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Background: This retrospective study investigated the prognostic value of serum inflammatory markers in nasopharyngeal carcinoma (NPC) patients, focusing on their association with overall survival (OS) and liver metastasis-free survival (LMFS). Methods: The study included 314 NPC patients treated between 2010 and 2020. Clinical characteristics, treatment methods, and serum inflammatory markers were assessed. Patients were categorized into two groups of with and without liver metastasis. Univariate and multivariate Cox regression and Kaplan–Meier survival analyses were performed to investigate the prognostic value of serum inflammatory markers in NPC patients with and without liver metastasis. Results: In the whole cohort, univariate Cox regression analysis singled out tumor necrosis factor-α (TNF-α) (HR = 1.57, 95% CI 1.44–4.90, p = 0.004) and neutrophil-to-lymphocyte ratio (NLR) (HR = 2.13, 95% CI 1.33–3.99, p = 0.009), which were significantly associated with poorer OS. In patients with liver metastasis, TNF-α and NLR could not independently predict OS. However, high TNF-α levels were independently associated with worse OS in patients without liver metastasis (HR (95% CI) = 2.75 (1.67–8.68), p < 0.001). High NLR levels could independently predict poor OS in both groups with (HR (95% CI) = 1.94 (1.77–6.38), p = 0.010) and without liver metastasis (HR (95% CI) = 1.58 (1.19–7.54), p = 0.009). Ultimately, TNF-α and NLR could not significantly predict LMFS. Conclusion: This study highlights the prognostic significance of TNF-α and NLR in NPC patients, especially in those with liver metastasis. These inflammatory markers could serve as valuable indicators for assessing the prognosis of NPC patients. Further research is warranted to validate their clinical utility and explore potential therapeutic implications. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate literature evidences about the efficacy and safety of anti-angiogenesis agents plus chemoradiotherapy versus chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma. Methods: The relevant literature was systematically searched from the date of establishment to April 2023 in PubMed, Embase, Web of Science, The Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biological Medicine, Wanfang and VIP database. Search terms included: Nasopharyngeal Neoplasms, Angiogenesis inhibitors, Endostar, Anlotinib, Apatinib, Bevacizumab, Sunitinib, Pazopanib, Chemoradiotherapy. The literature was strictly screened according to the inclusion and exclusion criteria, and 8 eligible studies were finally included in our meta-analysis (4 randomized controlled trials and 4 retrospective studies). Results: A total of 642 patients were included, with 316 in the anti-angiogenesis agents plus chemoradiotherapy group and 326 in the chemoradiotherapy group. The results of our meta-analysis showed that compared with chemoradiotherapy group, the complete response rate (RR = 1.35, 95% CI 1.05–1.74, P = 0.02), objective response rate (RR = 1.26, 95% CI 1.12–1.43, P = 0.0002) in the anti-angiogenesis agents plus chemoradiotherapy group were significantly improved. In terms of safety, there was a higher incidence of cardiac arrhythmia (RR = 3.63, 95% CI 1.16–11.37, P = 0.03) and hypertension (RR = 1.85, 95% CI 1.04–3.27, P = 0.004) in the anti-angiogenesis agents plus chemoradiotherapy group, while no statistically significant differences were reported in other adverse reactions (all P > 0.05). Conclusion: Compared with chemoradiotherapy, anti-angiogenesis agents plus chemoradiotherapy could bring more benefits in terms of short-term efficacy, particularly by notably improving both complete response rate and objective response rate, and overall adverse reactions were acceptable. Anti-angiogenesis agents plus chemoradiotherapy may provide a promising direction for the treatment of locally advanced nasopharyngeal carcinoma. Systematic Review Registration: https://inplasy.com/inplasy-2023-8-0076/, registration number INPLASY202380076. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the outcomes and toxicities of adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) in elderly (≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (LANPC, stage III‐IVa). Methods and Materials: Using an NPC‐specific database, 245 elderly patients with stage III‐IVa NPC, receiving CCRT +/− NAC, and an Adult Co‐morbidity Evaluation 27 (ACE‐27) score <2 were included. Recursive partitioning analysis (RPA) based on TNM stage and Epstein–Barr virus (EBV) DNA were applied for risk stratification. The primary end point was disease‐free survival (DFS). Results: Two risk groups were generated by the RPA model. In the high‐risk group (EBV DNA < 4000 copy/ml with stage IVa & EBV DNA ≥4000 copy/ml with stage III‐IVa), patients treated with NAC plus CCRT achieved improved 5‐year DFS rates compared to those who received CCRT alone (56.9% vs. 29.4%; p = 0.003). But we failed to observe the survival benefit of additional NAC in the low‐risk group (EBV DNA <4000 copy/ml with stage III). The most common severe acute toxic effects were leucopenia (46.8% vs. 24.4%) and neutropenia (43.7% vs. 20.2%) in the NAC plus CCRT group versus CCRT group with statistically significant differences. Conclusions: The addition of NAC to CCRT was associated with better DFS for the high‐risk group of elderly LANPC patients with ACE‐27 score <2. However, the survival benefit of additional NAC was not observed in low‐risk patients. [ABSTRACT FROM AUTHOR]

MiRNA (MicroRNA) can target and regulate mRNA, thereby influencing the biological processes of tumors. The extract of Tibetan medicine Rhodiola demonstrates anti-tumor effects by targeting and regulating cancer-related signaling molecules and pathways. This review aims to pave the way for integrating salidroside into clinical practice, fully leverage its multi-effective and multi-targeted biological effects, and innovate approaches to tumor prevention and management, thus enhancing cancer prognosis. We initially delve into the occurrence and mechanism of action of miRNA, as well as the anti-tumor mechanism of the miRNA-mRNA signaling axis. Additionally, it was described that salidroside can hinder cancer cell proliferation by inducing autophagy and apoptosis, inhibiting cell metastasis and invasion, and modulating the tumor microenvironment and cell cycle. Moreover, examples from lung cancer, gastric cancer, and nasopharyngeal carcinoma confirm that salidroside regulates the onset and progression of tumors through the miRNA-mRNA signaling axis. This groundbreaking discovery carries significant implications for cancer diagnosis and treatment, offering a novel pathway for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Introduction Juvenile nasopharyngeal angiofibroma (JNA) is a benign vascularized tumor that affects almost exclusively male adolescents. Surgery is the treatment of choice for JNA. Objectives The present study is a 42-year retrospective review of a series of JNA cases treated surgically without previous embolization. Methods The present is a retrospective, descriptive study based on medical records of 96 patients with JNA who underwent microscopic or endoscopic excision without previous embolization from 1978 to 2020 in a single institution. The patients were categorized according to the Andrews et al. stage, and data were collected on age, gender, tumor staging, surgical approach, affected side, and outcome. Results All patients were male, with an average age of 17 years. The predominant tumor stage consisted of type II, with 52.1%. A total of 33.3% of the patients were submitted to the microscopic technique and 66.7%, to the endonasal technique. The rate of intraoperative blood transfusion was of 17.7%. Conclusion The present study reinforces that resection of JNA in various stages is viable without previous artery embolization. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical implication of magnetic resonance imaging (MRI)-derived skeletal muscle index (SMI) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients undergoing induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) and further to develop a nomogram for predicting survival prognosis. Methods: SMI was determined through baseline MRI at the third cervical level. The nomogram was based on a training cohort involving 409 LANPC patients. We validated the prognostic accuracy of this prognostic model in an internal validation cohort (n = 204) and an external independent cohort (n = 272). Results: SMI was an independent risk factor for OS. A prognostic model comprising age, TNM stage and SMI for individual survival prediction was developed and graphically represented as a nomogram. The model showed favorable discrimination (C-index: 0.686), predictive accuracy [time dependent area under the curve (tAUC) at 5 years: 0.70], and calibration, and was further validated in the internal and external validation datasets. A risk stratification derived from the model stratified these patients into three prognostic subgroups with significantly different survival. Conclusions: Low SMI accessed by MRI was significantly associated with poor overall survival in LANPC patients undergoing IC + CCRT. Moreover, we established and validated a novel nomogram involving age, TNM stage and SMI that could provide accurate prognostic stratification among this population. [ABSTRACT FROM AUTHOR]

Purpose: To analyze oncological outcomes of endoscopic surgical treatment of locally recurrent EBV-related undifferentiated non-keratinizing nasopharyngeal carcinoma (uNK-NPC) in a non-endemic area. Methods: Retrospective review of patients affected by recurrent uNK-NPC treated with nasopharyngeal endoscopic resection (NER) in a tertiary-care referral center from 2003 to 2022, by evaluating survival rates, prognostic factors, and follow-up strategies. Results: The oncological outcomes of 41 patients were analyzed, over a mean follow-up period of 57 months. The 5-year overall, disease-specific, and disease-free survival of the cohort were 60.7% ± 8.9%, 69% ± 9%, and 39.7% ± 9.2%, respectively. The local (rT) and regional (rN) extension of recurrent disease, stage of disease, and status of resection margins appeared to significantly influence survivals. After a mean follow-up period of 21 months, a further recurrence after NER was observed in 36.6% of cases. Skull base osteonecrosis induced by previous irradiation and post-surgical bone remodeling represent the major challenges for early detection of further local relapses during postoperative follow-up. Conclusion: NER appeared as a safe and effective treatment for recurrent uNK-NPC. The adequate selection of patients eligible for NER is essential, to maximize the chances to cure and minimize the risk of local complications. [ABSTRACT FROM AUTHOR]

