Search Results (295)

Objectives: Nasopharyngeal carcinoma (NPC) arises in an immune-suppressive milieu that frequently undermines treatment efficacy. TPPP3 has been implicated as a negative regulator of NPC aggressiveness, yet its relevance to immune modulation or chaperone networks remains poorly defined. We therefore sought to determine how TPPP3 shapes the NPC immune landscape and to identify its interacting protein partners. Methods: Public single-cell RNA-sequencing datasets from head and neck squamous cell carcinoma and nasopharyngeal carcinoma were analyzed using R. HK-1 and C666-1 cells stably overexpressing TPPP3 were established. These cells were used to construct humanized xenograft tumor models, with intratumoral immune cell infiltration evaluated by immunohistochemistry. In vitro, the same cells and their controls were indirectly co-cultured with peripheral blood mononuclear cells. Cellular lysates from TPPP3-overexpressing cells were subjected to immunoprecipitation–mass spectrometry and immunofluorescence staining, which identified HSPA8 as a TPPP3-interacting protein. Three groups—control, TPPP3-overexpressing, and TPPP3-overexpressing plus the HSPA8 inhibitor VER155008—were then compared in wound healing, colony formation, cell-cycle, and xenograft assays, with immunohistochemical staining for Ki67, TPPP3, and CD3 performed on tumor sections. Results: TPPP3 transcripts were barely detectable across most tumor cell subsets but showed preferential enrichment in NPC epithelial clusters. Enforced TPPP3 expression curtailed xenograft outgrowth while increasing intratumoral abundance of CD3⁺ T cells, CD8⁺ T cells, and CD11c⁺ dendritic cells. Pharmacological blockade of HSPA8 with VER155008 further enhanced TPPP3-driven suppression of migration, clonogenicity, and tumor expansion, and also altered cell-cycle progression while boosting CD3⁺ T-cell accumulation within grafts. Conclusions: These findings suggest a functional association between TPPP3 and HSPA8 that may contribute to tumor growth suppression and immune microenvironment remodeling in NPC. Pharmacological disruption of HSPA8-dependent proteostasis enhanced TPPP3-associated antitumor activity in both in vitro and in vivo models, indicating that this chaperone pathway represents a candidate mechanism worthy of further mechanistic investigation and therapeutic exploration. Full article

Background/Objectives: Pediatric nasopharyngeal carcinoma (NPC) is a very rare childhood cancer strongly associated with Epstein–Barr virus (EBV) infection. We investigated the prognostic value of EBV DNA on staging and outcome in pediatric NPC from two large study centers, the Children’s Oncology Group (COG) in North America and the German Society of Pediatric Oncology and Hematology (GPOH) in Europe. Methods: Samples collected from NPC patients treated on the COG study ARAR0331 between 2006 and 2012 and the GPOH NPC protocol between 2003 and 2021 were retrospectively analyzed for the level of available plasma (P-EBV) or whole-blood EBV DNA (WB-EBV), both pre-treatment and post-induction chemotherapy. Patients were dichotomized into high and low groups based on the median pre-treatment EBV value. Results: Pre-treatment EBV DNA levels from 102 patients (50 and 23 P-EBV DNA from the COG and GPOH, respectively, and 29 WB-EBV from GPOH) and post-induction EBV DNA levels from 61 patients (31 and 12 P-EBV DNA from the COG and GPOH, respectively, and 18 WB-EBV DNA from GPOH) were evaluated. Patient characteristics, including age and disease stage, were not associated with high and low P-EBV values in any cohort. Disease stage correlated with high EBV levels in the WB-EBV GPOH cohort (p = 0.014). Pre-treatment P-EBV and WB-EBV levels showed no significant association with 5-year event-free survival (EFS: COG p = 0.65, GPOH P-EBV: p = 0.08, GPOH WB-EBV: p = 0.75) or 5-year overall survival (OS: COG p = 0.90, GPOH P-EBV p = 0.17, GPOH WB-EBV p = 0.19). Conclusions: Our study could not establish a significant correlation between outcome and pre-treatment EBV DNA in pediatric NPC patients from non-endemic areas. Full article

