LET-weighted doses effectively reduce biological variability in proton radiotherapy planning

Area of Science:

• Medical Physics
• Radiation Oncology
• Radiobiology

Background:

• Proton radiotherapy offers advantages over photon therapy due to its precise dose deposition.
• However, variations in relative biological effectiveness (RBE) with linear energy transfer (LET) introduce significant uncertainties in treatment planning.
• Accurate RBE modeling is crucial for optimizing proton therapy outcomes.

Purpose of the Study:

• To identify and evaluate metrics for mitigating RBE-related uncertainties in proton radiotherapy.
• To compare the effectiveness of dose, dose × LET, and an LET-weighted dose metric against experimental and clinical data.
• To quantify the reduction in biological effect variability achieved by the proposed metrics.

Main Methods:

• Compared three metrics (dose, dose × LET, LET-weighted dose) against in vitro proton RBE studies and clinical treatment plans.
• Plotted biological effects against each metric to assess variability.
• Evaluated the correlation between metrics and biological effects, particularly in prostate and medulloblastoma treatment plans.

Main Results:

• Dose alone showed significant biological effect variability due to LET-dependent RBE.
• Dose × LET metric overestimated the impact of LET on cell survival, leading to larger biological effect spreads.
• LET-weighted dose demonstrated superior correlation with biological effect, reducing variability from ±5% to <1% in clinical plans.

Conclusions:

• LET-weighted dose is a simplified yet effective metric for accounting for RBE variability in proton therapy.
• This metric can help identify regions of potential high biological effect in normal tissues.
• LET-weighted dose offers a practical tool for biological optimization in proton therapy, reducing reliance on complex RBE models.