Cost-effectiveness of stereotactic body radiation therapy versus video assisted thoracic surgery in medically operable stage I non-small cell lung cancer: A modeling study.

OBJECTIVES: Stage I non-small cell lung cancer (NSCLC) can be treated with either Stereotactic Body Radiotherapy (SBRT) or Video Assisted Thoracic Surgery (VATS) resection. To support decision making, not only the impact on survival needs to be taken into account, but also on quality of life, costs and cost-effectiveness. Therefore, we performed a cost-effectiveness analysis comparing SBRT to VATS resection with respect to quality adjusted life years (QALY) lived and costs in operable stage I NSCLC. MATERIALS AND METHODS: Patient level and aggregate data from eight Dutch databases were used to estimate costs, health utilities, recurrence free and overall survival. Propensity score matching was used to minimize selection bias in these studies. A microsimulation model predicting lifetime outcomes after treatment in stage I NSCLC patients was used for the cost-effectiveness analysis. Model outcomes for the two treatments were overall survival, QALYs, and total costs. We used a Dutch health care perspective with 1.5 % discounting for health effects, and 4 % discounting for costs, using 2018 cost data. The impact of model parameter uncertainty was assessed with deterministic and probabilistic sensitivity analyses. RESULTS: Patients receiving either VATS resection or SBRT were estimated to live 5.81 and 5.86 discounted QALYs, respectively. Average discounted lifetime costs in the VATS group were €29,269 versus €21,175 for SBRT. Difference in 90-day excess mortality between SBRT and VATS resection was the main driver for the difference in QALYs. SBRT was dominant in at least 74 % of the probabilistic simulations. CONCLUSION: Using a microsimulation model to combine available evidence on survival, costs, and health utilities in a cost-effectiveness analysis for stage I NSCLC led to the conclusion that SBRT dominates VATS resection in the majority of simulations.

MODEL-BASED COST-EFFECTIVENESS OF CONVENTIONAL AND INNOVATIVE CHEMO-RADIATION IN LUNG CANCER.

INTRODUCTION: Optimizing radiotherapy with or without chemotherapy through advanced imaging and accelerated radiation schemes shows promising results in locally advanced non-small-cell lung cancer (NSCLC). This study compared the cost-effectiveness of positron emission tomography-computed tomography based isotoxic accelerated sequential chemo-radiation (SRT2) and concurrent chemo-radiation with daily low-dose cisplatin (CRT2) with standard sequential (SRT1) and concurrent chemo-radiation (CRT1). METHODS: We used an externally validated mathematical model to simulate the four treatment strategies. The model was built using data from 200 NSCLC patients treated with curative sequential chemo-radiation. For concurrent strategies, data from a meta-analysis and a single study were included in the model. Costs, utilities, and resource use estimates were obtained from literature. Primary outcomes were the incremental cost-effectiveness and cost-utility ratio (ICUR) of each strategy. Scenario analyses were carried out to investigate the impact of uncertainty. RESULTS: Total undiscounted costs and quality-adjusted life-years (QALYs) for SRT1, CRT1, SRT2, and CRT2 were EUR 17,288, EUR 18,756, EUR 19,072, EUR 17,360 and QALYs 1.10, 1.15, 1.40, and 1.40, respectively. Compared with SRT1, the ICURs were EUR 38,024/QALY for CRT1, EUR 6,249/QALY for SRT2, and EUR 346/QALY for CRT2. CRT2 was highly cost-effective compared with SRT1. Moreover, CRT2 was more effective and less costly than CRT1 and SRT2. Therefore, these strategies were dominated by CRT2. CONCLUSION: Optimized sequential and concurrent chemo-radiation strategies are more effective and cost-effective than the current conventional sequential and concurrent strategies. Concurrent chemo-radiation with a daily low dose cisplatin regimen is the most cost-effective treatment option for locally advanced inoperable NSCLC patients.

Treatment Patterns and Differences in Survival of Non-Small Cell Lung Cancer Patients Between Academic and Non-Academic Hospitals in the Netherlands.

