Nasopharyngeal Cancer Research Articles

Nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Results of Polish multicenter observational study.

Patients with head and neck squamous cell carcinoma (HNSCC) who have progressed following primary treatment (PT) have a poor prognosis. In this group, nivolumab has been demonstrated to significantly improve outcomes. This study presents the efficacy of nivolumab in Polish patients with recurrent and/or metastatic (R/M) HNSCC using real-world data. The analyzed group consisted of 324 adult patients with R/M HNSCC following platinum-based therapy. Patients were divided into 3 groups based on the time from completion of PT to nivolumab initiation (tPT-N): within 6 months (refractory), between 6 and 24 months (sensitive, tPT-N ≤24), and beyond 24 months (sensitive, tPT-N >24). Survival analysis and the Cox proportional hazards model were performed to evaluate how various risk factors affect patient outcomes. The 1-year and 2-year overall survival (OS) was 19.1%, 6.1%, 30.7%, 9.4%, and 45.7%, 29.1% in refractory, sensitive tPT-N ≤24, sensitive tPT-N >24 patients, respectively and was higher for both sensitivity groups vs. refractory (p = .004) and for sensitive tPT-N >24 versus refractory and sensitive tPT-N ≤24 (p <.001). Patients with nasopharyngeal cancer had OS significantly higher than patients with other primary tumor localization. The multivariate Cox analysis showed a significant favorable effect of tPT-N >24 (HR = 0.53, p = .001) and nasopharyngeal cancer on OS (HR = 0.20, p = .008). Conversely, female sex was identified as an unfavorable factor for OS (HR = 1.48, p = .020). In our study, we established that the benefit of nivolumab increases with the increasing tPT-N. The probability of death is significantly lower in male patients and patients with nasopharyngeal cancer regardless of tPT-N.

Robust optimization incorporating weekly predicted anatomical CTs in IMPT of nasopharyngeal cancer.

Objective.This study proposes a robust optimization (RO) strategy utilizing virtual CTs (vCTs) predicted by an anatomical model in intensity-modulated proton therapy (IMPT) for nasopharyngeal cancer (NPC).Methods and Materials.For ten NPC patients, vCTs capturing anatomical changes at different treatment weeks were generated using a population average anatomy model. Two RO strategies of a 6 beams IMPT with 3 mm setup uncertainty (SU) and 3% range uncertainty (RU) were compared: conventional robust optimization (cRO) based on a single planning CT (pCT), and anatomical RO incorporating 2 and 3 predicted anatomies (aRO2 and aRO3). The robustness of these plans was assessed by recalculating them on weekly CTs (week 2-7) and extracting the voxel wise-minimum and maximum doses with 1 mm SU and 3% RU (voxmin\voxmax1mm3%).Results.The aRO plans demonstrated improved robustness in high-risk CTV1 and low-risk CTV 2 coverage compared to cRO plans. The weekly evaluation showed a lower plan adaptation rate for aRO3 (40%) vs. cRO (70%). The weekly nominal and voxmax1mm3%doses to OARs, especially spinal cord, are better controlled relative to their baseline doses at week 1 with aRO plans. The accumulated dose analysis showed that CTV1&2 had adequate coverage and serial organs (spinal cord and brainstem) were within their dose tolerances in the voxmin\voxmax1mm3%, respectively.Conclusion.Incorporating predicted weekly CTs from a population based average anatomy model in RO improves week-to-week target dose coverage and reduces false plan adaptations without increasing normal tissue doses. This approach enhances IMPT plan robustness, potentially facilitating reduced SU and further lowering OAR doses.

Biofilm formation and drug susceptibility of biofilm Candida spp. clinically isolated from nasopharyngeal cancer patients in Vietnam

Background and Objectives: The biofilm formation has been widely recognized as one of the main mechanisms of antimi- crobial resistance development in microorganisms. However, few studies are focusing on this phenomenon in Candida spp. in clinical settings, especially on immuno-compromised patients. Materials and Methods: In this study, both the rate of biofilm formation in those patients and its drug susceptibility in initial and mature biofilm were assessed using crystal violet assay and dilution method. Results: The results demonstrated that the biofilm formation rate was similar between albicans and non-albicans Candida. However, the biofilm formation capacity was more pronounced in non-albicans Candida, especially, C. glabrata. As expect- ed, there was a significant relationship between biofilm formation and drug resistance. In addition, our study reconfirmed that the age of high concentration of antifungal agents only affected Candida before its biofilm formation regardless of its biofilm formation capacity. In the contrary, once the biofilm was formed even elevated drug concentrations did not show sufficient efficacy, highlighting a need for high dosage at the early stage of treatment for those patients. Conclusion: The results of this study highlighted the importance of using appropriate antifungal agents for Candida treatment before the formation of biofilm.

