Physiological, Behavioral and Predictive Correlates of Ototoxicity in Humans

人类耳毒性的生理、行为和预测相关性

• 批准号: 10552578
• 负责人: DAWN L KONRAD-MARTIN
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10552578
• 关键词: Address; Adult; Adverse effects; Aftercare; Age; Aging; Animal Model; Audiology; Auditory; Auditory Brainstem Responses; Behavioral; Bladder; Cancer Center; Cancer Survivor; Carboplatin; Caring; Cisplatin; Clinic; Clinical; Cochlea; Cognitive; Communication; Communication impairment; Comprehensive Cancer Center; Counseling; Cueing for speech; Cues; Decision Making; Diagnosis; Dose; Early Diagnosis; Functional disorder; Generations; Goals; Guidelines; Head and Neck Neoplasms; Health; Healthcare; Hearing; Hearing Tests; Hearing problem; Human; Hyperacusis; Incidence; Individual; Injury; Intervention; Knowledge; Labyrinth; Learning; Lesion; Letters; Life; Lung; Measurement; Measures; Methods; Modeling; Monitor; Morbidity - disease rate; National Cancer Institute; Nerve Degeneration; Neuronal Plasticity; Noise; Oncologist; Oncology; Outcome; Outer Hair Cells; Ovary; Patient Self-Report; Patient risk; Patients; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Physiological; Platinum; Policies; Predisposition; Provider; Publishing; Quality of life; Questionnaires; Recommendation; Reflex action; Rehabilitation therapy; Research; Resource Allocation; Risk; Risk Assessment; Sampling; Sensory; Site; Solid Neoplasm; Speech; Speech Perception; Stimulus; Surveys; Symptoms; System; Testing; Testis; Therapeutic; Therapeutic Intervention; Time; Tinnitus; Toxic effect; Universities; Veterans; Visit; Washington; Work; acoustic reflex; auditory pathway; aural rehabilitation; chemobrain; chemotherapy; cisplatin induced hearing loss; cost effective; diagnostic tool; drug modification; early awareness; experience; follow-up; hearing impairment; high risk; improved; individual patient; insight; medical schools; neoplasm registry; neural; novel diagnostics; novel strategies; otoacoustic emission; ototoxicity; oxaliplatin; patient oriented; predictive modeling; prevent; processing speed; prospective; psychosocial; side effect; sound; speech in noise; standard of care; survivorship; tool

Ototoxicity is a well-established toxicity of the platinum-based chemotherapies that are in frequent use for the treatment of solid tumors of the head and neck, lung, ovary, testicle, and bladder in adults. Early indicators of ototoxicity, which could prompt intervention to potentially prevent the health-related and psychosocial impacts for these patients, are not apparent in the absence of direct auditory measurement. National audiology guidelines, have stipulated that prospective monitoring for ototoxicity (OM) be conducted for all patients at high risk for this harmful side effect to allow for early detection, aural rehabilitation, and potential modification of the drug treatment before the effects become disabling. Specifically, for patients receiving cisplatin, monitoring prior to each treatment is recommended practice (ASHA 1994; AAA 2009). Based on our current research, OM must target those patients who will receive the most benefit to be feasible for large-scale implementation in VA. The goal of this study is to address the critical need in hearing healthcare for improved OM, diagnoses and clinical interventions in patients receiving treatment with cisplatin, carboplatin, and oxaliplatin chemotherapeutics by providing new knowledge of the mechanisms of ototoxicity, its functional manifestation, and new insights on the patient and provider perspective. Our overall approach is to investigate relationships among the specific behavioral deficits, sites of lesion, and hearing healthcare priorities of chemotherapy patients to learn which patients will develop ototoxicity, how much damage they can expect, and whether it will impact their everyday life. This knowledge is needed to shift current OM practice patterns toward a more effective and clinically feasible approach so that Veterans at elevated risk for ototoxicity could have their auditory concerns addressed through patient-centered OM, rehabilitation and/or drug therapy interventions. Clinical impacts include estimates of ototoxicity incidence for Veterans receiving platinum-based chemotherapeutic treatments; and tools to generate an individual ototoxicity risk profile that when combined with the patient-provider team priorities, will inform OM resource allocation, pre-treatment counseling, and decision making for ototoxic drug treatment. Knowledge gains include increased understanding of tinnitus generation and speech understanding deficits and the implications of these symptoms regarding the underlying ototoxic injury. To understand more about the mechanisms underlying ototoxicity-caused tinnitus and hearing problems [Aim 1], we will refine and expand our previously published dose-ototoxicity model and determine its utility for predicting changes in auditory deficits for individual patients. One refinement will be to include pre-treatment ABR and DPOAE measures in the model because we expect post-treatment tinnitus and hearing status to be a function of the combination of any new (ototoxicity-induced) damage with pre-exposure (age and/or noise- related) damage. Sensory and neural damage will be indirectly estimated using a novel approach that combines ABRs and DPOAEs (e.g. Bramhall et al. 2017). Neurodegeneration will also be estimated using wideband acoustic reflex testing, which elicits the reflex to lower stimulus levels than traditional tests, and can be administered at bedside unlike ABR (Feeney et al. 2017). To determine the clinical impacts of ototoxicity [Aim 2] we will assess the extent to which speech understanding in background noise is compromised following chemotherapy treatment, using a task that manipulates the temporal cues used for localization (Gallun et al. 2013). Tinnitus and hearing handicap questionnaires will provide knowledge of perceived auditory dysfunction. Combined information about the clinical impacts and ototoxicity mechanisms will create ototoxicity risk profiles for individual patients based on their age, planned chemotherapy, and pre-exposure inner ear function. A national survey of oncologists will be used to review oncology- and OM-related practice patterns in the US. These results are expected to change current audiological best practice recommendations and are crucial to advance widespread implementation of OM both within and outside VA.

