Induction chemotherapy regimes in first-line treatment for locoregionally advanced nasopharyngeal carcinoma: A network meta-analysis and cost-effectiveness analysis.

OBJECTIVE: The aim of this study is to evaluate the efficacy and cost-effectiveness of various induction chemotherapy (IC) regimens as first-line treatment for Locoregionally advanced nasopharyngeal carcinoma (LA-NPC), aiming to provide clinicians and patients with informed insights to aid in treatment decision-making. PATIENTS AND METHODS: We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based on data from 10 clinical trials investigating IC regimens for the treatment of LA-NPC. A Bayesian NMA was performed, with the primary outcomes being hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS). To model the disease progression of LA-NPC, we developed a dynamic partitioned survival model consisting of three disease states: progression-free survival (PFS), progression disease (PD), and death. The model was run on a 3-week cycle for a research period of 10 years, with quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) serving as outcome measures. RESULTS: According to the surface under the cumulative ranking curve (SUCRA) estimates derived from the NMA, TPC and TP, as IC regimens, appear to exhibit superior efficacy compared to other treatment modalities. In terms of CEA, concurrent chemoradiotherapy (CCRT), TPF + CCRT, and GP + CCRT were found to be dominated (more costs and less QALYs). Comparatively, TPC + CCRT emerged as a cost-effective option with an ICER of $1260.57/QALY when compared to PF + CCRT. However, TP + CCRT demonstrated even greater cost-effectiveness than TPC + CCRT, with an associated increase in costs of $3300.83 and an increment of 0.1578 QALYs per patient compared to TPC + CCRT, resulting in an ICER of $20917.62/QALY. CONCLUSION: Based on considerations of efficacy and cost-effectiveness, the TP + CCRT treatment regimen may emerge as the most favorable first-line therapeutic approach for patients with LA-NPC.

Global burdens of nasopharyngeal carcinoma in children and young adults and predictions to 2040.

OBJECTIVES: To investigate the epidemiological trend for nasopharyngeal carcinoma among children and young adults and the disease burden they caused. MATERIALS AND METHODS: Data were collected from the Global Burden of Disease (GBD) study 2019. A comprehensive analysis was performed, with age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), disability-adjusted life-years (DALYs) and estimated annual percentage changes (EAPC). And decomposition and frontier analyses were done. Future trends were predicted using Bayesian age-period-cohort model. RESULTS: Globally, there were decreases in the ASIR (EAPC -0.175, 95 % confidence interval [CI]: -0.352 to 0.002), ASMR (EAPC -2.681, 95 % CI: -2.937 to -2.424), and age-standardized DALYs rates (EAPC -2.643, 95 % CI: -2.895 to -2.391). However, the ASIR for males in global (EAPC 0.454, 95 % CI: 0.302 to 0.606), Asia (EAPC 0.782, 95 % CI: 0.610 to 0.954) and America (EAPC 0.448, 95 % CI: 0.379 to 0.517), as well as females in European (EAPC 0.595, 95 % CI: 0.479 to 0.712) and American (EAPC 0.369, 95 % CI: 0.324 to 0.415), showed an increasing trend. The future ASIR per 100,000 will likely show a slight upward trend in 2020 to 2040 (increased from 0.254 to 0.284), particularly among females (increased from 0.177 to 0.206), and a continued decline in ASMR for both sexes (decreased from 0.070 to 0.061). CONCLUSIONS: Globally, NPC in children and young adults remains a major public health issue, with the global distribution and magnitude of the burden varies markedly, highlighting the need to formulate regional and population-based policies for primary prevention.

Optimization and Local Cost-Effectiveness of Nasopharyngeal Carcinoma Screening Strategies in Southern China: Secondary Analysis of the Guangdong Randomized Trial.

BACKGROUND: Screening with anti-Epstein-Barr virus (EBV) serology and endoscopy decreased nasopharyngeal carcinoma (NPC) mortality in Guangdong in a randomized trial. We conducted a secondary analysis of this trial using local incidence and cost data to optimize screening programs, hypothesizing that screening could be cost-effective in southern China. METHODS: Screening costs and life-years after NPC diagnosis were obtained from the Guangdong trial's intent-to-screen population (men and women aged 30-69). Seropositive subjects were rescreened annually for 5 years. Thereafter, we evaluated 12 screening strategies in Guangdong and Guangxi using a validated model. Strategies used combinations of serology, nasopharyngeal swab PCR (NP PCR), endoscopy, and MRI from trial subcohorts. Incidence data and costs were obtained from local cancer registries and the provincial healthcare system. RESULTS: In the intent-to-screen population, screening with serology and endoscopy was cost-effective (¥42,366/life-year, 0.52 GDP per capita). Screening for 5 to 15 years between ages 35 and 59 years met a willingness-to-pay threshold of 1.5 GDP/quality-adjusted life-years in all modeled populations. Despite doubling costs, adding MRI could be cost-effective via improved sensitivity. NP PCR triage reduced endoscopy/MRI referrals by 37%. One-lifetime screen could reduce NPC mortality by approximately 20%. CONCLUSIONS: EBV-based serologic screening for NPC is likely to be cost-effective in southern China. Among seropositive subjects, the preferred strategies use endoscopy alone or selective endoscopy triaged by MRI with or without NP PCR. These data may aid the design of screening programs in this region. IMPACT: These findings support population-based screening in southern China by defining the target population, cost-effectiveness, and optimized screening approach.

