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: 10023961
• 负责人: William Jeffrey Elias
• 金额: $ 57.55万
• 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/10023961
• 关键词: Ablation; Absence of pain sensation; Acute; Acute Pain; Affect; Affective; Anatomy; Area; Binding; Brain; Brain Stem; Cancer Etiology; Cancer Patient; Clinical; Clinical Trials; Cognitive; Devices; Disease; Dose; Effectiveness; Electroencephalography; Electrophysiology (science); Essential Tremor; Evoked Potentials; 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 structure; 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; Procedures; Psychometrics; Quality of life; Refractory; 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; minimally invasive; mortality; mu opioid receptors; new technology; pain relief; painful neuropathy; prescription opioid; relating to nervous system; response; 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.

项目摘要 头颈部癌症对伤害性疼痛和神经性疼痛特别敏感 因为它是密集的敏感解剖结构和丰富的神经支配， 神经系统事实上，头颈部癌症，估计为第九最常见的 癌症和癌症死亡率的原因，与疼痛的最高患病率有关。 这些颅颈部疼痛特别困难，原因有三。第一，医疗 治疗的效果通常会减弱和/或需要高剂量并伴有认知副作用。 其次，手术选择受限于神经轴的头侧范围。最后， 癌症及其晚期很难进行侵入性手术或植入装置， 需要强化管理。患者和他们的肿瘤科医生寻求简单的疼痛缓解， 安全，无认知副作用。 经颅磁共振引导聚焦超声是一种新的立体定向方法 能够通过完整的人类颅骨传递高强度能量， 亚毫米精度我们最初的FUS经验针对腹外侧 丘脑原发性震颤和帕金森病，最终导致FDA 批准。癌痛是考虑立体定向消融作为治疗的理想适应症。 疾病负担限制了选择。微创经颅治疗 难治性癌症疼痛将受到患者的欢迎-避免阿片类药物， 开放手术和器械植入。 这项探索性临床试验（已获FDA批准，IDE#G180222）将 通过进行单侧FUS，靶向脊髓丘脑和脊髓网状疼痛回路 中脑切开术，一种历史上有效的癌症疼痛治疗方法，但受到 时代的准确性。本研究的主要目的是评估安全性和初步 在六名患有阿片类药物抵抗性疼痛的头颈癌患者中的有效性。 此外，我们将研究疼痛缓解的潜在机制， 中脑切开术的目标涉及上行和下行疼痛的汇合 系统.目标2和3将研究这些系统的电生理学特性， 脊髓丘脑束和卡芬太尼PET成像， 内源性阿片样物质