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.

Homologous recombination deficiency (HRD) is associated with better prognosis and possibly causes a non-inflamed tumour microenvironment in nasopharyngeal carcinoma.

Homologous recombination deficiency (HRD) score is a reliable indicator of genomic instability. The significance of HRD in nasopharyngeal carcinoma (NPC), particularly its influence on prognosis and the immune microenvironment, has yet to be adequately explored. Understanding HRD status comprehensively can offer valuable insights for guiding precision treatment. We utilised three cohorts to investigate HRD status in NPC: the Zhujiang cohort from local collection and the Hong Kong (SRA288429) and Singapore (SRP035573) cohorts from public datasets. The GATK (genome analysis toolkit) best practice process was employed to investigate germline and somatic BRCA1/2 mutations and various bioinformatics tools and algorithms to examine the association between HRD status and clinical molecular characteristics. We found that individuals with a negative HRD status (no-HRD) exhibited a higher risk of recurrence [hazard ratio (HR), 1.43; 95% confidence interval (CI), 2.03-333.76; p = 0.012] in the Zhujiang cohort, whereas, in the Singapore cohort, they experienced a higher risk of mortality (HR, 26.04; 95% CI, 1.43-34.21; p = 0.016) compared with those in the HRD group. In vitro experiments demonstrated that NPC cells with BRCA1 knockdown exhibit heightened sensitivity to chemoradiotherapy. Furthermore, the HRD group showed significantly higher tumour mutational burden and tumour neoantigen burden levels than the no-HRD group. Immune infiltration analysis indicated that HRD tissues tend to have a non-inflamed tumour microenvironment. In conclusion, patients with HRD exhibit a comparatively favourable prognosis in NPC, possibly associated with a non-inflammatory immune microenvironment. These findings have positive implications for treatment stratification, enabling the selection of more precise and effective therapeutic approaches and aiding in the prediction of treatment response and prognosis to a certain extent.

The addition of nimotuzumab during concurrent chemoradiotherapy improved survival outcomes in locally advanced nasopharyngeal carcinoma patients with optimal response to induction chemotherapy.

OBJECTIVE: To investigate the impact of response to induction chemotherapy (IC) on survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LANPC) and evaluate the efficacy of adding nimotuzumab to concurrent chemoradiotherapy (CCRT) based on different responses to IC. METHODS: We retrospectively included patients with stage III-IVA NPC who underwent IC with and without nimotuzumab during CCRT. Statistical analysis included the chi-square test, propensity score matching, Kaplan-Meier survival analysis, and Cox proportional hazards model. RESULTS: Among 383 identified patients, 216 (56.4%) received nimotuzumab during CCRT, while 167 (43.6%) did not. Following IC, 269 (70.2%) patients showed a complete response (CR) or partial response (PR), and 114 (29.8%) had stable disease (SD) or progressive disease (PD). The response to IC independently influenced disease-free survival (DFS) and overall survival (OS). Patients achieving CR/PR demonstrated significantly higher 3-year DFS (80.3% vs. 70.6%, P = 0.031) and OS (90.9% vs. 83.2%, P = 0.038) than those with SD/PD. The addition of nimotuzumab during CCRT significantly improved DFS (P = 0.006) and OS (P = 0.037) for CR/PR patients but not for those with SD/PD. CONCLUSIONS: This study emphasizes the importance of IC response in LANPC and highlights the potential benefits of nimotuzumab during CCRT for improving survival outcomes in CR/PR patients. Tailored treatment approaches for SD/PD patients warrant further investigation.

ALYREF promotes the metastasis of nasopharyngeal carcinoma by increasing the stability of NOTCH1 mRNA.

