We developed and validated a decision model to evaluate long-term health effects, costs, and cost-effectiveness of radiation therapy strategies in non-small cell lung cancer (NSCLC).

Structure of the model

Four clinical states were included in the model: ‘Alive without progression’, ‘Local Recurrence’, ‘Metastasis’, and ‘Death’. Individual patients are simulated by repeatedly sampling a patient profile, consisting of patient and tumour characteristics. The model tracks clinical events over time and takes patient and tumour features into account. The transitioning of patients between the health states is governed by personalized time dependent hazard rates, which were obtained by multi-state statistical modelling. Model outcomes are life-years, quality-adjusted life-years (QALYs), and costs. The time horizon is life time. A hospital perspective was taken. Two types of cost-effectiveness evaluations were carried out using the model.

PET-based radiotherapy planning

We evaluated the cost-effectiveness of positron emission tomography (PET)-based isotoxic accelerated radiation therapy treatment (PET-ART) compared with conventional fixed-dose computed tomography (CT)-based radiation therapy treatment (CRT). Model predictions were obtained by simulating the life course of 50,000  patients. The average incremental costs per patient of PET-ART were €569 for 0.42 incremental life-years and 0.33 QALYs gained. The base-case scenario resulted in an incremental cost-effectiveness ratio of €1360 per life-year gained and €1744 per QALY gained. The probabilistic sensitivity 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. On the basis of the available data, individualized PET-ART for NSCLC seems to be cost-effective compared with conventional fixed-dose CT-based radiation therapy.

Optimizing chemo-radiation

In a subsequent cost-effectiveness analysis, four chemo-radiation strategies were evaluated: standard sequential chemo-radiation, standard concurrent chemo-radiation, a novel strategy consisting of PET-CT based isotoxic accelerated sequential chemo-radiation and a novel concurrent chemo-radiation strategy with daily low-dose cisplatin. Compared to standard sequential chemo-radiation, the incremental cost-effectiveness of standard concurrent chemo-radiation was €38024 per QALY gained. This was €6249 per QALY for the PET-CT based sequential strategy, and €346 per QALY for concurrent chemo-radiation with low-dose cisplatin. Based on our model, the novel, optimized, sequential and concurrent chemo-radiation strategies are more effective and cost-effective than the current conventional sequential and concurrent strategies.

Publications

van der Linden N, Bongers ML, Coupé VM, Smit EF, Groen HJ, Welling A, Schramel FM, Uyl-de Groot CA. Costs of non-small cell lung cancer in the Netherlands. Lung Cancer. 2015 Oct 17. pii: S0169-5002(15)30084-2. doi: 10.1016/j.lungcan.2015.10.015. [Epub ahead of print]

Bongers ML, Coupé VM, De Ruysscher D, Oberije C, Lambin P, Uyl-de Groot CA. Individualized positron emission tomography-based isotoxic accelerated radiation therapy is cost-effective compared with conventional radiation therapy: a model-based evaluation. Int J Radiat Oncol Biol Phys. 2015;91(4):857-65.

Bongers ML, De Ruysscher D, Oberije C, Lambin P, Uyl-de Groot CA, Coupé VM. Multistate Statistical Modeling: A Tool to Build a Lung Cancer Microsimulation Model That Includes Parameter Uncertainty and Patient Heterogeneity.  2015 Mar 2. pii: 0272989X15574500. [Epub ahead of print]