Background: IgG4-related disease (IgG4-RD) was characterized by single or multiple masses in organs, which may mimic various inflammatory and malignant diseases. Here, we summarize 4 patients with aggressive manifestations of IgG4-RD that mimic nasopharynx cancer to provide some new sights for the diagnosis of IgG4-RD. Case summary: Four patients were included in our series. The age ranged from 53 to 64 years old, and the duration of the disease ranged from 4 to 6 months. The chief complaints included headache, rhinorrhea, or diplopia. All patients had more than 10 IgG4+ plasma cells/HPF in immunohistochemistry with plasma lgG4 levels ranging from 218 mg/dL to 765 mg/dL. All of them met the diagnostic criteria of lgG4-RD. Conclusion: The described case is highly similar to the clinical manifestations of nasopharyngeal carcinoma. Although pathology is the gold standard, there are still limitations. Serological IgG4 can help confirm the diagnosis. Timely diagnosis of IgG4-RD is of great significance in preventing secondary organ damage in patients with active diseases. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is a type of malignant tumor with high morbidity. Aberrant levels of N7-methylguanosine (m7G) are closely associated with tumor progression. However, the characteristics of the tumor microenvironment (TME) in NPC associated with m7G modification remain unclear. Methods: A total of 68,795 single cells from single-cell RNA sequencing data derived from 11 NPC tumor samples and 3 nasopharyngeal lymphatic hyperplasia (NLH) samples were clustered using a nonnegative matrix factorization algorithm according to 61 m7G RNA modification regulators. Results: The m7G regulators were found differential expression in the TME cells of NPC, and most m7G-related immune cell clusters in NPC tissues had a higher abundance compared to non-NPC tissues. Specifically, m7G scores in the CD4+ and CD8+ T cell clusters were significantly lower in NPC than in NLH. T cell clusters differentially expressed immune co-stimulators and co-inhibitors. Macrophage clusters differentially expressed EIF4A1, and high EIF4A1 expression was associated with poor survival in patients with head and neck squamous carcinoma. EIF4A1 was upregulated in NPC tissues compared to the non-NPC tissues and mainly expressed in CD86+ macrophages. Moreover, B cell clusters exhibited tumor biological characteristics under the regulation of m7G-related genes in NPC. The fibroblast clusters interacted with the above immune cell clusters and enriched tumor biological pathways, such as FGER2 signaling pathway. Importantly, there were correlations and interactions through various ligand-receptor links among epithelial cells and m7G-related TME cell clusters. Conclusion: Our study revealed tumor-associated characteristics and immune dysregulation in the NPC microenvironment under the regulation of m7G-related TME cells. These results demonstrated the underlying regulatory roles of m7G in NPC. [ABSTRACT FROM AUTHOR]

Background: Treatment efficacy may differ among patients with nasopharyngeal carcinoma (NPC) at similar tumor–node–metastasis stages. Moreover, end-of-treatment tumor regression is a reliable indicator of treatment sensitivity. This study aimed to investigate whether quantitative dual-energy computed tomography (DECT) parameters could predict sensitivity to neck–lymph node radiotherapy in patients with NPC. Methods: Overall, 388 lymph nodes were collected from 98 patients with NPC who underwent pretreatment DECT. The patients were divided into complete response (CR) and partial response (PR) groups. Clinical characteristics and quantitative DECT parameters were compared between the groups, and the optimal predictive ability of each parameter was determined using receiver operating characteristic (ROC) analysis. A nomogram prediction model was constructed and validated using univariate and binary logistic regression. Results: DECT parameters were higher in the CR group than in the PR group. The iodine concentration (IC), normalized IC, Mix-0.6, spectral Hounsfield unit curve slope, effective atomic number, and virtual monoenergetic images were significantly different between the groups. The area under the ROC curve of the DECT parameters was 0.73–0.77. Based on the binary logistic regression, a column chart was constructed using 10 predictive factors, including age, sex, N stage, maximum lymph node diameter, arterial phase NIC, venous phase NIC, λHU and spectral Hounsfield units at 70 keV. The area under the ROC curve value of the constructed model was 0.813, with a sensitivity and specificity of 85.6% and 81.3%, respectively. Conclusion: Quantitative DECT parameters could effectively predict the sensitivity of NPC to radiotherapy. Therefore, DECT parameters and NPC clinical features can be combined to construct a nomogram with high predictive power and used as a clinical analytical tool. [ABSTRACT FROM AUTHOR]

Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18–65 years with newly diagnosed high-risk non-metastatic stage III–IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3–4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0–44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81–90] vs 76% [70–81]; stratified hazard ratio 0·59 [0·38–0·92]; p=0·019). Grade 3–4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3–4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the treatment response and toxicity of the combination of induction chemotherapy (IC) and PD-1 inhibitor in locally advanced nasopharyngeal carcinoma (LANPC). Methods: Patients with stage III--IVA NPC who received IC or IC + PD-1 inhibitor were included. The chi-square test and multivariate logistic regression analysis were used for statistical analysis. Results: A total of 225 patients were identified, including 193 (85.8%) and 32 (14.2%) who received IC alone and IC + PD-1 inhibitor, respectively. The addition of PD-1 inhibitor to IC significantly improved the tumor response than those treated with IC alone. The complete response (CR), partial response, stable disease, and progressive disease rates of 4.7% vs. 31.3%, 69.4% vs. 62.5%, 24.9% vs. 6.3%, and 1.0% vs. 0% in patients receiving IC alone and IC + PD-1 inhibitor, respectively (P<0.001). The results of the multivariate logistic regression showed that receiving PD-1 inhibitor was an independent predictor influencing the CR rate of patients (odds ratio 9.814, P<0.001). The most common toxicity by using IC and PD-1 inhibitor was hematological toxicity. In terms of non-hematological toxicity, 7 (21.9%) patients experienced thyroid dysfunction and all of them were hyperthyroidism. No grade 5 toxicities were found. In those who received IC and PD-1 inhibitor, the one-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival were 100%, 96.9%, 96.9%, and 100%, respectively. Conclusion: The addition of PD-1 inhibitor to IC has promise as an effective treatment approach for LANPC. More studies are expected to provide further insights into the optimal use of this treatment strategy, paving the way for more personalized and effective treatment options for patients with LANPC. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a highly prevalent head and neck malignancy in southern China frequently diagnosed at advanced stages owing to subtle early symptoms and associated metastasis. Angiogenesis emerges as a pivotal factor in NPC progression, with numerous angiogenesis-related factors showing aberrant expression and contributing to increased neovascularization within NPC tumors. These abnormal vessels not only nourish tumor growth but also facilitate metastasis, culminating in unfavorable patient outcomes. Multiple studies have demonstrated the applicability of various imaging techniques for assessing angiogenesis in NPC tumors, thus serving as a foundation for personalized treatment strategies and prognostic assessments. Anti-angiogenic therapies have exhibited significant potential for inhibiting NPC angiogenesis and exerting anti-tumor effects. To enhance efficacy, anti-angiogenic drugs are frequently combined with other treatment modalities to synergistically enhance anti-tumor effects while mitigating the side effects associated with single-agent therapies, consequently improving patient prognosis. Identifying the potential mechanisms and key targets underlying NPC angiogenesis and exploring more effective detection and treatment approaches holds promise for shaping the future of NPC diagnosis, treatment, and prognosis, thereby offering new avenues and perspectives for research and clinical practice. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is commonly diagnosed at an advanced stage with a high incidence rate in Southeast Asia and Southeast China. However, the limited availability of NPC patient survival data in public databases has resulted in less rigorous studies examining the prediction of NPC survival through construction of Kaplan-Meier curves. These studies have primarily relied on small samples of NPC patients with progression-free survival (PFS) information or data fromhead and neck squamous cell carcinoma (HNSCC) studies almost without NPC patients. Thus, we coanalyzed RNA expression profiles in eleven datasets (46 normal (control) vs 160 tumor (NPC)) downloaded from the Gene Expression Omnibus (GEO) database and survival data provided by Jun Ma from Sun Yat-sen University. Then, differential analysis, gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and network analysis were performed using STRING database. After that, 2142 upregulated differentially expressed genes (DEGs) and 3857 downregulated DEGs were screened. Twenty-five of them were identified as hub genes, which were enriched in several pathways (cilium movement, extracellular matrix structural constituent, homologous recombination and cell cycle). Utilizing the comprehensive dataset we amassed from GEO database, we conducted a survival analysis of DEGs and subsequently constructed survivalmodels. Seven DEGs (RASGRP2, MOCOS, TTC9, ARHGAP4, DPM3, CD37, and CD72) were identified and closely related to the survival prognosis of NPC. Finally, qRT-PCR, WB and IHC were performed to confirm the elevated expression of RASGRP2 and the decreased expression of TTC9, CD37, DPM3 and ARHGAP4, consistentwith theDEG analysis. Conclusively, our findings provide insights into the novel prognostic biomarkers of NPC by mega-data bioinformatics analysis, which suggests that they may serve special targets in the treatment of NPC. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton therapy allows for more effective organs at risk avoidance than photon radiotherapy, thus reducing both radiation-induced toxicity and second cancer risk. The aim of the present paper is to compare protons and photons outcomes in the context of oropharyngeal and nasopharyngeal cancer and provide an updated comprehensive overview of the most promising new approaches and methodologies for treating head and neck cancer with protons. The growing interest in proton therapy (PT) in recent decades is justified by the evidence that protons dose distribution allows maximal dose release at the tumor depth followed by sharp distal dose fall-off. But, in the holistic management of head and neck cancer (HNC), limiting the potential of PT to a mere dosimetric advantage appears reductive. Indeed, the precise targeting of PT may help evaluate the effectiveness of de-escalation strategies, especially for patients with human papillomavirus associated-oropharyngeal cancer (OPC) and nasopharyngeal cancer (NPC). Furthermore, PT could have potentially greater immunogenic effects than conventional photon therapy, possibly enhancing both the radiotherapy (RT) capability to activate anti-tumor immune response and the effectiveness of immunotherapy drugs. Based on these premises, the aim of the present paper is to conduct a narrative review reporting the safety and efficacy of PT compared to photon RT focusing on NPC and OPC. We also provide a snapshot of ongoing clinical trials comparing PT with photon RT for these two clinical scenarios. Finally, we discuss new insights that may further develop clinical research on PT for HNC. [ABSTRACT FROM AUTHOR]

