Early Detection of Taxane-induced Neuropathy in Women with Breast Cancer

 描述(由申请人提供)：拟议的培训计划将为申请人提供开始其跨学科、翻译研究计划所需的知识、培训和技能的基础。这项研究的重点是开发工具来测量接受化疗药物紫杉醇(Taxol(R)，Abraxane(R))的乳腺癌幸存者(BC)的化疗引起的周围神经病变(CIPN)。尽管紫杉醇对转移性和非转移性乳腺癌都非常有效，但在接受药物治疗的BC中，暴露于紫杉醇会导致50-80%的CIPN。CIPN对BCS的影响可能很严重；症状可能会干扰职业功能和生活质量，在某些情况下，会迫使提供者停止可能挽救生命的化疗。由于CIPN症状对BCS完成治疗、功能和维持生活质量的能力构成重大风险，因此尽早发现CIPN并在治疗期间仔细监测其进展至关重要。及早识别CIPN可以提醒提供者BCS有严重症状的风险，使提供者能够启动教学以将安全风险降至最低(例如跌倒、事故)，并开始使用可用的药物(例如度洛西汀、加巴喷丁)进行治疗。随着治疗的进展，对CIPN的准确监测可以帮助提供者确定化疗是否需要推迟或停止，并为团队提供帮助妇女计划生存所需的信息。不幸的是，虽然早期发现和准确监测对于有效管理CIPN非常重要，但目前测量CIPN的方法不太适合满足这些需求。评估CIPN的常见策略，如神经病分级量表或自我报告问卷，一旦开始就可以有效地衡量CIPN症状的严重性和类型，但无法检测到预测症状所需的CIPN早期迹象，并且容易被患者漏报。这些方法也缺乏针对特定类型神经损伤的能力。这在c-纤维的情况下尤其重要，它参与了疼痛信号的传递，并逐渐 已被证明在CIPN的发展和永续方面发挥了作用。最近的研究已经确定了一种准确、灵敏的方法来测量c-纤维神经病，这有望检测和监测BCS中的CIPN。该方法包括测量在用一种药物刺激对温度敏感的神经(c纤维)后，流向皮肤的血流量的增加。 热探头(称为轴突反射)。使用简单的热探头，轴突反射可以在短至20分钟的时间内被刺激，从而为临床上检测和监测CIPN打开了大门。本研究的目的是确定轴突反射是否可以用来准确测量每周接受紫杉醇治疗的BCS的c-纤维损伤(CIPN)。

 DESCRIPTION (provided by applicant): The proposed training plan will provide the applicant with the foundation of knowledge, training, and skills needed to begin his interdisciplinary, translational program of research. This research focuses on the development of tools for measuring chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer survivors (BCS) who have received the chemotherapy drug paclitaxel (Taxol(r), Abraxane(r)). Although paclitaxel is highly effective as a treatment for both metastatic and non-metastatic breast cancer, exposure to paclitaxel leads to CIPN in 50-80% of BCS who receive the drug. The impact of CIPN on BCS can be severe; symptoms can interfere with occupational function and quality of life, and in some cases, force providers to stop potentially life-saving chemotherapy. Because of significant risk that CIPN symptoms pose to BCS' ability to complete treatment, function, and maintain quality of life, it is critical to identify CIPN as early as possible and monitor its progression carefully during treatment. Identifying CIPN as early as possible can alert providers to BCS at risk for severe symptoms, allowing providers to initiate teaching to minimize safety risks (e.g., falls, accidents) and initiate treatment with available agents (e.g., duloxetine, gabapentin). As treatment progresses, accurate monitoring of CIPN can help providers determine if chemotherapy needs to be delayed or discontinued and provide the team with information needed to help women plan for survivorship. Unfortunately, while early detection and accurate monitoring are important to managing CIPN effectively, current approaches to measuring CIPN are poorly suited to meet these needs. Common strategies for assessing CIPN like neuropathy grading scales or self-report questionnaires can be effective for measuring the severity and type of CIPN symptoms once they've started, but cannot detect the early signs of CIPN needed to predict symptoms and are vulnerable to patient underreporting. These approaches also lack the ability to target damage to specific types of nerves. This is especially important in the case of c-fibers, which are involved in pain signaling and increasingly have been shown to play a role in the development and perpetuation of CIPN. Recent studies have identified an accurate, sensitive approach for measuring c-fiber neuropathy that holds promise for detecting and monitoring CIPN in BCS. The approach involves measuring the increase in blood flow to the skin after stimulating temperature-sensitive nerves (c-fibers) with a heat probe (which is known as an axon reflex). Axon reflexes can be stimulated in as short a time as 20 minutes using simple heat probes, opening the door to a clinically feasible method for detecting and monitoring CIPN. The purpose of this study is to determine if axon reflexes can be used to accurately measure c-fiber damage (CIPN) in BCS receiving weekly paclitaxel.