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: 9925740
• 负责人: Karun V Sharma
• 金额: $ 24.07万
• 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 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9925740
• 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.

摘要 骨样骨瘤是一种疼痛的局部骨肿瘤，最常见于儿童和青少年 5-25岁之间。它占所有良性骨肿瘤的14%。症状包括严重的骨痛， 畸形、肢体长度不等和脊柱侧凸。目前的标准治疗是在CT引导下 射频消融术（CT-RFA）已取代开放手术。在CT-RFA期间，将骨钻穿过 在CT引导下，将皮肤、肌肉和骨植入骨样骨瘤。然后使用RFA针探头进行燃烧 骨样骨瘤尽管CT-RFA的侵入性低于开放性手术切除，但潜在的并发症包括 出血、感染、皮肤和肌肉烧伤以及因钻穿组织并沿RFA探头沿着加热而造成的神经损伤。 此外，引导所需的CT成像的使用使患者和操作者暴露于电离辐射，这可以 有潜在的长期负面影响，特别是对成长中的儿童。 最佳的图像引导治疗疼痛的局部肿瘤，如骨样骨瘤， 完全无创、精确、无辐射。手术不需要任何皮肤切口或骨钻， 限制了潜在的附带组织损伤和并发症。它将通过实时成像反馈来执行， 可用于防止对附近关键结构的热损伤，也可用于确认治疗成功。磁 共振成像引导高强度聚焦超声（MR-HIFU）是一种新型的图像引导治疗， 这样的待遇。 我们的团队已经在美国进行了第一个I期临床试验，以评估MR-HIFU治疗疼痛的效果。 儿科队列中的骨样骨瘤（PI Sharma，NCT 02349971）。结果表明，MR-HIFU是可行的， 耐受性好，可安全用于疼痛性骨样骨瘤患儿。根据我们令人鼓舞的初步 结果，我们假设这种完全非侵入性和无辐射的MR-HIFU治疗将在临床上 有效治疗疼痛性骨样骨瘤;临床成功率与CT-RFA相当。为了验证这一 假设，我们提出了一个早期的II期临床试验，旨在进行彻底的安全性和有效性评估 MR-HIFU消融治疗疼痛性骨样骨瘤的临床研究。我们还将密切评估MR测温，内在 对比成像和弥散加权磁共振成像在治疗过程中获得，并确定这些 成像变化可以描绘消融区 并作为治疗效果的成像生物标志物。