耳毒性是经常用于治疗癌症的铂类化疗药物的一种公认的毒性。 治疗成人头颈、肺、卵巢、睾丸和膀胱的实体瘤。早期指标 耳毒性，这可能会促使干预措施预防与健康相关和社会心理的影响 对于这些患者来说，在没有直接听觉测量的情况下，这些症状并不明显。国家听力学 指南规定，对所有高危患者进行耳毒性 (OM) 前瞻性监测 这种有害副作用的风险，以便及早发现、听力康复和潜在的修改 在效果变得致残之前进行药物治疗。具体而言，对于接受顺铂的患者，应事先监测 每种治疗方法都有推荐的做法（ASHA 1994；AAA 2009）。根据我们目前的研究，OM 必须 针对那些将获得最大利益的患者，以便在 VA 大规模实施是可行的。 本研究的目标是满足听力保健领域对改善 OM、诊断和治疗的迫切需求。 对接受顺铂、卡铂和奥沙利铂化疗药物治疗的患者的临床干预 通过提供关于耳毒性机制、其功能表现的新知识以及关于耳毒性的新见解 患者和提供者的观点。我们的总体方法是调查特定因素之间的关系 化疗患者的行为缺陷、病变部位和听力保健重点，以了解哪些 患者是否会出现耳毒性，他们可能会受到多少损害，以及是否会影响他们的日常生活 生活。需要这些知识才能将当前的 OM 实践模式转向更有效和临床可行的模式 方法，以便耳毒性风险较高的退伍军人可以通过以下方式解决他们的听觉问题 以患者为中心的 OM、康复和/或药物治疗干预措施。临床影响包括估计 接受铂类化疗的退伍军人的耳毒性发生率；以及生成工具 个人耳毒性风险概况与患者-提供者团队的优先事项相结合，将告知 OM 耳毒性药物治疗的资源分配、治疗前咨询和决策。知识增益 包括加深对耳鸣产生和言语理解缺陷及其影响的了解 这些症状与潜在的耳毒性损伤有关。 进一步了解耳毒性引起的耳鸣和听力问题的潜在机制 [目标 1]，我们将完善和扩展我们之前发布的剂量耳毒性模型，并确定其实用性 预测个别患者听觉缺陷的变化。一项改进是包括预处理 模型中的 ABR 和 DPOAE 测量，因为我们预计治疗后耳鸣和听力状态将成为 任何新的（耳毒性引起的）损伤与预暴露（年龄和/或噪音）的组合的功能 相关）损坏。将使用一种新颖的方法来间接估计感觉和神经损伤，该方法结合了 ABR 和 DPOAE（例如 Bramhall 等人，2017 年）。神经退行性疾病也将使用宽带进行估计 声反射测试，与传统测试相比，它引发对较低刺激水平的反射，并且可以 与 ABR 不同，在床边给药（Feeney et al. 2017）。确定耳毒性的临床影响 [目的 2]我们将评估背景噪声中语音理解受到损害的程度，如下 化疗治疗，使用操纵用于定位的时间线索的任务（Gallun 等人，2017） 2013）。耳鸣和听力障碍问卷将提供感知听觉功能障碍的知识。 有关临床影响和耳毒性机制的综合信息将创建耳毒性风险概况 根据患者的年龄、计划的化疗和暴露前内耳功能对个体患者进行治疗。国家级 对肿瘤学家的调查将用于审查美国肿瘤学和 OM 相关的实践模式。 这些结果预计将改变当前的听力学最佳实践建议，并且对于 推动 OM 在 VA 内部和外部的广泛实施。

项目成果

Noise: Acoustic Trauma and Tinnitus, the US Military Experience.

• DOI: 10.1016/j.otc.2020.03.004
• 发表时间: 2020-08
• 期刊: OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA
• 影响因子: 1.7
• 作者: Theodoroff, Sarah M.;Konrad-Martin, Dawn
• 通讯作者: Konrad-Martin, Dawn

Audiologists' perceived value of ototoxicity management and barriers to implementation for at-risk cancer patients in VA: the OtoMIC survey.

• DOI: 10.1007/s11764-022-01316-7
• 发表时间: 2023-03
• 期刊: JOURNAL OF CANCER SURVIVORSHIP
• 影响因子: 3.7
• 作者: Konrad-Martin, Dawn;Polaski, Rachel;DeBacker, J. Riley;Theodoroff, Sarah M.;Garinis, Angela;Lacey, Cecilia;Johansson, Kirsten;Mannino, Rosemarie;Milnes, Trisha;Hungerford, Michelle;Clark, Khaya D.
• 通讯作者: Clark, Khaya D.

Potential Risks to Hearing Functions of Service Members From Exposure to Jet Fuels.

暴露于喷气燃料对军人听力功能的潜在风险。

• DOI: 10.1044/2021_aja-20-00226
• 发表时间: 2021
• 期刊: American journal of audiology
• 影响因子: 1.8
• 作者: Morata,ThaisC;Hungerford,Michelle;Konrad-Martin,Dawn
• 通讯作者: Konrad-Martin,Dawn