Pneumonitis after Stereotactic Thoracic Radioimmunotherapy with Checkpoint Inhibitors: Exploration of the Dose–Volume–Effect Correlation

SIMPLE SUMMARY: Stereotactic body radiation therapy (SBRT) is widely applied for treatment of early stage lung cancer and pulmonary metastases. Modern immune checkpoint blockade (ICB) is progressively used in cancer treatment. Pneumonitis is a relevant side effect of both thoracic SBRT and ICB. Currently, it remains unclear whether we can presume the same radiation dose–volume–effect correlations and dose constraints for safe application of SBRT + ICB. We present a dose–volume–effect correlation analysis method using pneumonitis contours and dose–volume histograms (DVH). We showed dosimetric differences for pneumonitis volumes between SBRT + ICB and SBRT alone. We found a large extent of pneumonitis, even bilateral and apart from the radiation field for combined SBRT + ICB. We noticed a shift in pneumonitis DVHs towards lower doses and a trend towards decreased areas under the curve (AUC) for SBRT + ICB. This provides a direction for re-evaluation and potential adaptation of lung dose constraints for combined SBRT and ICB. ABSTRACT: Thoracic stereotactic body radiation therapy (SBRT) is extensively used in combination with immune checkpoint blockade (ICB). While current evidence suggests that the occurrence of pneumonitis as a side effect of both treatments is not enhanced for the combination, the dose–volume correlation remains unclear. We investigate dose–volume–effect correlations for pneumonitis after combined SBRT + ICB. We analyzed patient clinical characteristics and dosimetric data for 42 data sets for thoracic SBRT with ICB treatment (13) and without (29). Dose volumes were converted into 2 Gy equivalent doses (EQD2), allowing for dosimetric comparison of different fractionation regimes. Pneumonitis volumes were delineated and corresponding DVHs were analyzed. We noticed a shift towards lower doses for combined SBRT + ICB treatment, supported by a trend of smaller areas under the curve (AUC) for SBRT+ ICB (median AUC 1337.37 vs. 5799.10, p = 0.317). We present a DVH-based dose–volume–effect correlation method and observed large pneumonitis volumes, even with bilateral extent in the SBRT + ICB group. We conclude that further studies using this method with enhanced statistical power are needed to clarify whether adjustments of the radiation dose constraints are required to better estimate risks of pneumonitis after the combination of SBRT and ICB.