, tumor cell invasion, and EMT, and interact with 4-1BB to produce CD8+ T cell exhaustion that inhibits tumor immunity. B7-H3 might serve as a novel target for treating NPC.

Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma.

Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.

[Dihydroartemisinin enhances sensitivity of nasopharyngeal carcinoma HNE1/DDP cells to cisplatin-induced apoptosis by promoting ROS production].

OBJECTIVE: To investigate the effect of dihydroartemisinin (DHA) for enhancing the inhibitory effect of cisplatin (DDP) on DDP-resistant nasopharyngeal carcinoma cell line HNE1/DDP and explore the mechanism. METHODS: CCK-8 method was used to assess the survival rate of HNE1/DDP cells treated with DHA (0, 5, 10, 20, 40, 80, and 160 µmol/L) and DDP (0, 4, 8, 16, 32, 64, 128 µmol/L) for 24 or 48 h, and the combination index of DHA and DDP was calculated using Compusyn software. HNE1/DDP cells treated with DHA, DDP, or their combination for 24 h were examined for cell viability, proliferation and colony formation ability using CCK-8, EdU and colony-forming assays. Flow cytometry was used to detect cell apoptosis and intracellular reactive oxygen species (ROS). The expression levels of apoptosis-related proteins cleaved PARP, cleaved caspase-9 and cleaved caspase-3 were detected by Western blotting. The effects of N-acetyl-cysteine (a ROS inhibitor) on proliferation and apoptosis of HNE1/DDP cells with combined treatment with DHA and DDP were analyzed. RESULTS: Different concentrations of DHA and DDP alone both significantly inhibited the viability of HNE1/DDP cells. The combination index of DHA (5 µmol/L) combined with DDP (8, 16, 32, 64, 128 µmol/L) were all below 1. Compared with DHA or DDP alone, their combined treatment more potently decreased the cell viability, colony-forming ability and the number of EdU-positive cells, and significantly increased the apoptotic rate, intracellular ROS level, and the expression levels of cleaved PARP, cleaved caspase-9 and cleaved caspase-3 in HNE1/DDP cells. N-acetyl-cysteine pretreatment obviously attenuated the inhibitory effect on proliferation and apoptosis-inducing effect of DHA combined with DDP in HNE1/DDP cells (P<0.01). CONCLUSION: DHA enhances the growth-inhibitory and apoptosis-inducing effect of DDP on HNE1/DDP cells possibly by promoting accumulation of intracellular ROS.

Comparing long-term efficacy and safety of GP versus TPF sequential chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a propensity score-matched analysis.

PURPOSE: To evaluate the long-term efficacy and safety of GP and TPF sequential chemotherapy regimens in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: From 2005 to 2016, a total of 408 LA-NPC patients treated with GP or TPF sequential chemoradiotherapy were retrospectively included. Propensity Score Matching (PSM) was employed to balance the baseline variables. Survival outcomes and acute toxicities were compared between both groups. RESULTS: A total of 230 patients were selected by 1:1 PSM. At a median follow-up of 91 months, no significant differences were observed between the matched GP and TPF groups regarding 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregionally relapse-free survival (83.4% vs. 83.4%, P = 0.796; 75.6% vs. 68.6%, P = 0.301; 86.7% vs. 81.1%, P = 0.096; and 87.4% vs. 87.2%, P = 0.721). Notable disparities in adverse effects were identified, with higher incidences of grade 3/4 thrombocytopenia in the GP group while grade 3/4 leukopenia and neutropenia in the TPF group. Though not recorded in our cohort, combined with the FAERS database, thrombotic adverse reactions are a concern for the GP regimen, while the TPF regimen requires vigilance for life-threatening adverse reactions such as septic shock, acute respiratory distress syndrome, and laryngeal edema. CONCLUSION: No significant difference in long-term outcomes was observed between the GP and TPF sequential chemotherapy regimens for LA-NPC. Differences in adverse effects should be noted when choosing the regimen.

