Nasopharyngeal Carcinoma Patients Research Articles

Evaluating the reduction of elective radiotherapy fields for de novo metastatic nasopharyngeal carcinoma in the immunotherapy era.

This study evaluates the outcomes of omitting the high- and low-risk clinical tumor volume (CTV1 and CTV2) radiation in de novo metastatic nasopharyngeal carcinoma (dnm-NPC) patients in the immunotherapy era. We retrospectively analyzed 45 consecutive dnm-NPC patients receiving chemotherapy and immunotherapy combined with radiotherapy (CIR) from October 9, 2018 to June 1, 2022. Irradiation was only delivered to the primary tumor and retropharyngeal nodes (GTVnx+rn) and gross cervical lymph nodes (GTVnd). The median follow-up was 45 (range, 15-67) months. There was no recurrence in the omitted elective regions. The 36-month LRRFS, PFS, and OS were 95.4%, 44.6%, and 90.8%, respectively. The main grade 3/4 hematologic toxicities were neutropenia (42.2%), anemia (20.0%), and thrombocytopenia (13.3%). The incidence of acute grade 3/4 dermatitis, mucositis, and xerostomia were 4.4%, 8.9%, and 4.4%, respectively. Omitting CTV1 and CTV2 was well-tolerated and provided favorable clinical outcomes in the era of immunotherapy.

Impact of the radiotherapy rhythm on prognosis in nasopharyngeal carcinoma

Objective The role of chronoradiobiology in nasopharyngeal carcinoma (NPC) has not been fully elucidated. We sought to investigate the impact of radiotherapy rhythm on the survival outcomes of individuals to explore a chronomodulated radiation strategy to improve prognosis of NPC. Methods A cohort comprising non-metastatic NPC patients subjected to intensity-modulated radiotherapy at Fujian Cancer Hospital between Jan. 2016 and Dec. 2019 was assembled. Rhythmic fluctuation of radiotherapy (RFRT) was quantified based on the temporal distribution of radiation delivery. Cox proportional hazard model was performed to explore the impact of radiotherapy rhythm on all-cause mortality. The maximally selected rank statistics method was employed to discern an optimal cutoff. Sensitivity analyses were conducted to ensure the robustness of observed associations. Results Our analysis encompassed 2245 patients, with a median follow-up duration of 55 months, during which 315 individuals succumbed. Multivariate Cox regression analysis unveiled a significant correlation between prolonged RFRT and heightened mortality risk in NPC patients (HR, 1.17, 95% CI, 1.07-1.27, p < .001), a relationship robust to comprehensive adjustment for confounding variables. A cutoff value of 3 h was selected for potential clinical application, beyond which patients exhibited markedly poorer survival outcomes. Subgroup analyses consistently underscored the directional consistency of observed effects. Conclusion Our study sheds light on the potential advantages of scheduling radiotherapy sessions at consistent times. These findings have implications for optimizing radiotherapy schedules and warrant further investigation into personalized chronotherapy approaches in NPC management.

Communication between cancer cell subtypes by exosomes contributes to nasopharyngeal carcinoma metastasis and poor prognosis.

Intratumor heterogeneity is common in cancers, with different cell subtypes supporting each other to become more malignant. Nasopharyngeal carcinoma (NPC), a highly metastatic cancer, shows significant heterogeneity among its cells. This study investigates how NPC cell subtypes with varying metastatic potentials influence each other through exosome-transmitted molecules. Exosomes were purified and characterized. MicroRNA expression was analyzed via sequencing and qRT-PCR. The effects of miR-30a-5p on migration, invasion, and metastasis were evaluated in vitro and in vivo. Its impact on desmoglein glycoprotein (DSG2) was assessed using dual-luciferase assays and Western blotting. Immunohistochemistry (IHC) and statistical models linked miR-30a-5p/DSG2 levels to patient prognosis. Different NPC cell subtypes transmit metastatic potential via exosomes. High-metastatic cells enhance the migration, invasion, and metastasis of low-metastatic cells through exosome-transmitted miR-30a-5p. Plasma levels of exosomal miR-30a-5p are reliable indicators of NPC prognosis. miR-30a-5p may promote metastasis by targeting DSG2 and modulating Wnt signaling. Plasma exosomal miR-30a-5p inversely correlates with DSG2 levels, predicting patient outcomes. High-metastatic NPC cells can increase the metastatic potential of low-metastatic cells through exosome-transmitted miR-30a-5p, which is a valuable prognostic marker assessable via liquid biopsy.

