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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.
Highlights
In this study, we consider adult base-of-skull sarcoma and chordoma cases plus pediatric craniopharyngioma cases, all widely regarded as priority candidates for proton therapy
For base-of-skull and pediatric craniopharyngioma cases, both physical and biological robustness analyses should be considered for intensity modulated proton therapy (IMPT): these analyses can substantially affect the sparing of organs at risk (OARs) and comparisons against volumetric modulated arc therapy (VMAT)
When comparing VMAT and nominal IMPT plans for our base-of-skull cohort, the dosimetric advantages of IMPT are clear: IMPT leads to reduced integral dose and generally to improved CTV coverage given the OAR constraints
Summary
We consider adult base-of-skull sarcoma and chordoma cases plus pediatric craniopharyngioma cases, all widely regarded as priority candidates for proton therapy. Base-of-skull tumors (skull base sarcomas, chordomas and chondrosarcomas) are radio resistant and are challenging to treat due to their proximity and sometimes overlap with organs at risk (OARs) such as the brainstem and optical apparatus. It is unsurprising that treatment planning studies demonstrate that for intracranial tumors proton therapy reduces the dose of radiation delivered to the whole brain [4]. Across a wide range of base-of-skull tumors, dosimetric studies have reported that proton plans better spare organs at risk such as the brainstem, optical apparatus and cochleae [5,6,7,8]. Physical and biological uncertainties are much more complicated for proton plans than for photon plans
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