Substantial Sparing of Organs at Risk with Modern Proton Therapy in Lung Cancer, but Altered Breathing Patterns Can Jeopardize Target Coverage

SIMPLE SUMMARY: Treatment of locally advanced non-small cell lung cancer (LA-NSCLC) is a fine balance between toxicity and cure. Modern proton therapy might offer a more gentle radiation treatment compared to state-of-the-art photon radiotherapy, but is also more susceptible to the influence of breathing motion and anatomical changes. In this study, the influence of such uncertainties on treatment delivery was thoroughly investigated. Modern proton therapy did indeed show potential to reduce the risk of toxicity for the heart and lungs. This potential was maintained under the influence of anatomical and delivery uncertainties. However, changes in breathing motion jeopardized the target dose distribution in a subset of patients. We therefore recommend imaging at onset or early in treatment to recognize these patients and adapt the treatment. ABSTRACT: Enhancing treatment of locally advanced non-small cell lung cancer (LA-NSCLC) by using pencil beam scanning proton therapy (PBS-PT) is attractive, but little knowledge exists on the effects of uncertainties occurring between the planning (Plan) and the start of treatment (Start). In this prospective simulation study, we investigated the clinical potential for PBS-PT under the influence of such uncertainties. Imaging with 4DCT at Plan and Start was carried out for 15 patients that received state-of-the-art intensity-modulated radiotherapy (IMRT). Three PBS-PT plans were created per patient: 3D robust single-field uniform dose (SFUD), 3D robust intensity-modulated proton therapy (IMPT), and 4D robust IMPT (4DIMPT). These were exposed to setup and range uncertainties and breathing motion at Plan, and changes in breathing motion and anatomy at Start. Target coverage and dose-volume parameters relevant for toxicity were compared. The organ at risk sparing at Plan was greatest with IMPT, followed by 4DIMPT, SFUD and IMRT, and persisted at Start. All plans met the preset criteria for target robustness at Plan. At Start, three patients had a lack of CTV coverage with PBS-PT. In conclusion, the clinical potential for heart and lung toxicity reduction with PBS-PT was substantial and persistent. Altered breathing patterns between Plan and Start jeopardized target coverage for all PBS-PT techniques.