Approximately 70% of treatment failures in nasopharyngeal carcinoma (NPC) patients are attributed to distant metastasis, yet the underlying mechanisms remain unclear. RNA 5-methylcytosine (m5C) is an emerging regulatory modification that controls gene expression and plays a critical role in tumor progression. However, there is little information on the potential roles of RNA m5C modification in NPC metastasis. In this study, we found that the m5C reader Aly/REF export factor (ALYREF) is significantly upregulated in NPC, whereby its high expression is associated with metastasis and poor prognosis. ALYREF overexpression was found to promote tumor metastasis of NPC cells in vitro and in vivo. Mechanistically, m5C-modified NOTCH1 mRNA was identified as a target of ALYREF. Moreover, ALYREF was found to upregulate NOTCH1 expression by enhancing its RNA stability in an m5C modification-dependent manner, thereby promoting the activation of the NOTCH signaling pathway and facilitating NPC metastasis. Overall, our data reveal the crucial role of ALYREF in NPC metastasis and provide a potential therapeutic target for NPC.

Establishment of a protocol for rapidly expanding Epstein-Barr-virus-specific cytotoxic T cells with enhanced cytotoxicity.

BACKGROUND: Lytic Epstein-Barr virus (EBV) infection plays a major role in the pathogenesis of nasopharyngeal carcinoma (NPC). For patients with recurrent or metastatic NPC and resistant to conventional therapies, adoptive cell therapy using EBV-specific cytotoxic T cells (EBV-CTLs) is a promising option. However, the long production period (around 3 to 4 weeks) and low EBV-CTL purity (approximately 40% of total CD8 T cells) in the cell product limits the application of EBV-CTLs in clinics. Thus, this study aimed to establish a protocol for the rapid production of EBV-CTLs. METHODS: By culturing peripheral blood mononuclear cells (PBMCs) from EBV-seropositive donors with EBV-specific peptides and interleukin (IL)-2, IL-15, and interferon α (IFN-α) for 9 days, we identified that IL-15 can enhance IL-2-mediated CTL activation and significantly increase the yield of CTLs. RESULTS: When IFN-α was used in IL-2/IL-15-mediated CTL production from days 0 to 6, the productivity of EBV-CTLs and EBV-specific cytotoxicity significantly were reinforced relative to EBV-CTLs from IL-2/IL-15 treatment. Additionally, IFN-α-induced production improvement of virus-specific CTLs was not only the case for EBV-CTLs but also for cytomegalovirus-specific CTLs. CONCLUSION: We established a novel protocol to rapidly expand highly pure EBV-CTLs from PBMCs, which can produce EBV-CTLs in 9 days and does not require feeder cells during cultivation.

Isoliquiritigenin diminishes invasiveness of human nasopharyngeal carcinoma cells associating with inhibition of MMP-2 expression and STAT3 signalling.

Nasopharyngeal carcinoma (NPC) is prevalent in Asia and exhibits highly metastatic characteristics, leading to uncontrolled disease progression. Isoliquiritigenin (ISL) have attracted attention due to their diverse biological and pharmacological properties, including anticancer activities. However, the impact of ISL on the invasive and migratory ability of NPC remains poorly understood. Hence, this study aimed to investigate the in vitro anti-metastatic effects of ISL on NPC cells and elucidate the underlying signalling pathways. Human NPC cell NPC-39 and NPC-BM were utilized as cell models. Migratory and invasive capabilities were evaluated through wound healing and invasion assays, respectively. Gelatin zymography was employed to demonstrate matrix metalloproteinase-2 (MMP-2) activity, while western blotting was conducted to analyse protein expression levels and explore signalling cascades. Overexpression of signal transducer and activator of transcription 3 (STAT3) was carried out by transduction of STAT3-expressing vector. Our findings revealed that ISL effectively suppressed the migration and invasion of NPC cells. Gelatin zymography and Western blotting assays demonstrated that ISL treatment led to a reduction in MMP-2 enzyme activity and protein expression. Investigation of signalling cascades revealed that ISL treatment resulted in the inhibition of STAT3 phosphorylation. Moreover, overexpression of STAT3 restored the migratory ability of NPC cells in the presence of ISL. Collectively, these findings indicate that ISL inhibits the migration and invasion of NPC cells associating with MMP-2 downregulation through suppressing STAT3 activation. This suggests that ISL has an anti-metastatic effect on NPC cells and has potential therapeutic benefit for NPC treatment.