Establishing subdivisions of M1 stage nasopharyngeal carcinoma based on decision tree classification: A multicenter retrospective study.

OBJECTIVES: To meet the demand for personalized treatment, effective stratification of patients with metastatic nasopharyngeal carcinoma (mNPC) is essential. Hence, our study aimed to establish an M1 subdivision for prognostic prediction and treatment planning in patients with mNPC. MATERIALS AND METHODS: This study included 1239 patients with mNPC from three medical centers divided into the synchronous mNPC cohort (smNPC, n = 556) to establish an M1 stage subdivision and the metachronous mNPC cohort (mmNPC, n = 683) to validate this subdivision. The primary endpoint was overall survival. Univariate and multivariate Cox analyses identified covariates for the decision-tree model, proposing an M1 subdivision. Model performance was evaluated using time-dependent receiver operating characteristic curves, Harrell's concordance index, calibration plots, and decision curve analyses. RESULTS: The proposed M1 subdivisions were M1a (≤5 metastatic lesions), M1b (>5 metastatic lesions + absent liver metastases), and M1c (>5 metastatic lesions + existing liver metastases) with median OS of 34, 22, and 13 months, respectively (p < 0.001). This M1 subdivision demonstrated superior discrimination (C-index = 0.698; 3-year AUC = 0.707) and clinical utility over those of existing staging systems. Calibration curves exhibited satisfactory agreement between predictions and actual observations. Internal and mmNPC cohort validation confirmed the robustness. Survival benefits from local metastatic treatment were observed in M1a, while immunotherapy improved survival in patients with M1b and M1c disease. CONCLUSION: This novel M1 staging strategy provides a refined approach for prognostic prediction and treatment planning in patients with mNPC, emphasizing the potential benefits of local and immunotherapeutic interventions based on individualized risk stratification.

Polygenic risk-stratified screening for nasopharyngeal carcinoma in high-risk endemic areas of China: a cost-effectiveness study.

Background: Nasopharyngeal carcinoma (NPC) has an extremely high incidence rate in Southern China, resulting in a severe disease burden for the local population. Current EBV serologic screening is limited by false positives, and there is opportunity to integrate polygenic risk scores for personalized screening which may enhance cost-effectiveness and resource utilization. Methods: A Markov model was developed based on epidemiological and genetic data specific to endemic areas of China, and further compared polygenic risk-stratified screening [subjects with a 10-year absolute risk (AR) greater than a threshold risk underwent EBV serological screening] to age-based screening (EBV serological screening for all subjects). For each initial screening age (30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 years), a modeled cohort of 100,000 participants was screened until age 69, and then followed until age 79. Results: Among subjects aged 30 to 54 years, polygenic risk-stratified screening strategies were more cost-effective than age-based screening strategies, and almost comprised the cost-effectiveness efficiency frontier. For men, screening strategies with a 1-year frequency and a 10-year absolute risk (AR) threshold of 0.7% or higher were cost-effective, with an incremental cost-effectiveness ratio (ICER) below the willingness to pay (¥203,810, twice the local per capita GDP). Specifically, the strategies with a 10-year AR threshold of 0.7% or 0.8% are the most cost-effective strategies, with an ICER ranging from ¥159,752 to ¥201,738 compared to lower-cost non-dominated strategies on the cost-effectiveness frontiers. The optimal strategies have a higher probability (29.4-35.8%) of being cost-effective compared to other strategies on the frontier. Additionally, they reduce the need for nasopharyngoscopies by 5.1-27.7% compared to optimal age-based strategies. Likewise, for women aged 30-54 years, the optimal strategy with a 0.3% threshold showed similar results. Among subjects aged 55 to 69 years, age-based screening strategies were more cost-effective for men, while no screening may be preferred for women. Conclusion: Our economic evaluation found that the polygenic risk-stratified screening could improve the cost-effectiveness among individuals aged 30-54, providing valuable guidance for NPC prevention and control policies in endemic areas of China.

Toripalimab plus chemotherapy in American patients with recurrent or metastatic nasopharyngeal carcinoma: A cost-effectiveness analysis.