Simple Summary: Juvenile nasopharyngeal angiofibroma (JNA) presents a therapeutic challenge in its advanced stages due to the close proximity to critical structures at the skull base. While radiotherapy is an effective treatment alternative, radiation-induced complications due to dose deposition in healthy tissue remain a major concern. Particle radiotherapy offers a high degree of conformality, and notably, helium ions present a promising treatment option due to their favorable biophysical characteristics between protons and carbon ions, supporting their reconsideration for clinical application. We retrospectively designed helium ion therapy (HRT) plans for all patients previously treated with proton therapy (PRT) at the Heidelberg Ion-Beam Therapy Center. Our findings indicate potential dosimetric advantages of HRT over PRT for advanced JNA, suggesting enhanced target coverage along with reduced dose deposition in healthy tissue, thereby potentially mitigating acute and late-term complications, including secondary neoplasms. This is particularly important given the benign nature of JNA and the patients' young age. Helium ion therapy (HRT) is a promising modality for the treatment of pediatric tumors and those located close to critical structures due to the favorable biophysical properties of helium ions. This in silico study aimed to explore the potential benefits of HRT in advanced juvenile nasopharyngeal angiofibroma (JNA) compared to proton therapy (PRT). We assessed 11 consecutive patients previously treated with PRT for JNA in a definitive or postoperative setting with a relative biological effectiveness (RBE) weighted dose of 45 Gy (RBE) in 25 fractions at the Heidelberg Ion-Beam Therapy Center. HRT plans were designed retrospectively for dosimetric comparisons and risk assessments of radiation-induced complications. HRT led to enhanced target coverage in all patients, along with sparing of critical organs at risk, including a reduction in the brain integral dose by approximately 27%. In terms of estimated risks of radiation-induced complications, HRT led to a reduction in ocular toxicity, cataract development, xerostomia, tinnitus, alopecia and delayed recall. Similarly, HRT led to reduced estimated risks of radiation-induced secondary neoplasms, with a mean excess absolute risk reduction of approximately 30% for secondary CNS malignancies. HRT is a promising modality for advanced JNA, with the potential for enhanced sparing of healthy tissue and thus reduced radiation-induced acute and long-term complications. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy affects salivary glands more intensely than it does other organs, and salivary gland dysfunction can continue during or after treatment. The aim of this study was to examine structural alterations in submandibular glands through ultrasonography following head-neck radiotherapy in patients and to evaluate the impact of radiation dose on these modifications. Methods: Forty-six submandibular glands were assessed ultrasonographically for the changes in echogenicity, echotexture, and margin and the influence of the radiation dose on these changes before radiotherapy at 3 time points: the second and sixth months following starting treatment. Statistical analysis of the data was performed using a chi-square test. Results: Significant relationship in 3 ultrasonographic structural chara cteri stics --echo genic ity, echotexture, and margin-- of submandibular glands (P < .001, P < .001, and P < .001, respectively) were observed before and at the second and sixth months after radiotherapy. There was found a significant correlation between the radiation dose groups in the change of echotexture at 2 different time periods after radiotherapy (P < .001, P < .05, respectively) and in the change of margin at the second month after radiotherapy onset (P < .05). Conclusion: Preceding radiotherapy, submandibular glands typically exhibited hyperechoic echogenicity, homogeneous ecotextures, and regular margins. However, after radiotherapy, there was an observable transformation characterized by isoechoic/hypoechoic features, heterogeneous textures, and irregular margins. With the passage of time following radiotherapy, there was a tendency for the parenchyma structure to gradually revert to a normal state. Also, the radiation dose generally has an effect on the structural changes of the submandibular glands. [ABSTRACT FROM AUTHOR]

Purpose: The aims of the study were to monitor circulating lymphocyte subset counts before and after therapy for nasopharyngeal carcinoma (NPC), and investigate their relationships with patient outcomes. Patients and Methods: Subjects comprised patients with TNM stage I–IVA NPC who underwent radiotherapy. Peripheral venous blood samples were collected before and after treatment. Lymphocyte subset counts were analyzed by flow cytometry. Differences between post-treatment and baseline counts were calculated to determine Δ values. Patients were divided into high and low groups, based on median lymphocyte subset counts; propensity score matching was applied to balance groups. Progression-free survival (PFS) and overall survival (OS) were plotted using Kaplan-Meier curves and compared using a Log rank test. Relationships between lymphocyte subset counts and patient survival were subjected to Cox regression analysis. Results: Patients with NPC (n=746) were enrolled from 2012– 2022. Higher CD8+ and total T cell baseline counts were associated with better 5-year PFS (73.7% vs 63.1%, P=0.002 and 73.8% vs 64.1%, P=0.005, respectively). Similarly, higher Δ values of CD4+ and total T cells were associated with higher 5-year PFS (76.2% vs 63.5%, P=0.001; 74.3% vs 65.4%, P=0.010) and OS (89.8% vs 81.6%, P=0.005; 88.6% vs 82.5%, P=0.009). Multivariate Cox regression revealed that CD8+ (hazard ratio (HR) 0.651, P=0.002) and total T (HR 0.600, P< 0.001) cells were significantly associated with PFS. CD4+ (HR 0.708, P=0.038) and total T (HR 0.639, P=0.031) cells were independent prognostic factors for OS. Conclusion: NPC patients with low total or CD8+ T cell counts before treatment had worse prognosis; however, those with more significant decreases in total or CD4+ T cells possibly had better outcomes. T cell counts can be reliable indicators to predict prognosis. [ABSTRACT FROM AUTHOR]