Xerostomia prediction in patients with nasopharyngeal carcinoma during radiotherapy using segmental dose distribution in dosiomics and radiomics models.

OBJECTIVES: This study aimed to integrate radiomics and dosiomics features to develop a predictive model for xerostomia (XM) in nasopharyngeal carcinoma after radiotherapy. It explores the influence of distinct feature extraction methods and dose ranges on the performance. MATERIALS AND METHODS: Data from 363 patients with nasopharyngeal carcinoma were retrospectively analyzed. We pioneered a dose-segmentation strategy, where the overall dose distribution (OD) was divided into four segmental dose distributions (SDs) at intervals of 15 Gy. Features were extracted using manual definition and deep learning, applying OD or SD and integrating radiomics and dosiomics, yielding corresponding feature scores (manually defined radiomics, MDR; manually defined dosiomics, MDD; deep learning-based radiomics, DLR; deep learning-based dosiomics, DLD). Subsequently, 18 models were developed by combining features and model types (random forest and support vector machine). RESULTS AND CONCLUSION: Under OD, O(DLR_DLD) demonstrated exceptional performance, with an optimal area under the curve (AUC) of 0.81 and an average AUC of 0.71. Within SD, S(DLR_DLD) surpassed the other models, achieving an optimal AUC of 0.90 and an average AUC of 0.85. Therefore, the integration of dosiomics into radiomics can augment predictive efficacy. The dose-segmentation strategy can facilitate the extraction of more profound information. This indicates that ScoreDLR and ScoreMDR were negatively associated with XM, whereas ScoreDLD, derived from SD exceeding 15 Gy, displayed a positive association with XM. For feature extraction, deep learning was superior to manual definition.

Integrative radiopathomics model for predicting progression-free survival in patients with nonmetastatic nasopharyngeal carcinoma.

PURPOSE: To construct an integrative radiopathomics model for predicting progression-free survival (PFS) in nonmetastatic nasopharyngeal carcinoma (NPC) patients. METHODS: 357 NPC patients who underwent pretreatment MRI and pathological whole-slide imaging (WSI) were included in this study and randomly divided into two groups: a training set (n = 250) and validation set (n = 107). Radiomic features extracted from MRI were selected using the minimum redundancy maximum relevance and least absolute shrinkage and selection operator methods. The pathomics signature based on WSI was constructed using a deep learning architecture, the Swin Transformer. The radiopathomics model was constructed by incorporating three feature sets: the radiomics signature, pathomics signature, and independent clinical factors. The prognostic efficacy of the model was assessed using the concordance index (C-index). Kaplan-Meier curves for the stratified risk groups were tested by the log-rank test. RESULTS: The radiopathomics model exhibited superior predictive performance with C-indexes of 0.791 (95% confidence interval [CI]: 0.724-0.871) in the training set and 0.785 (95% CI: 0.716-0.875) in the validation set compared to any single-modality model (radiomics: 0.619, 95% CI: 0.553-0.706; pathomics: 0.732, 95% CI: 0.662-0.802; clinical model: 0.655, 95% CI: 0.581-0.728) (all, P < 0.05). The radiopathomics model effectively stratified patients into high- and low-risk groups in both the training and validation sets (P < 0.001). CONCLUSION: The developed radiopathomics model demonstrated its reliability in predicting PFS for NPC patients. It effectively stratified individual patients into distinct risk groups, providing valuable insights for prognostic assessment.

