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 V569 (95% confidence interval [CI] (sic)-5327-(sic)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 (sic)1360 per LY gained and an ICUR of (sic)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

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

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

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

Acrylamide hazard ratios (and 95% CI) of multiple myeloma, diffuse large cell lymphoma and chronic lymphatic leukemia in <b>women</b> in strata of several covariables and <i>p</i> values for interaction: the Netherlands Cohort Study on diet and cancer, 1986–2002.

<p>Abbreviations: HR  =  hazard ratio; CI  =  confidence interval; AA/d  =  acrylamide per day, MM  =  multiple myeloma; CLL  =  chronic lymphatic leukemia; DLCL  =  diffuse large cell lymphoma.</p>1<p>Adjusted for age, sex, height (per 10 cm), education level, fiber (g/d), total fatty acids (g/d), trans unsaturated fatty acid (g/d), mono unsaturated fat (g/d), poly unsaturated fat (g/d), carbohydrates (g/d) and niacin (mg/d).</p>2<p>Insufficient number of cases.</p

Number of lymphatic malignancies in the Netherlands Cohort Study on diet and cancer (follow up: 16.3 years) according to the WHO classification.

<p>Abbreviations: ICD-O-3, International Classification of Diseases for Oncology, 3^rd edition; MALT, mucosa-associated lymphoid tissue; NOS, not otherwise specified.</p>1<p>N after exclusion of prevalent cases at baseline.</p>2<p>N cases available for analyses, after exclusion of missing and inconsistent data. Only case numbers for subtypes with sufficient number of cases are given (so subgroups do not add up to 1,233).</p

Association between continuously modeled dietary acrylamide intake (per 10 µg/d) and the risk of follicular lymphoma and Waldenstrom macroglobulinemia and immunocytoma (WMI); the Netherlands Cohort Study on diet and cancer, 1986–2002.¹

<p>HR  =  hazard ratio; CI  =  confidence interval; py  =  person years. The number of cases and person-years are the numbers that resulted after listwise deletion of observations with missing values for the selected confounders. HRs were calculated by using Cox proportional hazards analysis.</p>1<p>Adjusted for age and sex.</p>2<p>Adjusted for age (years), sex, height (per 10 cm), education level, fiber (g/d), total fatty acids (g/d), trans unsaturated fatty acid (g/d), mono unsaturated fat (g/d), poly unsaturated fat (g/d), carbohydrates (g/d) and niacin (mg/d).</p>3<p>Insufficient number of cases for analyses with acrylamide as a continuous variable (N>20 requiered).</p

Association between dietary acrylamide intake and the risk of multiple myeloma, diffuse large cell lymphoma, and chronic lymphocytic leukemia according to sex and smoking status; the Netherlands Cohort Study on diet and cancer, 1986–2002.¹

1<p>HR  =  hazard ratio; CI  =  Confidence Interval; py  =  person years; Q  =  quintile; T  =  tertile. The number of cases and person-years are the numbers that resulted after listwise deletion of observations with missing values for the selected confounders. HRs were calculated by using Cox proportional hazards analysis.</p>2<p>Adjusted for age and sex.</p>3<p>Adjusted for age (years), sex, height (per 10 cm), education level, fiber (g/d), total fatty acids (g/d), trans unsaturated fatty acid (g/d), mono unsaturated fat (g/d), poly unsaturated fat (g/d), carbohydrates (g/d) and niacin (mg/d).</p>4<p>Insufficient number of cases for analyses with tertiles (N>60 required) or with acrylamide as a continuous variable (N>20 required).</p>5<p>Proportional hazards assumption not met; therefore results not presented.</p

Flow diagram of subcohort members and cases used in the analysis.

<p>NCR  =  Netherlands Cancer Registry, PALGA  =  Netherlands Pathology Registry, LM  =  lymphatic malignancies, MM  =  multiple myeloma, DLCL  =  diffuse large cell lymphoma, CLL  =  chronic lymphocytic leukaemia, FL  =  follicular lymphoma, WMI  =  Waldenstrom macroglobulinemia and immunocytoma, MCL  =  mantle cell lymphoma, T-cell  =  T-cell lymphoma.</p