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

摘要 骨样骨瘤是一种疼痛的局限性骨肿瘤，最常见于儿童和青少年。 年龄在5-25岁之间。占所有良性骨肿瘤的14%。症状可能包括严重的骨痛和 畸形、四肢长度不等和脊柱侧弯。目前的护理标准是在CT引导下进行最终治疗 射频消融(CT-RFA)已取代开放手术。在CT-RFA过程中，将一个骨钻穿过 在CT引导下将皮肤、肌肉和骨骼转化为骨样骨瘤。然后使用RFA针探头来燃烧 骨样骨瘤。尽管CT-RFA比开放手术切除侵入性小，但潜在的并发症包括 穿透组织和沿RFA探头加热导致出血、感染、皮肤和肌肉灼伤以及神经损伤。 此外，使用指导所需的CT成像会使患者和操作员暴露在电离辐射中，这可能 有潜在的长期负面影响，特别是对成长中的儿童。 对于疼痛的局部肿瘤如骨样骨瘤的最佳影像引导治疗将是理想的 完全非侵入性、精确度和无辐射。它将在没有任何皮肤切开或骨钻孔的情况下进行， 限制潜在的附带组织损伤和并发症。它将与实时成像反馈一起执行，该反馈 可以用来防止对附近关键结构的热损伤，也可以用来确认治疗成功。磁性 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方法，它提供了 这样的待遇。 我们小组已经在美国进行了第一阶段临床试验，以评估MR-HIFU治疗疼痛的效果 儿童队列中的骨样骨瘤(Pi Sharma，NCT02349971)。结果表明，磁流变高强度聚焦超声是可行的，效果良好。 对于患有疼痛的骨样骨瘤的儿童，可以耐受并可以安全地进行治疗。根据我们令人鼓舞的初步调查 结果：我们假设这种完全无创、无辐射的mr-hifu疗法将在临床上应用。 有效治疗疼痛骨样骨瘤；临床疗效可与CT-RFA相媲美。为了测试这一点 假设，我们提出了一项早期II期临床试验，旨在进行彻底的安全性和有效性评估 高强度聚焦超声在疼痛骨样骨瘤患者中的应用。我们还将密切评估MR温度计，本征 在治疗过程中获得的对比度成像和扩散加权磁共振成像，并确定这些 成像改变可以描绘消融区，而不需要静脉注射基于Gd的造影剂 并可作为疗效的影像生物标志物。

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.