Purpose: Reducing variable relative biological effectiveness (RBE)-weighted proton dose in organs at risk (OAR) while maintaining clinical plan quality. Here, four RBE-related plan optimization strategies are introduced and compared.
Methods: Clinically acceptable multi-field optimized planning target volume-based reference plans were created for patients receiving cranial proton therapy using a constant RBE of 1.1 (DOSEopt). Variable RBE-related objective functions were added to penalize in OAR either proton track-ends (TEopt), proton dose-averaged linear energy transfer (LETd) in voxels above dose threshold (LETopt), dose contributions by high-LET protons (Dirty Dose, DDopt) or variable RBE-weighted dose (DRBEopt). Plan quality was defined by dose coverage (clinical target volume (CTV) D95%>95%), conformity index (CI), homogeneity index (HI) and robustness to the target volume with constant RBE-weighted dose (D1.1). The potential of each optimization strategy was assessed by recalculating variable RBE-weighted doses (DRBE) and corresponding normal tissue complication probabilities (NTCP) for critical OARs. Research version of RayStation v9 was used for plan optimizations and recalculations. For clarity, results are presented for one representative chondrosarcoma patient.
Results: Considering DRBE, estimated NTCP for brainstem necrosis decreased from 18.0% (DOSEopt) to 7.9-14.0% using RBE-related optimization strategies. Mean brainstem LETd was reduced from 3.1keV/µm to 2.1/2.3/2.8keV/µm for TEopt/LETopt/DDopt, respectively. DRBEopt primarily reduced D1.1 in the brainstem while slightly increasing its mean LETd to 3.2keV/µm. CI and HI remained comparable to the reference plan for all RBE-related strategies except for DRBEopt (CI reduced from 0.97 to 0.96 and HI from 0.89 to 0.85). RBE-guided plans were as robust as the DOSEopt plan (CTV D95%>95% fulfilled in ≥ 92% of scenarios), except for DRBEopt (fulfilled in 58%).
Conclusion: TEopt, LETopt and DDopt reduced NTCP in critical OARs while maintaining plan quality. These LET-redistributing optimization strategies allow for reducing RBE-related uncertainties in OARs while adhering to current dose reporting with constant RBE.
Funding Support, Disclosures, and Conflict of Interest: Jakob Oeden and Erik Traneus are employed at RaySearch Laboratories. Erik Traneus is the inventor of 432 patents EP3682945B1, EP3618924A1. The other authors report no conflict of interest.
TH- External Beam- Particle/high LET therapy: Proton therapy – dose optimization