Comparing focused ultrasound and uterine artery embolization for uterine fibroids

描述（由申请人提供）：本申请涉及挑战领域#15：转化科学和特定挑战主题，15-HD-102：骨盆疼痛。我们建议对子宫肌瘤患者在基线和微创治疗后的月经痛和非周期性盆腔痛进行描述。我们的提交文件还涉及挑战领域#5：比较有效性研究和特定挑战主题，05- EB-103无创超声技术的比较有效性。我们提出了一项随机临床试验，比较两种微创治疗子宫肌瘤后的症状缓解：子宫动脉栓塞术（UAE）和MRI引导的聚焦超声（MRgFUS）。四分之一的女性和高达75%的非洲裔美国女性被诊断出子宫平滑肌瘤（肌瘤或肌瘤）。平滑肌瘤的直接医疗费用每年超过21亿美元1。然而，我们的工作报告称，间接成本（残疾和缺勤）相当于患有临床显著肌瘤的女性的直接成本（11，720美元对11，752美元/女性/年）。当控制人口统计学和病例组合因素时，与对照组妇女相比，有症状的子宫肌瘤妇女的间接费用显着增加（11，752美元对8083美元，p<0.0001）2。因此，从社会角度来看，了解和解决临床上显著的子宫肌瘤症状，特别是疼痛，对于优化治疗结果和控制医疗保健成本非常重要。尽管其患病率，纤维瘤病理学仍然不完全理解。据报道，肌瘤会引起许多症状，包括大量或长期的月经出血，盆腔压力，月经疼痛（痛经）和肠道和膀胱功能障碍。然而，平滑肌瘤疼痛从来没有被研究的标准工具，评估和量化疼痛，麦吉尔疼痛问卷（MPQ）3。此外，大多数平滑肌瘤研究没有区分月经痛和非周期性盆腔痛。一个关于平滑肌瘤的专家评论建议，非周期性盆腔疼痛的存在应促使对其他疾病过程的研究。然而，子宫动脉栓塞治疗（UAE）后3年结局的研究表明，83%的女性盆腔疼痛长期改善5。本研究还将跟踪使用两种经FDA批准的微创子宫动脉栓塞（UAE）和MRI引导的聚焦超声手术（MRgFUS）治疗子宫肌瘤后盆腔疼痛和其他症状结局的变化。UAE和MRgFUS在方法、作用机制和副作用方面存在显著差异，并且从未在随机临床试验中进行过比较。UAE采用血管造影闭塞子宫动脉作为导致缺血性坏死的整体子宫治疗。在UAE之后，女性似乎在术后即刻有更多的疼痛，但研究证明在长期随访期间骨盆疼痛减少。相比之下，MRgFUS靶向单个肌瘤的子宫内膜，并产生热消融凝固性坏死。这种肌瘤特异性方法导致术后疼痛较少，允许门诊治疗，但不太全面，可能导致长期症状改善较少。因此，我们提出了PAM试验：肌瘤疼痛评估，一项随机临床试验，采用UAE或MRgFUS治疗220名患有症状性子宫平滑肌瘤的不同种族女性，并随访至少6个月。这一资助机制将涵盖每个受试者从基线到6个月的费用，我们正在积极寻求公共/私营合作伙伴关系，以便进行长期随访。将通过马约诊所和杜克大学招募受试者，以实现受试者的种族多样性。 公共卫生相关性：子宫平滑肌瘤或肌瘤是育龄妇女，特别是非洲裔美国妇女的一种非常常见的疾病。子宫肌瘤是子宫切除术的主要原因，但它们引起的盆腔疼痛的数量还没有明确的记录。这项研究将描述患有肌瘤的女性在月经期和本月其他时间的盆腔疼痛程度，以及子宫动脉栓塞术（UAE）和磁共振引导聚焦超声（MRgFUS）是否可以减轻疼痛，这两种方法是肌瘤的微创治疗

DESCRIPTION (provided by applicant): This application addresses Challenge Area #15:Translational Science and Specific Challenge Topic, 15-HD-102: Pelvic Pain. We propose to characterize the pain with menses and noncyclic pelvic pain in women with uterine leiomyomas at baseline and following minimally-invasive treatment. Our submission also addresses Challenge Area #5: Comparative Effectiveness Research and Specific Challenge Topic, 05- EB-103 Comparative Effectiveness of Non-Invasive Ultrasound Techniques. We propose a randomized clinical trial comparing symptomatic relief following two minimally invasive treatments for uterine leiomyomas: uterine artery embolization (UAE) and MRI guided focused ultrasound (MRgFUS). Uterine leiomyomas (fibroids or myomas) are diagnosed in one quarter of all women and up to 75 % of African-American women. The direct health care costs attributable to leiomyomas exceed $2.1 billion annually1. However, our work reported that indirect costs (disability and absenteeism) are equivalent to direct costs for women with clinically significant fibroids ($11,720 vs. $11,752/woman/year) 2. This is a significant increase in indirect costs for women with symptomatic fibroids compared to control women when controlled for demographic and case mix factors ($11,752 vs. $8083, p<0.0001)2. Thus, understanding and addressing the symptoms of clinically-significant uterine fibroids and particularly pain is important in optimizing treatment outcomes and controlling health care costs from a societal