Background: Lymph node characteristics markedly affect nasopharyngeal carcinoma (NPC) prognosis. Matted node (MN), an important characteristic for lymph node, lacks explored MRI‐based prognostic implications. Purpose: Investigate MRI‐determined MNs' prognostic value in NPC, including 5‐year overall survival (OS), distant metastasis‐free survival (DMFS), local recurrence‐free survival (LRFS), progression‐free survival (PFS), and its role in induction chemotherapy (IC). Study Type: Retrospective cohort survival study. Population: Seven hundred ninety‐two patients with non‐metastatic NPC (female: 27.3%, >45‐year old: 50.1%) confirmed by biopsy. Field Strength/Sequence: 5‐T/3.0‐T, T1‐, T2‐ and post‐contrast T1‐weighted fast spin echo sequences acquired. Assessment: MNs were defined as ≥3 nodes abutting with intervening fat plane replaced by extracapsular nodal spread (ENS). Patients were observed every 3 months for 2 years and every 6 months for 5 years using MRI. Follow‐up extended from treatment initiation to death or final follow‐up. MNs were evaluated by three radiologists with inter‐reader reliability calculated. A 1:1 matched‐pair method compared survival differences between MN‐positive patients with or without IC. Primary endpoints (OS, DMFS, LRFS, PFS) were calculated from therapy initiation to respective event. Statistical Tests: Kappa values assessed inter‐reader reliability. Correlation between MN, ENS, and LNN was studied through Spearman's correlation coefficient. Clinical characteristics were calculated via Fisher's exact, Chi‐squared, and Student's t‐test. Kaplan–Meier curves and log‐rank tests analyzed all time‐to‐event data. Confounding factors were included in Multivariable Cox proportional hazard models to identify independent prognostic factors. P‐values <0.05 were considered statistically significant. Results: MNs incidence was 24.6%. MNs independently associated with decreased 5‐year OS, DMFS, and PFS; not LRFS (P = 0.252). MN‐positive patients gained significant survival benefit from IC in 5‐year OS (88.4% vs. 66.0%) and PFS (76.4% vs. 53.5%), but not DMFS (83.1% vs. 69.9%, P = 0.145) or LRFS (89.9% vs. 77.8%, P = 0.140). Data Conclusion: MNs may independently stratify NPC risk and offer survival benefit from IC. Evidence Level: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Objective To study EBV infection in nasopharyngeal carcinoma screening population in Guangzhou and analyze the influencing factors. Methods The data of individuals (aged 20 years and above) having EBV antibody of VCA-IgA and NA1-IgA test in Guangzhou Cadre and Talent Health Management Center were collected. Current status of EBV infection was studied and its influencing factors were analyzed by logistic regression analysis. Results A total of 55 311 subjects were screened, including 35 429 males (64.05%) and 19,882 females (35.95%).The overall EBV infection rate was 8.00%. There was no significant differences in the infection rate between different sex groups (P > 0.05). The infection rate of EBV increased with age, with infection rate of 7.07% in individuals aged 20 ~ 39 years, 7.86% in those aged 40 ~ 59 years, 10.11 % in those of 60 ~ 79 years old, and 10.99% in those aged 5 80 years, showing statistical significance (χ² = 85.487, P < 0.01). Logistic regression analysis showed that EBV infection risk increased significantly with advancing age. The odds of EBV infection in individuals aged 40 ~ 59 years were 10.6% higher compared to those aged 20 ~ 39 years (OR = 1.106, 95% CI: 1.028 ~ 1.190). The odds of EBV infection in individuals aged 60 ~ 79 years were 42.2% higher compared to those aged 20 ~ 39 years (OR = 1.422, 95% CI: 1.288 ~ 1.569). Furthermore, the odds of EBV infection in individuals aged 5 80 years were 53.1% higher compared to those aged 20 ~ 39 years (OR = 1.531, 95% CI: 1.230 ~ 1.906). A prior diagnosis of hypertension significantly increased the odds of EBV infection (OR = 1.105, 95% C7: 1.003 ~ 1.218). However, diabetes history exerted no influence on the outcome of EBV infection (P > 0.05). Conclusions The overall infection rate of EBV in Guangzhou is 8.00%. Advanced age and hypertension history are the risk factors of EBV. The screening and prevention and control of EBV susceptible people should be strengthened. [ABSTRACT FROM AUTHOR]

Background: Locoregionally advanced nasopharyngeal carcinoma (NPC) is an epithelial malignancy that primarily occurs in East and Southeast Asia, and it is associated with relatively poor overall survival (OS). Currently, there is no reliably effective standard treatment for NPC that progresses after first-line therapy with platinum-based chemotherapy. Case report: A 55-year-old woman diagnosed with stage IVa NPC received two cycles of platinum-based chemotherapy but encountered an increase in the size of cervical lymph nodes and suffered from adverse events. The patient was then switched to toripalimab plus cetuximab combined with radical radiotherapy and had a complete clinical response within 2 months following the completion of radiotherapy without severe treatment-related adverse events. Conclusion: This case report showed that toripalimab plus cetuximab combined with radiotherapy for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma may result in a fast and durable response with a manageable safety profile. [ABSTRACT FROM AUTHOR]

Immunotherapy, particularly immune checkpoint inhibitors (ICIs), such as anti-programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) therapy, has emerged as a pivotal treatment modality for solid tumors, including recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). Despite the advancements in the utilization of ICIs, there is still room for further improving patient outcomes. Another promising approach to immunotherapy for R/M-NPC involves adoptive cell therapy (ACT), which aims to stimulate systemic anti-tumor immunity. However, individual agent therapies targeting dendritic cells (DCs) appear to still be in the clinical trial phase. This current review underscores the potential of immunotherapy as a valuable adjunct to the treatment paradigm for R/M-NPC patients. Further research is warranted to enhance the efficacy of immunotherapy through the implementation of strategies such as combination therapies and overcoming immune suppression. Additionally, the development of a biomarker-based scoring system is essential for identifying suitable candidates for precision immunotherapy. [ABSTRACT FROM AUTHOR]

Objective: This study aims to develop a nomogram integrating inflammation (NLR), Prognostic Nutritional Index (PNI), and EBV DNA (tumor burden) to achieve personalized treatment and prediction for stage IVA NPC. Furthermore, it endeavors to pinpoint specific subgroups that may derive significant benefits from S-1 adjuvant chemotherapy. Methods: A total of 834 patients diagnosed with stage IVA NPC were enrolled in this study and randomly allocated into training and validation cohorts. Multivariate Cox analyses were conducted to identify independent prognostic factors for constructing the nomogram. The predictive and clinical utility of the nomogram was assessed through measures including the AUC, calibration curve, DCA, and C-indexes. IPTW was employed to balance baseline characteristics across the population. Kaplan-Meier analysis and log-rank tests were utilized to evaluate the prognostic value. Results: In our study, we examined the clinical features of 557 individuals from the training cohort and 277 from the validation cohort. The median follow-up period was 50.1 and 49.7 months, respectively. For the overall cohort, the median follow-up duration was 53.8 months. The training and validation sets showed 3-year OS rates of 87.7% and 82.5%, respectively. Meanwhile, the 3-year DMFS rates were 95.9% and 84.3%, respectively. We created a nomogram that combined PNI, NRI, and EBV DNA, resulting in high prediction accuracy. Risk stratification demonstrated substantial variations in DMFS and OS between the high and low risk groups. Patients in the high-risk group benefited significantly from the IC + CCRT + S-1 treatment. In contrast, IC + CCRT demonstrated non-inferior 3-year DMFS and OS compared to IC + CCRT + S-1 in the low-risk population, indicating the possibility of reducing treatment intensity. Conclusions: In conclusion, our nomogram integrating NLR, PNI, and EBV DNA offers precise prognostication for stage IVA NPC. S-1 adjuvant chemotherapy provides notable benefits for high-risk patients, while treatment intensity reduction may be feasible for low-risk individuals. [ABSTRACT FROM AUTHOR]

Objective: Over the past decade, heat shock protein 90 (HSP90) inhibitors have emerged as promising anticancer drugs in solid and hematological malignancies. Flavokawain C (FKC) is a naturally occurring chalcone that has been found to exert considerable anti-tumor efficacy by targeting multiple molecular pathways. However, the efficacy of FKC has not been studied in nasopharyngeal carcinoma (NPC). Metabolic abnormalities and uncontrolled angiogenesis are two important features of malignant tumors, and the occurrence of these two events may involve the regulation of HSP90B1. Therefore, this study aimed to explore the effects of FKC on NPC proliferation, glycolysis, and angiogenesis by regulating HSP90B1 and the underlying molecular regulatory mechanisms. Methods: HSP90B1 expression was analyzed in NPC tissues and its relationship with patient's prognosis was further identified. Afterward, the effects of HSP90B1 on proliferation, apoptosis, glycolysis, and angiogenesis in NPC were studied by loss-of-function assays. Next, the interaction of FKC, HSP90B1, and epidermal growth factor receptor (EGFR) was evaluated. Then, in vitro experiments were designed to analyze the effect of FKC treatment on NPC cells. Finally, in vivo experiments were allowed to investigate whether FKC treatment regulates proliferation, glycolysis, and angiogenesis of NPC cells by HSP90B1/EGFR pathway. Results: HSP90B1 was highly expressed in NPC tissues and was identified as a poor prognostic factor in NPC. At the same time, knockdown of HSP90B1 can inhibit the proliferation of NPC cells, trigger apoptosis, and reduce glycolysis and angiogenesis. Mechanistically, FKC affects downstream EGFR phosphorylation by regulating HSP90B1, thereby regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. FKC treatment inhibited the proliferation, glycolysis, and angiogenesis of NPC cells, which was reversed by introducing overexpression of HSP90B1. In addition, FKC can affect NPC tumor growth and metastasis in vivo by regulating the HSP90B1/EGFR pathway. Conclusion: Collectively, FKC inhibits glucose metabolism and tumor angiogenesis in NPC by targeting the HSP90B1/EGFR/PI3K/Akt/mTOR signaling axis. [ABSTRACT FROM AUTHOR]

