WE-AB-207B-06: Dose and Biological Uncertainties in Sarcoma.
PURPOSE
To understand the clinical impact of key uncertainties in proton therapy potentially affecting the analysis of clinical trials, namely the assumption of using a constant relative biological effectiveness (RBE) of 1.1 compared to variable RBE for proton therapy and the use of analytical dose calculation (ADC) methods.


METHODS
Proton dose distributions were compared for analytical and Monte Carlo (TOPAS) dose calculations. In addition, differences between using a constant RBE of 1.1 (RBE-constant) were compared with four different RBE models (to assess model variations). 10 patients were selected from an ongoing clinical trial on IMRT versus scanned protons for sarcoma. Comparisons were performed using dosimetric indices based on dose-volume histogram analyses and γ-index analyses.


RESULTS
For three of the RBE-models the mean dose, D95, D50 and D02 (dose values covering 95%, 50% and 2% of the target volume, respectively) were up to 5% lower than for RBE-constant. The dosimetric indices for one of the RBE-models were around 9% lower than for the RBE-constant model. The differences for V90 (the percentage of the target volume covered by 90% of the prescription dose) were up to 40% for three RBE-models, whereas for one the difference was around 95%. All ADC dosimetric indices were up to 5% larger than for RBE-constant. The γ-index passing rate for the target volume with a 3%/3mm criterion was above 97% for all models except for one, which was below 24%.


CONCLUSION
Interpretation of clinical trials on sarcoma may depend on dose calculation uncertainties (as assessed by Monte Carlo). In addition, the biological dose distribution depends notably on which RBE model is utilized. The current practice of using a constant RBE of 1.1 may overestimate the target dose by as much as 5% for biological dose calculations. Performing an RBE uncertainty analysis is recommended for trial analysis. U19 projects - U19 CA 021239. PI: Delaney.