BACKGROUND: The aims of this study are to analyze differences in survival between academic and non-academic hospitals and to provide insight into treatment patterns for non-small cell lung cancer (NSCLC). Results show the state of NSCLC survival and care in the Netherlands. METHODS: The Netherlands Cancer Registry provided data on NSCLC survival for all Dutch hospitals. We used the Kaplan-Meier estimate to calculate median survival time by hospital type and a Cox proportional hazards model to estimate the relative risk of mortality (expressed as hazard ratios) for patients diagnosed in academic versus non-academic hospitals, with adjustment for age, gender, and tumor histology, and stratifying for disease stage. Data on treatment patterns in Dutch hospitals was obtained from 4 hospitals (2 academic, 2 non-academic). A random sample of patients diagnosed with NSCLC from January 2009 until January 2011 was identified through hospital databases. Data was obtained on patient characteristics, tumor characteristics, and treatments. RESULTS: The Cox proportional hazards model shows a significantly decreased hazard ratio of mortality for patients diagnosed in academic hospitals, as opposed to patients diagnosed in non-academic hospitals. This is specifically true for primary radiotherapy patients and patients who receive systemic treatment for non-metastasized NSCLC. CONCLUSION: Patients diagnosed in academic hospitals have better median overall survival than patients diagnosed in non-academic hospitals, especially for patients treated with radiotherapy, systemic treatment, or combinations. This difference may be caused by residual confounding since the estimates were not adjusted for performance status. A wide variety of surgical, radiotherapeutic, and systemic treatments is prescribed.

Multistate Statistical Modeling: A Tool to Build a Lung Cancer Microsimulation Model That Includes Parameter Uncertainty and Patient Heterogeneity.

With the shift toward individualized treatment, cost-effectiveness models need to incorporate patient and tumor characteristics that may be relevant to treatment planning. In this study, we used multistate statistical modeling to inform a microsimulation model for cost-effectiveness analysis of individualized radiotherapy in lung cancer. The model tracks clinical events over time and takes patient and tumor features into account. Four clinical states were included in the model: alive without progression, local recurrence, metastasis, and death. Individual patients were simulated by repeatedly sampling a patient profile, consisting of patient and tumor characteristics. The transitioning of patients between the health states is governed by personalized time-dependent hazard rates, which were obtained from multistate statistical modeling (MSSM). The model simulations for both the individualized and conventional radiotherapy strategies demonstrated internal and external validity. Therefore, MSSM is a useful technique for obtaining the correlated individualized transition rates that are required for the quantification of a microsimulation model. Moreover, we have used the hazard ratios, their 95% confidence intervals, and their covariance to quantify the parameter uncertainty of the model in a correlated way. The obtained model will be used to evaluate the cost-effectiveness of individualized radiotherapy treatment planning, including the uncertainty of input parameters. We discuss the model-building process and the strengths and weaknesses of using MSSM in a microsimulation model for individualized radiotherapy in lung cancer.

Individualized positron emission tomography-based isotoxic accelerated radiation therapy is cost-effective compared with conventional radiation therapy: a model-based evaluation.

PURPOSE: To evaluate long-term health effects, costs, and cost-effectiveness of positron emission tomography (PET)-based isotoxic accelerated radiation therapy treatment (PET-ART) compared with conventional fixed-dose CT-based radiation therapy treatment (CRT) in non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Our analysis uses a validated decision model, based on data of 200 NSCLC patients with inoperable stage I-IIIB. Clinical outcomes, resource use, costs, and utilities were obtained from the Maastro Clinic and the literature. Primary model outcomes were the difference in life-years (LYs), quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness and cost/utility ratio (ICER and ICUR) of PET-ART versus CRT. Model outcomes were obtained from averaging the predictions for 50,000 simulated patients. A probabilistic sensitivity analysis and scenario analyses were carried out. RESULTS: The average incremental costs per patient of PET-ART were €569 (95% confidence interval [CI] €-5327-€6936) for 0.42 incremental LYs (95% CI 0.19-0.61) and 0.33 QALYs gained (95% CI 0.13-0.49). The base-case scenario resulted in an ICER of €1360 per LY gained and an ICUR of €1744 per QALY gained. The probabilistic analysis gave a 36% probability that PET-ART improves health outcomes at reduced costs and a 64% probability that PET-ART is more effective at slightly higher costs. CONCLUSION: On the basis of the available data, individualized PET-ART for NSCLC seems to be cost-effective compared with CRT.