This narrative methodological review aims to critically assess whether current AJCC/UICC N3-defining criteria for nasopharyngeal carcinoma (NPC) represent validated biological and statistical thresholds or pragmatic staging boundaries. Specifically, it examines the evidential basis of the >6 cm nodal-size threshold, extension below the caudal border of the cricoid cartilage, and advanced radiologic extranodal extension (rENE), with emphasis on the distinction between prognostic-variable validity and threshold validity. The >6 cm criterion is a historically inherited threshold that predates contemporary MRI-based staging and may insufficiently capture the three-dimensional complexity of nodal tumor burden. Similarly, defining inferior nodal extension by the caudal border of the cricoid cartilage improves anatomical reproducibility compared with earlier lower-neck definitions, yet it remains a pragmatic imaging landmark rather than a validated biological boundary for lymphatic dissemination. By contrast, advanced rENE is more biologically informative because it reflects invasive tumor behavior; nonetheless, its staging utility depends on standardized imaging definitions, interobserver reliability, external validation, and incremental clinical utility. Emerging imaging-derived descriptors—including MRI-based nodal diameter, nodal volume, middle-neck involvement, total tumor volume, and integrated imaging–biological models—underscore the limitations of relying exclusively on single categorical thresholds. Future N3 refinement should move beyond substituting one cutoff for another by characterizing nodal descriptors in continuous, ordinal, volumetric, or severity-graded forms before adopting simplified categories. Future refinement of NPC nodal staging will likely require approaches that move beyond isolated anatomical thresholds and better account for the multidimensional nature of nodal disease, including tumor burden, spatial distribution, invasive characteristics, and biological risk. Full article

Background: Differentiating nasopharyngeal carcinoma (NPC) from benign nasopharyngeal lesions may be challenging because clinical and endoscopic findings can overlap. This study compared routine inflammatory and hematological biomarkers between patients with histopathologically confirmed NPC and patients with suspicious but histopathologically benign adenoid hypertrophy (AH). Methods: This retrospective single-center study included 72 adults evaluated between January 2024 and January 2026: 36 patients with NPC and 36 with AH. Routine hematological and inflammatory variables were compared between groups. After inconsistencies were identified in the originally derived indices, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were recalculated using the available absolute blood-cell-count variables. Receiver operating characteristic analyses and exploratory Firth penalized logistic regression were performed, with histopathologically confirmed NPC coded as the positive outcome. Results: Patients with NPC were younger than patients with AH (38.14 ± 7.64 vs. 56.06 ± 8.29 years; p < 0.001). CRP, ESR, and leukocyte count were significantly higher in the NPC group. PLR was significantly higher in the AH group, whereas NLR and SII did not differ significantly between groups. CRP demonstrated apparent complete discrimination between the two selected diagnostic groups (AUC 1.000), while ESR yielded an AUC of 0.948. In the Firth penalized logistic regression model adjusted for age, sex, and smoking status, each 10 mg/L increase in CRP was associated with higher odds of NPC (adjusted OR 3.16, 95% CI 1.68–16.72; p < 0.001). The addition of CRP increased the model AUC from 0.950 to 1.000. Conclusions: Routine inflammatory markers showed different cross-sectional distributions between patients with node-positive NPC and patients with suspicious benign adenoid hypertrophy. CRP provided incremental discriminatory information in this selected cohort but should not be interpreted as a validated stand-alone diagnostic marker. The findings require prospective external validation in a larger and clinically representative population. Full article

