Hypoglossal neuropathy in the pathogenesis of radiation associated dysphagia (hRAD)

放射相关吞咽困难 (hRAD) 发病机制中的舌下神经病变

• 批准号: 10645692
• 负责人: Katherine Arnold Hutcheson
• 金额: $ 19.04万
• 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: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10645692
• 关键词: Address; Algorithms; Aspiration Pneumonia; Barium swallow; Cancer Survivor; Cancer Survivorship; Cessation of life; Chronic; Classification; Clinic; Clinical; Clinical Data; Clinical Management; Clinical Trials; Continuance of life; Cranial nerve diseases; Data; Data Collection; Data Set; Deglutition; Deglutition Disorders; Denervation; Detection; Devices; Diagnosis; Diet; Dose; Early treatment; Edema; Electromyography; Electronics; Enrollment; Enteral Feeding; Fibrosis; Functional disorder; Goals; Head and Neck Cancer; Health; Incidence; Infrastructure; Injury; Life; Link; Long Term Survivorship; Long-Term Survivors; Malignant Neoplasms; Measurable; Measurement; Measures; Methods; Modernization; Modification; Monitor; Muscular Atrophy; Needles; Nerve; Neuropathy; Normal tissue morphology; Oral; Oropharyngeal; Outcome; Outcome Measure; Paralysed; Pathogenesis; Patient Outcomes Assessments; Patients; Pneumonia; Population; Positioning Attribute; Prevalence; Procedures; Publishing; Quality of life; Radiation; Radiation Fibrosis; Radiation Toxicity; Radiation therapy; Recovery of Function; Reproducibility; Research Personnel; Sampling; Severities; Signal Transduction; Surface; Survivors; Symptoms; System; Therapeutic; Time; Tongue; Toxic effect; Work; aspirate; cancer radiation therapy; clinical risk; cohort; density; genioglossus muscle; high reward; high risk; malignant oropharynx neoplasm; mortality risk; nerve injury; novel; personalized management; radiological imaging; screening; survivorship; targeted treatment; tissue injury

ABSTRACT/SUMMARY Radiation-associated dysphagia (RAD) is a leading driver of QOL and a potentially life-threatening survivorship issue, afflicting more than half of patients treated with curative radiotherapy (RT) for oropharyngeal cancers (OPC). Aspirators are almost 5-times more likely to develop pneumonia than non-aspirators, and pneumonia confers a 42% increased risk of mortality among cancer survivors. Radiation fibrosis has long been considered the primary driver of RAD, but the investigators’ preliminary work points to late cranial neuropathy as a major contributor to truly severe forms of delayed or late-RAD. Cranial neuropathy (denervation) is clinically detected a median of 5 to 8 years after RT after a “quiet period” of functional recovery. There is currently no early indicator for this injury. Delayed identification means that muscle atrophy and profound functional injury is typically present at the time of diagnosis, limiting therapeutic potential. The long-term goal of this work is to reduce dysphagia burden through mechanistically and technically nimble surveillance algorithms as a major step toward personalized management. Our central hypothesis is that subclinical hypoglossal neuropathy is prevalent and associates with severity of RAD early in HNC survivorship and novel non-invasive lingual high density surface electromyography (HDSEMG) is feasible for quantitative functional surveillance. The objective of the proposed study is to analyze gold-standard needle EMG and experimental HDSEMG of the tongue as an optional procedure in an existing large-scale OPC cohort and two clinical trial datasets that capture robust longitudinal swallowing outcomes data to: 1) estimate prevalence of hypoglossal neuropathy along continuum of survivorship (diagnosis, early, and late) after oropharyngeal radiation (Aim 1); 2) correlate EMG-detected hypoglossal neuropathy and swallowing function over time before and after oropharyngeal radiation (Aim 2); and 3) examine feasibility of HDSEMG as a rapid, non-invasive quantitative screening method for hypoglossal neuropathy (Aim 3). Building upon the highly curated functional data from the MD Anderson OPC Patient-Reported Outcomes/Function (PROF) Core and investigators’ track record of non-invasive signal measurement in the tongue, we are uniquely positioned to accomplish these complementary aims. This high risk/high reward work could lead to practice- change. We expect the outcomes to provide proof of concept that subclinical hypoglossal neuropathy is a mechanism underlying RAD that can be measured with a novel, non-invasive device. Thus, providing data to support a novel and measurable target (subclinical hypoglossal neuropathy) underlying a hugely impactful and potentially deadly common toxicity –RAD– in a fast growing, young OPC survivor population.

摘要/总结 放射相关性吞咽困难（RAD）是QOL的主要驱动因素，可能危及生命 这个问题困扰着一半以上接受过放射治疗的口咽癌患者 （OPC）。吸入者患肺炎的可能性几乎是非吸入者的5倍， 使癌症幸存者的死亡风险增加42%。放射性纤维化一直被认为是 RAD的主要驱动因素，但研究人员的初步工作指出，晚期颅神经病变是一个主要的 导致真正严重的延迟或迟发性RAD。临床检测到颅神经病变（去神经支配） 经过功能恢复的“平静期”后，RT后的平均时间为5至8年。目前还没有任何早期指标 对于这种伤害。延迟识别意味着肌肉萎缩和严重的功能损伤是典型的存在 在诊断时，限制了治疗潜力。这项工作的长期目标是减少吞咽困难 通过机械和技术上灵活的监控算法， 个性化管理我们的中心假设是，亚临床舌下神经病变是普遍的， 与HNC早期RAD的严重程度和新的非侵入性舌高密度表面相关 肌电图（HDSEMG）是可行的定量功能监测。建议的目标 本研究将金标针肌电图和实验性舌高分辨表面肌电作为一种可选择的程序进行分析 在现有的大规模OPC队列和两个临床试验数据集中， 结果数据：1）估计舌下神经病变沿着生存连续体的患病率（诊断， 早期和晚期）口咽放射后（目的1）; 2）相关肌电图检测舌下神经病变， 在口咽放射之前和之后随时间推移的吞咽功能（目标2）;以及3）检查 HDSEMG作为舌下神经病变的快速、非侵入性定量筛查方法（目的3）。建筑 根据MD安德森OPC患者报告结局/功能的高度策划的功能数据 （PROF）核心和研究人员的跟踪记录的非侵入性信号测量的舌头，我们是独一无二的 以实现这些互补的目标。这种高风险/高回报的工作可能会导致实践- 变化我们希望这些结果能为亚临床舌下神经病变是一种 RAD的潜在机制，可以用一种新的，非侵入性的设备来测量。因此，将数据提供给 支持一个新的和可测量的目标（亚临床舌下神经病变）， 潜在致命的常见毒性-RAD-在一个快速增长，年轻的OPC幸存者群体。