Hyalinizing clear cell carcinoma in the nasopharynx: A case report and literature review.

RATIONALE: Hyalinizing clear cell carcinoma (HCCC) arising from a minor salivary gland is a rare malignant neoplasm. Most HCCC has been reported in the palate and tongue base, and only rarely in the nasopharynx. Here, we report a rare case of nasopharyngeal HCCC. PATIENT CONCERNS: A 44-year-old male who complained of otorrhea and aural fullness for 5 years was found to have a nasopharyngeal mass. DIAGNOSES: HCCC by fluorescence in situ hybridization analysis. INTERVENTIONS: Surgical resection plus concurrent chemotherapy and radiation therapy were administered. OUTCOMES: The patient recovered well with symptoms improved at postoperative follow-up. LESSONS: HCCC should be included in the differential diagnosis of nasopharyngeal mass. Overall, the prognosis of HCCC is positive after tumor resection and adequate management.

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.

Impact of Matrix Metalloproteinase-8 Polymorphisms on Nasopharyngeal Carcinoma Risk.

BACKGROUND/AIM: Upregulation of matrix metallo-proteinase-8 (MMP-8) serves as a protein-based indicator for predicting nasopharyngeal carcinoma (NPC) metastasis. Nevertheless, the role of MMP-8 genotypes in NPC has never been investigated. This study aimed to explore the involvement of MMP-8 genotypes in NPC development. MATERIALS AND METHODS: We employed the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique to analyze MMP-8 genotypes, specifically C-799T (rs11225395), Val436Ala (rs34009635), and Lys460Thr (rs35866072), in a Taiwanese cohort comprising 208 NPC cases and 416 healthy controls. RESULTS: Individuals with either heterozygous or homozygous variant genotypes of MMP-8 rs11225395 showed no significant change in NPC risk compared to those with the wild-type genotype [odds ratio (OR)=0.97 and 0.79, 95% confidence intervals (95%CI)=0.68-1.38 and 0.46-1.36; p=0.9304 and 0.4736, respectively]. Similarly, there was no significant association between the heterozygous genotypes of MMP-8 rs34009635 and NPC risk (OR=0.66, 95%CI=0.24-1.84; p=0.5738). For MMP-8 rs35866072, all individuals in the study were of the TT genotype. Furthermore, the presence of variant alleles at MMP-8 rs11225395 or rs34009635 did not result in altered NPC risk (OR=0.91 and 0.66, 95%CI=0.71-1.16 and 0.24-1.84, p=0.4876 and 0.5769, respectively). Additionally, no significant association was observed between MMP-8 rs11225395 variant genotypes and NPC risk among individuals regardless of smoking, alcohol consumption, or betel quid chewing habits (all p>0.05). CONCLUSION: There was no association between the MMP-8 genotypes rs11225395, rs34009635, or rs35866072 and NPC risk among Taiwanese individuals. Moreover, no combined effects of MMP-8 genotype with smoking, alcohol consumption, or betel quid chewing habits on NPC risk were observed.

Mechanism of salidroside in tumor suppression through the miRNA-mRNA signaling axis. / 红景天苷通过miRNA-mRNA信号轴抑制肿瘤的机制.

With the rapid development of traditional Chinese medicine and the continuous discovery of various anticancer effects of salidroside (sal), it is known that sal inhibits tumor proliferation, invasion and migration by inducing apoptosis and autophagy, regulating the cell cycle, modulating the tumor microenvironment, and controlling cancer-related signaling pathways and molecules. The microRNA (miRNA)-mRNA signaling axis can regulate the expression of target mRNAs by altering miRNA expression, thereby affecting the growth cycle, proliferation, and metabolism of cancer cells. Studies have shown that sal can influence the occurrence and progression of various malignant tumors through the miRNA-mRNA signaling axis, inhibiting the progression of lung cancer, gastric cancer, and nasopharyngeal carcinoma, with a notable time and dose dependence in its antitumor effects. Summarizing the specific mechanism of sal regulating miRNA-mRNA signaling axis to inhibit tumors in recent years can provide a new theoretical basis, diagnosis, and therapeutic methods for the research on prevention and treatment of tumors.

