Prediction of Microscopic Metastases in Patients with Metachronous Oligo-Metastases after Curative Treatment of Non-Small Cell Lung Cancer: A Microsimulation Study.

Metachronous oligo-metastatic disease is variably defined as one to five metastases detected after a disease-free interval and treatment of the primary tumour with curative intent. Oligo-metastases in non-small cell lung cancer (NSCLC) are often treated with curative intent. However additional metastases are often detected later in time, and the 5-year survival is low. Burdensome surgical treatment in patients with undetected metastases may be avoided if patients with a high versus low risk of undetected metastases can be separated. Because there is no clinical data on undetected metastases available, a microsimulation model of the development and detection of metastases in 100,000 hypothetical stage I NSCLC patients with a controlled primary tumour was constructed. The model uses data from the literature as well as patient-level data. Calibration was used for the unobservable model parameters. Metastases can be detected by a scheduled scan, or an unplanned scan when the patient develops symptoms. The observable information at time of detection is used to identify subgroups of patients with a different risk of undetectable metastases. We identified the size and number of detected oligo-metastases, as well as the presence of symptoms that are the most important risk predictors. Based on these predictors, patients could be divided into a low-risk and a high-risk group, having a model-based predicted probability of 8.1% and 89.3% to have undetected metastases, respectively. Currently, the model is based on a synthesis of the literature data and individual patient-level data that were not collected for the purpose of this study. Optimization and validation of the model is necessary to allow clinical usability. We describe the type of data that needs to be collected to update our model, as well as the design of such a validation study.

Cost-Effectiveness of Surveillance Scanning Strategies after Curative Treatment of Non-Small-Cell Lung Cancer.

BACKGROUND: After curative treatment of primary non-small-cell lung cancer (NSCLC), patients undergo intensive surveillance with the aim to detect recurrences from the primary tumor or metachronous second primary lung cancer as early as possible and improve overall survival. However, the benefit of surveillance is debated. Available evidence is of low quality and conflicting. Microsimulation modeling facilitates the exploration of the impact of different surveillance strategies and provides insight into the cost-effectiveness of surveillance. METHODS: A microsimulation model was used to simulate a range of computed tomography (CT)-based surveillance schedules, differing in the frequency and duration of CT surveillance. The impact on survival, quality-adjusted life-years, costs, and cost-effectiveness of each schedule was assessed. RESULTS: Ten of 108 strategies formed the cost-effectiveness frontier; that is, these were the strategies with the optimal cost-health benefit balance. Per person, the discounted QALYs of these strategies varied between 5.72 and 5.81 y, and discounted costs varied between €9892 and €19,259. Below a willingness-to-pay threshold of €50,000/QALY, no scanning is the preferred option. For a willingness-to-pay threshold of €80,000/QALY, surveillance scanning every 2 y starting 1 y after curative treatment becomes the best option, with €11,860 discounted costs and 5.76 discounted QALYs per person. The European Society for Medical Oncology guideline strategy was more expensive and less effective than several other strategies. CONCLUSION: Model simulations suggest that limited CT surveillance scanning after the treatment of primary NSCLC is cost-effective, but the incremental health-benefit remains marginal. However, model simulations do suggest that the guideline strategy is not cost-effective.

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.

Patient-reported Outcomes After the Treatment of Early Stage Non-small-cell Lung Cancer With Stereotactic Body Radiotherapy Compared With Surgery.

INTRODUCTION: As there is increasing evidence for comparable survival after either stereotactic body radiotherapy (SBRT) or surgery for patients with stage I non-small-cell lung cancer (NSCLC), treatment impact on the quality of life (QoL) is essential for well-informed decision-making. Our previous work evaluated health utility between surgery and SBRT in stage I NSCLC. The aim of this secondary analysis is to directly compare QoL in the first year after SBRT and surgery. MATERIALS AND METHODS: QoL was assessed at baseline and 3, 6, and 12 months after treatment. Two prospectively collected databases of patients with clinically proven stage I NSCLC, from 2 large hospitals in the Netherlands, were pooled (n = 306; 265 patients were treated with SBRT and 41 patients with surgery). To correct for confounding, propensity scores were calculated, to be selected for surgical treatment. A mixed model analysis was used to study differences in QoL between the 2 treatments. RESULTS: The 41 surgical patients were matched to 41 SBRT patients on propensity score with a 1:1 ratio. At baseline, patients in the surgery group report a lower QoL compared with patients in the SBRT group. However, during the first year after treatment, no clinical meaningful differences were observed, except for role functioning, between patients treated using either modality. CONCLUSION: This study comparing a matched cohort revealed no clinically significant differences in QoL following either SBRT or surgery for early stage NSCLC. These results support the hypothesis that surgery and SBRT are comparable treatments.

