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.

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.

Selectively recommend 18F-FDG PET/CT for patients with de novo nasopharyngeal carcinoma in endemic areas.

INTRODUCTION: To identify the subset of patients with de novo nasopharyngeal carcinoma (NPC) for whom [18F] fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT) should be recommended, and to determine whether PET/CT is a cost-effective decision for precise M staging in endemic areas. MATERIALS AND METHODS: Retrospective analysis of data of 4469 patients diagnosed with de novo NPC between January 2014 and December 2019. The detection rate of distant metastasis was compared between different groups. Univariate and multiple logistic regression analysis was applied to identify the risk factors for distant metastasis. The cost-effectiveness of the diagnostic strategies was assessed. RESULTS: The detection rate of distant metastasis in the whole cohort was 5.46%. In multivariate analysis, male sex, T3-4 stage, N2-3 stage, and high plasma Epstein-Barr virus (EBV) DNA (≥ 14,650 copies/mL) were risk factors for distant metastases. NPC patients with T3-4 stage combined with N2-3 stage, high EBV DNA combined with male sex, or N2-3 stage combined with high EBV DNA were defined as recommended group with relatively higher tendency for metastasis. Distant metastasis incidence in recommended group and unrecommended group were 10.25% and 1.75%, respectively (P < 0.001). In the recommended group, PET/CT significantly improved the detection rate of distant metastasis (13.25% vs 9.02%, P = 0.005). Cost-effectiveness analysis revealed that additional cost for every one percent increase in distant metastasis detection rate was $22,785.58 in the recommended group (< Willingness-to-pay (WTP) threshold of $32,700.00) and $310,912.90 in the unrecommended group. CONCLUSIONS: In patients with de novo NPC, the tendency for metastasis can be predicted based on clinical parameters. 18F-FDG PET/CT should be selectively recommended for the subset of patients with a relatively higher tendency for metastasis.

Effectiveness and cost-effectiveness analysis of nimotuzumab for the radiotherapy of locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: This study aimed to assess the effectiveness and cost-effectiveness of nimotuzumab in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: LA-NPC patients treated between October 2013 and December 2016 were retrospectively reviewed. A well-balanced cohort of patients who received nimotuzumab in addition to standard treatment (n = 50) and patients who did not receive nimotuzumab (n = 100) was selected using propensity score-matching method (1:2 ratio) for the cost-effectiveness analysis. RESULTS: Compared with concurrent chemoradiotherapy (CCRT) alone, addition of nimotuzumab to CCRT significantly improved the 3-year overall survival (OS) (98.00% vs. 91.00%, P = 0.032). On multivariate analysis, nimotuzumab (hazard ratio = 0.124, 95% confidence interval: 0.017-0.902, P = 0.039) showed prognostic significance for OS. No serious treatment-related adverse events were observed in the nimotuzumab group (P > 0.05). Cost-effectiveness analysis revealed that addition of nimotuzumab increased the average treatment costs by $14,364.63. The additional cost for every one percent increase in OS rate was $ 2,052.09. CONCLUSION: Addition of nimotuzumab to CCRT for LA-NPC confers significant survival benefits; however, it is not cost-effective.

An optimal posttreatment surveillance strategy for cancer survivors based on an individualized risk-based approach.

The optimal post-treatment surveillance strategy that can detect early recurrence of a cancer within limited visits remains unexplored. Here we adopt nasopharyngeal carcinoma as the study model to establish an approach to surveillance that balances the effectiveness of disease detection versus costs. A total of 7,043 newly-diagnosed patients are grouped according to a clinic-molecular risk grouping system. We use a random survival forest model to simulate the monthly probability of disease recurrence, and thereby establish risk-based surveillance arrangements that can maximize the efficacy of recurrence detection per visit. Markov decision-analytic models further validate that the risk-based surveillance outperforms the control strategies and is the most cost-effective. These results are confirmed in an external validation cohort. Finally, we recommend the risk-based surveillance arrangement which requires 10, 11, 13 and 14 visits for group I to IV. Our surveillance strategies might pave the way for individualized and economic surveillance for cancer survivors.

Cost-effectiveness analysis of gemcitabine plus cisplatin versus docetaxel, cisplatin and fluorouracil for induction chemotherapy of locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: Recently, patients who received induction chemotherapy plus concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma were found to have survival advantages compared with those receiving concurrent chemoradiotherapy alone in two large randomized trials. Based on these two trials, we present a cost-effectiveness analysis to compare gemcitabine and cisplatin (GP) versus cisplatin, fluorouracil, and docetaxel (TPF) for induction chemotherapy to treat locoregionally advanced nasopharyngeal carcinoma. METHODS: We constructed a Markov model to compare the cost and effectiveness of GP versus TPF. Clinical data including the frequency of adverse events, recurrence and death obtained from two randomized phase III trials were used to calculate transition probabilities and costs. Health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollars per quality-adjusted life-year (QALY), were calculated, and incremental cost-effectiveness ratios less than $27,534.25/QALY (3 × the per capita GDP of China, 2018) were considered cost-effective. One-way sensitivity and probabilistic sensitivity analyses explored the robustness of the model. RESULTS: Our base case model found that the total cost was $53,082.68 in the GP group and $45,482.66 in the TPF group. The QALYs were 6.82 and 4.11, respectively. The incremental cost-effectiveness ratio favoured the GP regimen, at an incremental cost of $2,804.44 per QALY. The probabilistic sensitivity analysis found that treatment with the GP regimen was cost-effective 100% of the time at a willingness-to-pay threshold of $27,534.25‬/QALY. CONCLUSION: In this model, GP was estimated to be cost-effective compared with cisplatin, fluorouracil, and docetaxel for patients with locoregionally advanced nasopharyngeal carcinoma from the payer's perspectives in the China.

