Clinical Efficacy of Focused Ultrasound (MR-HIFU) Treatment of Symptomatic Osteoid Osteoma in Pediatrics

聚焦超声（MR-HIFU）治疗儿科症状性骨样骨瘤的临床疗效

• 批准号: 10308666
• 负责人: Karun V Sharma
• 金额: $ 19.5万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10308666
• 关键词: Ablation; Address; Adolescent; Adverse event; Aftercare; Age-Years; Aggressive Fibromatosis; Analgesics; Benign; Bone Marrow; Bone Pain; Bone neoplasms; Burn injury; Child; Chronic; Clinical; Clinical Trials Design; Coagulative necrosis; Common Terminology Criteria for Adverse Events; Contrast Media; Data; Deformity; Deposition; Development; Diffusion Magnetic Resonance Imaging; Drug usage; Edema; Enrollment; Evaluation; Excision; Feedback; Focused Ultrasound Therapy; Gadolinium; Gait abnormality; Heat Waves; Heating; Hemorrhage; Image; Infection; Injections; Injury; Intravenous; Ionizing radiation; Kidney; Knowledge; Length; Lesion; Limb structure; Literature; Magnetic Resonance Imaging; Methods; Monitor; Muscle; Needles; Non-Steroidal Anti-Inflammatory Agents; Normal tissue morphology; Operative Surgical Procedures; Osteoid osteoma; Outcome Measure; Pain; Parents; Patient Outcomes Assessments; Patients; Pediatric cohort; Pediatrics; Perfusion; Pharmaceutical Preparations; Phase I Clinical Trials; Phase II Clinical Trials; Physicians; Principal Investigator; Publishing; Quality of life; Radiation; Radiofrequency Interstitial Ablation; Recurrence; Reporting; Residual state; Risk; Safety; Signal Transduction; Skin; Sleep disturbances; Structure; Surgical incisions; Symptoms; Techniques; Temperature; Testing; Thermometry; Time; Tissues; Toxic effect; Treatment Efficacy; Treatment-related toxicity; Tumor Volume; Ultrasonic Transducer; United States; X-Ray Computed Tomography; alternative treatment; base; bone; clinical efficacy; clinical translation; contrast enhanced; contrast imaging; diaries; diffusion weighted; effective therapy; gastrointestinal; heat injury; image guided; image guided therapy; imaging biomarker; improved; individual patient; intravenous injection; nerve injury; new technology; novel; optimal treatments; overtreatment; pain relief; prevent; programs; real-time images; response; sarcoma; scoliosis; skin burn; soft tissue; sound; standard of care; success; symptom treatment; tumor

ABSTRACT Osteoid osteoma is a painful localized bone tumor that occurs most commonly in children and adolescents between 5-25 years of age. It accounts for 14% of all benign bone tumors. Symptoms can include severe bone pain and deformity, limb length discrepancy, and scoliosis. The current standard of care definitive treatment is with CT-guided radiofrequency ablation (CT-RFA), which has replaced open surgery. During CT-RFA, a bone drill is placed through the skin, muscle and bone into the osteoid osteoma using a CT imaging guidance. An RFA needle probe is then used to burn the osteoid osteoma. Although CT-RFA is less invasive than open surgical resection, potential complications include bleeding, infection, skin and muscle burn, and nerve injury from drilling through tissue and heating along the RFA probe. Furthermore, the use of CT imaging required for guidance exposes patients and operators to ionizing radiation, which can have potential long-term negative effects, especially for growing children. An optimal image-guided therapy for treatment of painful localized tumors such as osteoid osteoma would ideally be completely non-invasive, precise, and radiation-free. It would be performed without any skin incisions or bone drills, limiting potential collateral tissue damage and complications. It would be performed with real-time imaging feedback that could be used to prevent thermal injury to nearby critical structures and also to confirm treatment success. Magnetic resonance imaging-guided high intensity focused ultrasound (MR-HIFU) is a novel image-guided therapy which offers such treatment. Our group has performed the first Phase I clinical trial in the US to evaluate MR-HIFU treatment for painful osteoid osteoma in a pediatric cohort (PI Sharma, NCT02349971). The results show that MR-HIFU is feasible, well tolerated, and can be safely performed in children with painful osteoid osteoma. Based on our encouraging preliminary results, we hypothesize that this completely non-invasive and radiation-free MR-HIFU therapy will be clinically effective for treatment of painful osteoid osteoma; with clinical success comparable to CT-RFA. To test this hypothesis, we propose an early Phase II clinical trial designed to perform a thorough evaluation of the safety and efficacy of MR-HIFU ablation in patients with painful osteoid osteoma. We will also closely evaluate MR thermometry, intrinsic contrast imaging, and diffusion-weighted MR imaging obtained during the course of treatment and determine if these imaging changes can depict ablation zone without the use of intravenous injections of gadolinium-based contrast agents and serve as imaging biomarkers of treatment efficacy.

抽象的 骨质骨瘤是一种疼痛的局部骨肿瘤，最常见于儿童和青少年 在5-25岁之间。它占所有良性骨肿瘤的14％。症状可能包括严重的骨痛和 畸形，肢体长度差异和脊柱侧弯。当前的护理标准确定治疗是通过CT引导的 射频消融（CT-RFA）已取代开放手术。在CT-RFA期间，通过 皮肤，肌肉和骨骼使用CT成像指导进入骨软骨瘤。然后使用RFA针头探针燃烧 骨质骨瘤。尽管CT-RFA的侵入性不如开放手术切除，但潜在的并发症包括 出血，感染，皮肤和肌肉灼伤以及沿RFA探针加热而导致的神经损伤。 此外，指导所需的CT成像的使用使患者和操作员处于电离辐射中，这可以 具有潜在的长期负面影响，特别是对于成长中的儿童。 最佳图像引导的治疗用于治疗疼痛的局部肿瘤，例如骨质骨瘤，理想情况下将 完全无创，精确且无辐射。它将在没有任何皮肤切口或骨钻的情况下进行 限制潜在的附带组织损伤和并发症。将通过实时成像反馈执行 可用于防止附近关键结构的热损伤，并确认治疗成功。磁的 共振成像引导的高强度聚焦超声（MR-HIFU）是一种新型的图像引导疗法，提供 这样的治疗方法。 我们的小组已在美国进行了第一阶段的临床试验，以评估MR-HIFU治疗的痛苦 小儿队列中的骨质骨瘤（Pi Sharma，NCT02349971）。结果表明，hifu是可行的，很好 耐受性，可以在患有疼痛骨质骨瘤的儿童中安全地进行。基于我们令人鼓舞的初步 结果，我们假设这种完全无创和无辐射的MR-HIFU治疗将在临床上进行 有效治疗疼痛的骨质骨瘤；与CT-RFA相当的临床成功。测试这个 假设，我们提出了一项II期早期临床试验，旨在对安全性和有效性进行全面评估 疼痛性骨质骨瘤患者的Mr-Hifu消融。我们还将密切评估MR温度法，固有的 对比成像和在治疗过程中获得的扩散加权MR成像，并确定这些是否是否 成像变化可以描绘出消融区，而无需使用静脉注射基于Gadolinium的造影剂 并充当治疗功效的成像生物标志物。