perspective. Despite their prevalence, fibroid symptomatology is still incompletely understood. Myomas are reported to cause a number of symptoms including heavy or prolonged menstrual bleeding, pelvic pressure, pain with menses (dysmenorrhea) and bowel and bladder dysfunction. However leiomyoma pain has never been studied with the standard instrument for assessing and quantitating pain, the McGill Pain Questionnaire (MPQ) 3. Moreover, most leiomyoma studies have not differentiated between pain with menses and non cyclic pelvic pain. One expert review of leiomyomas suggests the presence of noncyclic pelvic pain should prompt investigation of other disease processes 4. Yet studies of 3 year outcomes following uterine artery embolization treatment (UAE) suggest that 83% of women have long term improvement in pelvic pain 5. This study will also track changes in pelvic pain and other symptomatic outcomes following treatment with two minimally-invasive FDA-approved techniques for leiomyoma treatment uterine artery embolization (UAE) and MRI-guided focused ultrasound surgery (MRgFUS). UAE and MRgFUS differ significantly in approach, mechanism of action and side effects and they have never been compared in a randomized clinical trial. UAE employs angiographic occlusion of the uterine arteries as a global uterine treatment leading to ischemic necrosis. Following UAE, women appear to have more pain in the immediate postoperative period, but studies document decreased pelvic pain during long term follow-up. In contrast, MRgFUS targets the interstitium of individual fibroids and produces thermoablative coagulative necrosis. This myoma-specific approach causes less postoperative pain and allows for outpatient treatment but is less comprehensive and may lead to less long term symptomatic improvement. We therefore propose the PAM Trial: Pain Assessment for Myomas, a randomized clinical trial treating 220 racially-diverse women with symptomatic uterine leiomyomas with UAE or MRgFUS and following them for a minimum of 6 months. This funding mechanism will cover costs from baseline to 6 months for each subject and we are actively pursuing public/private partnerships to allow long term follow up. A racially diverse cohort of subjects will be achieved by recruiting through Mayo Clinic and Duke University. PUBLIC HEALTH RELEVANCE: Uterine leiomyomas or fibroids are an extremely common disease in reproductive age women and particularly African-American women. Fibroids are the leading cause of hysterectomy, yet the amount of pelvic pain they cause has not been clearly documented. This study will characterize the amount of pelvic pain women with fibroids have with their menstrual periods and at other times in the month and whether pain is decreased by uterine artery embolization (UAE) and magnetic resonance guided focused ultrasound (MRgFUS), two minimally-invasive treatments for fibroids