Cost-effectiveness analysis of gemcitabine plus cisplatin versus fluorouracil plus cisplatin in the first-line setting for Chinese patients with metastatic nasopharyngeal carcinoma.

PURPOSE: A randomized phase III trial demonstrated that gemcitabine plus cisplatin (GP) prolonged progression-free survival and overall survival compared with fluorouracil plus cisplatin (FP) as first-line chemotherapy in patients with metastatic nasopharyngeal carcinoma (NPC). The cost-effectiveness analysis was designed to identify the economic option for metastatic NPC from a Chinese societal perspective. METHODS: We established a Markov model that involved three health states representing the stages of disease to simulate therapy. Survival data of clinical outcomes were derived from the trial and adjusted to quality-adjusted life years (QALYs). Transition probabilities and health utilities were obtained from the clinical trial and published literatures. The cost-effective strategy was estimated for these treatments using a willing-to-pay (WTP) threshold. A one-way sensitivity analysis was conducted to study the influences of parameters. RESULTS: GP treatment group produced a gain of 0.37 QALYs with an incremental cost of $2520.80, yielding an incremental cost-effectiveness ratio (ICER) of $6812.97 per QALY, compared with FP treatment ($15,530.96 versus $13,010.16). The ICER was lower than the accepted WTP threshold, which was 3 times gross domestic product per capita of China ($25,749 per QALY). CONCLUSION: GP regimen is more cost-effective compared with FP regimen as the first-line treatment for Chinese patients with metastatic NPC.

Minimally invasive surgery alone compared with intensity-modulated radiotherapy for primary stage I nasopharyngeal carcinoma.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend intensity-modulated radiotherapy (IMRT) as the primary curative treatment for newly diagnosed nasopharyngeal carcinoma (NPC), but the radiation-related complications and relatively high medical costs remain a consequential burden for the patients. Endoscopic nasopharyngectomy (ENPG) was successfully applied in recurrent NPC with radiation free and relatively low medical costs. In this study, we examined whether ENPG could be an effective treatment for localized stage I NPC. METHODS: Ten newly diagnosed localized stage I NPC patients voluntarily received ENPG alone from June 2007 to September 2017 in Sun Yat-sen University Cancer Center. Simultaneously, the data of 329 stage I NPC patients treated with IMRT were collected and used as a reference cohort. The survival outcomes, quality of life (QOL), and medical costs between two groups were compared. RESULTS: After a median follow-up of 59.0 months (95% CI 53.4-64.6), no death, locoregional recurrence, or distant metastasis was observed in the 10 patients treated with ENPG. The 5-year overall survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival among the ENPG-treated patients was similar to that among the IMRT-treated patients (100% vs. 99.1%, 100% vs. 97.7%, 100% vs. 99.0%, 100% vs. 97.4%, respectively, P > 0.05). In addition, compared with IMRT, ENPG was associated with decreased total medical costs ($ 4090.42 ± 1502.65 vs. $ 12620.88 ± 4242.65, P < 0.001) and improved QOL scores including dry mouth (3.3 ± 10.5 vs. 34.4 ± 25.8, P < 0.001) and sticky saliva (3.3 ± 10.5 vs. 32.6 ± 23.3, P < 0.001). CONCLUSIONS: ENPG alone was associated with promising long-term survival outcomes, low medical costs, and satisfactory QOL and might therefore be an alternative strategy for treating newly diagnosed localized stage I NPC patients who refused radiotherapy. However, the application of ENPG should be prudent, and prospective clinical trials were needed to further verify the results.

Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II-IVB nasopharyngeal carcinoma: A cost-effectiveness analysis.

BACKGROUND: Nedaplatin-based concurrent chemoradiotherapy became an alternative doublet treatment strategy to cisplatin-based concurrent chemoradiotherapy in patients with locoregional, advanced nasopharyngeal carcinoma. MATERIALS AND METHODS: Using a Markov model, we simulated patients with nasopharyngeal carcinoma from disease-free to death. Input data for the model were collected from published literature and the standard fee database of West China Hospital. The outcome was expressed in quality-adjusted-years (QALYs), net monetary benefit at the threshold of $25,841, three times the Gross Domestic Product of China in 2017. The costs and benefits were discounted at 3% annually and a half-cycle correction was considered. The input parameters were varied in one-way sensitivity analysis to confirm the robustness of the model. All of the primary analyses used second-order probabilistic sensitivity analysis to capture the impact of parameter uncertainty based on 10,000 Monte-Carlo simulations. RESULTS: The mean QALYs of treatment in stage II-IVB nasopharyngeal carcinoma were comparable: 2.90 QALYs for nedaplatin and 3.12 QALYs for cisplatin. Nedaplatin cost $34,505 compared with $27,167 for cisplatin, generating an incremental net monetary benefit of nedaplatin versus cisplatin of $-13,357 at the ceiling ratio of $25,841. The results of nedaplatin remained cost-ineffective over the majority of the sensitivity analyses. The cost-effectiveness curve showed that the probability of strategies being cost-effective were 0% for nedaplatin and 100% for cisplatin in stage II-IVB nasopharyngeal carcinoma at any willingness-to-pay threshold. CONCLUSIONS: Nedaplatin is a dominated, cost-ineffective alternative to concurrent chemoradiotherapy in stage II-IVB nasopharyngeal carcinoma compared with cisplatin from the perspective of Chinese society.