Joint modeling of longitudinal health-related quality of life during concurrent chemoradiotherapy period and long-term survival among patients with advanced nasopharyngeal carcinoma

BackgroundTo investigate the prognosis of longitudinal health-related quality of life (HRQOL) during concurrent chemoradiotherapy (CCRT) on survival outcomes in patients with advanced nasopharyngeal carcinoma (NPC).MethodsDuring 2012–2014, 145 adult NPC patients with stage II-IVb NPC were investigated weekly using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORCT QLQ-C30) during their CCRT period. The effects of longitudinal trends of HRQOL on survival outcomes were estimated using joint modeling, and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were reported as a 10-point increase in HRQOL scores.ResultsAfter a median follow-up of 83.4 months, the multivariable models showed significant associations of longitudinal increasing scores in fatigue and appetite loss during the CCRT period with distant metastasis-free survival: 10-point increases in scores of fatigue and appetite loss domains during CCRT period were significantly associated with 75% (HR: 1.75, 95% CI: 1.01, 3.02; p = 0.047) and 59% (HR: 1.59, 95% CI: 1.09, 2.59; p = 0.018) increase in the risk of distant metastasis, respectively. The prognostic effects of the longitudinal HRQOL trend on overall survival and progress-free survival were statistically non-significant.ConclusionIncreases in fatigue and appetite loss of HRQOL during the CCRT period are significantly associated with high risks of distant metastasis in advanced NPC patients. Nutritional support and psychological intervention are warranted for NPC patients during the treatment period.

Four-dimensional trapped ion mobility spectrometry proteomics reveals circulating extracellular vesicles encapsulated drivers of nasopharyngeal carcinoma distant dissemination

Nasopharyngeal carcinoma (NPC) is a head and neck cancer with a high propensity for early metastatic spread. Emerging evidence shows that extracellular vesicles (EVs) are key players in cancer metastasis, but their role in NPC metastasis remains poorly understood. We here present the first description of the proteomic and functional profiles of serum-derived circulating small EVs in metastatic NPC patients. To enhance the capture of low-abundance signaling proteins in EVs, timsTOF-based four-dimensional label-free quantitative proteomics was employed. We found that metastatic NPC patients (M-NPC-EVs) exhibited the highest serum EV levels compared to locoregional patients (L-NPC-EVs) and healthy subjects (Normal-EVs). The proteome of M-NPC-EVs differed substantially from L-NPC-EVs and was functionally enriched in pathways regulating cell polarity and motility, glucose metabolism, and angiogenesis. Functional assays testing individual EV samples demonstrated that M-NPC-EVs pronouncedly enhanced NPC cell migration, invasion, and the formation of lamellipodia and filopodia in vitro, and promoted angiogenesis in subcutaneous Matrigel plugs in vivo. In silico analyses suggested that PTPRA, TPI1 and GPI highly enriched in M-NPC-EVs were putative drivers underlying the motogenic and angiogenic activities of M-NPC-EVs, and their high expression levels were associated with a poor prognosis of NPC patients. The increased expression of PTPRA, TPI1 and GPI in M-NPC-EVs was then validated in an independent cohort consisting of 175 NPC patients (locoregional n = 114; metastatic n = 61). Together, utilizing patient-derived EVs, we mimicked the potential pro-metastatic functions of EVs in NPC patients in vitro and in vivo and provided novel insights into their bioactive cargoes.

Advanced-technique radiation therapy for nasopharyngeal carcinoma in a low resource setting: a review of treatment-related quality of life.

