Diffusion MRI of Treatment Response for De-escalation of Radiation Therapy

弥散 MRI 评估放射治疗降级的治疗反应

• 批准号: 10447196
• 负责人: Sungheon Gene Kim
• 金额: $ 38.07万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10447196
• 关键词: Acute; Animals; Biological Markers; Blood Volume; Caliber; Cancer Center; Cell Membrane Permeability; Cell Size; Cell Survival; Chronic; Clinical; Clinical Assessment Tool; Clinical Data; Clinical Research; Clinical Trials; Complex; Contrast Media; Data; Data Analyses; Dependence; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Disease Progression; Dose; Early treatment; Enrollment; Enteral Feeding; Evaluation; Goals; Head and Neck Squamous Cell Carcinoma; Human Papillomavirus; Imaging Techniques; Inflammatory Response; Intercellular Fluid; Ion Channel; Lead; Length; Lesion; Leukopenia; Link; Lymph Node of Head, Face and Neck; MRI Scans; Magnetic Resonance Imaging; Malignant Neoplasms; Measurable Disease; Measurement; Measures; Metabolism; Methods; Modeling; Monitor; Motion; Mucositis; Nodal; Oropharyngeal; Patient Selection; Patients; Perfusion; Phase II Clinical Trials; Population; Prognosis; Property; Radiation therapy; Risk; Scanning; Software Tools; Subgroup; Testing; Therapeutic; Time; Tissues; Toxic effect; Treatment Protocols; Tumor Biology; Tumor Volume; Uncertainty; Validation; Water; Weight; base; biophysical properties; cancer cell; cancer therapy; chemoradiation; contrast enhanced; data acquisition; disorder control; experience; fluorodeoxyglucose positron emission tomography; imaging biomarker; improved; in vivo; in vivo imaging; individual patient; innovation; insight; novel; personalized approach; pressure; recruit; response; simulation; standard care; success; tool; treatment response; tumor; tumor progression; water diffusion

PROJECT SUMMARY Chemo-radiation therapy is a standard treatment regimen for locally advanced head and neck squamous cell carcinoma (HNSCC). The treatment regimen, however, is difficult for patients as they experience high rates of grade 3 or higher toxicities including leukopenia (42%) and the need for feeding tube (52%). Recent studies showed that a subgroup of HNSCC patients with human-papilloma virus (HPV)-positive oropharyngeal (OP) SCC have significantly better prognosis. These clinical data lead to important considerations to de-intensify treatment for this low-risk, younger population in order to reduce acute and chronic toxicity without compromising disease control. It has been suggested that the adaptive de-escalation of treatment can be tailored for individual patients based on the early tumor volume change. However, volumetric assessment is often inadequate because the treatment response of a tumor can be heterogeneous in terms of (i) cell viability, (ii) cellular metabolism, and (iii) perfusion that are relevant to the success of any chemoradiation therapy. These complex changes may not be adequately represented by tumor volume change at the early stage. The proposed study is based on a combination of the quantitative diffusion MRI (dMRI) methods with their own technical innovations that can also be applied to other clinical studies. dMRI is a unique in vivo imaging technique sensitive to cellular microstructures at the scale of water diffusion length on the order of a few microns. However, quantitative dMRI remains challenging as dMRI data represent different biophysical properties of tissue depending on diffusion weighting strength (q) and diffusion time (t) used for the measurement. The scientific premise of the proposal is that this study will establish a quantitative way to utilize both q- and t-dependent dMRI data as a tailored approach to quantify cell viability, cellular metabolism and perfusion from this non-contrast MRI method. We demonstrated that both diffusion coefficient D and diffusional kurtosis coefficient K are promising imaging markers for cell viability. Cellular metabolism can be evaluated in terms of the water exchange τex, measured by the diffusion time-dependent K, that is regulated by the ATP- dependent trans-membrane ion channels co-transporting water molecules. Intravoxel incoherent motion MRI metrics (pseudo diffusivity, Dp; perfusion fraction, fp) can provide information about perfusion flow. Ultimately, these dMRI measures will better identify patients who have the potential to benefit from adaptive de-escalation or escalation of therapy. In this proposal, we will further optimize and establish a set of quantitative non-contrast imaging markers of cell viability (D and K), cellular metabolism (τex), and perfusion (fp⋅Dp) as a clinical tool for assessment of treatment response and validate it in a clinical trial. The data acquisition and analysis software tools to be developed in this study will enable comprehensive and quantitative assessment of cancer treatment response to tailor chemoradiation therapies for individual patients.

项目总结 放化疗是局部晚期头颈部鳞状细胞癌的标准治疗方案。 癌症(HNSCC)。然而，治疗方案对患者来说是困难的，因为他们经历了高比率的 3级或更高的毒性，包括白细胞减少(42%)和需要喂养管(52%)。最新研究 显示人类乳头状瘤病毒(HPV)阳性口咽(OP)的HNSCC患者中的一组 鳞状细胞癌的预后明显好于其他患者。这些临床数据导致了降低信号强度的重要考虑 为这一低风险、年轻人群提供治疗，以减少急性和慢性毒性，而不是 危害疾病控制。有人建议，治疗的适应性降级可以是 根据早期肿瘤体积变化为个体患者量身定做。然而，体积评估是 通常是不够的，因为肿瘤的治疗反应在(I)细胞活性方面可能是不同的， (Ii)细胞新陈代谢；及(Iii)与任何放化疗成功相关的灌注量。 早期的肿瘤体积变化可能不能充分反映这些复杂的变化。 这项拟议的研究是基于定量扩散磁共振成像(DMRI)方法与他们自己的方法相结合的基础上进行的 也可应用于其他临床研究的技术创新。Dmri是一种独特的活体成像技术。 在水扩散长度的数量级上对细胞微结构敏感的技术 微米。然而，定量dmri仍然具有挑战性，因为dmri数据代表不同的生物物理。 组织的特性取决于扩散加权强度(Q)和用于 测量。该提案的科学前提是，这项研究将建立一种量化的方法来利用 依赖于q和t的dMRI数据作为一种量身定制的方法来量化细胞活力、细胞代谢和 通过这种非对比MRI方法进行血流灌注检查。我们证明了扩散系数D和扩散系数 峰度系数K是一种很有前途的细胞活力的成像标志物。细胞新陈代谢可以在 水交换τex的术语，由扩散时间依赖的K测量，受ATP值调节。 依赖跨膜离子通道共同运输水分子。体素内非相干运动磁共振成像 指标(伪扩散率，DP；灌注分数，FP)可以提供有关灌注流量的信息。最终， 这些dmri措施将更好地识别有可能从适应性降级中受益的患者。 或者是治疗的升级。 在这个方案中，我们将进一步优化和建立一套细胞的定量非对比成像标记物 存活率(D和K)、细胞代谢(τEX)和血流灌注(FP⋅DP)作为评估治疗的临床工具 响应并在临床试验中进行验证。将开发的数据采集和分析软件工具 这项研究将使全面和定量评估癌症治疗反应成为可能 针对个别患者的放化疗疗法。