Background: Osteoradionecrosis of the jaw (ORNJ) remains a major late complication of head and neck radiotherapy, and risk assessment relies mainly on clinical and dosimetric factors. We constructed the Host Tissue Repair Vulnerability Index (HTRVI), a composite biomarker integrating inflammatory, immune-nutritional, and oxygenation-related parameters, to estimate biological susceptibility to ORNJ in locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: This retrospective cohort included 261 LA-NPC patients treated with definitive concurrent chemoradiotherapy between 2010 and 2021. HTRVI was calculated as (CRP × platelet × neutrophil)/(albumin × lymphocyte × hemoglobin). HTRVI was compared with hemoglobin (Hb) and the Global Immune-Nutrition-Inflammation Index (GINI) using receiver operating characteristic analysis. Multivariable logistic regression, restricted cubic spline analysis (RCS), and bootstrap resampling assessed independent association, continuous risk relationship, and internal validation. Results: During a median follow-up of 63.8 months, 24 patients (9.2%) developed ORNJ. HTRVI showed superior discrimination (AUC, 0.864; 95% CI, 0.769–0.932) compared with Hb (AUC, 0.785; p = 0.001) and GINI (AUC, 0.759; p = 0.045). HTRVI remained independently associated with ORNJ after adjustment for mandibular mean dose and post-CCRT tooth extraction burden (OR per standard deviation increase, 4.81; 95% CI, 1.10–20.99; p = 0.037). RCS analysis showed a significant continuous association between HTRVI and ORNJ risk (P_overall < 0.001) without nonlinearity (P_nonlinear = 0.736). Internal validation showed minimal optimism (bootstrap-corrected AUC, 0.993). Conclusions: HTRVI was independently associated with ORNJ and provided additional predictive information beyond established clinical and dosimetric factors in this single-center cohort. The continuous HTRVI–ORNJ association supports a biological continuum model of host tissue repair vulnerability. However, HTRVI should currently be regarded as an investigational biomarker requiring independent external and prospective validation before clinical implementation. Full article

Objectives: Pediatric nasopharyngeal carcinoma (NPC) is rare and often presents at an advanced stage. Although multimodal treatment can achieve favorable survival, long-term survivors may experience substantial treatment-related morbidity. We aimed to evaluate survival outcomes according to stage and metastatic status and to characterize late toxicity in a 20-year single-center pediatric NPC series. Methods. We retrospectively reviewed 24 pediatric patients diagnosed with NPC between 2003 and 2023. Histology was classified according to WHO criteria, and tumors were staged using the AJCC TNM system. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan–Meier method. Survival distributions were compared using the log-rank test. Late treatment-related toxicities documented during follow-up were recorded descriptively. Results: Twenty-four patients with WHO type III NPC were included. Fourteen patients had stage III disease and 10 had stage IV disease; three had distant metastasis at diagnosis. The median follow-up duration was 50.5 months. At last follow-up, 19 patients were alive and five had died. The estimated 5- and 10-year OS rates were both 72.7%, and the corresponding EFS rates were both 63.7%. Stage IV disease and metastatic presentation were associated with inferior OS. Dysphagia, malnutrition, xerostomia, fibrosis, hypothyroidism, and deafness were the most frequently recorded adverse health effects. Conclusions: This 20-year single-center experience shows that AJCC stage and metastatic status remain key determinants of survival in pediatric NPC. The high burden of late treatment-related complications highlights the importance of integrating long-term multidisciplinary survivorship surveillance into the care of pediatric NPC survivors. Full article

Background: Antibiotics are commonly prescribed to patients with nasopharyngeal carcinoma (NPC) during chemoradiotherapy; however, peri-treatment antibiotic use may adversely affect patients’ outcomes. Methods: A retrospective cohort study was conducted. The association between antibiotic use and patients’ survival time was analyzed using Kaplan–Meier and Cox proportional hazards regression models. Results: Among 455 NPC patients, 42.0% received antibiotics around primary treatment. Patients who had an advanced tumor stage (p = 0.019) or had received neoadjuvant chemotherapy (p = 0.008) or concurrent chemoradiotherapy (p = 0.002) were more likely to be prescribed antibiotics. Univariate analysis showed that antibiotic use around primary treatment was associated with worse disease-specific survival (DSS) at both 5 years (p = 0.043) and 10 years (p = 0.019). Subgroup analysis showed that 5-year and 10-year DSS were significantly shortened in patients receiving RT only and Abx within 2 w or 1 w around RT (5-year: 2 w p = 0.001, 1 w p < 0.001; 10-year 2 w p < 0.001, 1 w p = 0.005). Conclusions: In NPC, antibiotic use around primary treatment was associated with poorer disease-specific survival. Further prospective studies are warranted to clarify the causality and underlying mechanisms. Full article