Nasopharyngeal carcinoma (NPC) is a rare but significant public health concern, especially in Africa, with a rising global incidence. This study aimed to investigate the pattern of presentation, treatment outcomes and impact on health-related quality of life (HRQOL) of NPC patients at a tertiary institution in Lagos, Nigeria. A retrospective review of all nasopharyngeal cancer patients (n = 125) treated at a tertiary centre in Lagos, Nigeria, from May 2019 to 2022 was done. The European Organisation for Research and Treatment of Cancer (EORTC) H&N 35 questionnaire was used to assess HRQOL at 1-year post treatment and the data were analysed using a statistical package for the social sciences v26.0. Among 125 patients, the mean age was 46.21 ± 17.82 years with 76% male. Comorbidities were reported in 34 patients (27.2%), smoking history in 18 patients (14.4%) and 50 patients (40%) reported alcohol consumption. Environmental risk factors were identified in six patients (4.8%). The most prevalent histology was squamous cell carcinoma (92.8%), and stage IV was the most common stage (42.4%). Chemoradiation was the primary treatment (63.2%), with intensity-modulated radiotherapy being the most utilised approach (51.2%). Among 125 patients, 51 completed the EORTC questionnaire. Weight loss, sticky saliva, dry mouth, difficulties in swallowing and problems with the sense of taste and smell were the most severe symptoms reported by patients. In the follow-up, 79.2% of patients were reached (50.4% alive, 28.8% deceased). Mortality was significantly associated with age >65 years, weight loss at presentation and consumption of grilled/smoked food. The study highlights key aspects of NPC in our region including the predominance in males, advanced disease stage at presentation and persistent symptoms post-treatment. Our findings point to the need for targeted initiatives to improve early detection and quality of life for nasopharyngeal patients in the country.

The prognostic implications of radiologic extranodal extension in the lymph nodes of patients with nasopharyngeal cancer.

Objective: This study was developed to explore the prognostic relevance of radiologic extranodal extension (rENE) in lymph node-positive nasopharyngeal carcinoma (NPC) patients. Materials and methods: A retrospective review of data from 249 eligible patients with NPC was performed, with magnetic resonance imaging scans being used for rENE grading. The prognostic value of rENE was assessed through univariate and multivariate analyses. Results: Log-rank tests revealed significant differences between patients with and without rENE in terms of overall survival, progression-free survival (PFS) and distant metastasis-free survival (DMFS). G2 and G3 patients tended to exhibit worse PFS and DMFS relative to G0/G1 patients (p <0.05). Long-term chemotherapy cycles were associated with significant improvements in the PFS and DMFS of G2 and G3 patients. Conclusion: These results suggest that higher rENE grades (G2/G3) are independently associated with worse survival outcomes among NPC patients, with more aggressive treatment strategies potentially affording greater prognostic benefits to these individuals.

Establishment and validation of circulating cell-free DNA signatures for nasopharyngeal carcinoma detection

Early detection of nasopharyngeal carcinoma (NPC) poses a significant challenge. The absence of highly sensitive and specific diagnostic biomarkers for nasopharyngeal carcinoma contributes to the unfavourable prognosis of NPC patients. Here, we aimed to establish a non-invasive approach for detecting NPC using circulating cell-free DNA (cfDNA). We investigated the potential of next-generation sequencing (NGS) of peripheral blood cells as a diagnostic tool for NPC. We collected data on genome-wide nucleosome footprint (NF), 5'-end motifs, fragmentation patterns, CNV information, and EBV content from 553 Chinese subjects, including 234 NPC patients and 319 healthy individuals. Through case-control analysis, we developed a diagnostic model for NPC, and validated its detection capability. Our findings revealed that the frequencies of NF, fragmentation, and motifs were significantly higher in NPC patients compared to healthy controls. We developed an NPC score based on these parameters that accurately distinguished NPC from non-NPC cases according to the American Joint Committee on Cancer staging system from non-NPC (validation set: area under curve (AUC)=99.9% (95% CI: 99.8%-100%), se: 98.15%, sp: 100%). This model showed superior performance over plasma EBV DNA. Additionally, the NPC score effectively differentiated between NPC patients and healthy controls, even after clinical treatment. Furthermore, the NPC score was found to be independent of potential confounders such as age, sex, or TNM stage. We have developed and verified a non-invasive approach with substantial potential for clinical application in detecting NPC. A full list of funding bodies that contributed to this study can be found in Funding section.

