Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer

Purpose: To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC).Methods and Materials: Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with +/- 3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with +/- 3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D-2 - D-98, where D-2 and D-98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans.Results: The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to 98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively.Conclusions: In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters. (C) 2016 Elsevier Inc. All rights reserved.

目的：在针对Ⅲ期非小细胞肺癌（NSCLC）的稳健优化调强质子治疗（IMPT）中，研究设置和射程不确定性、呼吸运动以及相互作用效应使用扫描笔形束的影响。 方法和材料：使用最小最大稳健优化技术为10例NSCLC患者制定了三野IMPT计划。这些计划考虑了±3%射程不确定性下5毫米或7毫米的设置误差。通过考虑以下因素评估IMPT标称计划的稳健性：（1）具有±3%射程不确定性的各向同性5毫米设置误差；（2）呼吸运动；（3）相互作用效应；（4）第1项和第2项的组合。使用四维和平均强度投影计算机断层扫描图像计算计划。将内部临床靶区体积的靶区覆盖率（TC，接受95%处方剂量的体积）和均匀性指数（D - 2 - D - 98，其中D - 2和D - 98分别是2%和98%体积所接受的最小剂量）以及肺、食管、心脏和脊髓的剂量指标与临床容积旋转调强放疗计划进行比较。 结果：当分别考虑呼吸运动和相互作用效应时，所有计划的TC和均匀性指数均在临床限值内。当考虑设置和射程不确定性的综合效应时，其影响更大。对于所有患者，在稳健的7毫米评估中，TC降至98%。对于4种误差类型，在相应的稳健5毫米和稳健7毫米评估之间，危及器官剂量参数没有显著差异。与容积旋转调强放疗计划相比，IMPT计划显示出更好的靶区均匀性，平均肺剂量和心脏剂量参数分别降低了约40%和60%。 结论：在针对Ⅲ期NSCLC的稳健优化IMPT中，设置和射程不确定性、呼吸运动以及相互作用效应对靶区覆盖率、剂量均匀性和危及器官剂量参数的影响有限。（C）2016爱思唯尔公司。保留所有权利。