BACKGROUND: Toripalimab, combined with gemcitabine and cisplatin, has been approved as the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), representing a significant milestone as the first FDA-approved innovative therapy for this condition. Despite this achievement, there's a lack of data on the cost-effectiveness of toripalimab for RM-NPC patients in the American context. METHODS: To assess the cost-effectiveness of toripalimab plus chemotherapy versus chemotherapy alone, a 3-state partitioned survival model was constructed. The study involved participants with characteristics matching those in the JUPITER-02 trial. Cost and utility inputs were collected from literature. Main outcomes measured were quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). Univariate and probabilistic sensitivity analyses, subgroup analyses, and scenario analyses were conducted to verify the robustness of results. RESULTS: The study found that the toripalimab regimen resulted in 4.390 QALYs at a cost of $361,813, while the chemotherapy-only regimen yielded 1.685 QALYs at a cost of $161,632. This translates to an ICER of $74,004/QALY, below the willingness-to-pay threshold of $150,000/QALY. Sensitivity analyses indicated that utility values, discount rate, and the price of toripalimab significantly impact INMB. With an 87.10% probability of being cost-effective at a $150,000/QALY threshold, the probabilistic sensitivity analysis supports toripalimab plus chemotherapy as a viable option. Scenario analysis showed that toripalimab remains cost-effective unless its price increases by 125%. Additionally, a simulated 15-year study period increases the ICER to $88,026/QALY. Subgroup analysis revealed ICERs of $76,538/QALY for PD-L1 positive and $70,158/QALY for PD-L1 negative groups. CONCLUSIONS: Toripalimab in combination with chemotherapy is likely to be a cost-effective alternative to standard chemotherapy for American patients with RM-NPC. This evidence can guide clinical and reimbursement decision-making in treating RM-NPC patients.

Cost-efficiency and budget-neutral expanded access modeling of the novel PD-1 inhibitor toripalimab versus pembrolizumab in recurrent or metastatic nasopharyngeal carcinoma.

AIMS: To estimate, in the setting of recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) for an assumed 1,207 incident US cases in 2024, (1) the cost-efficiency of a toripalimab-gemcitabine-cisplatin regimen compared to a similar pembrolizumab regimen; and (2) the budget-neutral expanded access to additional toripalimab cycles and regimens afforded by the accrued savings. METHODS: Simulation modeling utilized two cost inputs (wholesale acquisition cost (WAC) at market entry and an ex ante toripalimab price point of 80% of pembrolizumab average sales price (ASP)) and drug administration costs over 1 and 2 years of treatment with treatment rates ranging from 45% to 90%. In the absence of trial data for pembrolizumab-gemcitabine-cisplatin in R/M NPC, it is assumed that such a regimen would be comparable to toripalimab-gemcitabine-cisplatin in efficacy and safety. RESULTS: In the models utilizing the WAC, toripalimab saves $2,223 per patient per cycle and $40,014 over 1 year of treatment ($77,805 over 2 years). Extrapolated to the 1,207-patient panel, estimated 1-year savings range from $21,733,702 (45% treatment rate) to $43,467,404 (90% rate). Reallocating these savings permits budget-neutral expanded access to an additional 2,359 (45% rate) to 4,717 (90% rate) toripalimab maintenance cycles or to an additional 126 (45% rate) to 252 (90%) full 1-year toripalimab regimens with all agents. Two-year savings range from $42,259,976 (45% rate) to $84,519,952 (90% rate). Reallocating these efficiencies provides expanded access, ranging from an additional 4,586 (45% rate) to 9,172 (90% rate) toripalimab cycles or to an additional 128-257 full 2-year toripalimab regimens. The ex ante ASP model showed similar results. CONCLUSION: This simulation demonstrates that treatment with toripalimab generates savings that enable budget-neutral funding for up to an additional 252 regimens with toripalimab-gemcitabine-cisplatin for one full year, the equivalent of approximately 21% of the 2024 incident cases of R/M NPC in the US.