5-Hydroxymethylcytosines in circulating cell-free DNA as a diagnostic biomarker for nasopharyngeal carcinoma

ObjectiveTo evaluate the diagnostic value of 5-hydroxymethylcytosines (5hmC) in circulating cell-free DNA (cfDNA) for nasopharyngeal carcinoma (NPC) and to develop a diagnostic model. MethodsGenome-wide 5hmC profiles in cfDNA from 174 NPC patients and 146 non-cancer individuals were analyzed using the 5hmC-Seal technique. A cfDNA 5hmC-based diagnostic model to identify NPC patients was developed using least absolute shrinkage and selection operator (LASSO) logistic regression, and performance was evaluated with receiver operating characteristic (ROC) curves and confusion matrices. ResultsThe 5hmC-Seal data from patients with NPC showed a different genome-wide distribution than non-tumor samples. Our initial analysis revealed a 12-gene-based 5hmC marker panel to be an accurate diagnostic model effectively distinguishing between NPC samples and non-cancerous samples (training set: area under curve (AUC)= 0.97 [95 % CI: 0.94–0.99]; and test set: AUC= 0.93 [95 % CI: 0.88–0.98]) superior to EBV DNA testing. The diagnostic score performed well in differentiating the non-cancer subjects from early-stage NPC (training set: AUC=0.99 [95 % CI: 0.98–1]; test set: AUC=0.98 [95 % CI: 0.95–1]), and advanced-stage NPC (training set: AUC=0.96 [95 % CI: 0.93–0.99]; test set: AUC=0.93 [95 % CI: 0.88–0.98]). Notably, in EBV-negative patients, the diagnostic scores showed excellent capacity for distinguishing EBV-negative patients with NPC from non-cancer subjects in both the training set (AUC= 0.94 [95 % CI: 0.88–1]) and test set (AUC=0.91 [95 % CI: 0.81–1]). Conclusion5hmC modifications in cfDNA are promising noninvasive biomarkers for NPC, offering high sensitivity and specificity, particularly for early-stage and EBV-negative NPC.

Efficacy of Thyroid Hormone Replacement Therapy in Nasopharyngeal Carcinoma Patients with Radiation-Induced Subclinical Hypothyroidism.

Hypothyroidism is a common side effect of radiotherapy for nasopharyngeal carcinoma. However, the impact of thyroid hormone replacement therapy on patients with radiation-induced subclinical hypothyroidism has not been extensively explored. This study aimed to analyze the efficacy of thyroid hormone replacement therapy in nasopharyngeal carcinoma patients with subclinical hypothyroidism. Patients diagnosed with nasopharyngeal carcinoma who developed subclinical hypothyroidism after definitive radiotherapy between September 2019 and December 2020 were selected for inclusion in this study. Prior to thyroid hormone replacement therapy and after maintaining euthyroidism for 6-12 months through thyroid hormone replacement therapy, assessments using the SF36 Brief Health Status Scale and the Hypothyroidism-related Symptom Questionnaire were conducted via trained questionnaires. Lipid profiles were assessed at baseline and after 6-12 months of thyroid hormone replacement therapy. Statistical analyses were performed using matched samples T-test or Mann-Whitney U test. The median follow-up period was 14.5 months. The median score of hypothyroid symptoms was 5.5 out of 19 points, with the most common symptoms being chills (65.0%), fatigue (50.0%), weight gain (45.0%), and limb numbness (40.0%). Thyroid hormone replacement therapy did not significantly improve the quality of life, hypothyroidism-related symptoms, or blood lipid profile in patients. However, there was an observed downward trend in serum cholesterol levels following treatment (P=0.052). Thyroid hormone replacement therapy did not have a significant impact on alleviating hypothyroid symptoms, improving quality of life, or enhancing lipid profiles in patients with radiation-induced subclinical hypothyroidism. Nevertheless, a potential decrease in serum cholesterol levels was noted after thyroid hormone replacement therapy.

Prognostic Study of Inflammatory Markers in Nasopharyngeal Carcinoma Patients Receiving Intensity-Modulated Radiotherapy.