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.

A nomogram based on circulating CD8+ T cell and platelet-to-lymphocyte ratio to predict overall survival of patients with locally advanced nasopharyngeal carcinoma.

PURPOSE: To explore the influence of circulating lymphocyte subsets, serum markers, clinical factors, and their impact on overall survival (OS) in locally advanced nasopharyngeal carcinoma (LA-NPC). Additionally, to construct a nomogram predicting OS for LA-NPC patients using independent prognostic factors. METHODS: A total of 530 patients with LA-NPC were included in this study. In the training cohort, Cox regression analysis was utilized to identify independent prognostic factors, which were then integrated into the nomogram. The concordance index (C-index) was calculated for both training and validation cohorts. Schoenfeld residual analysis, calibration curves, and decision curve analysis (DCA) were employed to evaluate the nomogram. Kaplan-Meier methods was performed based on risk stratification using the nomogram. RESULTS: A total of 530 LA-NPC patients were included. Multivariate Cox regression analysis revealed that the circulating CD8+T cell, platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), albumin (ALB), gender, and clinical stage were independent prognostic factors for LA-NPC (p < 0.05). Schoenfeld residual analysis indicated overall satisfaction of the proportional hazards assumption for the Cox regression model. The C-index of the nomogram was 0.724 (95% CI: 0.669-0.779) for the training cohort and 0.718 (95% CI: 0.636-0.800) for the validation cohort. Calibration curves demonstrated good correlation between the model and actual survival outcomes. DCA confirmed the clinical utility enhancement of the nomogram over the TNM staging system. Significant differences were observed in OS among different risk stratifications. CONCLUSION: Circulating CD8+ T cell, PLR, LDH, ALB, gender and clinical stage are independent prognostic factors for LA-NPC. The nomogram and risk stratification constructed in this study effectively predict OS in LA-NPC.

Cuproptosis related ceRNA axis AC008083.2/miR-142-3p promotes the malignant progression of nasopharyngeal carcinoma through STRN3.

Background: CeRNA axis is an important way to regulate the occurrence and development of Nasopharyngeal carcinoma (NPC). Although the research on inducing cuproptosis of tumor cells is in the early stage of clinical practice, its mechanism of action is still of great significance for tumor treatment, including NPC. However, the regulation mechanism of cuproptosis in NPC by ceRNA network remains unclear. Methods: The ceRNA network related to the survival of nasopharyngeal carcinoma related genes was constructed by bioinformatics. Dual-luciferase reporter assay and other experiments were used to prove the conclusion. Results: Our findings indicate that the AC008083.2/miR-142-3p axis drives STRN3 to promote the malignant progression of NPC. By performing enrichment analysis and phenotypic assays, we demonstrated that the changes in the expressions of AC008083.2/miR-142-3p/NPC can affect the proliferation of NPC. Mechanistically, luciferase reporter gene assays suggested that AC008083.2 acts as a ceRNA of miR-142-3p to regulate the content of STRN3. Furthermore, the regulations of STRN3 and the malignant progression of NPC by AC008083.2 depends on miR-142-3p to some extent. Conclusions: Our study reveals an innovative ceRNA regulatory network in NPC, which can be considered a new potential target for diagnosing and treating NPC.

Peripheral hemoglobin to albumin ratio predicts prognosis in patients with nasopharyngeal carcinoma underwent concurrent chemoradiotherapy.