An estimated 1,207 patients will be diagnosed with late-stage nasopharyngeal cancer in the US in 2024. Toripalimab is a novel PD-1 inhibitor drug approved by the US Food and Drug Administration on October 27, 2023 as first-line treatment for patients with recurrent or metastatic nasopharyngeal cancer when used in combination with gemcitabine and cisplatin. We conducted economic evaluations of the costs of this toripalimab regimen versus the costs of a similar regimen with the PD-1 inhibitor pembrolizumab. Our simulation models used two pricing scenarios: the wholesale acquisition cost (WAC) or "list price" at market entry and, as no average sales price (ASP) will be available for toripalimab for several quarters, an estimated toripalimab price point of 80% of the pembrolizumab ASP. We compared the savings in each scenario when between 45% and 90% of the 1,207 patients are treated with the toripalimab regimen. We then evaluated how these savings could be re-allocated, on a budget-neutral basis and without requiring extra cash outlays, to provide more patients with access to toripalimab treatment; specifically, how many toripalimab doses and how many full toripalimab regimens could be purchased to provide more patients with treatment. We found that, if 90% of new cases of recurrent or metastatic nasopharyngeal cancer were treated with toripalimab over 1 year, these savings are enough to purchase up to 4,717 additional doses on a budget-neutral basis, which could provide up to an additional 252 newly diagnosed patients with 1 year of treatment with toripalimab. In combination with gemcitabine and cisplatin, toripalimab can markedly improve access to care for patients with recurrent or metastatic nasopharyngeal cancer in a cost-responsible way.

Assessing malnutrition in patients with nasopharyngeal carcinoma: Diagnostic protocol for the development and validation of a new nutritional assessment tool.

INTRODUCTION: There is currently no gold standard or specific nutritional assessment tool to assess malnutrition in patients with nasopharyngeal carcinoma (NPC). Our study aims to develop a new nutritional assessment tool for NPC patients. METHODS AND ANALYSIS: NPC patients will be required to complete a risk factor questionnaire after obtaining their informed consent. The risk factor questionnaire will be used to collect potential risk factors for malnutrition. Univariate and multivariate logistic regression analyses will be used to identify risk factors for malnutrition. A new nutritional assessment tool will be developed based on risk factors. The new tool's performance will be assessed by calibration and discrimination. The bootstrapping will be used for internal validation of the new tool. In addition, external validation will be performed by recruiting NPC patients from another hospital. DISCUSSION: If the new tool is validated to be effective, it will potentially save medical staff time in assessing malnutrition and improve their work efficiency. Additionally, it may reduce the incidence of malnutrition and its adverse consequences. STRENGTHS AND LIMITATIONS OF THIS STUDY: The study will comprehensively analyze demographic data, disease status, physical examination, and blood sampling to identify risk factors for malnutrition. Furthermore, the new tool will be systematically evaluated, and validated to determine their effectiveness. However, the restricted geographical range may limit the generalizability of the results to other ethnicities. Additionally, the study does not analyze subjective indicators such as psychology. ETHICS AND DISSEMINATION: The ethical approval was granted by the Ethical Committee of the First Affiliated Hospital of Guangxi Medical University (NO. 2022-KT-GUI WEI-005) and the Second Affiliated Hospital of Guangxi Medical University (NO. 2022-KY-0752). CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2300071550.

Host genetic variants, Epstein-Barr virus subtypes, and the risk of nasopharyngeal carcinoma: Assessment of interaction and mediation.

Epstein-Barr virus (EBV) and human leukocyte antigen (HLA) polymorphisms are well-known risk factors for nasopharyngeal carcinoma (NPC). However, the combined effects between HLA and EBV on the risk of NPC are unknown. We applied a causal inference framework to disentangle interaction and mediation effects between two host HLA SNPs, rs2860580 and rs2894207, and EBV variant 163364 with a population-based case-control study in NPC-endemic southern China. We discovered the strong interaction effects between the high-risk EBV subtype and both HLA SNPs on NPC risk (rs2860580, relative excess risk due to interaction [RERI] = 4.08, 95% confidence interval [CI] = 2.03-6.14; rs2894207, RERI = 3.37, 95% CI = 1.59-5.15), accounting for the majority of genetic risk effects. These results indicate that HLA genes and the high-risk EBV have joint effects on NPC risk. Prevention strategies targeting the high-risk EBV subtype would largely reduce NPC risk associated with EBV and host genetic susceptibility.

Assessment of Prophylactic Internal Carotid Artery Management in Postradiation Nasopharyngeal Necrosis Patients.

OBJECTIVE: Postradiation nasopharyngeal necrosis (PRNN) frequently develops after second-course radiotherapy for nasopharyngeal carcinoma (NPC). PRNN can lead to internal carotid artery (ICA) massive hemorrhage due to ICA rupture, resulting in sudden death. This study aims to explore the pretreatment of the ICA to prevent fatal massive hemorrhage in PRNN patients. STUDY DESIGN: Retrospective cohort study. SETTING: Sun Yat-sen University Cancer Center. METHODS: Patients diagnosed with NPC and PRNN from January 2010 to September 2022 were included. The Cox proportional hazards regression analysis was performed to analyze risk factors for massive hemorrhage and survival. A nomogram was developed to integrate prognostic models and perform parameter calibration. RESULTS: Two hundred and fifty-four PRNN patients were included in this study. Prophylactic ICA occlusion significantly reduced the risk of ICA hemorrhage compared to no prophylactic ICA occlusion (3.6% vs 40.6%, P < .001). Surgical repair on necrosis significantly prevented hemorrhage and improved survival. The nomogram, incorporating the above 2 factors and the nearest distance from necrosis to ICA ≤ 3 mm, exhibited excellent discriminative ability for hemorrhage. We identified 3 high-risk factors that indicate the need for prophylactic ICA management in PRNN patients: (1) exposure of ICA by rhinoscopy; (2) signs of ICA erosion on MRA scanning; (3) the depth of soft tissue coverage surrounding the ICA wall within the necrotic cavity is less than 3 mm on magnetic resonance imaging. CONCLUSION: We have identified 3 high-risk factors for PRNN patients that necessitate prophylactic ICA management. These findings are expected to contribute to improving the quality of life and overall survival of PRNN patients.

