MultiRBE: Treatment planning for protons with selective radiobiological effectiveness

Abstract

Purpose Clinical treatment planning protocols for protons recommend a uniform value radiobiological effectiveness (RBE) of protons of 1.1 throughout the treatment field, despite evidence from in‐vitro and animal studies that proton RBE increases with linear energy transfer (LET), causing tissues placed distally to the target location to receive a presumably higher biological dose than estimated. While several voices in the medical physics community have advocated for variable RBE‐based optimization, the uncertainties in RBE models have prevented its implementation in clinical practice, since an overestimation of RBE could cause significant target underdosage. Methods We propose a mixed RBE model (MultiRBE), where a uniform RBE is used in the target contours to ensure an adequate tumor coverage in terms of physical dose, but a variable RBE is used elsewhere. Our model was implemented in the open‐source treatment planning system matRad and three example cases were planned: a homogeneous phantom, a prostate tumor and a head‐and‐neck case. MultiRBE was used for plan optimization, and the produced plans were subsequently evaluated in terms of physical dose coverage (V95%) and variable RBE‐weighted dose in organs at risk and normal tissue complication probabilities (NTCP), where prediction models were available. Results The planning algorithm showed potential for reducing the biological dose in organs surrounding the planning target and thus decreasing the probability for complications in normal tissue (by up to 62% in the prostate case and 37% in the head‐and‐neck patient). This was achieved without compromising the target coverage or homogeneity in terms of physical dose, as a result of a smarter redistribution of dose among the surrounding tissues with regard to the optimization constraints. Conclusions The results prove the ability of the MultiRBE model to reduce biological dose at healthy tissues without compromising the dose coverage of the tumor, with independence of the variable RBE models used.

Impact of range uncertainty on clinical distributions of linear energy transfer and biological effectiveness in proton therapy

“…However, LET d and RBE variability and range deviations should be considered in OARs, especially in brain tumor patients. This twofold strategy is in accordance with a recently suggested treatment planning approach 46 and might further reduce the risk of beams pointing at OARs as well as reduce the uncertainty related to RBE‐weighted dose.…”

Spatial correlation of linear energy transfer and relative biological effectiveness with suspected treatment‐related toxicities following proton therapy for intracranial tumors

“…Hence, a clinical balance between the gains and potential drawbacks of such objectives has to be found before introducing them clinically, as previously discussed . Direct RBE optimization using variable models might also be considered in order to find such clinical balance . However, the uncertainties regarding the selection of RBE model, tissue, and model parameter settings are large .…”

“…These kinds of observations have led to the exploration of variable proton RBE models in the plan optimization and evaluation . However, as endpoint‐specific in vivo RBE values are associated with large uncertainties, several optimization approaches have been suggested to reduce the LET as a surrogate to reduce the RBE‐weighted dose (D RBE ) in critical structures, without knowing the exact LET–RBE relationship .…”

Proton Therapy Review: Proton Therapy from a Medical

“…TPS has a limitation; it must calculate dose distribution accurately in the inhomogeneous tissue region with analytical beam modeling, and the Monte Carlo simulation method has recently been adapted to improve the dose calculation accuracy. The variable RBE[33] consideration is also a recent emerging issue in plan optimization. Currently, the recommendation for proton RBE values is 1.1 in clinic.…”