Background/Objectives: Prognostic stratification in non-metastatic nasopharyngeal carcinoma (NPC) remains challenging, particularly among patients within the same TNM stage. Readily available hematologic inflammatory indices may reflect host–tumor interactions and provide additional prognostic information beyond conventional clinicopathologic factors. This study evaluated the prognostic value of pretreatment hematologic inflammatory indices for overall survival (OS) and progression-free survival (PFS) in patients with non-metastatic NPC. Methods: This single-center retrospective cohort study included adult patients with non-metastatic NPC diagnosed at a tertiary referral center between 20 February 2014 and 2 May 2023, with outcomes ascertained through 12 December 2023. Pretreatment complete blood count and biochemical parameters were used to calculate the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, pan-immune-inflammation value (PIV), and hemoglobin–albumin–lymphocyte–platelet score. Receiver operating characteristic analysis determined optimal cut-off values for mortality discrimination. Associations with OS and PFS were assessed using Cox regression models. Results: Forty-six patients were analyzed, including 37 males. Median OS and PFS were 45.90 and 37.05 months, respectively. Compared with survivors, non-survivors were older and had lower hemoglobin and albumin levels, higher PIV, NLR, PLR, and SII values, and lower HALP scores. Although NLR showed the highest conventional ROC performance for mortality discrimination, PIV retained prognostic significance in multivariable Cox models and showed stable time-dependent discrimination for PFS. Conclusions: These preliminary findings suggest that pretreatment inflammatory indices, particularly composite markers such as PIV, may provide adjunctive prognostic information in treatment-naïve non-metastatic NPC, pending larger prospective validation. Full article

Background/Objectives: This retrospective study evaluated whether the association between post-CCRT dental extraction timing and osteoradionecrosis of the jaw (ORNJ) risk is modified by mandibular radiation exposure in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) treated with definitive concurrent chemoradiotherapy (CCRT). Methods: A total of 247 patients who did not undergo pre-CCRT dental extraction but underwent post-CCRT extraction were analyzed. Mandibular radiation exposure was quantified using EQD2. Associations between clinical, tumoral, dental, and dosimetric variables and ORNJ were assessed using multivariable logistic regression, including assessment of EQD2–timing interaction. ROC analyses were performed to evaluate discriminative performance and estimate exploratory thresholds. ORNJ developed in 23 patients (9.3%). Mandibular EQD2 was independently associated with ORNJ risk (OR 2.10 per 5 Gy; 95% CI 1.40–3.15; p < 0.001). A significant interaction between EQD2 and extraction timing was observed (OR 1.07; 95% CI 1.03–1.11; p = 0.023). EQD2 demonstrated excellent discrimination (AUC 0.885; cutoff 46.5 Gy), whereas extraction timing showed modest discrimination (AUC 0.691; cutoff 10 months). At <46.5 Gy, ORNJ rates remained low regardless of timing (1.0% vs. 3.9%). At ≥46.5 Gy, delayed extraction was associated with substantially higher ORNJ incidence (31.1% vs. 11.3%). Number of extracted teeth (OR 1.16; p = 0.012) and hemoglobin level (OR 0.62; p = 0.007) were also independent predictors. Conclusions: The effect of post-CCRT dental extraction timing on ORNJ risk is modified by mandibular radiation dose, supporting interpretation in conjunction with mandibular radiation exposure rather than as an isolated factor. Full article

