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.

项目摘要 放化疗是局部晚期头颈部鳞状细胞癌的标准治疗方案 癌（HNSCC）。然而，治疗方案对患者来说是困难的，因为他们经历了高的死亡率。 3级或更高的毒性，包括白细胞减少症（42%）和需要饲管（52%）。最近的研究 结果显示，一个人乳头状瘤病毒（HPV）阳性口咽部（OP）的HNSCC患者亚组， SCC预后明显好于SCC。这些临床数据导致了重要的考虑，以降低强度 为这一低风险的年轻人群提供治疗，以减少急性和慢性毒性， 危及疾病控制。有人建议，治疗的适应性降级可以 根据早期肿瘤体积变化为个体患者量身定制。然而，容量评估是 通常是不充分的，因为肿瘤的治疗反应在（i）细胞活力方面是不均匀的， (ii)细胞代谢，和（iii）灌注，其与任何放化疗治疗的成功相关。 这些复杂的变化在早期阶段可能无法通过肿瘤体积变化来充分表示。 该研究基于定量扩散MRI（dMRI）方法与其自身的 这些技术创新也可以应用于其他临床研究。dMRI是一种独特的体内成像技术， 在水扩散长度的量级上对细胞微观结构敏感的技术 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学特征。 取决于用于扩散的扩散加权强度（q）和扩散时间（t）的组织特性 测量.该建议的科学前提是，这项研究将建立一个量化的方式来利用 q和t依赖性dMRI数据作为定量细胞活力、细胞代谢和 这种非对比MRI方法的灌注。我们证明了扩散系数D和扩散系数 峰度系数K是细胞活力的有希望的成像标记。细胞代谢可在以下条件下进行评价： 水交换τex的项，通过依赖于扩散时间的K测量，由ATP调节， 依赖性跨膜离子通道共转运水分子。体素内非相干运动MRI 度量（伪扩散率，Dp;灌注分数，fp）可以提供关于灌注流的信息。最后， 这些dMRI测量将更好地识别有可能从适应性降级中受益的患者 或治疗升级。 本研究将进一步优化和建立一套细胞非造影定量成像标记物， 存活率（D和K）、细胞代谢（τex）和灌注（fp和Dp）作为评估治疗的临床工具 并在临床试验中进行验证。数据采集和分析软件工具将在 这项研究将能够全面和定量评估癌症治疗反应， 对个别患者进行放化疗。