Cost-effectiveness analysis of tislelizumab in combination with chemotherapy for the first-line treatment of patients with metastatic or recurrent nasopharyngeal carcinoma in China.

BACKGROUND: The combination of tislelizumab and gemcitabine plus cisplatin (GP) in the first-line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has yielded significant results. However, it is not clear whether this treatment option is cost-effective in China. The purpose of this study is to evaluate the cost-effectiveness of tislelizumab plus GP for the first-line treatment of R/M NPC from the perspective of the Chinese healthcare system. METHODS: A partitioned survival model with three discrete health states was constructed to evaluate the cost-effectiveness of tislelizumab plus GP versus GP in patients with R/M NPC. The target population enrolled in the RATIONALE-309 trial had previously not treated for R/M NPC. Drug costs were obtained from relevant databases, and the remaining cost and health utility data were collected from the literature. The main outcomes include the expected life years, quality-adjusted life years (QALYs), total cost, and incremental cost-benefit ratio (ICER). RESULTS: The tislelizumab plus GP regimen produced an additional cost ($18392.76) and additional 1.57 QALYs compared with GP used alone. The ICER was $18392.75/QALYs. Sensitivity analysis showed that the analysis was robust and the utility of PD status was most sensitive to the model results. The possibility of tislelizumab plus GP being cost-effective at the willingness-to-pay (WTP) threshold of $37 653/QALY was 99.8%. Subgroup analysis showed that high PD-L1 expression had little impact on the ICER of this regimen. CONCLUSION: In patients with R/M NPC, the regimen of tislelizumab plus GP, as the first-line treatment, is more cost-effective than the GP regimen in China.

Cost-effectiveness of camrelizumab combined with chemotherapy in the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma in China.

OBJECTIVE: This study aimed to investigate the cost-effectiveness of adding Chinese-developed anti-PD-1 antibody camrelizumab to first-line platinum-doublet chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (L/M NPC) from the perspective of Chinese healthcare system. DESIGN: A Markov model consisting of four health states, progression-free survival, first progression survival, second progression survival and death, was built to simulate 3-week patient transitions over a 20-year horizon. A direct comparison between first-line camrelizumab in combination with gemcitabine plus cisplatin and gemcitabine plus cisplatin was performed by calculating transition probabilities from the CAPTAIN-1st trial. Costs and utilities were collected from the local public database and literature. One-way and probabilistic sensitivity analyses were employed to evaluate the robustness of the model. SETTING: The Chinese healthcare system perspective. PARTICIPANTS: A hypothetical cohort of Chinese patients with pathologically diagnosed L/M NPC who had an Eastern Cooperative Oncology Group performance status of 0 or 1. INTERVENTIONS: First-line camrelizumab in combination with camrelizumab and gemcitabine plus cisplatin (CGP) versus gemcitabine plus cisplatin (GP). PRIMARY OUTCOME MEASURE: Cost, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER). RESULTS: The baseline analysis demonstrated that, compared with first-line GP, first-line CGP yields an effectiveness increase of 0.26 QALY, accompanied by an increment of US$6137.59 in healthcare cost. This results in an ICER of US$23 482.32/QALY. With the willingness-to-pay (WTP) threshold for a QALY set at US$37 654.50, first-line CGP proves to be cost-effective in 97.20% of the iterations. Deterministic sensitivity analyses indicated that the uncertainty in model parameters had no substantial effect on our results. Probability sensitivity analysis indicated that CGP was cost-effective at the assumed WTP threshold. CONCLUSION: For Chinese patients with L/M NPC, adding Chinese-developed anti-PD-1 antibody camrelizumab to the first-line GP chemotherapy may be cost-effective.

Application value of 3D pCASL in early assessment of potential radiation encephalopathy in nasopharyngeal carcinoma patients undergoing radiotherapy.