Mechanism of luteolin induces ferroptosis in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) originates from the nasopharynx epithelium, and luteolin is recognized as an important anti-cancer agent. This study investigated the effects of luteolin on ferroptosis in NPC cells. NPC cells were cultured and exposed to varying concentrations of luteolin. Cell viability, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, glutathione (GSH) levels, Fe2+ concentration, and glutathione peroxidase 4 (GPX4) protein level were assessed. Additionally, SRY-related high-mobility-group box 4 (SOX4) expression was measured. Subsequently, the binding of SOX4 to the growth differentiation factor-15 (GDF15) promoter and GDF15 mRNA levels were evaluated. The impact of the SOX4/GDF15 axis on luteolin-induced ferroptosis in NPC cells was assayed. Luteolin treatment induced cell ferroptosis, evidenced by decreased cell viability, increased MDA and Fe2+ levels, and reduced SOD, GSH, and GPX4 levels. Furthermore, luteolin downregulated SOX4 expression, while overexpression of SOX4 reversed luteolin's pro-ferroptotic effects in NPC cells. SOX4 was found to up-regulate GDF15 transcription by directly binding to its promoter. Conversely, overexpression of GDF15 mitigated the ferroptotic effects induced by luteolin in NPC cells. Therefore, luteolin induces ferroptosis in NPC cells via modulation of the SOX4/GDF15 axis. In conclusion, luteolin reduces the binding of SOX4 to the GDF15 promoter by suppressing SOX4 expression, thereby down-regulating GDF15 transcription levels and inducing ferroptosis in NPC cells.

Aquaporin-3 is down-regulated by LMP1 in nasopharyngeal carcinoma cells to regulate cell migration and affect EBV latent infection.

Epstein-Barr virus (EBV) infection has a strong correlation with the development of nasopharyngeal carcinoma (NPC). Aquaporin 3 (AQP3), a member of the aquaporin family, plays an important role in tumor development, especially in epithelial-mesenchymal transition. In this study, the expression of AQP3 in EBV-positive NPC cells was significantly lower than that in EBV-negative NPC cells. Western blot and qRT-PCR analysis showed that LMP1 down-regulated the expression of AQP3 by activating the ERK pathway. Cell biology experiments have confirmed that AQP3 affects the development of tumor by promoting cell migration and proliferation in NPC cells. In addition, AQP3 can promote the lysis of EBV in EBV-positive NPC cells. The inhibition of AQP3 expression by EBV through LMP1 may be one of the mechanisms by which EBV maintains latent infection-induced tumor progression.

A scoring system based on inflammatory and nutritional indicators to predict the long-term survival of patients with non-metastatic nasopharyngeal carcinoma.

To develop a simple scoring system based on baseline inflammatory and nutritional markers to predict the long-term prognosis of patients with nasopharyngeal carcinoma (NPC). Conducted a retrospective analysis of clinical data from 1024 newly diagnosed non-metastatic NPC patients. A total of 15 pre-treatment inflammatory and nutritional markers were collected as candidate variables. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff points for each parameter. Survival analysis was performed using Kaplan-Meier method and Cox regression analysis. Besides, the Inflammation Nutrition Risk Score (INRS) was calculated for each patient by assigning each independent prognostic factor a score of 1. Multivariate Cox regression analysis showed that serum albumin (ALB), systemic immune-inflammation index, and monocyte count (M) were independent prognostic factors for OS (P < 0.05). Survival analysis showed that higher INRS was associated with a worsened prognosis. Patients in the high-risk group had shorter OS than in the low-risk group. In the training group, the 3-, 5-, and 8-years OS rates for the low-risk group versus high-risk group were 92.5% versus 87.8%, 87.4% versus 75.1%, and 84.6% versus 62.2%, respectively (P < 0.05). In the validation group, the 3-, 5-, and 8-years OS rates for the low-risk group vs. high-risk group were 95.0% versus 86.4%, 92.1% versus 82.2%, and 89.5% versus 74.3%, respectively (P < 0.05). Further subgroup analysis showed a significant difference in the OS between the high-risk group and low-risk group in patients with locally advanced disease (P < 0.05). The ROC curve demonstrated that INRS had a similar predictive value for long-term survival in NPC patients compared to TNM staging and serum EBV-DNA levels. Pretreatment ALB, M, and SIRI are independent prognostic factors for long-term survival in patients with NPC. INRS constructed based on these three factors can serve as a long-term prognostic indicator for NPC.

Establishment of a visualized mouse orthotopic xenograft model of nasopharyngeal carcinoma.

