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。我们建议在基线和微创治疗后对子宫平滑肌瘤妇女的月经疼痛和非周期性盆腔疼痛进行表征。我们提交的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非侵入性超声技术的比较有效性。我们提出一项随机临床试验，比较两种微创治疗子宫平滑肌瘤的症状缓解：子宫动脉栓塞（UAE）和MRI引导聚焦超声（MRgFUS）。四分之一的女性和高达75%的非裔美国女性被诊断为子宫平滑肌瘤（肌瘤或肌瘤）。每年由平滑肌瘤引起的直接医疗费用超过21亿美元1。然而，我们的研究报告指出，患有临床显著肌瘤的女性的间接成本（残疾和旷工）与直接成本相当（11720美元vs 11752美元/名女性/年）2。在人口统计学和病例混合因素的控制下，有症状的肌瘤妇女的间接费用比对照组妇女显著增加（11752美元对8083美元，p<0.0001）2。因此，从社会的角度来看，了解和解决临床显著的子宫肌瘤的症状，特别是疼痛，对于优化治疗结果和控制医疗保健费用是重要的。尽管他们的患病率，肌瘤的症状仍然不完全了解。据报道，肌瘤会引起许多症状，包括大量或长时间的月经出血、盆腔压力、月经疼痛（痛经）以及肠道和膀胱功能障碍。然而，平滑肌瘤疼痛从来没有研究过评估和量化疼痛的标准工具，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疼痛和非周期性骨盆疼痛。一篇关于平滑肌瘤的专家评论认为，出现非周期性盆腔疼痛应提示对其他疾病过程的调查4。然而，子宫动脉栓塞治疗（UAE）后3年的研究结果表明，83%的女性盆腔疼痛有长期改善5。该研究还将追踪两种经fda批准的微创平滑肌瘤治疗技术（子宫动脉栓塞（UAE）和mri引导聚焦超声手术（MRgFUS））治疗后骨盆疼痛和其他症状结果的变化。UAE和MRgFUS在治疗方法、作用机制和副作用方面存在显著差异，从未在随机临床试验中进行过比较。阿联酋采用血管造影闭塞子宫动脉作为一种全面的子宫治疗导致缺血性坏死。在UAE后，女性在术后立即出现更多疼痛，但研究表明，在长期随访期间盆腔疼痛减轻。相反，MRgFUS靶向单个肌瘤的间质并产生热溶性凝固性坏死。这种肌瘤特异性入路术后疼痛较少，允许门诊治疗，但不太全面，可能导致较短的长期症状改善。因此，我们建议进行PAM试验：肌瘤疼痛评估，这是一项随机临床试验，治疗220名不同种族的有阿联酋或MRgFUS症状的子宫肌瘤妇女，并随访至少6个月。该资助机制将涵盖每个科目从基线至6个月的费用，我们正积极寻求公私合作伙伴关系，以便进行长期跟进。通过梅奥诊所（Mayo Clinic）和杜克大学（Duke University）的招募，将实现受试者的种族多元化。

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