Objectives: The association of migraine with the risk of certain cancer has been reported. The aim of this pilot study was to examine the associations between migraine and the onset of head and neck cancers (HNC). Materials and Methods: A total of 1755 individuals were identified through a nationwide population‐based cohort registry in Taiwan between 2000 and 2013. The primary end point variable was new‐onset head and neck cancers in patients with migraine versus non‐migraine controls. Cox proportional hazard regression was used to derive the risk of HNC. Subgroup analyses were performed to determine subpopulations at risk of migraine‐associated HNC. Sub‐outcome analyses were carried out to provide the subtypes of migraine‐associated HNC. Propensity score matching was utilized to validate the findings. Results: A total of four patients out of 351 patients with migraine and seven out of 1404 non‐migraine controls developed HNC. The incidence of HNC was higher in patients with migraine than that in non‐migraine controls (108.93 vs. 48.77 per 100,000 person‐years) (adjusted hazard ratio, aHR = 2.908, 95% CI = 0.808–10.469; p = 0.102). The risk of HNC in patients with migraine with aura (aHR = 5.454, 95% CI = 0.948–26.875; p = 0.264) and without aura (aHR = 2.777, 95% CI = 0.755–8.473; p = 0.118) was revealed. The incidence of non‐nasopharyngeal HNC secondary to migraine (112.79 per 100,000 person‐years) was higher than that of nasopharyngeal cancer secondary to migraine (105.33 per 100,000 person‐years). Conclusion: A higher incidence of HNC was observed in a small sample of patients with migraine, especially in those with migraine with aura. Migraine‐associated HNC included non‐nasopharyngeal HNC. Studies with a larger sample are needed to confirm the finding of the high risk of HNC in people with migraine. [ABSTRACT FROM AUTHOR]

Background: A high incidence rate of nasopharyngeal carcinoma (NPC) has been observed in Southeast Asia compared to other parts of the world. Radiomics is a computational tool to predict outcomes and may be used as a prognostic biomarker for advanced NPC treated with concurrent chemoradiotherapy. Recently, radiomic analysis of the peripheral tumor microenvironment (TME), which is the region surrounding the gross tumor volume (GTV), has shown prognostic usefulness. In this study, not only was gross tumor volume (GTVt) analyzed but also tumor peripheral regions (GTVp) were explored in terms of the TME concept. Both radiomic features and delta radiomic features were analyzed using CT images acquired in a routine radiotherapy process. Methods: A total of 50 patients with NPC stages III, IVA, and IVB were enrolled between September 2004 and February 2014. Survival models were built using Cox regression with clinical factors (i.e., gender, age, overall stage, T stage, N stage, and treatment dose) and radiomic features. Radiomic features were extracted from GTVt and GTVp. GTVp was created surrounding GTVt for TME consideration. Furthermore, delta radiomics, which is the longitudinal change in quantitative radiomic features, was utilized for analysis. Finally, C-index values were computed using leave-one-out cross-validation (LOOCV) to evaluate the performances of all prognosis models. Results: Models were built for three different clinical outcomes, including overall survival (OS), local recurrence-free survival (LRFS), and progression-free survival (PFS). The range of the C-index in clinical factor models was (0.622, 0.729). All radiomics models, including delta radiomics models, were in the range of (0.718, 0.872). Among delta radiomics models, GTVt and GTVp were in the range of (0.833, 0.872) and (0.799, 0.834), respectively. Conclusions: Radiomic analysis on the proximal region surrounding the gross tumor volume of advanced NPC patients for survival outcome evaluation was investigated, and preliminary positive results were obtained. Radiomic models and delta radiomic models demonstrated performance that was either superior to or comparable with that of conventional clinical models. [ABSTRACT FROM AUTHOR]

A 63-year-old man with diabetes presented with unilateral ptosis and an exotropia. A diagnosis of isolated diabetic III nerve palsy was made. Subsequent neuro-ophthalmologic evaluation showed multiple cranial nerves involvement consistent with a diagnosis of orbital apex syndrome. Review of past medical history was significant for a previous nasopharyngeal carcinoma, and biopsy of the involved site was consistent with tumor recurrence. This case highlights the importance of correct medical history taking and anatomo-clinical correlation in neuro-ophthalmology. [ABSTRACT FROM AUTHOR]

Background: Anterior endoscopic access to middle cranial base lesions becomes feasible in the presence of infratemporal fossa (ITF) involvement. Various approaches, including endoscopic endonasal, transoral sublabial, and transorbital methods, have been described for accessing the ITF through a transmaxillary corridor. Among these approaches, endonasal access is the most commonly preferred, while the transorbital approach is a novel technique gaining popularity. The transoral sublabial approach is considered suitable for selected lesions. Methods: Patients who underwent the anterior endoscopic transoral/sublabial transmaxillary approach to middle cranial base lesions at a single institute from 2016 to 2023 were included in this retrospective study. Malignant lesions were excluded from the study. The sublabial approach was exclusively performed in all cases, with the exception of one patient who required a combined approach. Results: The anterior endoscopic transoral sublabial transmaxillary approach to the infratemporal fossa, upper parapharyngeal space, and middle cranial fossa was performed on 14 patients. The underlying conditions for these patients were as follows: trigeminal schwannomas (n = 8), meningiomas (n = 2), juvenile nasopharyngeal angiofibroma, osteochondroma, arachnoid cyst and encephalocele (n = 1 each). Gross total resection was achieved in 11 cases. The most common complication was numbness in the territory of the maxillary and mandibular nerves (n = 4). Two patients needed endoscopic maxillary antrostomy for persistent suppuration. No wound problems or CSF rhinorrhea occurred. The average follow‐up time was 26.6 months. Conclusion: The endoscopic sublabial transmaxillary approach provides direct access to the infratemporal fossa and middle cranial base, enhancing the surgical range of maneuverability while sparing the sinonasal cavity. This procedure is safe, less invasive, and could be used as an efficient corridor for the resection of selected infratemporal fossa lesions with or without extension to the middle cranial base and parapharyngeal space. [ABSTRACT FROM AUTHOR]

Background: The effect of radiotherapy waiting time after last induction chemotherapy (IC‐RT) on prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC) needs further discussion. Methods: Three hundred and six patients with LANPC diagnosed pathologically by induction chemotherapy (IC) and radiotherapy (RT) from 2013 to 2018 were selected for this study. Results: The IC‐RT was a risk factor for the post‐treatment progression of LANPC (OR = 1.017 95%CI: 1.003–1.031), For patients with LANPC, the IC‐RT > 40 days significantly reduced 5‐year PFS (70% vs. 55%; p = 0.0012), 5‐year OS (84% vs. 73%; p = 0.028), 5‐year DMFS (80% vs. 66%; p = 0.003), 5‐year LRFS (77% vs. 67%; p = 0.012). Indicating that patients with stage IVa who IC‐RT > 40 days were found to be a significant predictor of aggravated PFS (HR = 2.69; 95%CI: 1.57–4.6), OS (HR = 2.55; 95%CI: 1.29–5.03), DMFS (HR = 3.07; 95%CI: 1.64–5.76) and LRFS (HR = 2.26; 95%CI: 1.21–4.21). Conclusion: The prognosis of patients will be adversely affected if the IC‐RT exceeds 40 days, especially for stage IVa patients. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming induced by Epstein‐Barr virus (EBV) often mirrors metabolic changes observed in cancer cells. Accumulating evidence suggests that lytic reactivation is crucial in EBV‐associated oncogenesis. The aim of this study was to explore the role of metabolite changes in EBV‐associated malignancies and viral life cycle control. We first revealed that EBV (LMP1) accelerates the secretion of the oncometabolite D‐2HG, and serum D‐2HG level is a potential diagnostic biomarker for NPC. EBV (LMP1)‐driven metabolite changes disrupts the homeostasis of global DNA methylation and demethylation, which have a significantly inhibitory effect on active DNA demethylation and 5hmC content. We found that loss of 5hmC indicates a poor prognosis for NPC patients, and that 5hmC modification is a restriction factor of EBV reactivation. We confirmed a novel EBV reactivation inhibitor, α‐KG, which inhibits the expression of EBV lytic genes with CpG‐containing ZREs and the latent‐lytic switch by enhancing 5hmC modification. Our results demonstrate a novel mechanism of which metabolite abnormality driven by EBV controls the viral lytic reactivation through epigenetic modification. This study presents a potential strategy for blocking EBV reactivation, and provides potential targets for the diagnosis and therapy of NPC. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy stands to be one of the primary approaches in the clinical treatment of malignant tumors. Nasopharyngeal Carcinoma, a malignancy predominantly treated with radiation therapy, provides an invaluable model for investigating the mechanisms underlying radiation therapy resistance in cancer. While some reports have suggested the involvement of circRNAs in modulating resistance to radiation therapy, the underpinning mechanisms remain unclear. Methods: RT-qPCR and in situ hybridization were used to detect the expression level of circCDYL2 in nasopharyngeal carcinoma tissue samples. The effect of circCDYL2 on radiotherapy resistance in nasopharyngeal carcinoma was demonstrated by in vitro and in vivo functional experiments. The HR-GFP reporter assay determined that circCDYL2 affected homologous recombination repair. RNA pull down, RIP, western blotting, IF, and polysome profiling assays were used to verify that circCDYL2 promoted the translation of RAD51 by binding to EIF3D protein. Results: We have identified circCDYL2 as highly expressed in nasopharyngeal carcinoma tissues, and it was closely associated with poor prognosis. In vitro and in vivo experiments demonstrate that circCDYL2 plays a pivotal role in promoting radiotherapy resistance in nasopharyngeal carcinoma. Our investigation unveils a specific mechanism by which circCDYL2, acting as a scaffold molecule, recruits eukaryotic translation initiation factor 3 subunit D protein (EIF3D) to the 5′-UTR of RAD51 mRNA, a crucial component of the DNA damage repair pathway to facilitate the initiation of RAD51 translation and enhance homologous recombination repair capability, and ultimately leads to radiotherapy resistance in nasopharyngeal carcinoma. Conclusions: These findings establish a novel role of the circCDYL2/EIF3D/RAD51 axis in nasopharyngeal carcinoma radiotherapy resistance. Our work not only sheds light on the underlying molecular mechanism but also highlights the potential of circCDYL2 as a therapeutic sensitization target and a promising prognostic molecular marker for nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Background: [18 F]-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has the ability to detect local and/or regional recurrence as well as distant metastasis. We aimed to evaluate the prognosis value of PET/CT in locoregional recurrent nasopharyngeal (lrNPC). Methods: A total of 451 eligible patients diagnosed with recurrent I-IVA (rI-IVA) NPC between April 2009 and December 2015 were retrospectively included in this study. The differences in overall survival (OS) of lrNPC patients with and without PET/CT were compared in the I-II, III-IVA, r0-II, and rIII-IVA cohorts, which were grouped by initial staging and recurrent staging (according to MRI). Results: In the III-IVA and rIII-IVA NPC patients, with PET/CT exhibited significantly higher OS rates in the univariate analysis (P = 0.045; P = 0.009; respectively). Multivariate analysis revealed that with PET/CT was an independent predictor of OS in the rIII-IVA cohort (hazard ratio [HR] = 0.476; 95% confidence interval [CI]: 0.267 to 0.847; P = 0.012). In the rIII-IVA NPC, patients receiving PET/CT sacns before salvage surgery had a better prognosis compared with MRI alone (P = 0.036). The recurrent stage (based on PET/CT) was an independent predictor of OS. (r0-II versus [vs]. rIII-IVA; HR = 0.376; 95% CI: 0.150 to 0.938; P = 0.036). Conclusion: The present study showed that with PET/CT could improve overall survival for rIII-IVA NPC patients. PET/CT appears to be an effective method for assessing rTNM staging. [ABSTRACT FROM AUTHOR]