Background: Nasopharyngeal carcinoma (NPC) presents significant diagnostic and therapeutic challenges, often due to late-stage detection and its complex anatomical location. The increasing integration of artificial intelligence (AI) into oncology offers potential opportunities to enhance the precision of NPC management. This systematic review aims to synthesise the current evidence of AI applications in NPC diagnosis, prognostication, and treatment planning. Methods: A systematic literature search was conducted following PRISMA guidelines across multiple databases (PubMed, Scopus, Embase, Google Scholar, IEEE Xplore) for studies published up to June 2025. From an initial pool of 2549 articles, 55 studies meeting the inclusion criteria were selected for qualitative analysis. The review focuses on AI models applied to key diagnostic modalities: computed tomography (CT), magnetic resonance imaging (MRI), and histopathological whole-slide images (WSI). Results: AI, particularly deep learning (DL), shows promising performance in automating critical tasks across all modalities. For CT and MRI, models have been reported to achieve accurate tumor and organ-at-risk segmentation, potentially supporting radiotherapy planning, and show strong performance in predicting survival outcomes and treatment toxicity. In digital pathology, AI enables automated diagnosis and facilitates the extraction of prognostic “pathomic” features from WSIs, with some studies suggesting performance comparable to or exceeding traditional radiomics. The most significant advances are seen in multimodal AI systems that integrate radiological, pathological, and clinical data, which, in some studies, show modest improvements in prognostic performance compared to single-modality approaches. However, these findings are preliminary, as none of the reviewed multimodal models underwent rigorous external validation in large, multi-center cohorts. Reported performance varies considerably across studies, and claims of superiority should be interpreted with caution. Full article

Natural killer (NK) cells are increasingly recognized as a complementary platform to T-cell-based cancer immunotherapies. Their innate, MHC-unrestricted recognition, capacity to mediate antibody-dependent cellular cytotoxicity (ADCC) and comparatively favorable toxicity profile have given rise to a broad therapeutic pipeline that includes cytokine-supported regimens, adoptive NK products, bispecific and trispecific NK engagers, and chimeric antigen receptor (CAR)-engineered NK cells. Clinical data, particularly in hematologic malignancies, show that NK-cell-based strategies can be safe and biologically active, although limited persistence, suboptimal trafficking and immune escape remain key challenges. Nasopharyngeal carcinoma (NPC), an Epstein–Barr virus (EBV)-driven epithelial cancer, illustrates how a tumor microenvironment (TME) can simultaneously impair NK function and create specific vulnerabilities that NK-focused therapies can exploit. This review summarizes NK biology and current therapeutic platforms, analyzes major limitations, highlights the specific context of NK-cell-based strategies in NPC and compares NK- and T-cell-based therapies with an emphasis on clinical translation. Full article

Background: Tooth extraction (TE) after chemoradiotherapy is common in locally advanced nasopharyngeal carcinoma (LA-NPC), yet its determinants remain unclear. We evaluated the association between the Comprehensive Repair–Inflammation Index (CRII), reflecting systemic inflammation and host repair capacity, and TE risk after concurrent chemoradiotherapy (CCRT). Methods: We conducted a retrospective analysis of 354 patients with LA-NPC treated with definitive CCRT. The primary endpoint was post-treatment TE (none vs. ≥1). CRII was calculated from pre-treatment laboratory parameters and analyzed continuously, with a breakpoint identified via segmented regression. Logistic regression and restricted cubic splines were used. Multivariable models adjusted for clinical variables and mandibular dosimetric parameters (mean dose, V50, V60). Results: TE occurred in 70.1% of patients. CRII was significantly higher in those with TE (147.5 vs. 122.0; p < 0.001). CRII was strongly associated with TE (per 10-unit increase: OR 1.49, 95% CI 1.34–1.66; p < 0.001). A nonlinear relationship was observed, with a breakpoint at 145.7, above which TE rates increased markedly (90.5% vs. 58.8%; p < 0.001). CRII remained independently predictive after adjustment (adjusted OR 1.46; ≥145.7: OR 5.1; both p < 0.001). Mandibular dose parameters were not significantly associated with tooth extraction in this analysis. Conclusions: CRII independently predicts post-CCRT TE with a nonlinear risk pattern, highlighting the potential contribution of systemic host-related factors alongside conventional dosimetric parameters. Full article

