Patient-reported Symptoms of Tenosynovial Giant Cell Tumors.
Patient-reported Symptoms of Tenosynovial Giant Cell Tumors.
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DOI：
10.1016/j.clinthera.2016.03.008
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发表时间：
2016-04
影响因子：
3.2
通讯作者：
Tap WD
中科院分区：
文献类型：
--
作者：
Gelhorn HL;Tong S;McQuarrie K;Vernon C;Hanlon J;Maclaine G;Lenderking W;Ye X;Speck RM;Lackman RD;Bukata SV;Healey JH;Keedy VL;Anthony SP;Wagner AJ;Von Hoff DD;Singh AS;Becerra CR;Hsu HH;Lin PS;Tap WD
肌腱滑膜巨细胞瘤(TGCT)是一种罕见的关节滑膜和腱鞘局部侵袭性肿瘤，与关节破坏、炎症、疼痛和肿胀有关，部分原因是携带集落刺激因子1受体的巨噬细胞通过基因上调集落刺激因子1活性而被招募到肿瘤中。最常见的治疗方法是手术，尽管有希望的药物治疗正在开发中。患者报告结果(PRO)工具是证明标准肿瘤结果测量的临床相关性和新型药物疗法在TGCT等非恶性肿瘤疾病中的整体影响的关键终点。与TGCT患者相关的PROS的内容有效性还没有正式调查，也不存在用于评估这种情况的结果的工具。通过文献回顾以及临床和PRO专家对潜在相关性的PRO工具进行评估。TGCT患者通过临床网站和互联网被招募参加定性研究访谈，以确定主要症状，并测试几种预防措施的相关性和内容有效性。选定的PRO措施包括在I期临床试验中，PRO终点的初步结果被描述性地报告。在参与定性访谈的22名受试者中，73%为女性，她们的平均年龄为42.5岁(范围为27-56岁)。弥漫性19例，局限性3例，分别位于膝部15例，髋部3例，踝部2例，肘部和前臂各1例。最常见的症状是疼痛(82%)、肿胀(86%)、僵硬(73%)、活动范围缩小(%)和关节不稳(%)，这与临床专家的输入和专业专家选择的器械内容一致。最严重疼痛数字评定量表、患者报告结果测量信息系统身体功能项目、西安大略大学和麦克马斯特大学骨关节炎指数，以及为TGCT开发的最差僵硬数字评定表，被确认为TGCT患者症状的有意义的衡量标准，并在定性访谈中得到了很好的理解。I期试验的结果显示，随着时间的推移，疼痛和僵硬都有改善的趋势。这项研究是第一次直接从TGCT患者那里收集关于他们的症状经历的信息。疼痛、僵硬和身体功能是TGCT患者的重要治疗结果。我们已经确定了这些概念的内容有效的PRO措施，这些措施包括在正在进行的Pexidartinib(PLX3397)TGCT临床试验(NCT02371369)中。
Tenosynovial giant cell tumor (TGCT), a rare locally aggressive neoplasm of the synovium of joints and tendon sheaths, is associated with joint destruction, inflammation, pain, and swelling, in part due to colony-stimulating factor 1 receptor–bearing macrophages recruited to the tumor by genetic elevation of colony-stimulating factor 1 activity. The most common treatment is surgery, although promising pharmacologic treatments are in development. Patient-reported outcome (PRO) instruments are critical end points in demonstrating the clinical relevance of standard oncologic outcome measures and the overall impact of novel pharmacologic therapies in nonmalignant neoplastic conditions such as TGCT. The content validity of PROs relevant to patients with TGCT has not been formally investigated, and instruments to evaluate such outcomes do not exist for this condition. PRO instruments of potential relevance were evaluated by using a literature review and by clinical and PRO experts. Patients with TGCT were recruited through clinical sites and the Internet for participation in qualitative research interviews to identify predominant symptoms and to test the relevance and content validity of several PRO measures. Select PRO measures were included in a Phase I clinical trial, and preliminary results of the PRO end points are reported descriptively. Of the 22 subjects who participated in qualitative interviews, 73% were female, and their mean age was 42.5 years (range, 27–56 years). The TGCTs (19 diffuse and 3 localized) were located in the knee (n = 15), hip (n = 3), ankle (n = 2), elbow (n= 1), and forearm (n = 1). The most common symptoms cited were pain (82%), swelling (86%), stiffness (73%), reduced range of motion (64%), and joint instability (64%), which were consistent with clinical expert input and with the content of instruments chosen by PRO experts. The worst pain numeric rating scale, Patient Reported Outcomes Measurement Information System physical functioning items, and the Western Ontario and McMaster Universities Osteoarthritis Index, as well as a worst stiffness numeric rating scale developed for TGCT, were confirmed as meaningful measures of TGCT patient symptoms and were well understood in qualitative interviews. Results from the Phase I trial showed trends of improvement in both pain and stiffness over time. This study is the first to gather information directly from patients with TGCT regarding their symptom experiences. Pain, stiffness, and physical functioning are important treatment outcomes in patients with TGCT. We have identified content-valid PRO measures of these concepts, which are included in an ongoing Phase III TGCT clinical trial with pexidartinib (PLX3397) (NCT02371369).