Analysis of patients with parotid recurrence after parotid-sparing IMRT for nasopharyngeal carcinoma: case series and review of the literature.

Intensity-modulated radiotherapy (IMRT) is the standard treatment approach for nasopharyngeal cancer (NPC). IMRT enables effective sparing of the parotid glands and reduces the risk of xerostomia, acommon complication of head and neck irradiation. Nevertheless, it is essential to determine whether the parotid-sparing IMRT (ps-IMRT) technique yields increased intra-/periparotid recurrence rates, which constitutes the main purpose of this study. Patients with adiagnosis of NPC that received definitive chemoradiotherapy/radiotherapy (CRT/RT) between 1991 and 2021 were evaluated retrospectively. Patients with intra-/periparotid recurrence were detected and prognostic factors for recurrence were sought. Atotal of 746 patients were evaluated. Two-dimensional (2D)-RT was applied to 541, 3D conformal RT (3D-CRT) to 10, and ps-IMRT to 195 patients. After amedian 85-month follow-up, one (0.18%) patient who received 2D-RT and four (2%) patients who received ps-IMRT experienced an intra-/periparotid recurrence. The median time to intra-/periparotid recurrence was 11.9 months. All patients had been diagnosed with ametastatic lymph node > 2 cm at levelII of the ipsilateral neck. In addition, all recurrences occurred on the same side as the positive neck at the time of diagnosis. The 3‑year overall survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 80%, 40%, and 60%, respectively. Intra-/periparotid recurrence is extremely rare in NPC. However, it is still possible to identify and characterize particular risk factors, which include ametastatic lymph node at levelII, particularly > 2 cm, and multinodal disease at the time of diagnosis.

The prognostic value of tumor-infiltrating lymphocytes in head and neck squamous cell carcinoma: A systematic review and meta-analysis

Head and neck squamous cell carcinoma (HNSCC) is experiencing a rising incidence and mortality worldwide, emphasizing the need for reliable prognostic markers. Tumor-infiltrating lymphocytes (TILs) have emerged as a promising biomarker for predicting HNSCC prognosis, yet no systematic reviews have exclusively focused on hematoxylin and eosin (H&E)–stained formalin-fixed paraffin-embedded (FFPE) samples, which are routinely used in clinical practice. This systematic review and meta-analysis followed the PRISMA guidelines to examine the prognostic value of TILs in HNSCC using H&E-stained FFPE samples. Data were pooled from 43 studies, including 26 studies in a meta-analysis, analyzing 5037 HNSCC samples. We found that a high TIL count associated with a significantly improved overall survival (OS) (HR 0.47, 95 % CI 0.41–0.55, p < 0.0001), disease-free survival (DFS) (HR 0.55, 95 % CI 0.41–0.55, p < 0.0001), and disease-specific survival (DSS) (HR 0.58, 95 % CI 0.46–0.73, p < 0.0001). The heterogeneity was moderate for the pooled analysis (OS: I² = 40 %; DFS: I² = 39 %; DSS: I² = 51 %), but low for the subgroup analysis based on tumor site in oral, oropharyngeal, laryngeal, and nasopharyngeal cancer (OS and DFS: I² = 0–14 %). This review is the first to systematically evaluate TILs in HNSCC using H&E-stained samples, confirming their prognostic value. A high TIL count is associated with improved survival outcomes, suggesting their potential as prognostic biomarkers in clinical settings.

Salvage Endoscopic Nasopharyngectomy for Recurrent Nasopharyngeal Cancer: an Institutional Experience.

This study aims to present the surgical and oncological long-term outcomes of patients with locally recurrent nasopharyngeal cancer (NPC) following endoscopic endonasal nasopharyngectomy (EEN). The medical records of 11 patients who underwent EEN due to recurrent NPC were retrospectively reviewed. The mean age of the patient cohort, consisting of 10 males (90.9%) and one female (9.1%), was 44±13.01 years at the time of initial diagnosis. Seven patients (63.7%) had local recurrence, and four patients (36.3%) had loco-regional recurrence. The mean time to first recurrence from the initial diagnosis was 40.3 months, with a 5-year overall survival (OS) rate of 72.7% and a disease-free survival (DFS) rate of 27.3%. There were no significant differences between the concurrent chemoradiotherapy (CRT) and induction chemotherapy+concurrent CRT treatment groups in terms of DFS and OS as a first-line treatment (p=0.645). EEN is a viable alternative approach for selected cases of locally recurrent NPC, considering the morbidities associated with re-irradiation.

