Optimization and Evaluation of Anatomical Models of Liver Radiation Response

肝脏辐射反应解剖模型的优化与评估

• 批准号: 10188461
• 负责人: Kristy Brock
• 金额: $ 36.24万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-03 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10188461
• 关键词: Ablation; Anatomic Models; Anatomy; Area; Atrophic; Biomechanics; Chronic; Clinical; Clinical Research; Complex; Confidence Intervals; Data; Development; Diet; Disease; Disease-Free Survival; Dose; Enrollment; Ensure; Evaluation; Fibrosis; Functional Imaging; Funding; Hepatotoxicity; Hypertrophy; Image; Incidence; Investigation; Life Style; Link; Liver; Liver diseases; Liver neoplasms; Local Therapy; Magnetic Resonance Imaging; Malignant neoplasm of liver; Mechanics; Metastatic Neoplasm to the Liver; Methodology; Methods; Modeling; Necrosis; Normal tissue morphology; Oligonucleotides; Organ; Patients; Play; Primary carcinoma of the liver cells; Radiation; Radiation Toxicity; Radiation therapy; Recurrence; Registries; Research Priority; Retreatment; Risk; Role; Site; Sum; Technology; Time; Toxic effect; Translations; Transplantation; Treatment Protocols; Tumor Tissue; Uncertainty; Validation; Variant; Work; base; biomechanical model; convolutional neural network; design; early experience; experience; follow-up; improved; irradiation; liver function; liver transplantation; patient population; patient response; phase III trial; predictive modeling; prospective; radiation effect; radiation response; response; serial imaging; success; therapy design; tool; treatment response; tumor; working group

The full utilization of radiation for liver cancer is limited by uncertainty in the radiation toxicity risk for patients with underlying liver disease and the inability to compute aggregate dose in the re-treatment setting due to large anatomical changes in responses to therapy. The NCI hepatocellular cancer working group has stated that the use of radiation to downstage prior to liver transplant should be a clinical research priority. In this setting, it is essential to induce complete ablation of the macroscopic disease, which has been shown to correlate with increased disease free survival, while maintaining a low toxicity profile. Functional imaging is beginning to play a role in understanding the impact of radiation on liver function, however the translation of image-based assessments have been hampered by the inability to accurately link the serially acquired images indicating response over time with an accurate assessment of the therapy that was delivered. Early experience with dynamic multi-organ anatomical models demonstrated that deformation technologies can improve treatment design, delivery, and evaluation of the accumulated dose in both the tumor and normal tissues. However, it was noted in these investigations that currently available anatomical models were not sufficient to describe complex deformation due the therapeutic response, notably in the liver where hypertrophy is observed in areas receiving minimal dose and fibrosis/necrosis/atrophy occurs in higher dose regions. Currently, there is not a clear understanding of determinants of hypertrophy/atrophy and methods to optimize this effect. We hypothesize that the differential anatomical changes in otherwise normal liver in response to radiation therapy of liver tumors can be described via dose-driven expansions/contractions in biomechanical models. Our preliminary data shows that these initial models can predict, a priori, the induced hypertrophy and fibrosis/necrosis/atrophy rates to within a 95% confidence interval in 80% of the cases. The sensitivity of the models to the optimization parameters indicate that additional refinement of the models can further improve this accuracy. The combination of this dose-driven expansion/contraction component of the model with the overall biomechanics describing stiffness and deformation, can facilitate safe dose-escalation to the tumor either in the definitive setting or as a bridge to transplant, enable quantitative assessment of therapy response during therapy and throughout follow up via deformable dose summation of the treatment received, and allow accurate correlation between longitudinal imaging of functional response and the delivered radiation therapy dose. IMPACT: The successful completion of this work will develop metrics to aid in the safe utilization of radiotherapy for the liver, improve correlation of functional imaging with delivered therapy, and, where necessary, enable the safe treatment of subsequent tumors in the liver, should they arise.

由于肝癌患者放射毒性风险的不确定性，放射治疗的充分利用受到限制。 潜在的肝病以及由于大剂量而无法计算再治疗环境中的总剂量 对治疗反应的解剖学变化。 NCI 肝细胞癌工作组表示， 肝移植前使用放射​​治疗应成为临床研究的重点。在这个设定下，就是 对于诱导宏观疾病的完全消融至关重要，这已被证明与 提高无病生存率，同时保持低毒性。功能成像开始发挥作用 在理解辐射对肝功能的影响方面发挥着作用，但是基于图像的翻译 由于无法准确链接连续采集的图像，评估受到了阻碍 随着时间的推移，对所提供的治疗进行准确评估的反应。早期经验 动态多器官解剖模型证明变形技术可以改善治疗 肿瘤和正常组织中累积剂量的设计、输送和评估。然而，这是 在这些调查中指出，目前可用的解剖模型不足以描述复杂的 由于治疗反应而变形，特别是在接受治疗的区域观察到肥大的肝脏中 最小剂量和纤维化/坏死/萎缩发生在较高剂量区域。目前，尚无明确的 了解肥大/萎缩的决定因素以及优化这种效果的方法。 我们假设正常肝脏对辐射的反应存在不同的解剖变化 肝脏肿瘤的治疗可以通过生物力学模型中剂量驱动的扩张/收缩来描述。我们的 初步数据表明，这些初始模型可以先验地预测诱导的肥大和 80% 的病例纤维化/坏死/萎缩率在 95% 置信区间内。的灵敏度 模型的优化参数表明，模型的额外细化可以进一步改善这一点 准确性。该模型的剂量驱动扩张/收缩部分与整体的组合 描述刚度和变形的生物力学可以促进肿瘤的安全剂量递增 明确的设置或作为移植的桥梁，能够在治疗期间定量评估治疗反应 并通过所接受治疗的可变形剂量总和进行全程随访，并允许准确 功能反应的纵向成像与放射治疗剂量之间的相关性。 影响：这项工作的成功完成将制定有助于安全利用放射治疗的指标 对于肝脏，提高功能成像与治疗的相关性，并在必要时启用 如果随后出现肝脏肿瘤，可以对其进行安全治疗。