Inflammatory markers in the blood have been linked to tumor prognosis, but their specific prognostic significance in nasopharyngeal carcinoma (NPC) patients undergoing intensity-modulated radiotherapy (IMRT) is not well established. This study aims to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in this patient population. A total of 406 non-metastatic NPC patients were included in the study. NLR, PLR, and LMR were stratified according to their average values. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS). Cox multivariate regression analysis was performed to evaluate the associations of NLR, PLR, and LMR with PFS and OS. Patients with NLR > 2.78had worse PFS (P = 0.008) and OS (P < 0.001); PLR > 162.48 was related to lower PFS (P = 0.018) but not OS (P = 0.29); LMR > 5.05 showed no significant difference in PFS and OS compared to LMR ≤ 5.05 (P values were 0.13 and 0.94, respectively). Multivariate analysis indicated that NLR was an independent prognostic factor for PFS (HR, 1.674; 95% CI, 1.006-2.784; P = 0.047) and OS (HR, 4.143; 95% CI, 2.111-8.129; P = 0.000), while PLR and LMR did not demonstrate significant associations with PFS and OS. This study identifies NLR as a novel and independent prognostic indicator for NPC patients receiving IMRT, offering valuable insights that could inform future clinical decision-making. In contrast, PLR and LMR did not demonstrate significant prognostic value in this context.

Circulating mRNA Expression of VEGF, PTEN, and SOCS1 as Potential Prognostic Predictor for Nasopharyngeal Carcinoma Progression.

The molecular mechanisms underlying nasopharyngeal carcinoma (NPC) progression remain poorly understood. In particular, the roles of circulating mRNAs encoding key regulatory proteins have yet to be explored. This study aimed to identify NPC-associated expression signatures of circulating VEGF, PTEN, and SOCS1 mRNAs and their potential as biomarkers. A case-control study was conducted comprising 160 nasopharyngeal carcinoma (NPC) patients and 80 controls, from whom peripheral blood samples. Total RNA was extracted and the levels of VEGF, PTEN, and SOCS1 mRNAs were quantified using reverse transcription quantitative PCR (RT-qPCR). Relative expression was calculated using the 2-ΔΔCt method. Bioinformatic analyses, including GeneMANIA, Gene Ontology (GO), and KEGG pathway analysis, were performed to predict the functional roles and interactions of these mRNAs. We identified significantly increased circulating VEGF mRNA in lymph node metastases (1.66-fold, p<0.05) and elevated SOCS1 mRNA in late-stage NPC (20-fold, p<0.05). PTEN mRNA was reduced 4.26-fold in NPC patients. These data suggest that circulating VEGF, PTEN, and SOCS1 mRNAs represent signatures of NPC progression and can potentially be biomarkers. Network analyses implicate these mRNAs in mechanisms enabling NPC pathogenesis. Our study reveals NPC-associated expression changes of circulating VEGF, PTEN, and SOCS1 mRNAs. These molecular signatures may serve as biomarkers during NPC progression and provide insights into underlying mechanisms. Further validation of their utility as prognostic indicators of NPC is warranted.

Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) combined with conventional MRI for the detection of skull-base invasion in nasopharyngeal carcinoma: comparison with 18F-sodium fluoride (18F-NaF) positron emission tomography/computed tomography (PET/CT).

The extent of skull base invasion (SBI) in nasopharyngeal carcinoma (NPC) directly impacts tumor staging, treatment strategies, and prognosis assessment for NPC patients, emphasizing the critical need for prompt diagnosis and precise assessment of invasion. Thus, we aimed to integrate the advantages of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and conventional magnetic resonance imaging (cMRI), and assess their combined diagnostic efficacy versus that of 18F-sodium fluoride (18F-NaF) positron emission tomography/computed tomography (PET/CT) for detecting SBI in NPC patients. The study prospectively and randomly recruited 62 patients newly diagnosed with NPC by pathological biopsy at the Cancer Center of Affiliated Hospital of Guangdong Medical University from January 2021 to September 2022. All patients underwent baseline cMRI, IVIM-DWI, and PET/CT scans. The IVIM-DWI analysis included 3 primary parameters: true diffusion coefficient (D), pseudodiffusion coefficient (D*), and pseudodiffusion fraction (f). SBI was defined as the involvement of any substructure confirmed by follow-up MRI and clinical symptoms. Inter-observer agreement was evaluated utilizing the intraclass correlation coefficients (ICC) and kappa coefficients. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of cMRI, IVIM-DWI plus cMRI, and PET/CT. DeLong test was used to compare the areas under the curve (AUC) of the 3 modalities. Excellent inter-observer reliability was observed (range, 0.841-0.946). Among the IVIM-DWI parameters, D* + f demonstrated comparable accuracy to D + D* + f (AUC 0.906 vs. 0.904; sensitivity 88.9% vs. 89.8%; specificity 92.3% vs. 91.0%). IVIM-DWI plus cMRI yielded an overall AUC of 0.947, sensitivity of 92.6%, and specificity of 96.8%, surpassing cMRI alone with an AUC of 0.914 (P=0.025), sensitivity of 91.2%, and specificity of 91.7%, as well as 18F-NaF PET/CT with an AUC of 0.852 (P<0.001), sensitivity of 80.1%, and specificity of 90.4%. In detecting substructures of SBI, IVIM-DWI plus cMRI showed superior performance compared to 18F-NaF PET/CT within the petrous part of the temporal bone (AUC 0.968 vs. 0.871, P=0.011; sensitivity 93.5% vs. 87.1%, specificity 100% vs. 87.1%), pterygopalatine fossa (AUC 0.935 vs. 0.831, P=0.032; sensitivity 93.9% vs. 69.7%, specificity 93.1% vs. 96.6%), and foramen ovale (AUC 0.885 vs. 0.710, P=0.019; sensitivity 76.9% vs. 61.5%, specificity 100% vs. 80.6%). IVIM-DWI plus cMRI can accurately detect SBI and the substructures in NPC, providing a valuable reference for personalized treatment strategies and precise prognosis assessment.