Staging and Prognosis of Nasopharyngeal Cancer

Staging and Prognosis of Nasopharyngeal Cancer

The unique CARWL score stratifies locally advanced nasopharyngeal cancer patients receiving concurrent chemoradiotherapy into risk groups for radiation-induced trismus

PurposeTo determine the utility of the novel CARWL score, which integrates C-reactive protein-to-albumin ratio (CAR) and significant weight loss (SWL), in stratifying the locally advanced nasopharyngeal carcinoma (LA-NPC) patients into significantly different radiation-induced trismus (RIT) risk groups following definitive C-CRT.Patients and methodsThis retrospective study analyzed the medical records of 286 LA-NPC patients who received C-CRT between January 2010 and December 2022. The maximum mouth opening (MMO) was measured before the C-CRT, at 1, 3, 6, 9, and 12 months, and every 6 months after that during the follow-up. Additionally, the CAR value just before the commencement of C-CRT and SWL defined as a weight loss > 5% in the preceding six months were documented for each patient. RIT was defined as a MMO ≤ 35 mm.ResultsThe optimal CAR cut-off was 3.03 (area under the curve: 87.3%; sensitivity: 82.6%; specificity: 80.9%, J-index: 0.635), using receiver operating characteristic (ROC) curve analysis, with RIT incidence being the event. We stratified the patients into three CARWL score groups. CARWL-0: CAR < 3.0 and WL ≤ 5.0% (N = 92), CARWL-1: CAR < 3.0 and WL > 5.0% or CAR ≥ 3.0 (N = 99), and WL ≤ 5.0% and CARWL-2: CAR > 3.0 and WL > 5.0% (N = 95). The incidence of RIT increased significantly across CARWL score groups (8.7% for CARWL-0, 23.2% for CARWL-1, and 44.2% for CARWL-2; P < 0.001).ConclusionThe current study indicated that the novel CARWL scoring system is efficient in precisely stratifying LA-NPC patients into distinct RIT risk groups after C-CRT.

Ninth Version of the AJCC and UICC Nasopharyngeal Cancer TNM Staging Classification

Accurate staging is a fundamental step in treating patients with nasopharyngeal carcinoma (NPC) worldwide; this is crucial not only for prognostication, but also for guiding treatment decisions. The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) system is the global language for clinicians, researchers, and cancer registries. Continual improvement that aligns with contemporary pattern of care is essential. To improve the prognostic accuracy and clinical applicability of the eighth edition (TNM-8) for NPC. This multicenter study analyzed patients with NPC with detailed tumor features during January 2014 and December 2015 and was reviewed by experienced radiologists. The data analysis was completed in December 2023. The findings were further confirmed with internal and external validation. Statistical analyses and clinical considerations were reviewed by the AJCC/UICC multidisciplinary head and neck panels and attained consensus. The recommendations were evaluated by the AJCC Evidence-Based Medicine Committee before final endorsement as the ninth version (TNM-9). The primary end point was overall survival. Adjusted hazard ratios of different subgroups were then assessed for confirmation of optimal stage grouping. Of the 4914 patients analyzed, 1264 (25.7%) were female and 3650 (74.3%) were male; the median (SD) age was 48.1 (12.0) years. Advanced radiological extranodal extension (with involvement of adjacent muscles, skin, and/or neurovascular bundles) was identified as an independent adverse factor for all end points: this was added as a criterion for N3. Patients with nonmetastatic disease were regrouped into stages I to III instead of TNM-8 stages I to IVA. Significant hazard discrimination was achieved by grouping T1-2N0-1 as stage I, T3/N2 as stage II, and T4/N3 as stage III. Although the T1-2N0-1 subgroups had comparable 5-year overall survival, subdivisions into IA (T1-T2N0) and IB (T1-T2N1) were recommended due to the distinction in adjusted hazard ratios following adjustment for chemotherapy use. Metastatic disease was exclusively classified as stage IV, and prognostication was further refined by subdivision into IVA (M1a, ≤3 lesions) and IVB (M1b, >3 lesions). TNM-9 demonstrated superiority compared with TNM-8 in major statistical aspects. The results of this diagnostic study suggest that the ninth version of TNM staging for NPC, based on robust analyses and a comprehensive review by the AJCC/UICC staging committees, provides an improved staging system for global application and a framework for future incorporation of nonanatomical factors. This will be launched for global application in January 2025.

