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 化学辐射疗法是用于局部高级头颈鳞状细胞的标准治疗方案 癌（HNSCC）。但是，患者的治疗方案很难 3级或更高的毒性包括白细胞减少症（42％）和喂养管的需求（52％）。最近的研究 表明人类毛细血管瘤病毒（HPV）阳性口咽（OP）的HNSCC亚组 SCC的预后明显更好。这些临床数据导致重要的考虑因素去启用 为了降低急性和慢性毒性而没有 损害疾病控制。已经提出，治疗的自适应降低可以是 根据早期肿瘤体积变化为个别患者量身定制。但是，体积评估是 通常是不足的，因为肿瘤的治疗反应在（i）细胞活力方面可能是异质的 （ii）与任何化学放射疗法成功有关的细胞代谢和（iii）灌注。 这些复杂的变化可能不会在早期的肿瘤体积变化中充分代表。 拟议的研究基于定量扩散MRI（DMRI）方法的组合 也可以应用于其他临床研究的技术创新。 DMRI是一个独特的体内成像 在水扩散长度的尺度上对细胞微观结构敏感的技术在少数 微米。但是，定量DMRI仍然受到挑战，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）和扩散时间（T） 测量。该提案的科学前提是，这项研究将建立一种定量方法来利用 Q-和T依赖性DMRI数据都是定制细胞活力，细胞代谢和 这种非对比度MRI方法的灌注。我们证明了两种差异的差异和差异 峰度关键K是细胞活力的有希望的成像标记。可以评估细胞代谢 通过扩散时间依赖性k测量的水交换τex的术语，由ATP-调节 依赖的跨膜离子通道共同传输水分子。 Intravoxel不一致的运动MRI 指标（伪难度，DP；灌注部分，FP）可以提供有关灌注流的信息。最终， 这些DMRI措施将更好地识别有可能受益于自适应降级的患者 或治疗的升级。 在此提案中，我们将进一步优化并建立一组细胞的定量非对比度成像标记 生存能力（D和K），细胞代谢（τEX）和灌注（FP·DP）作为评估治疗的临床工具 在临床试验中反应并验证它。数据采集​​和分析软件工具将在 这项研究将对对裁缝的癌症治疗反应进行全面和定量评估 单个患者的化学放疗疗法。