Differences in Longitudinal Health Utility between Stereotactic Body Radiation Therapy and Surgery in Stage I Non-Small Cell Lung Cancer.

INTRODUCTION: There is an ongoing debate on the optimal treatment for stage I NSCLC, with increasing evidence for comparable health outcomes after surgery and stereotactic body radiation therapy (SBRT). For clinical decision making, the experienced quality of life, summarized as health utility, is of importance to choosing between treatments. In this study, we evaluated differences in longitudinal health utility in stage I NSCLC in the first year after surgical resection versus after SBRT before any recurrence of disease. We also assessed the impact of potential prognostic variables on health utility. METHODS: Prospectively collected databases containing data on patients with stage I NSCLC treated with either SBRT or surgery were pooled from two large hospitals in the Netherlands. Quality of life data were measured by the Quality of Life Questionnaire-Core 30 questionnaire at baseline and 3, 6, and 12 months after treatment. Health utility (measured using the European Quality of Life Five-Dimension questionnaire) was calculated from the Quality of Life Questionnaire-Core 30 questionnaire by using a mapping algorithm. Propensity score matching was used to adjust for selection bias. Treatment effects were estimated for the matched patients by using a longitudinal mixed model approach. RESULTS: After correction for Eastern Cooperative Oncology Group score, sex, and age, the difference in 1-year averaged health utility between the SBRT and surgery groups was 0.026 (95% confidence interval: 0.028-0.080). Differences in health utility decreased over time. CONCLUSIONS: A small but not statistically significant difference in health utility was found between patients with stage I NSCLC treated with surgery and those treated with SBRT. Current analysis strengthens existing evidence that SBRT is an equivalent treatment option for early-stage NSCLC. Comparative cost-effectiveness remains to be determined.

Post-treatment Surveillance for Stage I and II Non-small Cell Lung Cancer: Impact on Clinical Outcome.

BACKGROUND/AIM: Patients treated for early-stage non-small cell lung cancer (NSCLC) need post-treatment surveillance for detecting recurrence of disease. The aim of this study was to provide evidence for the appropriate follow-up. PATIENTS AND METHODS: The overall survival (OS), 1- and 3-year survival and progression-free survival (PFS) were retrospectively compared between two imaging modality groups. One group received only chest radiographs (CR group) and one group received chest radiographs and at least one computed tomography scan (CT group). RESULTS: Patients in the CR group (n=50) had no inferior OS (hazard ratio (HR)=1.427, 95% confidence interval (CI)=0.755-2.695, p=0.273) and PFS (HR=1.156, 95% CI=0.645-2.069, p=0.627) compared to patients in the CT group (n=23). Both 1- and 3-year survival were equal in the two groups (HR=5.544, 95% CI=0.530-58.031, p=0.153 and HR=1.540, 95% CI=0.752-3.154, p=0.238, respectively). CONCLUSION: Follow-up with a chest radiography did not result in inferior clinical outcomes compared to follow-up with a CT scan.

Changes in Pulmonary Function After Stereotactic Body Radiotherapy and After Surgery for Stage I and II Non-small Cell Lung Cancer, a Description of Two Cohorts.

AIM: To evaluate changes in pulmonary function tests (PFTs) at different follow-up durations after stereotactic body radiotherapy (SBRT) and surgery in stage I and II non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Differences between pre-treatment- and follow-up PFTs were analyzed in 93 patients treated with surgery and 30 patients treated with SBRT for NSCLC. Follow-up durations were categorized into: early (0-9 months), middle (10-21 months) and late (≥22 months). Wilcoxon signed-rank test was used to analyze differences between pre-treatment and follow-up PFTs. RESULTS: Forced expiratory volume in one second, forced vital capacity and diffusion capacity for carbon monoxide corrected for the actual hemoglobin level significantly diminished after surgery for all follow-up durations: 11-17% of predicted values. After SBRT, PFTs remained stable, but a declining trend of 6% (p=0.1) was observed after 22 months. CONCLUSION: SBRT might lead to less treatment-related toxicity measured by PFTs than surgery in both the short and long term.