Dosiomics and radiomics to predict pneumonitis after thoracic stereotactic body radiotherapy and immune checkpoint inhibition

Introduction: Pneumonitis is a relevant side effect after radiotherapy (RT) and immunotherapy with checkpoint inhibitors (ICIs). Since the effect is radiation dose dependent, the risk increases for high fractional doses as applied for stereotactic body radiation therapy (SBRT) and might even be enhanced for the combination of SBRT with ICI therapy. Hence, patient individual pre-treatment prediction of post-treatment pneumonitis (PTP) might be able to support clinical decision making. Dosimetric factors, however, use limited information and, thus, cannot exploit the full potential of pneumonitis prediction. Methods: We investigated dosiomics and radiomics model based approaches for PTP prediction after thoracic SBRT with and without ICI therapy. To overcome potential influences of different fractionation schemes, we converted physical doses to 2 Gy equivalent doses (EQD2) and compared both results. In total, four single feature models (dosiomics, radiomics, dosimetric, clinical factors) were tested and five combinations of those (dosimetric+clinical factors, dosiomics+radiomics, dosiomics+dosimetric+clinical factors, radiomics+dosimetric+clinical factors, radiomics+dosiomics+dosimetric+clinical factors). After feature extraction, a feature reduction was performed using pearson intercorrelation coefficient and the Boruta algorithm within 1000-fold bootstrapping runs. Four different machine learning models and the combination of those were trained and tested within 100 iterations of 5-fold nested cross validation. Results: Results were analysed using the area under the receiver operating characteristic curve (AUC). We found the combination of dosiomics and radiomics features to outperform all other models with AUC_{radiomics+dosiomics, D} = 0.79 (95% confidence interval 0.78-0.80) and AUC_{radiomics+dosiomics, EQD2} = 0.77 (0.76-0.78) for physical dose and EQD2, respectively. ICI therapy did not impact the prediction result (AUC ≤ 0.5). Clinical and dosimetric features for the total lung did not improve the prediction outcome. Conclusion: Our results suggest that combined dosiomics and radiomics analysis can improve PTP prediction in patients treated with lung SBRT. We conclude that pre-treatment prediction could support clinical decision making on an individual patient basis with or without ICI therapy.