Dietary acrylamide intake and the risk of lymphatic malignancies: the Netherlands Cohort Study on diet and cancer.

BACKGROUND: Acrylamide, a probable human carcinogen, is present in many everyday foods. Since the finding of its presence in foods in 2002, epidemiological studies have found some suggestive associations between dietary acrylamide exposure and the risk of various cancers. The aim of this prospective study is to investigate for the first time the association between dietary acrylamide intake and the risk of several histological subtypes of lymphatic malignancies. METHODS: The Netherlands Cohort Study on diet and cancer includes 120,852 men and women followed-up since September 1986. The number of person years at risk was estimated by using a random sample of participants from the total cohort that was chosen at baseline (n =5,000). Acrylamide intake was estimated from a food frequency questionnaire combined with acrylamide data for Dutch foods. Hazard ratios (HRs) were calculated for acrylamide intake as a continuous variable as well as in categories (quintiles and tertiles), for men and women separately and for never-smokers, using multivariable-adjusted Cox proportional hazards models. RESULTS: After 16.3 years of follow-up, 1,233 microscopically confirmed cases of lymphatic malignancies were available for multivariable-adjusted analysis. For multiple myeloma and follicular lymphoma, HRs for men were 1.14 (95% CI: 1.01, 1.27) and 1.28 (95% CI: 1.03, 1.61) per 10 µg acrylamide/day increment, respectively. For never-smoking men, the HR for multiple myeloma was 1.98 (95% CI: 1.38, 2.85). No associations were observed for women. CONCLUSION: We found indications that acrylamide may increase the risk of multiple myeloma and follicular lymphoma in men. This is the first epidemiological study to investigate the association between dietary acrylamide intake and the risk of lymphatic malignancies, and more research into these observed associations is warranted.

Cost effectiveness of treatment with new agents in advanced non-small-cell lung cancer: a systematic review.

In past decades, studies focusing on new chemotherapeutic agents for patients with inoperable non-small-cell lung cancer have reported only modest gains in survival. These health gains are achieved at considerable cost, but economic evidence is lacking on superiority of one agent in terms of cost effectiveness. The objective of this systematic review was to assess fully published cost-effectiveness studies comparing the new agents docetaxel, paclitaxel, vinorelbine, gemcitabine and pemetrexed, and the targeted therapies erlotinib and gefitinib with one another. We performed systematic searches in the bibliographic databases PubMed, EMBASE and Health Economic Evaluations (HEED) [via the Cochrane Library] for fully published studies from the past 10 years. Studies were screened by two independent reviewers according to a priori inclusion criteria. The methodological quality of the included studies was evaluated by two independent reviewers using standardized assessment tools. A total of 222 potential studies were identified; 11 studies and six reviews were included. The methodological quality of the full economic evaluations was fairly good. Transparency in costs and resource use, details on statistical tests and sensitivity analysis were points for improvement. In first-line treatment, gemcitabine+cisplatin was cost effective compared with other platinum-based regimens (paclitaxel, docetaxel and vinorelbine). In one study, pemetrexed+cisplatin was cost effective compared with gemcitabine+cisplatin in patients with non-squamous-cell carcinoma. In second-line treatment, docetaxel was cost effective compared with best supportive care; erlotinib was cost effective compared with placebo; and docetaxel and pemetrexed were dominated by erlotinib. We found indications of superiority in terms of cost effectiveness for gemcitabine+cisplatin in a first-line setting, and for erlotinib in a second-line setting.