Nasopharyngeal, tongue and laryngeal cancer in Southern Ethiopia: a seven-year retrospective cross-sectional review

Nasopharyngeal, tongue and laryngeal cancer in Southern Ethiopia: a seven-year retrospective cross-sectional review

Dosimetric Comparison and Selection Criteria of Intensity-Modulated Proton Therapy and Intensity-Modulated Radiation Therapy for Adaptive Re-Plan in T3-4 Nasopharynx Cancer Patients.

Proton therapy requires caution when treating patients with targets near neural structures. Intuitive and quantitative guidelines are needed to support decision-making concerning the treatment modality. This study compared dosimetric profiles of intensity-modulated proton therapy (IMPT) and intensity-modulated radiation therapy (IMRT) using helical tomotherapy (HT) for adaptive re-planning in cT3-4 nasopharyngeal cancer (NPCa) patients, aiming to establish criteria for selecting appropriate treatment modalities. HT and IMPT plans were generated for 28 cT3-4 NPCa patients undergoing definitive radiotherapy. Dosimetric comparisons were performed for target coverage and high-priority organs at risk (OARs). The correlation between dosimetric parameters and RT modality selection was analyzed with the target OAR distances. Target coverages were similar, while IMPT achieved better dose spillage. HT was more favorable for brainstem D1, optic chiasm Dmax, optic nerves Dmax, and p-cord D1. IMPT showed advantages for oral cavity Dmean. Actually, 14 IMPT and 14 HT plans were selected as adaptive plans, with IMPT allocated to most cT3 patients (92.9% vs. 42.9%, p = 0.013). The shortest distances from the target to neural structures were negatively correlated with OAR doses. Receiver operating characteristic curve analyses were carried out to discover the optimal cut-off values of the shortest distances between the target and the OARs (temporal lobes and brainstem), which were 0.75 cm (AUC = 0.908, specificity = 1.00) and 0.85 cm (AUC = 0.857, specificity = 0.929), respectively. NPCa patients with cT4 tumor or with the shortest distance between the target and critical neural structures < 0.8 cm were suboptimal candidates for IMPT adaptive re-planning. These criteria may improve resource utilization and clinical outcomes.

Association between cigarette smoking and nasopharyngeal cancer risk: a meta-analysis.

Nasopharyngeal cancer (NPC) is a relatively rare yet aggressive malignancy, primarily affecting regions of East and Southeast Asia. This study aims at providing an up-to-date quantification of the association between cigarette smoking and NPC risk, overall and by histological subsites. We conducted a systematic review and meta-analysis of case-control and cohort studies on the association between cigarette smoking and NPC risk published up to May 2023. The methodology used is original and efficient and includes both a comprehensive umbrella review and a traditional review. We estimated pooled relative risks (RR) of NPC according to smoking status, intensity, duration, and time since quitting. Among 46 eligible articles, 40 original studies were included in this meta-analysis. Compared with never smokers, the pooled RR of NPC was 1.61 for current, 1.28 for former, and 1.62 for ever smokers. The RR for ever compared with never smokers was 2.37 for squamous cell NPC and 1.06 for undifferentiated NPC. NPC risk significantly increased linearly with smoking intensity and duration, and decreased linearly with increasing time since quitting. This meta-analysis confirms the link between tobacco smoking and NPC, highlighting the significant risk posed even by moderate cigarette consumption. Additionally, our findings underscore the differential risk between squamous cell and undifferentiated subtypes of NPC, shedding light on the distinct implications for NPC prevention strategies.

