Why RBE must be a variable and not a constant in proton therapy

Area of Science:

• Radiation oncology
• Medical physics
• Radiobiology

Background:

• Proton therapy (PT) currently utilizes a constant relative biological effect (RBE) of 1.1 for treatment planning.
• This simplification may not accurately reflect the complex biological response to proton radiation.
• Understanding RBE variability is crucial for optimizing PT efficacy and safety.

Purpose of the Study:

• To critically evaluate the assumption of a constant RBE for proton therapy.
• To investigate the factors influencing proton RBE and its implications for treatment outcomes.
• To advocate for a more nuanced approach to RBE in PT planning.

Main Methods:

• Analysis of existing in vitro and in vivo data sets using linear regression and the linear-quadratic (LQ) radiation model.
• Comparison of RBE variations across different dose per fraction regimens.
• Assessment of data heterogeneity and its impact on statistical conclusions.

Main Results:

• In vitro data demonstrate a clear trend of increasing RBE with decreasing dose per fraction.
• The linear-quadratic (LQ) model provides a more appropriate fit to the data than simple linear regression.
• Data heterogeneity in some studies limits definitive conclusions, but homogeneous data show unequivocal RBE variation.
• In vivo data are less suitable for assessing late normal tissue effects.

Conclusions:

• The constant RBE of 1.1 for protons is theoretically and practically questionable.
• A variable RBE, particularly when analyzed with the LQ model, is more accurate.
• Further research, including studies on late normal tissue effects, is needed to refine RBE assignments and improve PT outcomes.