BACKGROUND: Recently, the hemoglobin to albumin ratio (HAR) has been shown to be closely associated with the survival of certain malignancies. However, its prognostic value in nasopharyngeal carcinoma (NPC) remained to be elucidated. Herein, we aimed to explore the correlation between HAR and overall survival (OS) in NPC patients treated with concurrent chemoradiotherapy (CCRT). METHODS: This retrospective study included a total of 858 patients with NPC receiving CCRT between January 2010 and December 2014 in Sun Yat-sen University Cancer Center. We randomly divided them into the training cohort (N = 602) and the validation cohort (N = 206). We performed univariate and multivariate Cox regression analyses to identify variables associated with OS, based on which, a predictive nomogram was constructed and assessed. RESULTS: In both the training and validation cohorts, patients were classified into low- and high-HAR groups according to the cutoff value determined by the maximally selected rank statistics. This HAR cutoff value effectively divided patients into two distinct prognostic groups with significant differences. Multivariable Cox analysis revealed that higher T-stage, N-stage, and HAR values were significantly related to poorer prognosis in NPC patients and served as independent prognostic factors for NPC. Based on these, a predictive model was constructed and graphically presented as a nomogram, whose predictive performance is satisfactory with a C-index of 0.744 [95%CI: 0.679-0.809] and superior to traditional TNM staging system [C-index = 0.609, 95%CI: 0.448-0.770]. CONCLUSION: The HAR value was an independent predictor for NPC patients treated with CCRT, the predictive model based on HAR with superior predictive performance than traditional TNM staging system might improve individualized survival predictions.

An individualized immune prognostic signature in nasopharyngeal carcinoma.

BACKGROUND: Immune-related characteristics can serve as reliable prognostic biomarkers in various cancers. Herein, we aimed to construct an individualized immune prognostic signature in nasopharyngeal carcinoma (NPC). METHODS: This study retrospectively included 455 NPC samples and 39 normal healthy nasopharyngeal tissue specimens. Samples from Gene Expression Omnibus (GEO) were obtained as discovery cohort to screen candidate prognostic immune-related gene pairs based on relative expression ordering of the genes. Quantitative real-time reverse transcription-PCR was used to detect the selected genes to construct an immune-related gene pair signature in training cohort, which comprised 118 clinical samples, and was then validated in validation cohort 1, comprising 92 clinical samples, and validation cohort 2, comprising 88 samples from GEO. RESULTS: We identified 26 immune-related gene pairs as prognostic candidates in discovery cohort. A prognostic immune signature comprising 11 immune gene pairs was constructed in training cohort. In validation cohort 1, the immune signature could significantly distinguish patients with high or low risk in terms of progression-free survival (PFS) (hazard ratio [HR] 2.66, 95 % confidence interval (CI) 1.17-6.02, P=0.015) and could serve as an independent prognostic factor for PFS in multivariate analysis (HR 2.66, 95 % CI 1.17-6.02, P=0.019). Similar results were obtained using validation cohort 2, in which PFS was significantly worse in high risk group than in low risk group (HR 3.02, 95 % CI 1.12-8.18, P=0.022). CONCLUSIONS: The constructed immune signature showed promise for estimating prognosis in NPC. It has potential for translation into clinical practice after prospective validation.