Mouse orthotopic xenograft tumor models are commonly employed in studies investigating the mechanisms underlying the development and progression of tumors and their preclinical treatment. However, the unavailability of mature and visualized orthotopic xenograft models of nasopharyngeal carcinoma limits the development of treatment strategies for this cancer. The aim of this study was to provide a simple and reliable method for building an orthotopic xenograft model of nasopharyngeal carcinoma. Human nasopharyngeal carcinoma (C666-1-luc) cells, stably expressing the firefly luciferase gene, were injected subcutaneously into the right axilla of BALB/C nude mice. Four weeks later, the resulting subcutaneous tumors were cut into small blocks and grafted into the nasopharynx of immunodeficient BALB/C nude mice to induce tumor formation. Tumor growth was monitored by bioluminescence imaging and small animal magnetic resonance imaging (MRI). The expression of histological and immunological antigens associated with orthotopic xenograft nasopharyngeal carcinoma was analyzed by tissue section analysis and immunohistochemistry (IHC). A visualized orthotopic xenograft nasopharyngeal carcinoma model was successfully developed in this study. Luminescence signal detection, micro-MRI, and hematoxylin and eosin staining revealed the successful growth of tumors in the nasopharynx of the nude mice. Moreover, IHC analysis detected cytokeratin (CK), CK5/6, P40, and P63 expression in the orthotopic tumors, consistent with the reported expression of these antigens in human nasopharyngeal tumors. This study established a reproducible, visual, and less lethal orthotopic xenograft model of nasopharyngeal carcinoma, providing a platform for preclinical research.

Baseline SUVmax is correlated with tumor hypoxia and patient outcomes in nasopharyngeal carcinoma.

To evaluate the prognostic significance of the maximum standardized uptake value (SUVmax) in nasopharyngeal carcinoma (NPC), establish a gene signature that correlates with SUVmax, and explore the underlying biological behaviors associated with these correlations for the prediction of clinical outcomes. A cohort of 726 patients with NPC was examined to identify correlations between SUVmax and various clinical variables. RNA sequencing was performed to identify genes related to SUVmax, and these genes were used to develop an SUV signature. Additionally, transcriptome enrichment analysis was conducted to investigate the potential biological behaviors underlying the observed correlations. Higher SUVmax was associated with an increased tumor burden and worse prognosis. The SUV signature, which consisted of 10 genes, was positively correlated with SUVmax, and it predicted worse survival outcomes. This signature was highly expressed in malignant epithelial cells and associated with hypoxia and resistance to radiotherapy. Additionally, the signature was negatively correlated with immune function. SUVmax is a valuable prognostic indicator in NPC, with higher values predicting worse outcomes. The SUV signature offers further prognostic insights, linking glucose metabolism to tumor aggressiveness, treatment resistance, and immune function, and it could represent a potential biomarker for NPC.

Radiotherapy for recurrent juvenile nasopharyngeal angiofibroma.

Juvenile nasopharyngeal angiofibroma (JNA) is a rare paediatric tumour known for its local destructiveness and high recurrence rate. Surgery is the primary treatment modality for JNA, though other options, such as hormonal therapy, embolisation and radiotherapy, exist for inoperable cases. The location of the tumour makes surgical intervention challenging. A 14-year-old male presented with epistaxis and headaches as the chief complaints and was diagnosed with nasopharynx angiofibroma by computed tomography (CT) scan in 2018. Pre-operative embolisation was performed and followed by surgical removal of a 4 cm tumour in January 2019. Pathological examination revealed CD34 positivity, S100 negativity and Ki-67 positivity (5 to 10%), confirming angiofibroma. In October 2019, a 3.6 cm recurrent tumour was treated with embolisation and a second surgery. Pathological findings again confirmed JNA. The patient underwent four surgeries in total, but epistaxis persisted. In 2021, local radiotherapy was administered using intensity-modulated radiation therapy (IMRT) at a dose of 60 Gy in 25 fractions. Serial magnetic resonance imaging (MRI) post-radiotherapy showed a decreasing tumour size, with no further epistaxis and no observed radiation side effects 2 years post-treatment. Radiation therapy remains a strong alternative for managing recurrent JNA.