Adoptive transfer of T cell receptor-engineered T cells (TCR-T) is a promising strategy for immunotherapy against solid tumors. However, the potential of CD4+ T cells in mediating tumor regression has been neglected. Nasopharyngeal cancer is consistently associated with EBV. Here, to evaluate the therapeutic potential of CD4 TCR-T in nasopharyngeal cancer, we screened for CD4 TCRs recognizing EBV nuclear antigen 1 (EBNA1) presented by HLA-DP5. Using mass spectrometry, we identified EBNA1567-581, a peptide naturally processed and presented by HLA-DP5. We isolated TCR135, a CD4 TCR with high functional avidity, that can function in both CD4+ and CD8+ T cells and recognizes HLA-DP5-restricted EBNA1567-581. TCR135- transduced T cells functioned in two ways: directly killing HLA-DP5+EBNA1+ tumor cells after recognizing EBNA1 presented by tumor cells and indirectly killing HLA-DP5-negative tumor cells after recognizing EBNA1 presented by antigen-presenting cells. TCR135-transduced T cells preferentially infiltrated into the tumor microenvironment and significantly inhibited tumor growth in xenograft nasopharyngeal tumor models. Additionally, we found that 62% of nasopharyngeal cancer patients showed 50%-100% expression of HLA-DP on tumor cells, indicating that nasopharyngeal cancer is well suited for CD4 TCR-T therapy. These findings suggest that TCR135 may provide a new strategy for EBV-related nasopharyngeal cancer immunotherapy in HLA-DP5+ patients. [ABSTRACT FROM AUTHOR]

The article provides information on Toripalimab-tpzi, a programmed death receptor-1 (PD-1)-blocking antibody, an antineoplastic agent. Toripalimab-tpzi is used in combination with cisplatin and gemcitabine for first-lien treatment of adults with metastatic or recurrent locally advanced nasopharyngeal carcinoma (NPC). Also mentioned are its dosage and administration, drug interactions, and advice to patients.

Objective: Circular RNAs (circRNAs), pivotal in the pathogenesis and progression of nasopharyngeal carcinoma (NPC), remain a significant point of investigation for potential therapeutic interventions. Our research was driven by the objective to decipher the roles and underlying mechanisms of hsa_circ_0044569 (circCOL1A1) in governing the malignant phenotypes and the Warburg effect in NPC. Methods: We systematically collected samples from NPC tissues and normal nasopharyngeal epithelial counterparts. The expression levels of circCOL1A1, microRNA-370-5p (miR-370-5p), and prothymosin alpha (PTMA) were quantitatively determined using quantitative polymerase chain reaction (qPCR) and Western blotting. Transfections in NPC cell lines were conducted using small interfering RNAs (siRNAs) or vectors carrying the pcDNA 3.1 construct for overexpression studies. We interrogated the circCOL1A1/miR-370-5p/PTMA axis's role in cellular functions through a series of assays: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide for cell viability, colony formation for growth, Transwell assays for migration and invasion, and Western blotting for protein expression profiling. To elucidate the molecular interactions, we employed luciferase reporter assays and RNA immunoprecipitation techniques. Results: Our investigations revealed that circCOL1A1 was a stable circRNA, highly expressed in both NPC tissues and derived cell lines. A correlation analysis with clinical pathological features demonstrated a significant association between circCOL1A1 expression, lymph node metastasis, and the tumor node metastasis staging system of NPC. Functionally, silencing circCOL1A1 led to substantial suppression of cell proliferation, migration, invasion, and metabolic alterations characteristic of the Warburg effect in NPC cells. At the molecular level, circCOL1A1 appeared to modulate PTMA expression by acting as a competitive endogenous RNA or 'sponge' for miR-370-5p, which in turn promoted the malignant characteristics of NPC cells. Conclusion: To conclude, our findings delineate that circCOL1A1 exerts its oncogenic influence in NPC through the modulation of the miR-370-5p/PTMA signaling axis. [ABSTRACT FROM AUTHOR]

Background: Dysregulation of iron metabolism has been shown to have significant implications for cancer development. We aimed to investigate the prognostic and immunological significance of iron metabolism-related genes (IMRGs) in nasopharyngeal carcinoma (NPC). Methods: Multiple Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were analyzed to identify key IMRGs associated with prognosis. Additionally, the immunological significance of IMRGs was explored. Results: A novel risk model was established using the LASSO regression algorithm, incorporating three genes (TFRC, SLC39A14, and ATP6V0D1).This model categorized patients into low and high-risk groups, and Kaplan–Meier analysis revealed significantly shorter progression-free survival for the high-risk group (P < 0.0001). The prognostic model's accuracy was additionally confirmed by employing time-dependent Receiver Operating Characteristic (ROC) curves and conducting Decision Curve Analysis (DCA). High-risk patients were found to correlate with advanced clinical stages, specific tumor microenvironment subtypes, and distinct morphologies. ESTIMATE analysis demonstrated a significant inverse relationship between increased immune, stromal, and ESTIMATE scores and lowered risk score. Immune analysis indicated a negative correlation between high-risk score and the abundance of most tumor-infiltrating immune cells, including dendritic cells, CD8+ T cells, CD4+ T cells, and B cells. This correlation extended to immune checkpoint genes such as PDCD1, CTLA4, TIGIT, LAG3, and BTLA. The protein expression patterns of selected genes in clinical NPC samples were validated through immunohistochemistry. Conclusion: This study presents a prognostic model utilizing IMRGs in NPC, which could assist in assessing patient prognosis and provide insights into new therapeutic targets for NPC. [ABSTRACT FROM AUTHOR]

Cranial chordoma is a rare neoplasm that is challenging to both diagnose and manage. We present our experience in treating a case of clival chordoma mimicking a nasopharyngeal mass without any signs of cranial deficits or intracranial insult. Management was comprised of endoscopic transnasal debulking surgery followed by radiotherapy. However, we failed to achieve an oncologic outcome due to the development of lethal central nervous system and respiratory infections 1 month after the surgery. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the predictive significance of hemoglobin (Hb) values in the incidence of radiation‐induced trismus (RIT) in locally advanced nasopharyngeal carcinoma (LA‐NPC) patients who received concurrent chemoradiotherapy (C‐CRT). Methods: Data of LA‐NPC patients were examined before and after C‐CRT and to confirm the presence of RIT, maximum mouth openings (MMO) were measured; RIT is defined as an MMO of ≤35 mm. All Hb values were derived from complete blood count tests obtained on the first day of C‐CRT. The receiver operating characteristic (ROC) curve analysis was used to scrutinize a possible connection between pre‐treatment Hb values and RIT status. Results: Two hundred and twenty three patients were included in the study and RIT was diagnosed in 46 (20.6%) patients. The Hb cutoff in ROC curve analysis that separated the patients into two groups was 12.05 g/dL [Area under the curve (AUC): 82.7%; sensitivity: 72.9%; and specificity: 71.3%]. RIT was significantly more prevalent in the Hb ≤ 12 g/dL group than in its counterpart (41.9% vs. 7.3%; p < 0.001). In multivariate analysis, Hb ≤ 12, anemia, pre‐C‐CRT MMO < 41.4 mm, and masticatory apparatus doseV58 Gy < 32% groups were found to be independently associated with significantly increased rates of RIT. Conclusion: Low pre‐C‐CRT Hb and anemia status are novel biological markers that independently predict higher RIT rates in LA‐NPC undergoing C‐CRT. [ABSTRACT FROM AUTHOR]