OBJECTIVE: The study explores the application value of three-dimensional arterial spin labeling magnetic resonance imaging (3D pCASL) in early assessment of radiation encephalopathy (REP) in patients with nasopharyngeal carcinoma (NPC). METHODS: A retrospective analysis of 39 cases of NPC was performed. Routine enhanced MRI scan and 3D pCASL imaging were used to examine the apparent diffusion coefficient (ADC) and brain blood flow (CBF) before and after treatment with intensity-modulated radiotherapy (IMRT). Dosimetric analysis of irradiation was performed. Receiver operating characteristic curve (ROC) was used to analyze diagnostic performance of two imaging methods. RESULTS: There was no statistically significant difference between the two methods for the measurement of temporal white matter ADC, but statistically significant difference was found in CBF. 3D pCASL imaging showed more sensitivity, specificity and higher accuracy than conventional MRI enhanced scan in showing REP. The maximum dose of the temporal lobe was at the enhanced area. CONCLUSION: The present study demonstrates that 3D pCASL scan at month 3 can reflect blood flow perfusion differences in NPC patients after IMRT and can accurately assess the possibility of REP at early stage. Enhanced areas have a higher probability of REP than the surrounding areas. ADVANCES IN KNOWLEDGE: There is few magnetic resonance angiography studies used to evaluate arterial circulation on its application on potential REP after radiotherapy for NPC. In our study, we evaluate the application value of 3D pCASL in the early assessment of potential REP in patients with NPC after radiotherapy. The study was to provide an improved understanding of the early specific characteristics on MRI imaging and evolution of potential radiation encephalopathy using 3D pCASL technique, which can quantitatively evaluate the changes of blood flow in tissues at early stage and help to diagnose and treat potential radiation encephalopathy as early as possible.

First-line immunotherapy combinations for recurrent or metastatic nasopharyngeal carcinoma: An updated network meta-analysis and cost-effectiveness analysis.

OBJECTIVES: Recently updated results of randomized clinical trials (RCTs) have confirmed that toripalimab, camrelizumab, and tislelizumab plus chemotherapy (TOGP, CAGP, and TIGP) significantly prolonged survival compared to placebo plus chemotherapy (PLGP) in the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). However, the high cost of immunotherapies imposes a huge financial burden on patients and health care systems. MATERIALS AND METHODS: RCTs estimating immunotherapies for R/M-NPC were searched. A Bayesian network meta-analysis (NMA) was carried out; the main outcomes were hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS). The cost and efficacy of four first-line therapies were evaluated using the Markov model. The main outcome in the cost-effectiveness analysis (CEA) was incremental cost-utility ratios (ICURs). The model robustness was assessed by one-way, three-way, and probabilistic sensitivity analyses. RESULTS: Three RCTs (JUPITER-02, CAPTAIN-1st, and RATIONALE-309) involving 815 patients were included in the NMA. Compared with PLGP, chemo-immunotherapies have significantly longer PFS and OS. Compared to the PLGP group, TOGP, CAGP, and TIGP groups resulted in additional costs of $48 339, $22 900, and $23 162, with additional 1.89, 0.73, and 0.960 QALYs, respectively, leading to the ICURs of $25 576/QALY, $31 370/QALY, and $31 729/QALY. Pairwise comparisons showed TOGP was the most cost-effective option among chemo-immunotherapy groups. CONCLUSION: From the Chinese payers' perspective, first-line immunotherapy combination therapies provided significant survival and cost-effectiveness superiority over chemotherapy alone for patients with R/M-NPC at the WTP of $38 029/QALY. Among the three chemo-immunotherapy groups, TOGP was the most cost-effective option.

Association of public health insurance with cancer-specific mortality risk among patients with nasopharyngeal carcinoma: a prospective cohort study in China.

Objective: Health insurance programs are effective in preventing financial hardship in patients with cancer. However, not much is known about how health insurance policies, especially in Southwest China with a high incidence of nasopharyngeal carcinoma (NPC), influence patients' prognosis. Here, we investigated the association of NPC-specific mortality with health insurance types and self-paying rate, and the joint effect of insurance types and self-paying rate. Materials and methods: This prospective cohort study was conducted at a regional medical center for cancer in Southwest China and included 1,635 patients with pathologically confirmed NPC from 2017 to 2019. All patients were followed up until May 31, 2022. We determine the cumulative hazard ratio of all-cause and NPC-specific mortality in the groups of various insurance kinds and the self-paying rate using Cox proportional hazard. Results: During a median follow-up period of 3.7 years, 249 deaths were recorded, of which 195 deaths were due to NPC. Higher self-paying rate were associated with a 46.6% reduced risk of NPC-specific mortality compared to patients with insufficient self-paying rate (HR: 0.534, 95% CI: 0.339-0.839, p = 0.007). For patients covered by Urban and Rural Residents Basic Medical Insurance (URRMBI), and for patients covered by Urban Employee Basic Medical Insurance, each 10% increase in the self-paying rate reduced the probability of NPC-specific death by 28.3 and 25%, respectively (UEBMI). Conclusion: Results of this study showed that, despite China's medical security administration improved health insurance coverage, NPC patients need to afford the high out-of-pocket medical costs in order to prolong their survival time.

