Linear energy transfer-guided optimization in intensity modulated proton therapy: feasibility study and clinical...

Area of Science:

• Medical Physics
• Radiation Oncology
• Computational Biology

Background:

• Intensity modulated proton therapy (IMPT) offers precise dose delivery.
• Optimizing IMPT plans traditionally focuses on physical dose distributions.
• Linear energy transfer (LET) variations can significantly impact biological outcomes.

Purpose of the Study:

• To assess the feasibility of using LET-guided optimization in IMPT.
• To explore the potential clinical benefits of LET-guided IMPT plan optimization.
• To investigate the impact of LET variations on dose and biological effectiveness.

Main Methods:

• Generated Pareto-optimal IMPT base plans (BPs) using multicriteria optimization (MCO) for head-and-neck and pancreatic cancer patients.
• Calculated dose and LET distributions using a Monte Carlo platform.
• Utilized an MCO navigation module for interpolating between BPs and an LET-based relative biological effectiveness (RBE) model.

Main Results:

• Significant variations in mean LET (up to 30% in targets, up to 2x in organs at risk) were observed among BPs.
• An inverse relationship between dose and LET in organs at risk was typically found.
• LET-guided navigation showed potential for up to 40% improvement in RBE-weighted dose.

Conclusions:

• LET variations in IMPT base plans can lead to substantial differences in RBE-weighted doses.
• A novel strategy for optimizing proton therapy maximizes tumor LET while minimizing normal tissue LET.
• Pareto-surface navigation using dose and LET distributions aids in identifying clinically optimal IMPT plans.