Objectives: This study compared the efficacy and safety of a single oral dose of a fixed-dose combination of netupitant and palonosetron (NEPA) with an intravenous regimen of fosaprepitant (FosAPR, 150 mg) plus palonosetron (PALO, 0.25 mg) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: This single-center retrospective cohort study included patients with stage III–IVa NPC who received cisplatin-based induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) from January 2020 to October 2025. Propensity score matching (PSM) generated 214 patients per group. All patients also received olanzapine and dexamethasone. Complete response (CR, defined as no emesis and no rescue medication), nausea control, adverse events, and nutritional status changes were assessed across the acute, delayed, overall, and extended (0–168 h) phases. Results: After PSM, 214 patients were included in each group. During the first IC cycle, the oral NEPA group achieved a higher CR rate in the extended overall phase (0–168 h) than the FosAPR + PALO group (80.0% vs. 70.1%, p = 0.019). A similar difference was seen in the first CCRT cycle (74.8% vs. 64.5%, p = 0.021). The advantage persisted across subsequent cycles, with no between-group difference in the acute phase. Nausea control also favored oral NEPA: rates of no significant nausea (visual analog scale < 25 mm) during the extended overall phase were 77.1% versus 65.9% in the first IC cycle (p= 0.010) and 72.9% versus 60.3% in the first CCRT cycle (p = 0.006). Fewer patients in the NEPA group required rescue antiemetics (14.5% vs. 22.0% in the first IC cycle, p = 0.045), and the median time to first rescue was longer (58.3 vs. 51.3 h, p < 0.001). Adverse event profiles were similar between groups, with constipation being the most common. Nutritional outcomes, including weight loss ≥ 5% and severe malnutrition, did not differ significantly. Conclusions: For patients with LA-NPC receiving highly emetogenic chemotherapy (HEC), oral NEPA appears to offer superior and sustained chemotherapy-induced nausea and vomiting (CINV) prophylaxi with a simplified administration schedule compared with the intravenous FosAPR plus PALO regimen. These findings warrant confirmation in prospective studies. Full article

Nasopharyngeal carcinoma (NPC) presents unique clinical and biological characteristics that distinguish it from other head and neck malignancies. It poses a great therapeutic challenge for many specialists. It is associated with Epstein–Barr virus (EBV) infection, genetic predisposition, and environmental risk factors. With advancements in radiotherapy and systemic therapy, new treatment options have emerged. We want to focus on contemporary therapeutic strategies for NPC, emphasizing breakthroughs in intensity-modulated radiotherapy (IMRT), chemoradiotherapy, targeted therapy, immunotherapy, and emerging cellular therapies. By integrating recent discoveries with clinical evidence, we aim to provide state-of-the-art information, along with a comprehensive understanding of current best practices, emerging treatments, and critical prognostic determinants in NPC. Full article

Habitat analysis enables spatial characterization of intratumoral heterogeneity; however, its application in nasopharyngeal carcinoma (NPC), particularly regarding metastatic lymph node (MLN), remains limited. This study aims to systematically compare the prognostic performance of various models using different sequences and spatial region combinations for predicting overall survival in NPC. The study retrospectively included 725 NPC patients (543 training, 182 testing). Habitat analysis was conducted based on T1, T1C, and T2 sequences in three regional strategies: primary gross tumor volume (GTVp), metastatic lymph nodes (MLNs), and the combined region of GTVp-MLN. The tumor area was divided into six subregions, and a multi-region spatial interaction (MSI) matrix was constructed to extract MSI features. On this basis, a radiomics model (R Model) and a clinical–radiomics model (CR Model) were established, and the model performance was evaluated using C-index and Kaplan–Meier survival analysis. The results show that the combined GTVp-MLN model based on the T1 sequence achieved the best overall predictive performance (R Model: C-index = 0.693; CR Model: C-index = 0.722). Significant survival differences were observed between the high- and low-risk groups. These findings suggest that habitat analysis incorporating the combined GTVp–MLN region may improve prognostic prediction and risk stratification in patients with NPC. Full article