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

动态对比增强 MRI 的定量成像生物标志物前瞻性验证作为放射治疗后口腔牙齿损伤的指标 (QI-ProVE-MRI)

• 批准号: 10668570
• 负责人: Clifton David Fuller
• 金额: $ 71.73万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10668570
• 关键词: Abate; Acute; Adjuvant; Algorithms; American; Award; Benchmarking; Biological Markers; Blood Vessels; Bone Injury; Bone Tissue; Cancer Survivorship; Caring; Categories; Chronic; Clinical; Clinical Research; Communities; Complication; Computer software; Data; Data Analyses; Deglutition; Deglutition Disorders; Dental; Development; Diagnosis; Disease; Disease Surveillance; Dose; Drug Kinetics; Drug Monitoring; Early Diagnosis; Ensure; Epidemic; Exhibits; Exposure to; Fracture; Funding; Habilitation; Head and Neck Cancer; Health; Healthcare; Human Papillomavirus; Image; Incidence; Individual; Injury; Institution; Intervention; Investigation; Knowledge; Letters; Life Expectancy; Longevity; Magnetic Resonance Imaging; Malignant Neoplasms; Mandible; Mandibular Injuries; Masticatory muscles; Measures; Medical; Mission; Monitor; Morbidity - disease rate; Muscle; National Institute of Dental and Craniofacial Research; Natural History; Necrosis; Normal tissue morphology; Oral; Organ; Organ Preservation; Osteoradionecrosis; Outcome; Outcome Measure; Parotid Gland; Patients; Performance; Prevention; Preventive; Process; Prognosis; Public Health; Qualifying; Quality of life; Radiation; Radiation therapy; Research; Research Design; Resolution; Risk; Salivary Glands; Secure; Soft Tissue Injuries; Source; Staging; Standardization; Statistical Models; Structure; Surrogate Endpoint; Surrogate Markers; Survivors; Symptoms; System; Testing; Therapeutic Intervention; Tissues; Tooth Diseases; Toxic effect; Translating; Treatment-related toxicity; United States National Institutes of Health; Validation; Work; Xerostomia; biomarker validation; bone; bone healing; cancer therapy; candidate marker; clinical practice; contrast enhanced; craniofacial; diagnostic biomarker; disorder control; effectiveness evaluation; environmental agent; experience; imaging biomarker; improved; in vivo; innovation; interest; long-term sequelae; mortality; multimodality; open source; oral HPV-positive head and neck cancers; patient biomarkers; patient population; patient stratification; population based; predicting response; programs; prospective; quantitative imaging; radiation effect; side effect; soft tissue; standard of care; surrogacy; survivorship; tissue injury; tool; treatment response; treatment strategy; usability; validation studies; working group

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”.

项目摘要 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年轻和健康患者数量迅速增加 治疗（RT）。虽然有效地治愈癌症，但有害的RT对危险器官（OAR）的影响， 由于唾液腺、吞咽/咀嚼肌和下颌骨可导致终身 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）， 分别这些长期后遗症在患者人群中具有良好的临床结局和延长的寿命 预期作为癌症存活率中发病率和死亡率的潜在来源越来越相关。尽管 这一紧迫性，一个标准化的分期和监测系统，以确定患者在发展ORN的风险， 其他发病率，并评估介入治疗的有效性，目前还没有。 在我们的机构，动态对比增强磁共振成像（DCE-MRI）正在进行 整合到一个多模态临床算法，旨在改善诊断，分期和监测， 疾病和毒性。DCE-MRI可以检测与骨愈合、坏死和骨坏死相关的骨血管分布改变， 转移性受累，具有出色的空间分辨率。根据我们以前的NIH资助的研究，我们 假设DCE-MRI参数的增加（即，Ktranss/Ve）超过3个月的任何时间点 RT后显示正常组织治疗相关毒性率的风险增加。我们的目标是 进行生物标志物分析和临床验证研究，旨在确认DCE-MRI参数为 定量成像生物标志物，FDA生物标志物鉴定申请的正式交付， 通过以下特定目的完成研究：1）DCE-MRI Ktranss/Ve的前瞻性确认和验证 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 用于作为软组织结构的定量成像生物标志物的资格预审的候选生物标志物; 3） 口腔DCE-MRI图像采集和开源计算/分析软件的标准化 作为FDA生物标志物鉴定的潜在组成部分。 成功完成这一提案有可能彻底改变诊断和管理 晚期RT诱导的发病率，并为临床医生提供可靠的FDA生物标志物资格认证计划 经验证的生物标志物，用于对RT后OAR损伤风险患者进行分层，监测骨和软组织损伤， 随后口腔发病率，并适当管理RT后护理。这项工作与NIDCR的 使命是“推进有关牙科、口腔和颅面健康和疾病的基础知识， 将这些发现转化为预防，早期发现和治疗策略，以改善整体健康状况， 所有个人和社区的生命周期”。