Moffitt Cancer Center, Department of Radiation Oncology, Tampa, Florida.
Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois.
Int J Radiat Oncol Biol Phys. 2021 Jun 1;110(2):551-565. doi: 10.1016/j.ijrobp.2020.12.028. Epub 2020 Dec 26.
Preclinical radiation replicating clinical intensity modulated radiation therapy (IMRT) techniques can provide data translatable to clinical practice. For this work, treatment plans were created for oxygen-guided dose-painting in small animals using inverse-planned IMRT. Spatially varying beam intensities were achieved using 3-dimensional (3D)-printed compensators.
Optimized beam fluence from arbitrary gantry angles was determined using a verified model of the XRAD225Cx treatment beam. Compensators were 3D-printed with varied thickness to provide desired attenuation using copper/polylactic-acid. Spatial resolution capabilities were investigated using printed test-patterns. Following American Association of Physicists in Medicine TG119, a 5-beam IMRT plan was created for a miniaturized (∼1/8th scale) C-shape target. Electron paramagnetic resonance imaging of murine tumor oxygenation guided simultaneous integrated boost (SIB) plans conformally treating tumor to a base dose (Rx) with boost (Rx) based on tumor oxygenation. The 3D-printed compensator intensity modulation accuracy and precision was evaluated by individually delivering each field to a phantom containing radiochromic film and subsequent per-field gamma analysis. The methodology was validated end-to-end with composite delivery (incorporating 3D-printed tungsten/polylactic-acid beam trimmers to reduce out-of-field leakage) of the oxygen-guided SIB plan to a phantom containing film and subsequent gamma analysis.
Resolution test-patterns demonstrate practical printer resolution of ∼0.7 mm, corresponding to 1.0 mm bixels at the isocenter. The miniaturized C-shape plan provides planning target volume coverage (V = 95%) with organ sparing (organs at risk D < 50%). The SIB plan to hypoxic tumor demonstrates the utility of this approach (hypoxic tumor V = 91.6%, normoxic tumor V = 95.7%, normal tissue V = 7.1%). The more challenging SIB plan to boost the normoxic tumor rim achieved normoxic tumor V = 90.9%, hypoxic tumor V = 62.7%, and normal tissue V = 5.3%. Average per-field gamma passing rates using 3%/1.0 mm, 3%/0.7 mm, and 3%/0.5 mm criteria were 98.8% ± 2.8%, 96.6% ± 4.1%, and 90.6% ± 5.9%, respectively. Composite delivery of the hypoxia boost plan and gamma analysis (3%/1 mm) gave passing results of 95.3% and 98.1% for the 2 measured orthogonal dose planes.
This simple and cost-effective approach using 3D-printed compensators for small-animal IMRT provides a methodology enabling preclinical studies that can be readily translated into the clinic. The presented oxygen-guided dose-painting demonstrates that this methodology will facilitate studies driving much needed biologic personalization of radiation therapy for improvements in patient outcomes.
临床强度调制放射治疗（IMRT）技术的临床前放射复制可以提供可转化为临床实践的数据。为此，我们使用逆向计划的 IMRT 为小动物的氧引导剂量绘画创建了治疗计划。使用 3D 打印的补偿器实现了空间变化的光束强度。
使用经过验证的 XRAD225Cx 治疗光束模型确定了来自任意旋转架角度的优化射束通量。使用铜/聚乳酸来提供所需的衰减，从而 3D 打印补偿器。使用打印的测试图案研究了空间分辨率能力。根据美国医学物理学家协会 TG119，为小型化（约 1/8 比例）C 形靶创建了 5 束 IMRT 计划。使用电子顺磁共振成像对小鼠肿瘤氧合进行成像，指导同时进行综合增量（根据肿瘤氧合对肿瘤进行基础剂量（Rx）的增量（Rx））。通过单独将每个场传递到包含放射性色迹胶片的体模中，并随后进行每个场的伽马分析，评估 3D 打印补偿器的强度调制准确性和精度。通过将氧引导 SIB 计划的复合交付（包括减少场外泄漏的 3D 打印钨/聚乳酸射线修剪器）到包含胶片的体模中，并随后进行伽马分析，对整个端到端方法进行了验证。
分辨率测试图案显示实用的打印机分辨率约为 0.7 毫米，在等中心处对应于 1.0 毫米 bixels。小型化的 C 形计划提供了计划靶区体积覆盖（V = 95%），同时保留了器官（风险器官 D < 50%）。缺氧肿瘤的 SIB 计划证明了这种方法的实用性（缺氧肿瘤 V = 91.6%，正常肿瘤 V = 95.7%，正常组织 V = 7.1%）。更具挑战性的是，对正常肿瘤边缘进行增量的 SIB 计划，使正常肿瘤 V = 90.9%，缺氧肿瘤 V = 62.7%，正常组织 V = 5.3%。使用 3%/1.0 毫米、3%/0.7 毫米和 3%/0.5 毫米标准，分别获得了 98.8%±2.8%、96.6%±4.1%和 90.6%±5.9%的平均每个场伽马通过率。复合交付的缺氧增量计划和伽马分析（3%/1 毫米）在两个测量的正交剂量平面上的通过率分别为 95.3%和 98.1%。
这种使用 3D 打印补偿器进行小动物 IMRT 的简单且具有成本效益的方法提供了一种方法，可用于可以轻松转化为临床实践的临床前研究。所呈现的氧引导剂量绘画表明，这种方法将促进对肿瘤进行急需的生物学个性化研究，以改善患者的治疗效果。
