Fan Xiaoying, Wang Shuting, Li Weijie, Meng Kangning, Huang Wei, Yin Yong, Dai Tianyuan
Department of Graduate, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China.
Department of Radiation Oncology Physics and Technology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China.
BMC Cancer. 2025 Jul 1;25(1):1112. doi: 10.1186/s12885-025-14504-2.
Proton therapy of esophageal cancer is beneficial to spare normal tissue in clinical practice. However, intra-fractional and inter-fractional variance of tumor motion during treatment may compromise target coverage. The purpose of this study was to investigate the interplay effect due to intra-fractional motion and the effect of the robust optimization parameters for inter-fractional motion in the intensity modulation proton therapy (IMPT).
This study retrospectively analyzed 42 patients with esophageal cancer treated at Shandong Cancer Hospital. The patients were divided into two groups. Twenty-one patients had a 4DCT image with 10 respiratory phases reconstructed (G). In addition, twenty-one patients underwent a second 3D CT scan following the initial one (G). The RayStation11B treatment planning system was used to create the IMPT plans for these two groups of patients. All patients were planned with a prescribed dose of 50.4 Gy (RBE) in 28 fractions for clinical target volume (CTV). 4D dynamic dose (4DDD) was then calculated to assess the interplay effect by considering respiratory motion and dynamic beam delivery for G. Seven IMPT plans with different robust optimization parameters were designed for the 21 G patient. The setup uncertainties were set to ± 0-6 mm for G. Plan quality and dose-volume histogram (DVH) parameters for the target and organs at risk (OARs) were then analyzed.
For G, 4DDD was slightly perturbated compared to the nominal plan dose. The mean value of CTV D of nominal dose and 4DDD were 49.9 and 49.1 Gy (RBE), respectively, and the CTV D were 50.4 and 49.9 Gy (RBE), respectively. For G, the DVH parameters of the target area and the OARs showed a linear relationship with the corresponding robust optimization parameters in IMPT. When the robust optimization parameters were set with a larger value, the dose coverage of the target was improved. However, the dose of OARs increased at the same time. The D of the target for the seven plans (setup6, setup5, setup4, setup3, setup2, setup1, setup0 plan) were 49.42 ± 0.75, 48.95 ± 1.21, 48.54 ± 1.48, 47.55 ± 2.31, 47.07 ± 2.71, 44.58 ± 4.20 and 44.02 ± 4.44 Gy(RBE), respectively. The D of heart were 12.18 ± 3.05, 11.28 ± 2.86, 10.90 ± 2.77, 9.76 ± 2.39, 9.73 ± 2.39, 8.33 ± 2.22 and 8.22 ± 2.20 Gy (RBE), respectively.
In this study, the differences in dose distributions between the 4DDD and nominal plans for G can be attributed to the interplay effects. While target coverage remained stable, variations in OAR doses should be evaluated for G. For G, smaller setup uncertainty parameters may not fully mitigate inter-fractional tumor motion, leading to greater variation in target dose and potential inadequate coverage. The linear relationship between setup uncertainty and D suggested that improved setup uncertainties can enhance target coverage, while higher setup uncertainties tend to increase OARs doses, particularly to the heart and lungs.
在临床实践中，食管癌的质子治疗有利于保护正常组织。然而，治疗期间肿瘤运动的分次内和分次间差异可能会影响靶区覆盖。本研究的目的是探讨强度调制质子治疗（IMPT）中分次内运动引起的相互作用效应以及分次间运动的稳健优化参数的影响。
本研究回顾性分析了山东肿瘤医院收治的42例食管癌患者。患者分为两组。21例患者重建了具有10个呼吸相位的4DCT图像（G组）。此外，21例患者在首次3D CT扫描后又进行了一次3D CT扫描（G'组）。使用RayStation11B治疗计划系统为这两组患者制定IMPT计划。所有患者临床靶区（CTV）的处方剂量均为50.4 Gy（相对生物效应），分28次照射。然后计算4D动态剂量（4DDD），通过考虑呼吸运动和动态束流输送来评估G组的相互作用效应。为21例G组患者设计了7个具有不同稳健优化参数的IMPT计划。G组的摆位不确定性设定为±0 - 6 mm。然后分析靶区和危及器官（OARs）的计划质量和剂量体积直方图（DVH）参数。
对于G组，与标称计划剂量相比，4DDD略有扰动。标称剂量和4DDD的CTV D均值分别为49.9和49.1 Gy（相对生物效应），CTV D分别为50.4和49.9 Gy（相对生物效应）。对于G组，靶区和OARs的DVH参数与IMPT中相应的稳健优化参数呈线性关系。当稳健优化参数设置为较大值时，靶区的剂量覆盖得到改善。然而，同时OARs的剂量增加。七个计划（setup6、setup5、setup4、setup3、setup2、setup1、setup0计划）的靶区D分别为49.42±0.75、48.95±1.21、48.54±1.48、47.55±2.31、47.07±2.71、44.58±4.20和44.02±4.44 Gy（相对生物效应）。心脏的D分别为12.18±3.05、11.28±2.86、10.90±2.77、9.76±2.39、9.73±2.39、8.33±2.22和8.22±2.20 Gy（相对生物效应）。
在本研究中，G组4DDD与标称计划之间的剂量分布差异可归因于相互作用效应。虽然靶区覆盖保持稳定，但对于G组应评估OARs剂量的变化。对于G组，较小的摆位不确定性参数可能无法完全减轻分次间肿瘤运动，导致靶区剂量变化更大且可能覆盖不足。摆位不确定性与D之间的线性关系表明，改善摆位不确定性可提高靶区覆盖，而较高的摆位不确定性往往会增加OARs的剂量，尤其是对心脏和肺部。
