Prediction of microscopic metastases in patients with metachronous oligo-metastases after curative treatment of Non-Small Cell Lung Cancer

Abstract

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 5-year survival is low. Burdensome surgical treatment in patients with undetected metastases may be avoided if patients with high versus lowrisk 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 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 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 different risk of undetectable metastases. We identified size and number of detected oligo-metastases, as well as presence of symptoms to be 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 literature data and individual patient-level data that was not collected for the purpose of this study. Optimisation 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 validation study.

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

“…Most parameters remained the same as in the previous publications. 18 , 22 Many parameters were drawn from a truncated normal distribution, to prevent negative parameters from being drawn, even though the frequency of this occurring was low. As such, we do not expect truncation to affect the mean values of the parameters and outcomes.…”

“…The combination of the hazards for detection of the largest metastasis, either through symptoms or surveillance; the VDT of all metastases; the size ratio between consecutive metastases; and the timing of surveillance scans together determine whether a patient is diagnosed with metastatic recurrence of disease and the number of metastases found. l detectable was calibrated to progression-free survival in curatively treated stage I NSCLC patients, [20][21][22] l symptom was calibrated to the percentage of patients with symptomatic detection, [22][23][24] and the number of detected metastases was calibrated against the prevalence of detected oligo recurrences supplemented with expert opinion. [23][24][25][26][27][28][29]…”