The price of robustness; impact of worst-case optimization on organ-at-risk dose and complication probability in intensity-modulated proton therapy for oropharyngeal cancer patients.

To quantify the impact of the degree of robustness against setup errors and range errors on organ-at-risk (OAR) dose and normal tissue complication probabilities (NTCPs) in intensity-modulated proton therapy for oropharyngeal cancer patients.

For 20 oropharyngeal cases (10 unilateral and 10 bilateral), robust treatment plans were generated using 'minimax' worst-case optimization. We varied the robustness against setup errors ('setup robustness') from 1 to 7mm and the robustness against range errors ('range robustness') from 1% to 7% (+1mm). We evaluated OAR doses and NTCP-values for xerostomia, dysphagia and larynx edema.

Varying the degree of setup robustness was found to have a considerably larger impact than varying the range robustness. Increasing setup robustness from 1mm to 3, 5, and 7mm resulted in average NTCP-values to increase by 1.9, 4.4 and 7.5 percentage point, whereas they increased by only 0.4, 0.8 and 1.2 percentage point when increasing range robustness from 1% to 3%, 5% and 7%. The degree of setup robustness was observed to have a clinically significant impact in bilateral cases in particular.

For oropharyngeal cancer patients, minimizing setup errors should be given a higher priority than minimizing range errors.