Primary and Orthotopic Murine Models of Nasopharyngeal Carcinoma Reveal Molecular Mechanisms Underlying its Malignant Progression.

Nasopharyngeal carcinoma (NPC), a squamous cell carcinoma originating in the nasopharynx, is a leading malignancy in south China and other south and east Asia areas. It is frequently associated with Epstein-Barr virus (EBV) infection, while there are also some NPC patients without EBV infection. Here, it is shown that the EBV+ (EBV positive) and EBV- (EBV negative) NPCs contain both shared and distinct genetic abnormalities, among the latter are increased mutations in TP53. To investigate the functional roles of NPC-associated genetic alterations, primary, orthotopic, and genetically defined NPC models were developed in mice, a key tool missed in the field. These models, initiated with gene-edited organoids of normal nasopharyngeal epithelium, faithfully recapitulated the pathological features of human disease. With these models, it is found that Trp53 and Cdkn2a deficiency are crucial for NPC initiation and progression. And latent membrane protein1 (LMP1), an EBV-coding oncoprotein, significantly promoted the distal metastasis. Further, loss of TGFBR2, which is frequently disrupted both in EBV- and EBV+ NPCs, dramatically accelerated the progression and lung metastasis of NPC probably by altering tumor microenvironment. Taken together, this work establishes a platform to dissect the genetic mechanisms underlying NPC pathogenesis and might be of value for future translational studies.

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

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

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.

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. 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. 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. A feasible and applicative prognostic score was established and validated to discriminate NPC patients into low- and high-risk groups.

Comparative dosimetric analysis of normal brain tissue in patients with Nasopharyngeal carcinoma at different stages after radiation therapy

IntroductionRadiotherapy (RT) is the main treatment for patients with nasopharyngeal carcinoma (NPC). NPC patients at different stages have varying levels of damage to normal brain tissue after RT. No study has yet thoroughly analyzed the variations in radiation dosages in the brain for different stages of NPC patients treated with RT. This study aims to examine these variations. Methods1446 NPC patients’ CT and RTdose data were retrospectively reviewed. Analysis of the radiation dosage was executed on these 803 patients. The RTdose images for several patient groups were averaged after registering each patient’s RTdose data to the CT brain template created in our earlier study. The voxel-based (VB) analysis was used to examine the dose variations in the brains of three groups of NPC patients: the early-stage group, the stage III group, and the stage IV group. ResultsAs the disease progresses from early to advanced stages, the intensity and volume of radiation in the brain increase. The normal brain tissue accepted a substantially larger dosage in more advanced NPC patients. Differences in brain regions between stage III and early-stage patients were minimal compared to any other two groups. Brain regions exhibited substantial variations between the stage IV group and all other patient groups were broadly distributed. ConclusionOur findings highlight the critical role of NPC staging in the therapeutic strategy, emphasizing the heterogeneity of radiation-induced tissue damage across disease stages and implying the need to develop stage-specific RT plans.

