Transcranial Focused Ultrasound for Head and Neck Cancer Pain. A Pilot Study

经颅聚焦超声治疗头颈癌疼痛。

• 批准号: 10242191
• 负责人: William Jeffrey Elias
• 金额: $ 33.63万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242191
• 关键词: Ablation; Absence of pain sensation; Acute; Acute Pain; Affect; Affective; Anatomy; Area; Binding; Brain; Brain Stem; Cancer Etiology; Cancer Patient; Cephalic; Clinical; Clinical Trials; Cognitive; Devices; Disease; Dose; Effectiveness; Electroencephalography; Electrophysiology (science); Essential Tremor; Evoked Potentials; Exclusion; FDA approved; Focused Ultrasound; Frequencies; Fright; Head and Neck Cancer; High Prevalence; Human; Lasers; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Medial; Medical; Medication Management; Midbrain structure; Modality; Movement Disorders; Nervous System; Neurology; Nociception; Oncologist; Operative Surgical Procedures; Ophthalmology; Opioid; Opioid Receptor Binding; Outcome; Pain; Pain management; Parkinson Disease; Pathway interactions; Patients; Periodicity; Pilot Projects; Positron-Emission Tomography; Predisposition; Procedures; Psychometrics; Quality of life; Resistance; Safety; Spinothalamic Tracts; Surgical incisions; Symptoms; System; Thalamic structure; adverse event monitoring; burden of illness; cancer pain; carfentanil; chronic pain; cranium; endogenous opioids; experience; head and neck cancer patient; implantable device; implantation; innovation; midbrain central gray substance; millimeter; minimally invasive; mortality; mu opioid receptors; neural; new technology; pain relief; painful neuropathy; prescription opioid; refractory cancer; response; safety assessment; side effect; transmission process

PROJECT SUMMARY Head and neck cancer is particularly susceptible to nocioceptive and neuropathic pains because it is dense with sensitive anatomic structures and richly innervated by the nervous system. In fact, head and neck cancer, estimated as the ninth most common cancer and cause of cancer mortality, is associated with the highest prevalence of pain. These craniocervical pains are particularly difficult for three reasons. Firstly, medical therapy often wanes in effect and/or high doses are required with cognitive side effects. Secondly, surgical options are limited by the cephalad extent in the neural axis. Lastly, cancer and its terminal stages are difficult for invasive surgery or implanted devices that require intensive management. Patients and their oncologists seek pain relief that is easy, safe, and without cognitive side effects. Transcranial MRI-guided focused ultrasound (FUS) is a new stereotactic modality capable of delivering high intensity energy through the intact human skull with submillimeter precision. Our initial experience with FUS targeted the ventrolateral thalamus for essential tremor and Parkinson’s disease, eventually leading to FDA approvals. Cancer pain is an ideal indication to consider stereotactic ablation as the disease burden limits the options. A minimally invasive, transcranial option to treat refractory cancer pain would be welcomed by patients – avoiding opioid medications, open surgery, and device implantation. This exploratory clinical trial (already approved by the FDA under IDE#G180222) will target both the spinothalamic and spinoreticular pain circuits by performing unilateral FUS mesencephalotomy, a historically effective procedure for cancer pain but limited by the accuracy of its era. The primary aim of this study is to assess the safety and preliminary effectiveness in six head and neck cancer patients with opioid-resistant pain. Additionally, we will investigate the potential mechanism of pain relief as the mesencephalotomy target involves the confluence of the ascending and descending pain systems. Aims 2 and 3 will investigate these systems with electrophysiology specific for the spinothalamic tract and carfentanil PET imaging that measures the brain’s endogenous opioids.

项目总结 头颈部癌症特别容易受到伤害性和神经性疼痛的影响。 因为它致密，具有敏感的解剖结构，并由丰富的 神经系统。事实上，据估计，头颈癌是最常见的第九种癌症 癌症和癌症致死的原因，与疼痛的患病率最高有关。 这些头颈疼痛特别困难，有三个原因。第一，医疗 治疗效果往往减弱，和/或需要高剂量的认知副作用。 其次，手术选择受到神经轴上头侧范围的限制。最后， 癌症及其晚期对于侵入性手术或植入设备来说是困难的， 需要集约化管理。患者和他们的肿瘤学家寻求轻松的止痛方法， 安全，无认知副作用。 经颅脑MRI引导下的聚焦超声(FUS)是一种新型的立体定向治疗方法。 能够通过完整的人类头骨传递高强度能量 亚毫米精度。我们最初使用FUS的经验是针对腹外侧区 丘脑治疗特发性震颤和帕金森氏症，最终导致FDA 批准。癌性疼痛是考虑立体定向消融术的理想适应症 疾病负担限制了选择。一种微创、经颅治疗的选择 顽固性癌症疼痛将受到患者的欢迎-避免阿片类药物， 开放手术和装置植入。 这项探索性临床试验(已由FDA根据IDE#G180222批准)将 单侧FUS定位脊髓丘脑和脊髓网状痛环 中脑切开术是治疗癌症疼痛的一种历史上有效的手术，但受到 其时代的精确度。本研究的主要目的是评估该药的安全性和初步应用。 阿片类药物耐受疼痛对6例头颈癌患者的疗效。 此外，我们将研究止痛的潜在机制，因为 中脑切开靶点涉及上行和下行疼痛的汇合 系统。AIMS 2和AIMS 3将研究这些系统的电生理学 脊髓丘脑束和卡芬太尼PET成像测量大脑的 内源性阿片类药物。