Quantitative Imaging Biomarker Prospective Validation of Dynamic Contrast-Enhanced MRI as a Metric of Orodental Injury After Radiotherapy (QI-ProVE-MRI)

项目总结 与人乳头瘤病毒(HPV)相关的头颈部鳞状细胞癌(HNSCC)的增加 导致接受局部放射治疗的更年轻、更健康的患者数量迅速增加 治疗(RT)。虽然在治疗癌症方面有效，但有害的RT对危险器官(OAR)的影响 因为唾液腺、吞咽/咀嚼肌和下颌骨可以导致终生。 RT正常组织损伤的后遗症，如口干、吞咽困难和放射性骨坏死(ORN)， 分别进行了分析。这些患者的长期后遗症具有良好的临床结果和延长的生命 预期作为癌症存活期发病率和死亡率的潜在来源越来越重要。尽管 这种紧迫性，一个标准化的分期和监测系统，以识别有发生ORN风险的患者和 其他发病率，以及评估介入治疗的有效性，目前还不可用。 在我们机构，动态对比增强磁共振成像(DCE-MRI)正在进行 集成到旨在改进诊断、分期和监测的多模式临床算法中 疾病和毒性。DCE-MRI可以检测与骨愈合、坏死和 转移灶累及，具有良好的空间分辨率。基于我们之前由美国国立卫生研究院资助的研究，我们 假设在3个月以上的任何时间点，DCE-MRI参数(即，Ktras/Ve)的增加 放疗后表现出正常组织治疗相关毒副作用增加的风险。我们的目标是 进行生物标记物分析和临床验证研究，旨在确认DCE-MRI参数 定量成像生物标记物，FDA生物标记物资格申请的正式交付，地址为 通过以下具体目标完成研究：1)DCE-MRI KTRANS/VE的预期资格和验证 作为ORN风险的“FDA最佳定义”定量成像监测生物标志物；2)DCE-MRI研究 作为软组织结构定量成像生物标志物资格预审的候选生物标志物；3) 口腔DCE-MRI图像采集标准化及开源计算/分析软件 作为FDA生物标记物资格的潜在组成部分。 这项建议的成功完成有可能使诊断和管理发生革命性变化 并为临床医生提供可靠的FDA生物标志物资格认证计划 经过验证的生物标记物可以对RT后有桨损伤风险的患者进行分层，监测骨和软组织损伤，并 随之而来的口腔发病率，以及适当的放射治疗后护理。这项工作与NIDCR的 促进牙科、口腔和颅面部健康和疾病的基础知识和 将这些发现转化为预防、早期发现和治疗战略，以改善儿童的整体健康 所有个人和社区在整个生命周期内“。

PROJECT SUMMARY The rise in human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) has resulted in a rapidly increasing number of younger and healthier patients being treated with locoregional radiation therapy (RT). Although effective in curing the cancer, deleterious RT effects upon organs-at-risk (OARs) such as the salivary glands, swallowing/masticatory muscles, and mandibular bone can result in lifelong sequelae of RT normal tissue injury such as xerostomia, dysphagia, and osteoradionecrosis (ORN), respectively. These long-term sequelae in a patient population with good clinical outcomes and extended life expectancy are increasingly relevant as latent sources of morbidity and mortality in cancer survivorship. Despite this urgency, a standardized staging and monitoring system to identify patients at risk for developing ORN and other morbidities, and to assess the effectiveness of interventional therapies, is not currently available. At our institution, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is being integrated into a multimodality clinical algorithm aimed at improving diagnosis, staging, and surveillance of disease and toxicity. DCE-MRI can detect altered bone vascularity associated with bone healing, necrosis, and metastatic involvement, with excellent spatial resolution. Based on our previous NIH-funded research, we hypothesize that an increase in DCE-MRI parameters (i.e., Ktrans/Ve) at any timepoint more than 3 months after RT demonstrates increased risk of normal tissue treatment-related toxicity rates. Our objective is to conduct a biomarker analytic and clinical validation study designed to confirm DCE-MRI parameters as quantitative imaging biomarkers, with the formal deliverable of an application for FDA Biomarker Qualification at study completion, via the following specific aims: 1) Prospective qualification and validation of DCE-MRI Ktrans/Ve as an “FDA BEST-defined” quantitative imaging monitoring biomarker of ORN risk; 2) Investigation of DCE-MRI candidate biomarkers for pre-qualification as quantitative imaging biomarkers of soft-tissue structures; 3) Standardization of image acquisition and open source computational/analytic software for orodental DCE-MRI as a potential component of FDA biomarker qualification. Successful completion of this proposal has the potential to revolutionize the diagnosis and management of late RT-induced morbidities and offer clinicians a reliable and FDA Biomarker Qualification Program validated biomarker to stratify patients at risk for OARs injury after RT, monitor bone and soft tissue injury and subsequent oral morbidity, and manage post-RT care appropriately. This work is particularly relevant to NIDCR’s mission of “advancing fundamental knowledge about dental, oral, and craniofacial health and disease and translate these findings into prevention, early detection, and treatment strategies that improve overall health for all individuals and communities across the lifespan”.