Single-cell resolution profiling of the immune microenvironment in primary and metastatic nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an assertive malignancy with partially understood underlying mechanisms, urging further study into its diverse and dynamic tumor microenvironment (TME) to bolster diagnosis, treatment, and prognostic accuracy. AIMS: To track the evolutionary route of metastasis, here we perform a yielding scRNA-seq data from 24 primary carcinoma, 7 peripheral blood mononuclear cell (PBMC) nasopharyngeal carcinoma, and 7 metastatic carcinoma patients' sample. MATERIALS AND METHODS: Following high quality control and filtration, a total of 292,298 cells from these tumors were classified into 10 clusters: T cells, B cells, Macrophages/Monocytes, Natural Killer (NK) cells, Plasma cells, plasmacytoid Dendritic Cells, Migratory Dendritic Cells, Mast cells, Cancer-Associated Fibroblasts, and Epithelial cells. RESULTS: By comparing and analyzing the different functional capacities of cellular entities within primary and metastatic nasopharyngeal carcinoma, coupled with a detailed investigation into the heterogeneity and differential fate trajectories of T cells, B cells, and myeloid cells, as well as assessing the interactions of cell-cell communicative heterogeneity between these carcinogenic states, we established single-cell atlases for primary and metastatic tumors and identified a large number of potential therapeutic targets. CONCLUSION: This comprehensive analysis significantly advances our understanding of nasopharyngeal carcinoma (NPC) metastasis by detailing the evolutionary dynamics and the impact of the tumor microenvironment at a single-cell resolution, thereby laying a crucial foundation for future metastatic tumor research and providing new insights into immune heterogeneity, molecular interactions, and potential therapeutic strategies for NPC.

Development and validation of a practical score to predict 3-year distant metastatic free survival in nasopharyngeal carcinoma incorporating the number of lymph node regions.

INTRODUCTION: The improvement in diagnosis and treatment for nasopharyngeal carcinoma (NPC) has shifted the pattern of failure toward distant metastasis. This study aimed to develop a simplified prognostic scoring model to predict distant metastatic free survival (DMFS) for NPC patients. MATERIALS AND METHODS: Patients with non-metastatic NPC were identified from a retrospective cohort diagnosed between 2010 and 2018. Flexible parametric survival analysis was used to identify potential predictors for DMFS and establish a scoring model. The prognostic accuracy between the 8th AJCC system and the scoring model was compared using Harrell's C-index. RESULTS: Of the total 393 patients, the median follow-up time was 85 months. The 3-year DMFS rate was 83.3%. Gender, T-stage, pre-EBV (cut-off 2300 copies/ml), and the number of metastatic lymph node regions were identified as independent risk factors for distant metastasis and were included in the final scoring model. Our established model achieved a high C-index in predicting DMFS (0.79) and was well-calibrated. The score divided patients into two categories: low-risk (score 0-4) and high-risk (score 5-7), corresponding with the predicted 3-year DMFS of 96% and 64.5%, respectively. CONCLUSIONS: A feasible and applicative prognostic score was established and validated to discriminate NPC patients into low- and high-risk groups.

The prognostic value of pretreatment 18F-FDG PET-CT parameters with peripheral blood markers in patients with de novo metastatic nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To develop and validate a prognostic nomogram based on pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT)radiomics parameters and peripheral blood markers for risk stratification in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC). MATERIALS AND METHODS: A total of 558 patients with dmNPC were retrospectively enrolled between 2011 and 2019. Eligible patients were randomly divided into training and validation cohorts (7:3 ratio). A Cox regression model was used to identify prognostic factors for overall survival (OS). The predictive accuracy and discriminative ability of the prognostic nomogram were determined using the concordance index (C-index) and calibration curve. RESULTS: Independent factors derived from multivariable analysis of the training cohort to predict death were lactate dehydrogenase levels, pretreatment Epstein-Barr virus DNA, total lesion glycolysis of locoregional lesions, number of metastatic lesions, and age, all of which were assembled into a nomogram with (nomogram B) or without PET-CT parameters (nomogram A). The C-index of nomogram B for predicting death was 0.70, which was significantly higher than the C-index values for nomogram A. Patients were then stratified into low- and high-risk groups based on the scores calculated using nomogram B for OS. The median OS was significantly higher in the low-risk group than in the high-risk group (69.60 months [95 % CI: 58.50-108.66] vs. 21.40 months [95 % CI: 19.20-23.90]; p＜0.01). All the results were confirmed in the validation cohort. CONCLUSION: The proposed nomogram including PET-CT parameters yielded accurate prognostic predictions for patients with dmNPC, enabling effective risk stratification for these patients.