Fractionated irradiation promotes radioresistance and decreases oxidative stress by increasing Nrf2 of ALDH-positive nasopharyngeal cancer stem cells

Radiotherapy is widely regarded as the primary therapeutic modality for nasopharyngeal cancer (NPC). Studies have shown that cancer cells with high resistance to radiation, known as radioresistant cancer cells, may cause residual illness, which in turn might contribute to the occurrence of cancer recurrence and metastasis. It has been shown that cancer stem-like cells (CSCs) exhibit resistance to radiation therapy. In the present study, fractionated doses of radiation-induced epithelial-mesenchymal transition (EMT) and ALDH+ CSCs phenotype of NPC tumor spheroids. Furthermore, it has been shown that cells with elevated ALDH activity have increased resistance to the effects of fractionated irradiation. Nuclear factor erythroid-2-related factor 2 (Nrf2) plays a pivotal role in regulating cellular antioxidant systems. A large body of evidence suggests that Nrf2 plays a significant role in the development of radioresistance in cancer. The authors’ research revealed that the application of fractionated irradiation resulted in a decline in Nrf2-dependent reactive oxygen species (ROS) levels, thereby mitigating DNA damage in ALDH+ stem-like NPC cells. In addition, immunofluorescence analysis revealed that subsequent to the process of fractionated irradiation of ALDH+ cells, activated Nrf2 was predominantly localized inside the nucleus. Immunofluorescent analysis also revealed that the presence of the nuclear Nrf2+/NQO1+/ALDH1+ axis might potentially serve as an indicator of poor prognosis and resistance to radiotherapy in patients with NPC. Thus, the authors’ findings strongly suggest that the radioresistance of ALDH-positive NPC CSCs to fractionated irradiation is regulated by nuclear Nrf2 accumulation. Nrf2 exerts its effects through the downstream effector NQO1/ALDH1, which depends on ROS attenuation.

Impacts of Employment Status, Partnership, Cancer Type, and Surgical Treatment on Health-Related Quality of Life in Irradiated Head and Neck Cancer Survivors

Objectives: This study aimed to examine the relationship between health-related quality of life (HRQoL) and sociodemographic and clinical variables in survivors of head and neck cancer (HNC) treated with radiotherapy, with or without surgery. Materials and Methods: HRQoL was measured using the functional assessment of cancer therapy—head and neck (FACT-H&amp;N) in a cross-sectional survey involving 150 patients. Of these, 60 had nasopharyngeal cancer (NPC), treated exclusively with radiotherapy, while 90 had oral cavity squamous cell cancer (OSCC), undergoing radical surgery followed by adjuvant radiotherapy. Key variables included cancer type, age, gender, partnership status, education, and employment, with additional clinical variables assessed in patients with OSCC. Statistical analyses included multiple regression, ANOVA, and t-tests to explore relationships between variables and HRQoL. Results: Cancer type, surgical treatment, and employment status emerged as significant independent predictors of HRQoL in HNC patients. Patients with NPC reported better HRQoL on three FACT-H&amp;N subscales—social/family well-being, functional well-being, and additional concerns—compared to patients with OSCC. Unemployed individuals exhibited lower HRQoL on four subscales. In patients with OSCC, partnership status and segmental mandibulectomy were found to predict HRQoL independently. Conclusions: This study concludes that cancer type, surgical intervention, and employment status notably influence HRQoL among HNC patients undergoing radiotherapy. In addition, partnership status is a key factor affecting HRQoL in patients with OSCC.

Boosting Antioxidant Defense: The Effect of Astaxantin on Superoxidase Dismutase and Malondialdehyde Reduction in Patients with Head and Neck Cancer Receiving Cisplatin Chemotherapy.

Background: Superoxide dismutase (SOD) can be decreased and malondialdehyde (MDA) can be increased in patients with head and neck cancer (HNC) as a result of reactive oxygen species (ROS) brought on by cisplatin. Astaxanthin is one of the external antioxidants required to combat ROS by raising SOD and lowering MDA. The purpose of this study is to demonstrate that astaxanthin can raise SOD and lower MDA in patients with HNC caused by cisplatin. Methods: 42 research subjects were randomly assigned to two groups in a double-blind, randomized controlled trial pre-post test design. Astaxanthin 4 mg BID was administered to the treatment group, whereas a single dosage of 500 mg of vitamin C and 250 mg of vitamin E IU was given to the control group. According to the Mann Whitney test, if p < 0.05, there is a significant difference in the delta of the decrease in SOD and MDA levels between the astaxanthin and vitamin C & E groups. Results: There were 42 research subjects, with a mean age of 48.2 years, a 2:1 male to female ratio, 23 (54.8%) with nasopharyngeal cancer, 32 (76.2%) with stage IV, 14 (33.3%) with cycle IV, 24 (57.1%) with paclitaxel-Cisplatin, 31 (73.8%) with Eastern Cooperative Oncological Group (ECOG) I, and 31 (73.8%) with Normal Body Mass Index. While there was a substantial drop in MDA (p=0.000), there was no significant difference in the delta reduction in SOD (p=0.443). Conclusion: Patients with HNC who receive cisplatin chemotherapy can have an increase in SOD and a decrease in MDA after receiving astaxanthin for 21 days.

