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.

完全利用辐射对肝癌的利用受到辐射毒性风险的不确定性的限制 肝病的潜在肝脏疾病以及由于大量而无法在重新治疗的情况下计算总剂量 对治疗反应的解剖学变化。 NCI肝细胞癌工作组表示 在肝移植之前使用辐射到下降阶段应为临床研究的优先级。在这种情况下，是 诱导宏观疾病的完全消融至关重要，该疾病已证明与 无疾病生存的增加，同时保持低毒性特征。功能成像开始播放 在理解辐射对肝功能的影响方面的作用，但是基于图像的翻译 无法准确链接表明的串行获取图像，这使评估受到了阻碍 随着时间的流逝，对所提供的治疗的准确评估。早期经验 动态多器官解剖模型表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，递送和评估。但是，是 在这些调查中指出，当前可用的解剖模型不足以描述复杂 由于治疗反应的变形，特别是在肝脏中观察到肥大的区域 最小剂量和纤维化/坏死/萎缩发生在较高剂量区域。目前，尚不清楚 了解肥大/萎缩的决定因素和优化这种效果的方法。 我们假设响应辐射时，否则正常肝的差异解剖学变化 可以通过生物力学模型中的剂量驱动的膨胀/收缩来描述肝肿瘤的治疗。我们的 初步数据表明，这些初始模型可以预测先验，诱导的肥大和 在80％的病例中，纤维化/坏死/萎缩率达到95％的置信区间。敏感性 优化参数的模型表明，对模型的附加改进可以进一步改进 准确性。模型的这种剂量驱动的扩展/收缩成分与整体的结合 描述刚度和变形的生物力学可以促进对肿瘤的安全剂量升级 确定的环境或作为移植的桥梁，可以在治疗过程中定量评估治疗反应 并通过可变形的剂量求和接受的治疗剂量，并允许准确 功能反应的纵向成像与传递的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指标，以帮助安全利用放射疗法 对于肝脏，改善功能成像与已递送治疗的相关性，并在必要时启用 如果出现后，肝脏中随后的肿瘤的安全治疗。