Simple Summary: Nasopharyngeal carcinoma (NPC) is an epithelial cancer associated with Epstein–Barr virus (EBV) infection. EBV infection contributes to not only the tumorigenesis of NPC but also the formation of a complicated tumor immune microenvironment (TIME) in NPC. Natural killer (NK) cells are lymphoid members of the innate immune system exhibiting both anti-tumor and anti-virus abilities. The cytokine and cellular interaction features of NK cells are distinct from those of CD8+ cytotoxic T cells. This unique characteristic has not been fully described in EBV+ NPC. This review provides an overview of the complicated crosstalk between NK cells and the TIME of EBV+ NPC and potential therapeutic strategies. A new perspective is proposed to direct future exploration. Endemic nasopharyngeal carcinoma (NPC) is closely associated with the Epstein–Barr virus (EBV), which contributes to tumor development and influences the tumor immune microenvironment (TIME) in NPC. Natural killer (NK) cells, as part of the innate immune system, play a crucial role in responding to viral infections and malignant cell transformations. Notably, NK cells possess a unique ability to target tumor cells independent of major histocompatibility complex class I (MHC I) expression. This means that MHC I-deficient tumor cells, which can escape from effective T cell attack, are susceptible to NK-cell-mediated killing. The activation of NK cells is determined by the signals generated through inhibitory and activating receptors expressed on their surface. Understanding the role of NK cells in the complex TIME of EBV+ NPC is of utmost importance. In this review, we provide a comprehensive summary of the current understanding of NK cells in NPC, focusing on their subpopulations, interactions, and cytotoxicity within the TIME. Moreover, we discuss the potential translational therapeutic applications of NK cells in NPC. This review aims to enhance our knowledge of the role of NK cells in NPC and provide valuable insights for future investigations. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma is one of the most common malignant tumors in the head and neck region. The carcinogenesis is a complex process stimulated by many factors. Although the etiological factors and pathogenic mechanisms are not elucidated, the genetic susceptibility, environmental factors, and association with latent infection with Epstein–Barr Virus play an important role. The aim of this study was to present the main clinical and epidemiological data, as well as the morphological aspects and the immunohistochemical profile, of patients with nasopharyngeal carcinoma diagnosed in western Romania. The study was retrospective and included 36 nasopharyngeal carcinomas. The histopathological diagnosis was completed using immunohistochemical reactions for the following antibodies: p63, p53 and p16 protein, cytokeratins (CK) AE1/AE3, CK5, CK7, CK20 and 34βE12, epithelial membrane antigen (EMA), Epstein–Barr virus (EBV), leukocyte common antigen (LCA), CD20, CD4, CD8, CD68, CD117, and CD1a. The squamous malignant component of nasopharyngeal carcinoma presented with positivity for cytokeratins AE1/AE3, CK5, 34βE12, and p63. Undifferentiated nasopharyngeal carcinoma was positive for EMA in 67% of cases, and 28% of cases showed an immunoreaction for CD117 in the malignant epithelial component. Also, the p53 protein was positive in all the cases. One case of undifferentiated nasopharyngeal carcinoma was p16-positive, and two cases were positive for EBV. A peri- and intratumor cellular infiltrate rich in lymphocytes, with a predominance of CD20-positive B lymphocytes, interspersed with T lymphocytes, was observed. The T cells were CD4- and CD8-positive, predominantly intratumoral, and the CD4:CD8 ratio was 1:1 for 75% of the undifferentiated subtype and 89% for differentiated non-keratinized squamous cell carcinoma. All subtypes of nasopharyngeal carcinoma presented with an inflammatory infiltrate with numerous plasma cells, eosinophils, and dendritic cells, presenting as antigen CD1a- and CD68-positive, as well as in CD117-positive mast cells. [ABSTRACT FROM AUTHOR]

Objective: To determine the predictive value of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-eosinophil ratio (NER), lymphocyte-to-eosinophil ratio (LER), monocyte-to-eosinophil ratio (MER), systemic inflammatory response index (SIRI), and ratio of inflammatory cells before and after treatment for predicting survival in advanced nasopharyngeal carcinoma (NPC) and to provide a reference for treatment. Methods: A retrospective review of 70 patients was performed. Serological indexes were obtained by drawing blood before and after systemic therapy. The cutoff values of these indexes were determined by receiver operating characteristic (ROC) curves. The prognostic value of the indexes for overall survival (OS) and distant metastasis free survival (DMFS) was evaluated. Results: Survival analysis showed that a smaller pretreatment LMR value was associated with poor OS; larger pretreatment NER, LER, MER, and SIRI values were associated with poor OS; a smaller posttreatment LMR value was associated with poor OS; larger posttreatment NLR, NER, MER, and SIRI values were associated with poor OS; a smaller pretreatment LMR value was associated with poor DMFS; larger pretreatment NLR, NER, LER, and MER values were associated with poor DMFS; and larger posttreatment NLR, NER, LER, and MER values were associated with poor DMFS. Furthermore, a larger neutrophil after treatment-to-neutrophil before treatment ratio was associated with poor OS and DMFS. Logistic regression analysis showed that pretreatment MER and posttreatment NLR were independent predictors of OS in patients with advanced NPC; moreover, pretreatment and posttreatment MER and NLR were independent prognostic factors for DMFS in patients with advanced NPC. Conclusions: The NLR, NER and MER can be used to predict survival in advanced NPC patients. Eosinophils might be one of the factors for the good prognosis of NPC patients. In addition, an increased number of neutrophils after treatment may indicate a favorable prognosis. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the epidemiological, clinical, and therapeutic aspects and prognosis of juvenile nasopharyngeal carcinoma in Tunis country. Materials and Methods: This study included 68 patients, younger than 18 years of age. All the patients had a clinical and para-clinical tumoral assessment. The study of survival and prognostic factors was done after a descriptive analysis. These prognostic factors were studied through uni and multivariate analysis. Results: The median age was 14.7 years and the sex ratio was 2 male to 1 female. The average time to first consultation was 4 months. Rhinological signs were the most frequent symptom for consultation (n= 41). The T3-T4 tumors accounted for 78% of patients and there was a lymph node invasion stage N2-N3 in 63% of cases. Non-metastatic patients had radiotherapy associated with chemotherapy in 97% of cases. Metastatic patients received hypofractionated radiotherapy on bone metastasis, and first-line chemotherapy followed by radiotherapy on the primitive tumor and lymph node areas in case of good response to chemotherapy (n= 2). The mean follow-up was 94 months; 78% of these patients were alive and in complete remission, 19% were in therapeutic failure, and 16% of them had metachronous metastases. The five-year-overall survival was 95%. Hyposialia and skin dystrophy were the most frequent late complications. In univariate analyses, significant prognostic factors were cranial nerve invasion, intracranial invasion, and infra-temporal fossa invasion. In multivariate analysis, the most parsimonious model associated extension to the infratemporal fossa, endo-cranial extension, and initial therapeutic modality (treatment failures were less frequent with neoadjuvant chemotherapy (p= 0.22)). Conclusion: Treatment of nasopharyngeal carcinoma in children consists of chemotherapy and radiotherapy. Synchronous or metachronous metastases are common in this patient population. Modern radiotherapy techniques, including conformal radiotherapy with intensity modulation, are promising and could overcome toxicities in long-term survivors. [ABSTRACT FROM AUTHOR]

Objective: Early diagnosis and treatment of nasopharyngeal carcinoma (NPC) are vital for a better prognosis. Still, because of obscure anatomical sites and insidious symptoms, nearly 80% of patients with NPC are diagnosed at a late stage. This study aimed to validate a machine learning (ML) model utilizing symptom‐related diagnoses and procedures in medical records to predict nasopharyngeal carcinoma (NPC) occurrence and reduce the prediagnostic period. Materials and Methods: Data from a population‐based health insurance database (2001–2008) were analyzed, comparing adults with and without newly diagnosed NPC. Medical records from 90 to 360 days before diagnosis were examined. Five ML algorithms (Light Gradient Boosting Machine [LGB], eXtreme Gradient Boosting [XGB], Multivariate Adaptive Regression Splines [MARS], Random Forest [RF], and Logistics Regression [LG]) were evaluated for optimal early NPC detection. We further use a real‐world data of 1 million individuals randomly selected for testing the final model. Model performance was assessed using AUROC. Shapley values identified significant contributing variables. Results: LGB showed maximum predictive power using 14 features and 90 days before diagnosis. The LGB models achieved AUROC, specificity, and sensitivity were 0.83, 0.81, and 0.64 for the test dataset, respectively. The LGB‐driven NPC predictive tool effectively differentiated patients into high‐risk and low‐risk groups (hazard ratio: 5.85; 95% CI: 4.75–7.21). The model‐layering effect is valid. Conclusions: ML approaches using electronic medical records accurately predicted NPC occurrence. The risk prediction model serves as a low‐cost digital screening tool, offering rapid medical decision support to shorten prediagnostic periods. Timely referral is crucial for high‐risk patients identified by the model. [ABSTRACT FROM AUTHOR]

