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

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.

Impact of Interplay Effects on Spot Scanning Proton Therapy with Motion Mitigation Techniques for Lung Cancer: SFUD versus Robustly Optimized IMPT Plans Utilizing a Four-dimensional Dynamic Dose Simulation Tool

“…In addition, we considered that since the mean absolute dose differences were 0.1 GyRBE for both techniques, the OAR doses in the SFUD and IMPT plans might not be signi cantly affected by the interplay effect. Moreover, when comparing the OAR doses with both techniques, the IMPT plan could considerably spare the doses because robust optimization tends to shrink the irradiation volume more than the conservative beam-speci c margin concept, which is consistent with several previous studies [41][42][43]. However, it is worth noting that the dose constraints for the OARs were not applied in the optimization process in this study.…”

“…Regarding the OAR doses, there were no statistically signi cant differences between SD and 4DDD, except for the esophagus in the 5-phase plans. This might be because the esophagus is highly mobile and often resides close to the target [41]; thus, the interplay effects might have increased the dose. In addition, we considered that since the mean absolute dose differences were 0.1 GyRBE for both techniques, the OAR doses in the SFUD and IMPT plans might not be signi cantly affected by the interplay effect.…”

Immune System Dose With Proton Versus Photon Radiotherapy for Treatment of Locally Advanced NSCLC

“… 22 In addition, a recent analysis of patients with stage III NSCLC showed that IMPT can significantly reduce radiation dose to the heart and lungs as compared to IMRT, which both influence EDIC and modeled OS2. 23 Additional studies are needed to more precisely model the association between EDIC, immune biomarkers, and survival outcomes to inform the selection of radiotherapy modality in UNSCLC.…”

Radiation Therapy in Thoracic Tumors: Recent Trends and Current Issues

“…In particular, intensity-modulated PT (IMPT) has the potential to improve the conformality of the dose distributions when compared with conventional photon plans [ 12 ]. However, IMPT is also more affected by the influence of uncertainties due to breathing and anatomical changes, as argued by Boer et al [ 13 ]. In their prospective simulation study, the influence of such uncertainties on treatment delivery was thoroughly investigated.…”