The genetically predicted causal associations between circulating 3-hydroxybutyrate levels and malignant neoplasms: A pan-cancer Mendelian randomization study

The ketogenic diet or exogenous supplementation with 3-hydroxybutyrate (3HB) is progressively gaining recognition as a valuable therapeutic or health intervention strategy. However, the effects of 3HB on cancers have been inconsistent in previous studies. This study aimed to comprehensively investigate the causal effects of circulating 3HB levels on 120 cancer phenotypes, and explore the 3HB mediation effect between liver fat accumulation and cancers. Univariate Mendelian randomization (UVMR) was used in this study to investigate the causal impact of circulating 3HB levels on cancers. We conducted meta-analyses for 3HB-cancer associations sourced from different exposure data. In multivariate MR(MVMR), the body mass index, alcohol frequency and diabetes were included as covariates to investigate the independent effect of 3HB on cancer risk. Additionally, utilizing mediation MR analysis, we checked the potential mediating role of 3HB in the association between liver fat and cancer. Integrating findings from UVMR and MVMR, we observed that elevated circulating 3HB levels were associated with reduced risk of developing diffuse large B-cell lymphoma(DLBCL) (OR[95%CI]=0.28[0.14-0.57] p=3.92e-04), biliary malignancies (OR[95%CI]=0.30[0.15-0.60], p=7.67e-04), hepatocellular carcinoma(HCC) (OR[95%CI]=0.25[0.09-0.71], p=9.33e-03), primary lymphoid and hematopoietic malignancies (OR[95%CI]=0.76[0.58-0.99], p=0.045). Further UVMR analysis revealed that an increase in the percent liver fat was associated with reduced 3HB levels (Beta[95%CI]=-0.073[-0.122∼-0.024], p=0.0034) and enhanced susceptibility to HCC (OR[95%CI]=13.9[9.76-19.79], p=3.14e-48), biliary malignancies (OR[95%CI]=4.04[3.22-5.07], p=1.64e-33), nasopharyngeal cancer (OR[95%CI]=3.26[1.10-9.67], p=0.03), and primary lymphoid and hematopoietic malignancies (OR[95%CI]=1.27[1.13-1.44], p=1.04e-4). Furthermore, 3HB fully mediated the effect of liver fat on susceptibility to DLBCL (OR[95%CI]=1.076[1.01-1.15], p=0.034). Circulating 3HB is associated with a reduced susceptibility to developing DLBCL, HCC, biliary malignancies, and primary lymphoid and hematopoietic malignancies. The impaired ketogenesis induced by metabolic-dysfunction associated fatty liver disease (MAFLD) contributes to risk of DLBCL.

RRFERV stabilizes TEAD1 expression to mediate nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis.

Long noncoding RNAs (lncRNAs) regulate various essential biological processes, including cell proliferation, differentiation, apoptosis, migration, and invasion. However, in nasopharyngeal carcinoma (NPC), the clinical significance and mechanisms of lncRNAs in malignant progression are unknown. RNA sequencing and bioinformatic analysis were used to determine the potential function of RRFERV (radiation-resistant but ferroptosis vulnerable), and its biological effects were investigated using in vitro and in vivo experiments. Western blotting, quantitative real-time reverse transcription PCR, RNA immunoprecipitation (RIP) assays, and flow cytometry detected RRFERV expression. Ferroptosis and lipid peroxidation were added to evaluate the relationship between it and radiotherapy resistance. LncRNA-RRFERV was both highly expressed in NPC tissues and radiation-resistant cells. RRFERV is associated with poor clinical outcomes of NPC patients and stabilizes TEAD1 by competitive binding with microRNA-615-5p and microRNA-1293. RRFERV-TEAD1 signaling axis leads to malignant progression and radiotherapy resistance of NPC. Furthermore, we observed that NPC radiotherapy resistance cells exist in a fragile oxidative stress equilibrium, which makes them more sensitive to ferroptosis inducers. Surprisingly, we found that RRFERV-TEAD1 signaling axis also plays a key role in mediating the lipid peroxidation levels of NPC radiotherapy resistance cells through transcriptional activation of ACSL4/TFRC. RRFERV serves as an independent prognostic factor in NPC. During the malignant progression of NPC caused by high expression of RRFERV, ferroptosis can be induced to effectively kill cancer cells and reverse the radiotherapy resistance of NPC cells, suggesting a potential treatment approach for recurrent and refractory NPC.

