Robust intensity‐modulated proton therapy to reduce high linear energy transfer in organs at risk

Abstract

Purpose We propose a robust treatment planning model that simultaneously considers proton range and patient setup uncertainties and reduces high linear energy transfer (LET) exposure in organs at risk (OARs) to minimize the relative biological effectiveness (RBE) dose in OARs for intensity-modulated proton therapy (IMPT). Our method could potentially reduce the unwanted damage to OARs. Methods We retrospectively generated plans for 10 patients including 2 prostate, 4 head and neck, and 4 lung cancer patients. The “worst-case robust optimization” model was applied. One additional term as a “biological surrogate (BS)” of OARs due to the high LET-related biological effects was added in the objective function. The biological surrogate was defined as the sum of the physical dose and extra biological effects caused by the dose-averaged LET. We generated 9 uncertainty scenarios that considered proton range and patient setup uncertainty. Corresponding to each uncertainty scenario, LET was obtained by a fast LET calculation method developed in-house and based on Monte Carlo simulations. In each optimization iteration, the model used the worst-case BS among all scenarios and then penalized overly high BS to organs. The model was solved by an efficient algorithm (limited-memory Broyden-Fletcher-Goldfarb-Shanno) in a parallel computing environment. Our new model was benchmarked with the conventional robust planning model without considering BS. Dose-volume histograms (DVHs) of the dose assuming a fixed RBE of 1.1 and BS for tumor and organs under nominal and uncertainty scenarios were compared to assess the plan quality between the two methods. Results For the 10 cases, our model outperformed the conventional robust model in avoidance of high LET in OARs. At the same time our method could achieve dose distributions and plan robustness of tumors assuming a fixed RBE of 1.1 almost the same as those of the conventional robust model. Conclusions Explicitly considering LET in IMPT robust treatment planning can reduce the high LET to OARs and minimize the possible toxicity of high RBE dose to OARs without sacrificing plan quality. We believe this will allow one to design and deliver safer proton therapy.

What will the medical physics of proton therapy look like 10 yr from now? A personal view

“…In much, the same way that the EUD concept (Equivalent Uniform Dose) in biological modeling has been successful for comparing dose distributions in a biologically relevant, but non‐absolute way (EUD itself makes no prediction on the actual magnitude of biological outcome), then LET can provide a metric whereby its value provides an indication of a potential increase in biological effect, without actually predicting the magnitude of that increase. Although this may seem somewhat of a lame advantage, LET will nevertheless provide a parameter, which could be “steered” away from critical structures, or concentrated into tumor regions, by an optimization process . Such an approach makes no assumption about the relationship of LET and biological effect, other than the knowledge that a higher LET could relate to an increased biological effect, even if that increase is of unknown magnitude.…”

“…Although this may seem somewhat of a lame advantage, LET will nevertheless provide a parameter, which could be "steered" away from critical structures, or concentrated into tumor regions, by an optimization process. [43][44][45] Such an approach makes no assumption about the relationship of LET and biological effect, other than the knowledge that a higher LET could relate to an increased biological effect, even if that increase is of unknown magnitude.…”

Hybrid 3D analytical linear energy transfer calculation algorithm based on precalculated data from Monte Carlo simulations

“…Pencil beam scanning (PBS) is a fast‐developing proton delivery technique offering improved conformal dose coverage of targets and reduced dose to organs at risk (OARs) compared to the conventional photon‐based radiotherapy. However, the relative biological effectiveness (RBE) of protons is to date poorly understood due to its complex dependence on several factors including the linear energy transfer (LET), biological endpoint, tissue type, physical dose, and the uncertainty of experimental results . As a result, it is difficult to give an accurate estimate of proton RBE for clinical dose calculations.…”

“…However, the relative biological effectiveness (RBE) of protons is to date poorly understood [3][4][5][6][7] due to its complex dependence on several factors including the linear energy transfer (LET), biological endpoint, tissue type, physical dose, 6,8 and the uncertainty of experimental results. [9][10][11][12][13][14] As a result, it is difficult to give an accurate estimate of proton RBE for clinical dose calculations. The current practice is to use a constant value of 1.1 to convert physical dose to RBE-weighted dose.…”

New Hybrid 3D Analytical Linear Energy Transfer (LET) Calculation Algorithm Based on the Pre-Calculated Data from Monte Carlo (MC) Simulations

“…Due to the strong correlation between LET and RBE, several groups have developed LET-guided optimization techniques 4,8,13,[19][20][21][22][23][24][25] that shift high LET toward the target volume and away from the OARs to reduce toxicity. The recently published TG-256 report 15 also suggested assessing the potential clinical consequences associated with variable RBE models and recommended LET-guided optimization in treatment planning systems (TPSs).…”