The dirty and clean dose concept: Towards creating proton therapy treatment plans with a photon‐like dose response

Abstract

BackgroundApplying tolerance doses for organs at risk (OAR) from photon therapy introduces uncertainties in proton therapy when assuming a constant relative biological effectiveness (RBE) of 1.1.PurposeThis work introduces the novel dirty and clean dose concept, which allows for creating treatment plans with a more photon‐like dose response for OAR and, thus, less uncertainties when applying photon‐based tolerance doses.MethodsThe concept divides the 1.1‐weighted dose distribution into two parts: the clean and the dirty dose. The clean and dirty dose are deposited by protons with a linear energy transfer (LET) below and above a set LET threshold, respectively. For the former, a photon‐like dose response is assumed, while for the latter, the RBE might exceed 1.1. To reduce the dirty dose in OAR, a MaxDirtyDose objective was added in treatment plan optimization. It requires setting two parameters: LET threshold and max dirty dose level. A simple geometry consisting of one target volume and one OAR in water was used to study the reduction in dirty dose in the OAR depending on the choice of the two MaxDirtyDose objective parameters during plan optimization. The best performing parameter combinations were used to create multiple dirty dose optimized (DDopt) treatment plans for two cranial patient cases. For each DDopt plan, 1.1‐weighted dose, variable RBE‐weighted dose using the Wedenberg RBE model and dose‐average LETd distributions as well as resulting normal tissue complication probability (NTCP) values were calculated and compared to the reference plan (RefPlan) without MaxDirtyDose objectives.ResultsIn the water phantom studies, LET thresholds between 1.5 and 2.5 keV/µm yielded the best plans and were subsequently used. For the patient cases, nearly all DDopt plans led to a reduced Wedenberg dose in critical OAR. This reduction resulted from an LET reduction and translated into an NTCP reduction of up to 19 percentage points compared to the RefPlan. The 1.1‐weighted dose in the OARs was slightly increased (patient 1: 0.45 Gy(RBE), patient 2: 0.08 Gy(RBE)), but never exceeded clinical tolerance doses. Additionally, slightly increased 1.1‐weighted dose in healthy brain tissue was observed (patient 1: 0.81 Gy(RBE), patient 2: 0.53 Gy(RBE)). The variation of NTCP values due to variation of α/β from 2 to 3 Gy was much smaller for DDopt (2 percentage points (pp)) than for RefPlans (5 pp).ConclusionsThe novel dirty and clean dose concept allows for creating biologically more robust proton treatment plans with a more photon‐like dose response. The reduced uncertainties in RBE can, therefore, mitigate uncertainties introduced by using photon‐based tolerance doses for OAR.

Impact of Relative Biologic Effectiveness for Proton Therapy for Head and Neck and Skull-Base Tumors: A Technical and Clinical Review

“…In addition to the indirect approaches commonly applied in current clinical practice, various LET/RBE-guided plan optimization approaches have been proposed [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ]. These approaches aim to achieve more favorable LET and RBE distributions, thereby minimizing the biological dose in OAR without compromising target volume coverage.…”

“…These approaches aim to achieve more favorable LET and RBE distributions, thereby minimizing the biological dose in OAR without compromising target volume coverage. Several methods have been introduced, including optimizing LET [ 75 , 77 , 79 , 80 ], variable RBE-weighted dose [ 82 ], track-end distributions [ 84 ], and introducing “clean dose” (dose deposited by low-LET protons) and “dirty dose” (dose deposited by high-LET protons), penalizing the latter in OAR [ 83 , 85 ]. Early work by Grassberger et al [ 78 ] has demonstrated that pencil beam scanning provides the opportunity to optimize LET distribution without significantly altering the distribution of physical dose.…”