Robustness analysis of CTV and OAR dose in clinical PBS-PT of neuro-oncological tumors: prescription-dose calibration and inter-patient variation with the Dutch proton robustness evaluation protocol.

The Dutch proton robustness evaluation protocol prescribes the dose of the clinical target volume (CTV) to the voxel-wise minimum (VWmin) dose of 28 scenarios. This results in a consistent but conservative near-minimum CTV dose (D98%,CTV). In this study, we analyzed: (i) correlations between VWmin/VWmax metrics and actually delivered dose to the CTV and OARs under the impact of treatment errors, and (ii) the performance of the protocol before and after its calibration with adequate prescription dose levels.
Approach: 21 neuro-oncological patients were included. Polynomial Chaos Expansion (PCE) was applied to perform a probabilistic robustness evaluation using 100,000 complete fractionated treatments per patient. Patient-specific scenario distributions of clinically relevant dosimetric parameters for the CTV and OARs were determined and compared to clinical VWmin and VWmax dose metrics for different scenario subsets used in the robustness evaluation protocol. 
Main results: The inclusion of more geometrical scenarios leads to a significant increase of the conservativism of the protocol in terms of clinical VWmin and VWmax values for the CTV and OARs. The protocol could be calibrated using VWmin dose evaluation levels of 93.0% to 92.3%, depending on the scenario subset selected. Despite this calibration of the protocol, robustness recipes for proton therapy showed remaining differences and an increased sensitivity to geometrical σ errors compared to photon-based margin recipes.
Significance: The Dutch proton robustness evaluation protocol, combined with the photon-based margin recipe, could be calibrated with a VWmin evaluation dose level of 92.5%. However, it shows limitations in predicting robustness in dose, especially for the near-maximum dose metrics to OARs. Consistent robustness recipes could improve proton treatment planning to calibrate residual differences from photon-based assumptions.
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