Prediction of Distant Metastases After Stereotactic Body Radiation Therapy for Early Stage NSCLC: Development and External Validation of a Multi-Institutional Model

Introduction: Distant metastases (DMs) are the primary driver of mortality for patients with early stage NSCLC receiving stereotactic body radiation therapy (SBRT), yet patient-level risk is difficult to predict. We developed and validated a model to predict individualized risk of DM in this population. Methods: We used a multi-institutional database of 1280 patients with cT1-3N0M0 NSCLC treated with SBRT from 2006 to 2015 for model development and internal validation. A Fine and Gray (FG) regression model was built to predict 1-year DM risk and compared with a random survival forests model. The higher performing model was evaluated on an external data set of 130 patients from a separate institution. Discriminatory performance was evaluated using the time-dependent area under the curve (AUC). Calibration was assessed graphically and with Brier scores. Results: The FG model yielded an AUC of 0.71 (95% confidence interval [CI]: 0.57–0.86) compared with the AUC of random survival forest at 0.69 (95% CI: 0.63–0.85) in the internal test set and was selected for further testing. On external validation, the FG model yielded an AUC of 0.70 (95% CI: 0.57–0.83) with good calibration (Brier score: 0.08). The model identified a high-risk patient subgroup with greater 1-year DM rates in the internal test (20.0% [3 of 15] versus 2.9% [7 of 241], p = 0.001) and external validation (21.4% [3 of 15] versus 7.8% [9 of 116], p = 0.095). A model nomogram and online application was made available. Conclusions: We developed and externally validated a practical model that predicts DM risk in patients with NSCLC receiving SBRT which may help select patients for systemic therapy.