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

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.

Palliative extracranial radiotherapy in patients receiving immunotherapy for non-small cell lung cancer: a narrative review

“…No such case was observed in the SBRT alone group. In general, a shift towards correlation of lower doses for a risk of pneumonitis was observed in SBRT + ICIs group compared to SBRT alone group (59). This suggestion of different correlation of dose-volume-effect for pneumonitis was not supported by the largest published series of thoracic SBRT and IO evaluating lung dose-volume parameters in patients receiving ICIs either sequentially (within 7 days after completion of SBRT) or concurrently (before or at the start of SBRT) in 123 patients participating in three phase I trials on combination SBRT and IO.…”

A retrospective study comparing the efficacy of microwave ablation and stereotactic body radiotherapy in colorectal cancer lung metastases

“…However, SBRT exhibits a distinct advantage over other methods for larger tumors near blood vessels and both the number and location of lung lesions and the presence of synchronous extrapulmonary metastases and mediastinal lymph metastases are important prognostic factors. Nevertheless, use of SBRT often leads to radiation pneumonitis during the treatment of lung metastases while the lesions shrink, causing irreversible damage to the lungs of patients ( 20 ).…”