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Fig. 4 | BMC Medicine

Fig. 4

From: Trade-off between benefits, harms and economic efficiency of low-dose CT lung cancer screening: a microsimulation analysis of nodule management strategies in a population-based setting

Fig. 4

Schematic representation of modelled tumour growth and interaction between the natural history, screening, clinical diagnosis and survival modules. NMP nodule management protocol. The curve schematically represents the tumour growth. Figure does not reflect the scales. The natural history module contains a biological two-stage clonal expansion (TSCE) model and a tumour growth component and simulates for each individual the age at the onset of carcinogenesis, its histological features, the age and tumour size at the lymph nodes involvement and distant metastasis. The TSCE model simulates age at the cancer onset for each histological class. The final histological class for the individual is determined based on the competing risk (the lowest age at onset). The tumour growth component applies a Gompertz function which describes the relation between time (age) and the tumour volume. The clinical diagnosis model determines the age at lung cancer diagnosis and stage of the tumour according to TNM classification using the tumour growth model and information on the tumour progression from the natural history module. The screening module simulates an individual screening schedule based on the eligibility criteria. It applies the tumour growth module to determine the tumour volume at age of screening and uses information on the tumour progression for staging the screen-detected tumour according to TNM classification. The survival model determines the age of death based on the tumour stage and histological class. The figure illustrates a case where an individual in the no screening scenario develops a lung cancer tumour and is eventually symptomatically diagnosed with lung cancer at stage IV. The patient dies from lung cancer in the no screening scenario. In the screening scenario, a nodule (tumour) is detected in the first round of screening. The screen-detected nodule is small for the patient to undergo an immediate diagnostic evaluation. The patient undergoes a follow-up exam, where the growth is assessed according to the NMP. The growth and/or the volume doubling time meet the definition of cancer according to the NMP. The screen-detected tumour is at the local stage, and the patient is diagnosed with lung cancer at stage I in the screening scenario. The patient is cured and dies from other causes. The model calculates life years gained for each individual in the screened cohort

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