Effects of oxaliplatin-based chemotherapy on proprioception in cancer survivors

以奥沙利铂为基础的化疗对癌症幸存者本体感觉的影响

• 批准号: 10284926
• 负责人: Allison Bingqing Wang
• 金额: $ 4.23万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10284926
• 关键词: Activities of Daily Living; Adjuvant; Adverse effects; Age; Animal Experimentation; Back; Cancer Patient; Cancer Survivor; Chemotherapy-Oncologic Procedure; Clinical; Colorectal Cancer; Complement; Conscious; Cross-Sectional Studies; Data; Development; Disease; Disease-Free Survival; Distal; Dose; Elbow; Evolution; Functional disorder; Future; Gastrointestinal Neoplasms; Goals; Guidelines; Human; Impairment; Intervention; Joints; Knowledge; Lead; Limb structure; Malignant Neoplasms; Measurement; Measures; Methods; Monitor; Motion; Motor; Movement; Neoplasm Metastasis; Neural Conduction; Neuropathy; Patients; Perception; Physiological; Population; Positioning Attribute; Posture; Prevalence; Prevention; Proprioception; Quality of life; Reflex action; Rehabilitation therapy; Reporting; Research Design; Research Proposals; Robotics; Rodent Model; Shoulder; Spinal Cord; Subconscious; Testing; Time; Touch sensation; Triceps Brachii Muscle; Upper Extremity; Volition; Work; afferent nerve; base; biceps brachii muscle; chemotherapy; clinical practice; dexterity; dosage; falls; gastrointestinal; improved; motor behavior; motor disorder; motor impairment; nerve conduction study; neurophysiology; neurotoxicity; novel; oxaliplatin; prevent; recruit; response; sensor; sensory neuropathy; side effect; stretch reflex; vibration

PROJECT SUMMARY Oxaliplatin (OX) is effective as the primary treatment for metastasized colorectal cancer and an adjuvant treatment for other gastrointestinal neoplasms. Despite its efficacy, OX can lead to neurotoxicity, resulting in physical dysfunctions including a loss of dexterity, postural imbalance, and falls that not only limit treatment, but also impact the quality of life for patients long into disease-free survival. These physical dysfunctions are commonly attributed to the degeneration of sensory nerves that disrupt distal sensations of touch, vibration and proprioception, termed ‘sensory neuropathy’. However, recent animal research has demonstrated that OX alters the proprioceptive information reaching the spinal cord and that these alterations occur independently from sensory neuropathy. These changes in the absence of sensory neuropathy can lead to substantial motor dysfunction in a rodent model with cancer. Unlike sensory neuropathy, these changes are not restricted to distal limbs but rather impair proximal and distal movement control. Furthermore, they occur before sensory neuropathy is present, suggesting that the current clinical measures for terminating OX treatment may not be sufficient for preventing motor impairments. It is not yet known if similar mechanisms of proprioceptive dysfunction are present in human cancer survivors treated with OX. This proposal will focus on this population, quantifying the time course of proprioceptive changes and comparing them to the evolution of sensory neuropathy. Cancer patients during the early, middle and late periods of OX treatments and age-matched healthy controls will be recruited. Aim 1 will quantify the conscious use of proprioception to generate volitional motions and forces. Aim 2 will quantify subconscious, involuntary motor actions (e.g. reflexes) generated in response to proprioceptive inputs. Both aims will use nerve conduction studies to monitor for signs of sensory neuropathy. OX-related changes in ability to perceive limb position and force, the size of reflex responses and the nerve conduction studies will be evaluated at different stages of OX treatment to determine if proprioceptive dysfunction exists separately from sensory neuropathy. This proposal will provide the first assessment of OX-induced proprioceptive dysfunction with respect to the development of sensory neuropathy in humans. The result will make a significant contribution toward determining if proprioceptive dysfunction contributes to motor impairments prior to the commonly assessed distal sensory neuropathy. Our work will be directly relevant to the current and future guidelines of dosing OX so as to minimize cancer-related physical dysfunction, and possibly for developing rehabilitation interventions to minimize the impact of OX treatments.

项目总结 奥沙利铂(Oxaliplatin，OX)是转移性结直肠癌的主要治疗药物和辅助药物 其他胃肠道肿瘤的治疗。尽管OX有疗效，但它会导致神经毒性，导致 身体功能障碍包括失去灵活性，姿势不平衡和摔倒，这些不仅限制了治疗，而且 也影响患者长期无病生存的生活质量。这些身体机能障碍是 通常归因于感觉神经的退化，扰乱了远端的触摸、振动和 本体感觉，称为“感觉神经病”。然而，最近的动物研究表明，牛会改变 本体感觉信息到达脊髓，这些改变独立于 感觉神经病。在没有感觉神经病变的情况下，这些变化可以导致实质性的运动 患癌症的啮齿动物模型中的功能障碍。与感觉神经病不同，这些变化并不局限于远端。 而是损害近端和远端的运动控制。此外，它们发生在感官之前 神经病变是存在的，提示目前终止OX治疗的临床措施可能不是 足以预防运动损伤。目前尚不清楚是否有类似的本体感觉机制 接受OX治疗的人类癌症幸存者存在功能障碍。这项提案将把重点放在这个人群上， 量化本体感觉变化的时间进程，并将其与感觉进化进行比较 神经病。OX治疗早、中、晚期癌症患者与年龄匹配的健康人群 控制组将被招募。目标1将量化有意识地使用本体感觉来产生意志性运动 和力量。目标2将量化潜意识的、非自愿的运动动作(例如，反射) 本体感觉输入。这两个目标都将使用神经传导研究来监测感觉神经病的迹象。 与OX相关的感知肢体位置和力量、反射反应大小和神经的能力变化 传导研究将在OX治疗的不同阶段进行评估，以确定本体感觉功能障碍 与感觉神经病分开存在。这项提案将提供第一次评估OX诱导的 本体感觉障碍与人类感觉神经病的发展。结果将是 在确定本体感觉障碍是否会导致运动障碍方面做出了重大贡献 在通常评估的远端感觉神经病之前。我们的工作将直接与当前和 未来给OX剂量的指导方针，以最大限度地减少癌症相关的身体功能障碍，并可能用于开发 康复干预措施，以最大限度地减少牛治疗的影响。