The impact of proton LET/RBE modeling and robustness analysis on base-of-skull and pediatric craniopharyngioma proton plans relative to VMAT

Abstract

Purpose: Pediatric craniopharyngioma, adult base-of-skull sarcoma and chordoma cases are all regarded as priority candidates for proton therapy. In this study, a dosimetric comparison between volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) was first performed. We then investigated the impact of physical and biological uncertainties. We assessed whether IMPT plans remained dosimetrically superior when such uncertainty estimates were considered, especially with regards to sparing organs at risk (OARs).Methodology: We studied 10 cases: four chondrosarcoma, two chordoma and four pediatric craniopharyngioma. VMAT and IMPT plans were created according to modality-specific protocols. For IMPT, we considered (i) variable RBE modeling using the McNamara model for different values of (α/β)x, and (ii) robustness analysis with ±3 mm set-up and 3.5% range uncertainties.Results: When comparing the VMAT and IMPT plans, the dosimetric advantages of IMPT were clear: IMPT led to reduced integral dose and, typically, improved CTV coverage given our OAR constraints. When physical robustness analysis was performed for IMPT, some uncertainty scenarios worsened the CTV coverage but not usually beyond that achieved by VMAT. Certain scenarios caused OAR constraints to be exceeded, particularly for the brainstem and optical chiasm. However, variable RBE modeling predicted even more substantial hotspots, especially for low values of (α/β)x. Variable RBE modeling often prompted dose constraints to be exceeded for critical structures.Conclusion: For base-of-skull and pediatric craniopharyngioma cases, both physical and biological robustness analyses should be considered for IMPT: these analyses can substantially affect the sparing of OARs and comparisons against VMAT. All proton RBE modeling is subject to high levels of uncertainty, but the clinical community should remain cognizant possible RBE effects. Careful clinical and imaging follow-up, plus further research on end-of-range RBE mitigation strategies such as LET optimization, should be prioritized for these cohorts of proton patients.

Combining Clinical and Dosimetric Features in a PBS Proton Therapy Cohort to Develop a NTCP Model for Radiation-Induced Optic Neuropathy

“…It has been shown that this assumption affects the range and biological effectiveness of protons in the patient and is therefore linked to a non-negligible amount of uncertainty. 40,41 Not taking into account variable RBE, possible variations in proton range 42 31 would have led to dosimetric differences of about 1% with minor impact on the modelling results.…”

Study of relationship between dose, LET and the risk of brain necrosis after proton therapy for skull base tumors

“…When the plan included more than one stage, an average LET d was computed, by calculating for each voxel an average LET value weighted by the dose delivered in each stage. For each patient, we analysed deposited D RBE calculated with cRBE (RBE=1.1) and vRBE parametric model by McNamara [19], assuming α/β=4 Gy in PTV (based on [26], [27]) and α/β=2 Gy for brain, left and right temporal lobe (LTL and RTL, respectively). The choice of α/β ratio was based on the tumor type and data presented in van Leeuwen et al [27].…”

Reformulated McNamara RBE‐weighted beam orientation optimization for intensity modulated proton therapy

“…[13][14][15][16][17][18] Second, the optimization problem was divided into subproblems calculating McNamara RBE, physical dose, and LET separately. The RBE dose was evaluated at the end of treatment planning 19,20 or sequentially in an iterative process, 21 which does not promise problem convergence.…”