LncRNA HOTAIRM1 promotes radioresistance in nasopharyngeal carcinoma by modulating FTO acetylation-dependent alternative splicing of CD44.

BACKGROUND: Radiotherapy is the primary treatment for patients with nasopharyngeal carcinoma (NPC); however, almost 20% of patients experience treatment failure due to radioresistance. Therefore, understanding the mechanisms of radioresistance is imperative. HOTAIRM1 is deregulated in various human cancers, yet its role in NPC radioresistance are largely unclear. METHODS: This study investigated the association between HOTAIRM1 and radioresistance using CCK8, flow cytometry, and comet assays. Additionally, xenograft mice and patient-derived xenografts (PDX) models were employed to elucidate the biological functions of HOTAIRM1, and transcriptomic RNA sequencing was utilized to identify its target genes. RESULTS: Our study revealed an upregulation of HOTAIRM1 levels in radioresistant NPC cell lines and tissues. Furthermore, a positive correlation was noted between high HOTAIRM1 expression and increased NPC cell proliferation, reduced apoptosis, G2/M cell cycle arrest, and diminished cellular DNA damage following radiotherapy. HOTAIRM1 modulates the acetylation and stability of the FTO protein, and inhibiting FTO elevates the m6A methylation level of CD44 precursor transcripts in NPC cells. Additionally, silencing the m6A reading protein YTHDC1 was found to increase the expression of CD44V. HOTAIRM1 enhances NPC cell resistance to ferroptosis and irradiation through the HOTAIRM1-FTO-YTHDC1-CD44 axis. Mechanistically, HOTAIRM1 interacts with the FTO protein and induces m6A demethylation of the CD44 transcript. The absence of m6A modification in the CD44 transcript prevents its recognition by YTHDC1, resulting in the transition from CD44S to CD44V. An abundance of CD44V suppresses ferroptosis induced by irradiation and contributes to NPC radioresistance. CONCLUSIONS: In conclusion, the results in this study support the idea that HOTAIRM1 stimulates CD44 alternative splicing via FTO-mediated demethylation, thereby attenuating ferroptosis induced by irradiation and promoting NPC radioresistance.

Development and application of a serious adverse events risk model for concurrent chemoradiotherapy in patients with nasopharyngeal carcinoma.

The objective of this study was to construct a concise prediction model for serious adverse events (SAEs) in order to assess the likelihood of SAE occurrence among hospitalized patients undergoing concurrent chemoradiotherapy. An electronic database of a Cancer Centre was utilized to conduct a cross-sectional review survey. Our research involved the recruitment of 239 patients who were undergoing concurrent chemoradiotherapy in the Department of Nasopharynx and Radiotherapy. The clinical prediction rule was derived using logistic regression analysis, with SAE serving as the primary outcome. Internal verification was conducted. The occurrence rate of SAE in the derivation cohort was 59.4%. The ultimate model used had 3 variables, namely cystatin C, C-reactive protein, and serum amyloid A. The model exhibited an area under the curve of 0.626 (95% CI: 0.555-0.696; P < .001). The model accurately predicts the occurrence of SAE, and the variable data can be easily obtained, and the assessment technique is straightforward.

Multimodal treatment according to the NPC-GPOH trials in adult patients with nasopharyngeal cancer-Analysis based on a single-center experience.