Treatment Responses of Pakistani Nasopharyngeal Carcinoma Patients Treated with Induction Chemotherapy Followed by Concurrent Chemoradiotherapy

Objective: To investigate the response of nasopharyngeal cancer patients to induction chemotherapy, followed by concurrent chemoradiation, in our patient population. Study Design: Retrospective cohort study

Optimizing Hearing Outcomes in Nasopharyngeal Cancer Survivors in the Era of Modern Radiotherapy and Systemic Therapy.

Intensity-modulated radiation therapy (IMRT) improves disease control and reduces treatment-related toxicity in patients with localized nasopharyngeal carcinoma (NPC). However, due to the proximity of the auditory apparatus to the treatment volume and the frequent incorporation of cisplatin-based chemotherapy, treatment-related sensorineural hearing loss (SNHL) remains a common debilitating complication among NPC survivors. The reported crude incidence of SNHL following IMRT for NPC varies widely at 1-46% due to differences in auditory assessment methods and thresholds, follow-up durations, chemotherapy usage, and patient compositions. International guidelines and radiation dosimetric studies have recommended constraining the cochlear mean dose to less than 44-50 Gy, but the risk of SNHL remains high despite adherence to these constraints. Potential strategies to improve hearing outcomes in NPC survivors include cautious de-escalation of radiotherapy dose and volume, individualization of cochlear constraints, optimization of radiotherapy planning techniques, and the use of substitutes or alternative schedules for cisplatin-based chemotherapy. The addition of immune checkpoint inhibitors to chemoradiotherapy did not impact ototoxicity. Prospective studies that employ both objective and patient-reported auditory outcomes are warranted to test the long-term benefits of various approaches. This article aims to provide a comprehensive review of the incidence and radiation dose-toxicity relationship of SNHL in NPC survivors and to summarize potential strategies to optimize hearing outcomes in relation to nuances in radiotherapy planning and the selection of systemic therapy.

Predicting osteoradionecrosis risk in patients with locoregionally advanced nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy: The value of the CARWL index.

Osteoradionecrosis (ORN) is a severe complication that can arise in patients with nasopharyngeal carcinoma due to the aggressive nature of chemoradiotherapy treatment. The purpose of our study was to assess the utility of the recently introduced CARWL index, which integrates the C-reactive protein-to-albumin ratio (CAR) and significant weight loss (SWL), in predicting the risk of ORN in patients with locoregionally advanced nasopharyngeal cancer (LA-NPC) undergoing concurrent chemoradiotherapy (CCRT). We conducted a retrospective cohort analysis on 304 patients with LA-NPC treated with CCRT. Patients were categorized into CARWL index groups based on CAR (cut-off: 3.0) and SWL (weight loss > 5% over the past six months): CARWL-0 (CAR < 3.0, SWL ≤ 5%), CARWL-1 (CAR < 3.0 with SWL > 5% or CAR ≥ 3.0 with SWL ≤ 5%), and CARWL-2 (CAR ≥ 3.0 and SWL > 5%). The primary endpoint was the incidence of ORN in each CARWL index group. At a median follow-up of 67.2 months, 28 patients (9.2%) developed ORN. The incidence of ORN was 2.1%, 9.4%, and 16.3% in the CARWL-0, CARWL-1, and CARWL-2 groups, respectively (P < 0.001). Multivariate analysis identified smoking status (HR: 2.58, P = 0.034), N-stage (HR: 1.96, P = 0.008), T-stage (HR: 1.84, P = 0.017), pre-CCRT tooth extraction status (HR: 5.81, P < 0.001), post-CCRT tooth extraction status (HR: 6.82, P < 0.001), mandibular V55.8 Gy (HR: 6.12, P < 0.001), and CARWL score (HR: 5.67, P = 0.002) as significant predictors of ORN. The CARWL index is a reliable predictive tool for evaluating the risk of ORN in LA-NPC patients undergoing CCRT. If further validated, its use in clinical settings could aid in the early identification of high-risk patients and enable the implementation of personalized preventive strategies.