Assessment of bone lesions with 18 F-FDG PET/MRI in patients with nasopharyngeal carcinoma.

PURPOSE: The purpose of this study is to evaluate the role of 18 fluorodeoxyglucose ( 18 F) PET/MRI ( 18 F-FDG PET/MRI) for detecting bone metastasis in nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Between May 2017 and May 2021, 58 histologically proven NPC patients who underwent both 18 F-FDG PET/MRI and 99m Tc-MDP planar bone scintigraphy (PBS) for tumor staging were included. With the exception of the head, the skeletal system was classified into four groups: the spine, the pelvis, the thorax and the appendix. RESULTS: Nine (15.5 %) of 58 patients were confirmed to have bone metastasis. There was no statistical difference between PET/MRI and PBS in patient-based analysis ( P = 0.125). One patient with a super scan was confirmed to have extensive and diffuse bone metastases and excluded for lesion-based analysis. Of the 57 patients, all 48 true metastatic lesions were positive in PET/MRI whereas only 24 true metastatic lesions were positive in PBS (spine: 8, thorax: 0, pelvis: 11 and appendix: 5). PET/MRI was observed to be more sensitive than PBS in lesion-based analysis (sensitivity 100.0% versus 50.0 %; P < 0.001). CONCLUSIONS: Compared with PBS for tumor staging of NPC, PET/MRI was observed to be more sensitive in the lesion-based analysis of bone metastasis.

Assessment of Response to Different Induction Chemotherapy Regimens in Locally Advanced Nasopharyngeal Carcinoma.

Purpose: To compare the short-term treatment response and survival of the three induction chemotherapy (IC) regimens, including gemcitabine and cisplatin (GP), docetaxel and cisplatin (TP), and docetaxel, cisplatin, and fluoropyrimidines (TPF) in locally advanced nasopharyngeal carcinoma (LANPC). Methods: We included stage III-IVA NPC patients who received ≥3 cycles of IC in this study. The chi-square test, multivariate logistic regression analysis, and Kaplan-Meier method were used for statistical analysis. Results: A total of 227 patients were included. The overall response rate (ORR) of the primary nasopharyngeal tumors after IC with GP, TP, and TPF was 91.9%, 83.8%, and 91.7%, respectively (P=0.729), and the ORR of the cervical lymph nodes was 94.6%, 72.3%, and 85.0%, respectively (P<0.001). For the primary nasopharyngeal tumor, there was no significant difference in the ORR among the three IC regimens. For cervical lymph nodes, patients treated with GP had significantly higher ORR compared to those treated with the TP regimen (P=0.014), and comparable ORR was found between TPF and GP regimens (P=0.161). Similar progression-free survival (PFS) (P=0.501) and overall survival (OS) (P=0.504) were found among three IC regimens. There were comparable PFS (P=0.123) and OS (P=0.478) among those with complete response (CR), partial response (PR), and stable disease (SD)/progressive disease (PD) in the primary nasopharyngeal tumors. However, patients who had CR in the primary nasopharyngeal tumor (P=0.014) and the cervical lymph nodes (P=0.022) had better PFS compared to those who had PR or SD/PD. Conclusion: GP and TPF regimens are equivalent to the TP regimen in the response to primary nasopharyngeal tumors after IC, but with better ORR in the cervical lymph nodes than the TP regimen. The response to IC may be a powerful indicator for predicting prognosis and developing individualized follow-up and treatment strategies for LANPC patients.

Association Between Mortality Due to Nasopharyngeal Carcinoma and Race in the United States From 2007 to 2016.

BACKGROUND: Asians and Pacific Islanders (API) exhibit increased incidence of nasopharyngeal carcinoma (NPC). However, they are often excluded when the disease is studied. Risk-factors and incidence are well-researched while cancer-specific mortality trends remain unclear. We aimed to determine whether insurance status modifies the association between race and cancer-specific mortality in NPC patients. METHODS: This retrospective cohort study used secondary data analysis from the Surveillance, Epidemiology, and End Results Program database. Patients ≥18 years with histologically confirmed primary NPC from 2007 - 2016 were included. The main outcome assessed was 5-year survival and the main exposure variable was race (API, white, black). Insurance status was classified into uninsured, any Medicaid, and insured (with any insurance). Potential confounders included age, sex, marital status, stage at diagnosis, and surgical treatment. Adjusted Cox regression analysis was used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (CI). RESULTS: 1610 patients were included (72.98% male, 27.02% female). 49.8% were API, 40.5% were Whites, and 9.8% Blacks. Maximum follow-up was 5-years. The adjusted hazards of 5-year cancer-specific death for API and Blacks compared with Whites were 0.77 (95% CI 0.62 - 0.96) and 0.92 (95% CI 0.65 - 1.31), respectively. Cases decreased with age in API and Blacks. 8.2% of cases had localized disease, 45.3% had local spread, and 44.6% had distant metastasis. Insurance status did not modify the association between race and mortality. CONCLUSION: Race is an important prognostic factor to account for in NPC patients. Investigating risk-factors and subtypes stratified by race may explain our findings.