BACKGROUND AND AIM: The German NPC-GPOH trials introduced treatment including neoadjuvant chemotherapy, radiochemotherapy (RCT) and antiviral treatment in patients aged 25 years or younger with nasopharyngeal cancer (NPC). We conducted a retrospective study on outcomes of patients at the age of ≥26 years treated accordingly at our institution. METHODS: Consecutive patients who received primary RCT for NPC were included. The Kaplan-Meier method was used to calculate survival probabilities, and the Cox regression analysis was used to test for an influence of the variables on outcomes. Acute and late toxicity were evaluated via CTCAE criteria and LENT/SOMA criteria, respectively. RESULTS: In total, 30 patients were included. Diagnosis was made from 09/1994 to 11/2016. The median 5 year overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS) and locoregional recurrence-free survival (LRC) were 75%, 56%, 83%, and 85%, respectively. We found a negative impact on outcomes (p < .05) in case of older age (OS), history of smoking (OS), and T4 stage/ UICC stage IV (DFS). WHO histologic type significantly influenced outcomes, with best outcomes for type III and worst outcomes for type I. The rates of acute and late toxicities were acceptable. CONCLUSION: We found excellent outcomes and good feasibility of the NPC-GPOH trials regimen in adult patients. Additionally, we identified patients with outcomes which need to be improved (smokers, histologic type I tumors) and with particularly excellent outcomes (histologic type III tumors). This stimulates further studies on treatment intensification or de-escalation aiming at reduced side effects with optimal tumor control in NPC.

Tumor-associated macrophage-derived itaconic acid contributes to nasopharyngeal carcinoma progression by promoting immune escape via TET2.

Nasopharyngeal carcinoma (NPC) is a malignant tumor of epithelial origin in head and neck with high incidence rate in South China, Southeast Asia and North Africa. The intervention of tumor-associated macrophages (Mφs) (TAMs)-mediated immunosuppression is a potential therapeutic strategy against tumor metastasis, but the exact mechanisms of TAM-mediated immunosuppression in nasopharyngeal carcinoma are unclear. Furthermore, how TAM affects the occurrence and development of nasopharyngeal carcinoma through metabolism is rarely involved. In this work, we revealed that NPC cells promoted M2-type Mφ polarization and elevated itaconic acid (ITA) release. Also, TAMs facilitated NPC cell proliferation, migration, and invasion through immune response gene 1 (IRG1)-catalyzed ITA production. Then, IRG1-mediated ITA production in TAMs repressed the killing of CD8+ T cells, induced M2-type polarization of TAMs, and reduced the phagocytosis of TAMs. Moreover, we demonstrated ITA played a tumor immunosuppressive role by binding and dampening ten-eleven translocation-2 (TET2) expression. Finally, we proved that ITA promotes NPC growth by facilitating immune escape in CD34+ hematopoietic stem cell humanized mice. In Conclusion, TAM-derived ITA facilitated NPC progression by enhancing immune escape through targeting TET2, highlighting that interfering with the metabolic pathway of ITA may be a potential strategy for NPC treatment.

Challenges and innovations in managing a complex giant bilateral juvenile nasopharyngeal angiofibroma with intracranial extension.

Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascular, benign and locally aggressive tumour that predominantly affects adolescent males. Recognised for its persistence and propensity to recur, patients usually present with gradual development of symptoms such as epistaxis and nasal obstruction over several months to years. Diagnosis typically combines clinical assessments and radiographic studies, often involving preoperative angiography to identify feeder vessels and facilitate embolisation, reducing intraoperative bleeding during surgical interventions. A comprehensive approach to treatment, considering both tumour characteristics and patient well-being, is crucial, particularly when dealing with cases involving intracranial extension. Surgical excision remains the primary treatment for angiofibroma, though radiotherapy is considered for cases with intracranial extension. This case report outlines a case involving a young man in his 20s with a large bilateral JNA extending into the intracranial area. The patient underwent preoperative embolisation followed by surgical resection using a nasofrontomaxillary swing approach with a bifrontal craniotomy window. This alternative approach provided enhanced exposure to address the involvement of the infratemporal fossa, anterior and middle skull base. Postoperatively, residual intracranial tumour was managed with radiation therapy. Over a 2-year follow-up, the patient remains asymptomatic, with a minor postradiation reduction in the intracranial component's size.

Failure patterns and individualized treatment plans of reirradiation for inoperable locally recurrent nasopharyngeal carcinoma.

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.