Inter-subject cerebrovascular variability: a source of uncertainty for dose calculation to circulating blood cells for glioblastoma patients treated with modern radiotherapy techniques.

Purpose. To assess how inter-subject variations in brain vasculature among glioblastoma (GBM) patients affects the calculated dose received by circulating blood cells (CBC) during radiotherapy and its subsequent impact on CBC depletion. Methods. Ten GBM patients treated with either intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) were selected. For each patient, 23 cerebrovascular models were developed based on 23 healthy subject MR-angiography data to simulate intra- and inter-subject blood vessel diversity. Based on the corresponding treatment plan of the patient, the dose to CBC was calculated for all the 230 scenarios. The impact of inter-subject variation on fraction of irradiated blood volume ( V D >0 cGy ) and lymphocyte kill rates as a function of the clinical target volume (CTV) size and treatment technique were analyzed. Results. The dose fluctuation to CBC was higher in IMRT plans compared to VMAT plans. The uncertainty in the V D >0 cGy was 18.3% for IMRT and 2.0% (CI 95% ) for VMAT and the dispersion of the D 2% index was 6 cGy for IMRT and 1 cGy for VMAT (CI 95% ) for one single treatment fraction of 200 cGy. The uncertainty in killed CBC due to inter-subject diversity in brain blood vessel increased with increasing CTV size and was σ = 11.2%. Conclusions . VMAT showed greater robustness against inter-subject variation in blood vessels compared to IMRT. We recommend considering the uncertainty in depleting CBC resulting from the use of less patient-specific and generic blood vessel phantoms to improve the radiation-induced lymphopenia assessments.