Comparing biological effectiveness guided plan optimization strategies for cranial proton therapy: potential and...

Area of Science:

• Radiation Oncology
• Medical Physics
• Proton Therapy

Background:

• Variable relative biological effectiveness (RBE) in proton therapy can increase dose burden in organs at risk (OARs).
• Optimizing proton plans to account for variable RBE is crucial for minimizing toxicity while maintaining treatment efficacy.

Purpose of the Study:

• To introduce and compare multiple biological effectiveness guided (BG) proton plan optimization strategies.
• To minimize variable RBE-induced dose burden in OARs while preserving plan quality.
• To assess the impact of these strategies on normal tissue complication probabilities (NTCPs).

Main Methods:

• Generated dose-optimized (DOSEopt) proton pencil beam scanning plans for ten cranial patients.
• Created four BG plans minimizing proton track-ends, dose-averaged linear energy transfer (LETd), high-LET energy deposition, or variable RBE-weighted dose (DRBE) in OARs.
• Assessed plan quality, derived LETd, DRBE, and NTCPs for blindness and brainstem necrosis; statistically compared plans.

Main Results:

• All BG plans significantly reduced near-maximum DRBE in critical OARs compared to DOSEopt plans.
• LETd-optimizing strategies showed greater robustness against range and setup uncertainties than DRBE optimization.
• All BG strategies reduced NTCP for brainstem necrosis and blindness by an average of 47%.

Conclusions:

• BG strategies effectively reduced variable RBE-induced NTCPs in OARs.
• Reducing LETd in high-dose voxels is a promising approach for clinical translation.
• These strategies represent a step towards safely implementing variable RBE optimization in clinical practice.