Feasibility of reduced setup uncertainty in intensity-modulated proton therapy for mediastinal lymphoma

Mediastinal lymphoma patients are typically young and are at risk of long-term radiation-induced adverse events, making organ of interest (OOI) sparing a key objective of radiotherapy. This study investigated whether reducing setup uncertainty during robust intensity-modulated proton therapy (IMPT) planning is feasible without compromising target coverage and delivered dose robustness.

Ten consecutive mediastinal lymphoma patients treated with IMPT were retrospectively analyzed. Treatment plans were generated on the four-dimensional average computed tomography (4DCT) using a 5 mm setup uncertainty (clinical standard). Additional plans with 4 and 3 mm setup uncertainties were created using a dose-mimicking optimization approach while maintaining identical clinical priorities. Robustness was evaluated using a three-dimensional robustness evaluation method (3DREM) and a longitudinal four-dimensional robustness evaluation method (4DREM), incorporating setup and range variations, machine uncertainties, respiratory motion, and weekly anatomical changes.

All plans achieved adequate target coverage in the 3D-nominal and 4DREM voxel-wise mean dose distributions (V_{95 %} > 99.6 %). The voxel-wise minimum dose distributions from 4DREM confirmed robust target coverage (V_{95 %} > 98 %, D_{98 %} > 95 % of prescription dose) for all setup uncertainties, with one clinically accepted exception. Reducing setup uncertainty resulted in statistically significant reductions in organs of interest doses (p < 0.01), corresponding to median reductions in predicted lifetime acute coronary event risk of 0.17 % and 0.32 % for 4 mm and 3 mm setup uncertainties, respectively (p < 0.01).

Reducing setup uncertainty during robust IMPT planning for mediastinal lymphoma patients was feasible and improved OOI sparing without compromising delivered dose robustness.