4D robust optimization including uncertainties in time structures can reduce the interplay effect in proton pencil...

Interplay effects in proton radiotherapy can create large distortions in the dose distribution and severely degrade the plan quality. Standard methods to mitigate these effects include abdominal compression, gating, and rescanning. We propose a new method to include the time structures of the delivery and organ motion in the framework of four-dimensional (4D) robust optimization to generate plans that are robust against interplay effects.

The method considers multiple scenarios reflecting the uncertainties in the delivery and in the organ motion. In each scenario, the pencil beam scanning spots are distributed to different phases of the breathing cycle according to each individual spot time stamp, and a partial beam dose is calculated for each phase. The partial beam doses are accumulated on a reference phase through deformable image registrations. Minimax optimization is performed to take all scenarios into account simultaneously. For simplicity, the uncertainties in this proof of concept study are limited to variations in the breathing pattern. The method is evaluated for three different nonsmall cell lung cancer patients and compared to plans using conventional 4D robust optimization both with and without rescanning. We assess the ability of the method to mitigate distortions from the interplay effect over multiple evaluation scenarios using 4D dose calculations. This interplay evaluation is performed in an experimentally validated framework, which is independent of the optimization in the plan generation step.

For the three studied patients, 4D optimization including time structures is efficient, especially for large tumor motions, where rescanning of conventional 4D robustly optimized plans is not sufficient to mitigate the interplay effect. The most efficient approach of the new method is achieved when it is combined with rescanning. For the patient with the largest motion, the mean V95% is 99.2% and mean V107% is 3.65% for the best rescanned 4D plan optimized with time structure. This can be compared to conventional 4D optimized plans with mean V95% of 92.7% and mean V107% of 13.1%.

The current study shows the potential of reducing interplay effects in proton pencil beam scanning radiotherapy by incorporating organ motion and delivery characteristics in a 4D robust optimization.