Background: Inflammatory markers, including the product of neutrophil count, platelet count, and monocyte count divided by lymphocyte count (PIV) and the platelet‐to‐white blood cell ratio (PWR), have not been previously reported as prognostic factors in nasopharyngeal carcinoma (NPC) patients. In order to predict overall survival (OS) in NPC patients, our goal was to create and internally evaluate a nomogram based on inflammatory markers (PIV, PWR). Methods: A retrospective study was done on patients who received an NPC diagnosis between January 2015 and December 2018. After identifying independent prognostic indicators linked to OS using Cox proportional hazards regression analysis, we created a nomogram with the factors we had chosen. Results: A total of 630 NPC patients in all were split into training (n = 441) and validation sets (n = 189) after being enrolled in a population‐based study in 2015–2018 and monitored for a median of 5.9 years. In the training set, the age, PIV, and PWR, selected as independent predictors for OS via multivariate Cox's regression model, were chosen to develop a nomogram. Both training and validation cohorts had C‐indices of 0.850 (95% confidence interval [CI]: 0.768–0.849) and 0.851 (95% CI: 0.765–0.877). Furthermore, compared with traditional TNM staging, our nomogram demonstrated greater accuracy in predicting patient outcomes. The risk stratification model derived from our prediction model may facilitate personalized treatment strategies for NPC patients. Conclusion: Our findings confirmed the prognostic significance of the PWR and PIV in NPC. High PIV levels (>363.47) and low PWR (≤36.42) values are associated with worse OS in NPC patients. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate 5-year outcomes and the late toxicity profile of chrono-chemotherapy with different infusion rates in patients with locally advanced nasopharyngeal carcinoma (NPC). Methods and materials: Our retrospective analysis included 70 patients with locally advanced NPC stages III and IVB (according to the 2010 American Joint Committee on Cancer staging system). Patients were treated with two cycles of induction chemotherapy (IC) before concurrent chemoradiotherapy (CCRT) at Guizhou Cancer Hospital. The IC with docetaxel, cisplatin (DDP) and fluorouracil regimen. Patients were divided into two groups during CCRT. Using a "MELODIE" multi-channel programmed pump, DDP (100 mg/m²) was administered for 12 hours from 10:00 am to 10:00 pm and repeated every 3 weeks for 2-3 cycles. DDP was administered at the peak period of 4:00 pm in the sinusoidal chronomodulated infusion group (Arm A, n=35). The patients in Arm B received a constant rate of infusion. Both arms received radiotherapy through the same technique and dose fraction. The long-term survival and disease progression were observed. Results: After a median follow-up of 82.8 months, the 5-year progression-free survival rate was 81.3% in Arm A and 79.6% in Arm B (P = 0.85). The 5-year overall survival rate was not significantly different between Arm A and Arm B (79.6% vs 85.3%, P = 0.79). The 5-year distant metastasis-free survival rate was 83.6% in Arm A and 84.6% in Arm B (P = 0.75). The 5-year local recurrence-free survival rate was 88.2% in Arm A and 85.3% in Arm B (P = 0.16). There were no late toxicities of grade 3-4 in either group. Both groups had grade 1-2 late toxicities. Dry mouth was the most common late toxic side effect, followed by hearing loss and difficulty in swallowing. There was no statistically significant difference between Arm A and Arm B in terms of side effects. Conclusion: Long-term analysis confirmed that in CCRT, cisplatin administration with sinusoidal chrono-modulated infusion was not superior to the constant infusion rate in terms of long-term toxicity and prognosis. [ABSTRACT FROM AUTHOR]

Background: Brain metastasis is rare in nasopharyngeal carcinoma (NPC), with only anecdotal cases reported. Conducting a systematic study is crucial for improving the management of these patients. Materials and Methods: Forty‐one patients with brain metastasis were retrospectively included between February 2000 and February 2023. The clinical characteristics and treatment information of patients were analyzed. Overall survival (OS) was estimated by Kaplan–Meier survival analysis, and Cox proportional hazard regression analysis was performed to explore prognostic factors. Results: The median OS for patients was 11.2 months, with a 3‐year OS rate of 16.3%. The number of extracranial metastatic organs (HR = 5.533, P = 0.041) and the response of extracranial tumors to treatment (HR = 0.079, P = 0.003) were independent prognostic factors in the cohort. Conclusions: Brain metastasis in NPC is a devastating condition that commonly occurs through hematogenous dissemination. Systemic therapy remains fundamental treatment, while local therapy for brain metastases may further improve survival in selected patients. [ABSTRACT FROM AUTHOR]

Objective: Juvenile Nasopharyngeal Angiofbroma (JNA) is a benign, yet locally aggressive tumor with a rich blood supply. Surgical management is the mainstay treatment for JNA, however, blood loss is a big concern during surgery. This retrospective study aims to evaluate the efcacy of ligating the feeding vessels of JNA based on preoperative imaging, potentially eliminating the need for preoperative embolization. Methods: We retrospectively analyzed the medical records of 380 patients who underwent surgery for JNA at our tertiary care, high volume center, without prior embolization. Preoperative scans were reviewed to identify the location of feeding vessels. Surgical techniques were adapted to ligate the major feeding vessel(s) identifed preoperatively. Intraoperative blood loss was meticulously recorded. Results: In the 380 patients, the mean blood loss increased with advancing disease stage. The average blood loss across all stages was 635.54 mL. This observed blood loss was signifcantly lower compared to data published by other studies that employed preoperative embolization for blood loss reduction. Conclusion: Preoperative evaluation of imaging for feeding vessel localization accurately correlated with intraoperative fndings. Ligation of identifed feeding vessels might eliminate the need for preoperative embolization in JNA surgery. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the nasopharyngeal epithelial cells. Common treatment methods for NPC include radiotherapy, chemotherapy, and surgical intervention. Despite these approaches, the prognosis for NPC remains poor due to treatment resistance and recurrence. Hence, there is a crucial need for more comprehensive research into the mechanisms underlying treatment resistance in NPC. Long non coding RNAs (LncRNAs) are elongated RNA molecules that do not encode proteins. They paly significant roles in various biological processes within tumors, such as chemotherapy resistance, radiation resistance, and tumor recurrence. Recent studies have increasingly unveiled the mechanisms through which LncRNAs contribute to treatment resistance in NPC. Consequently, LncRNAs hold promise as potential biomarkers and therapeutic targets for diagnosing NPC. This review provides an overview of the role of LncRNAs in NPC treatment resistance and explores their potential as therapeutic targets for managing NPC. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor that develops in the nasopharynx. It has a distinct ethnic and geographical distribution, and emerging evidence suggests that it is an ecological disease. Most patients respond well to radiation combined with chemotherapy as the primary treatment for NPC. However, some patients will eventually develop radio resistance and chemoresistance, resulting in recurrence and metastasis, which is a primary cause of poor prognosis. The processes underlying radio resistance and chemoresistance in NPC are complex and unknown. MicroRNAs (miRNAs) are endogenic non-coding RNA molecules. They play a role in a variety of cell functions as well as development of disease such as cancer. There has been considerable data demonstrating the existence of numerous aberrant miRNAs in cancer tissues, cells, and biofluids, which indicates the importance of studying the influence of miRNAs on NPC. Therefore, this review comprehensively analyzes the elaborate mechanisms of miRNAs affecting the radio resistance and chemoresistance of NPC. Multiple tumor-specific miRNAs can be employed as therapeutic and prognostic biological indicators. [ABSTRACT FROM AUTHOR]

Sequential immunotherapy has shown certain advantages in malignancy. Here, we aim to evaluate the efficacy of sequential anti-CTLA-4 and anti-PD-1 treatment for recurrent or metastatic nasopharyngeal carcinoma patients (R/M NPC). We retrospectively analysis 2 phase I trial of ipilimumab and camrelizumab in Chinese R/M NPC patients. These patients were initially treated with ipilimumab, a CTLA4 blockade, followed by anti-PD-1 treatment. We observed a durable tumor remission in these patients (mPFS: 12.3 months; mDoR: 20.9 months). Multimodal investigations of biopsy samples disclosed remodeling of tumor-immune microenvironment triggered by ipilimumab. In responders, we found increased tumoral PD-L1/PD-L2 expression and T-cell infiltration after ipilimumab treatment, accompanied by reduced stroma and malignant cell components. In contrast, non-responders exhibited increased B-cell infiltration and increased peripheral CD19 + B cells, suggesting a defective transition from memory B cells to plasma cells. This study proposes that sequential therapy can potentially enhance treatment efficacy in chemotherapy-resistant NPC patients and provides insights into how preexisting anti-CTLA4 blockade can influence subsequent anti-PD-1 efficacy by remodeling the TME. Additionally, our results highlight the need for therapeutic strategies targeting naïve/memory B cells. [ABSTRACT FROM AUTHOR]