Assessment and management of radiation-induced trismus in patients with nasopharyngeal carcinoma: a best practice implementation project.

INTRODUCTION AND AIMS: Intensity-modulated radiotherapy (IMRT) is the most commonly used radiotherapy technology in oncology, which enables precise conformation of the radiation dose to the target volume and reduces the risk of radiation damage to the adjacent normal structures. Nevertheless, it is still inevitable for IMRT of head and neck cancer to cause radiation-related toxic and side effects, such as dry mouth, mucositis, oral dysarthria, taste disorder, osteonecrosis, and trismus. Trismus is one of the most common late side effects caused by radiotherapy of nasopharyngeal carcinoma (NPC), which seriously affects the quality of life for patients with NPC. However, the current clinical assessment and management of trismus after radiotherapy for NPC are still imperfect. This best practice implementation project aimed to implement an evidence-based practice in assessing and managing trismus for NPC patients who underwent radiotherapy, thereby improving the compliance of clinical practice with the best evidence and the quality of life of patients with NPC. METHODS: This evidence-based audit and feedback project was implemented using a three-phase approach at a third-class hospital in China, following JBI's Practical Application of Clinical Evidence System (PACES) and GRiP evidence application. The first phase included a baseline audit with six evidence-based audit criteria derived from the best available evidence. The second phase included analyzing the results of the baseline audit, identifying barriers to compliance with best practice principles, and developing and implementing strategies to address the barriers identified in the baseline audit. The third phase involved a follow-up audit to assess the results of the interventions implemented to improve practice. RESULTS: After evidence application, the compliance rate for audit criterion 1 increased from 0% at baseline audit to 70% at follow-up audit. The compliance rate for audit criterion 2 increased from 0% to 100%. The compliance rate for audit criterion 3 increased from 22 to 62%. The compliance rate for audit criterion 4 increased from 88 to 100%. The compliance rate for audit criterion 5 was 100% at baseline audit and follow-up audit. The compliance rate for audit criterion 6 increased from 0 to 55%. CONCLUSION: Implementation of the best evidence for the assessment and management of trismus of patients with NPC after radiotherapy is conducive to improving the compliance of clinical practice with the best evidence, standardizing clinical nursing practice, improving the quality of clinical nursing, and better preventing severe trismus in patients with NPC after radiotherapy.

[Cost-effectiveness of endoscopic nasopharyngectomy in locally recurrent rT1-rT3 nasopharyngeal carcinoma: a study based on Markov model].

Objective: To perform a cost-effectiveness analysis of endoscopic surgery versus intensity-modulated radiotherapy in the treatment of locally recurrent nasopharyngeal carcinoma (rNPC) from a health-economic perspective. Methods: From September 30, 2011 to January 16, 2017, a total of 200 patients were enrolled in the First Affiliated Hospital of Sun Yat-sen University, the First People's Hospital of Foshan, and Sun Yat-sen University Cancer Center. These patients were diagnosed as locally rT1-rT3 stage rNPC and were randomly assigned 1︰1 to the endoscopic surgery group (ENPG) and the intensity-modulated radiotherapy group (IMRT). There were 69 males and 31 females in ENPG, aging from 38 to 55 years. There were 72 males and 28 females in IMRT aging from 41 to 54 years. A retrospective cost-effectiveness analysis of the cohort was conducted using a Markov model. For each modality, data on survival and quality-adjusted life year (QALY) were sourced from relevant articles, and cost prices were included regarding treatment. Weibull distribution was used to estimate time-dependent transition probability. Beta-regression was used to convert the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) to utility. Results: The total cost of ENPG was 29 611.88 yuan, and the total cost of IMRT was 110 082.51 yuan. The incremental cost-effectiveness ratio (ICER) of ENPG versus radiotherapy for locally rNPC was -85 555.88 yuan/QALY, which was less than 3 times of Chinese gross domestic product (GDP) per capita. Sensitivity analysis showed that the cost of IMRT had the greatest impact on ICER. ICER was stable within 10% fluctuation of all the parameters. Conclusion: It is economical cost-effective to treat locally rNPC with ENGP versus IMRT.