Identifying biomarkers for nasopharyngeal carcinoma diagnosis and chemoradiotherapy response using serum endogenous small molecules profiling

Changes in metabolic characteristics are important features of tumor progression and prognosis, including nasopharyngeal carcinoma (NPC). Identifying serum metabolites as potential diagnostic and chemoradiotherapy response biomarkers for NPC is therefore crucial. In this study, ultra-performance liquid chromatography coupled with linear ion trap quadrupole orbitrap high-resolution mass spectrometry (UPLC-LTQ-Orbitrap MS) was used to analyze metabolic variations among controls, NPC patients, and NPC patients undergoing chemoradiotherapy (CRT). Univariate and multivariate analyses revealed seven differential metabolites between the control and NPC groups and eleven metabolites between the CRT and NPC groups. Five common metabolites, gluconic acid, palmitic acid, LysoPC (15:0/0:0), stearic acid, and LysoPC (20:2(11Z,14Z)/0:0), were consistently altered across groups. Notably, the first four metabolites were adjusted closer to normal after chemoradiotherapy, while this change is not reflected at LysoPC (20:2(11Z,14Z)/0:0). These common metabolites were enriched in five pathways. These findings underscore the importance of serum metabolite profiling in NPC diagnosis and treatment response assessment and offer a promising foundation for further clinical research.

Intratumoral habitat radiomics based on magnetic resonance imaging for preoperative prediction treatment response to neoadjuvant chemotherapy in nasopharyngeal carcinoma.

The aim of this study is to determine intratumoral habitat regions from multi-sequences magnetic resonance imaging (MRI) and to assess the value of those regions for prediction of patient response to neoadjuvant chemotherapy (NAC) in nasopharyngeal carcinoma (NPC). Two hundred and ninety seven patients with NPC were enrolled. Multi-sequences MRI data were used to outline three-dimensional volumes of interest (VOI) of the whole tumor. The original imaging data were divided into two groups, which were resampled to an isotropic resolution of 1 × 1 × 1mm3 (group_1mm) and 3 × 3 × 3mm3 (group_3mm). Nineteen radiomics features were computed for each voxel of three sequences in group_3mm, within the tumor region to extract local information. Then, k-means clustering was implemented to segment the whole tumor regions in two groups. After radiomics features were extracted and dimension reduction, habitat models were built using Multi-Layer Perceptron (MLP) algorithm. Only T stage was included as the clinical model. The habitat3mm model, which included 10 radiomics features, achieved AUCs of 0.752 and 0.724 in the training and validation cohorts, respectively. Given the slightly better outcome of habitat3mm model, nomogram was developed in combination with habitat3mm model and T stage with the AUC of 0.749 and 0.738 in the training and validation cohorts. The decision curve analysis provides further evidence of the nomogram's clinical practicality. A nomogram based on intratumoral habitat predicts the efficacy of NAC in NPC patients, offering the potential to improve both the treatment plan and patient outcomes.

Efficacy analysis of endovascular treatment for ruptured internal carotid artery pseudoaneurysm hemorrhage in patients with nasopharyngeal carcinoma after radiotherapy.

This study aims to evaluate the efficacy and complications of endovascular treatment for hemorrhage caused by ruptured internal carotid artery pseudoaneurysms following radiotherapy in nasopharyngeal carcinoma (NPC) patients. This study retrospectively analyzed NPC patients who underwent endovascular treatment for ruptured internal carotid artery pseudoaneurysm hemorrhage after radiotherapy at Zhongshan People's Hospital from January 2016 to December 2022. The study aims to assess the postoperative hemostasis rate, postoperative rebleeding rate, complication rate, and 1-year postoperative survival rate. During the study period, 36 patients underwent endovascular treatment, of which 24 patients underwent embolization of the internal carotid artery and 12 patients underwent stenting of the internal carotid artery. The procedure success rate was 100%. The rebleeding rate at 1 year after the procedure was 5.6% (2/36, one patient with stent placement and one patient with coil embolization), and the complication rate was 11.1% (4/36, four patients with coil embolization patients). Two patients developed large-area cerebral infarction after the procedure, and two patients had different degrees of neurological impairment after the procedure. The 1-year survival rate was 91.7% (33/36). Ruptured internal carotid artery pseudoaneurysm hemorrhage after radiotherapy is rare but life-threatening. Endovascular treatment with coil occlusion or stenting reconstruction of the internal carotid artery provides immediate hemostasis and elimination of the pseudoaneurysm with a low rate of recurrence, which may be effective in reducing patient mortality.