Radiation-Induced Fibrosis and Co-occurring Adverse Treatment-Related Effects in Head and Neck Cancer Survivors

头颈癌幸存者中放射诱发的纤维化和同时发生的不良治疗相关影响

基本信息

批准号：
10734092
负责人：
MARCI LEE NILSEN
金额：
$ 59.92万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10734092
关键词：
Acute Adverse effects Alcohol consumption Aspiration Pneumonia Biological Factors Biological Markers Cancer Survivor Characteristics Clinical Common Terminology Criteria for Adverse Events Data Deglutition Deglutition Disorders Development Distress Elastic Tissue Fibrosis Goals Head and Neck Cancer Health Image Impairment Incidence Individual Inflammation Intervention Life Link Logistic Regressions Malignant Neoplasms Malnutrition Medical Records MicroRNAs Modeling Morbidity - disease rate National Cancer Institute Neck Outcome Pain Participant Patients Pattern Perception Personal Satisfaction Phenotype Plague Play Prospective Studies Quality of life Radiation Radiation Fibrosis Regimen Reporting Research Role Severities Site Survivors Symptoms Time Tissues Toxic effect Treatment Factor Validation Variant Whole Blood Work acute toxicity aggressive therapy cancer therapy chemoradiation circulating microRNA common treatment cost differential expression disability experience follow-up head and neck cancer patient improved indexing insight longitudinal design mortality nonhuman primate potential biomarker prognosis biomarker radiation mitigation radiation risk standard care survivorship therapy adverse effect transcriptome sequencing treatment effect treatment response

项目摘要

PROJECT SUMMARY. The intensity of standard treatments (i.e., chemoradiation) for head and neck cancer (HNC) has amplified over the last two decades, resulting in a 500% increase in acute toxicities. These demanding regimens leave 90% of HNC survivors with adverse treatment effects. For some, radiation-induced fibrosis (RIF) is progressive, leading to debilitating treatment-related effects. The most serious sequelae are neck disability and dysphagia, which reduces QOL and survival. Our research team has empirically described the burden and impact of neck disability and impairment in HNC survivors. Results showed that 54% of HNC survivors reported neck disability and that increasing neck disability was associated with worsening dysphagia symptoms. However, we know very little about the characterization of RIF and its co-occurring adverse treatment effects trajectories (i.e., patterns of change over time), thus prohibiting the development of tailored interventions to mitigate morbidity. Also, while reliable biomarkers to determine those at greatest risk for RIF do not exist, our preliminary work indicates that specific circulating microRNAs (miRNAs) may be associated with late RIF. There is a critical need to appreciate the clinical trajectories of RIF and subsequent adverse effects and elucidate the factors underlying the development and variability in these trajectories to optimize HNC survivors’ well-being. The purpose of this study is to determine the distinct trajectories of RIF and co-occurring adverse treatment effects (i.e., neck disability, dysphagia) and the factors that impact those trajectories. Our central hypothesis is that 1) substantial variability in RIF and co-occurring adverse treatment effects exist in HNC patients receiving radiation, 2) this variability will cluster into distinct trajectories, and 3) group membership will be explained by individual factors, cancer/cancer treatment characteristics, and miRNA variations. This prospective study (n=334) uses a longitudinal design with assessments at pre-radiation (Time 0) and follow-up at 1 (Time 1), 6 (Time 2), 12 (Time 3), and 24 months (Time 4, exploratory) post-radiation. Aim 1 is to characterize the trajectories of RIF and co-occurring adverse treatment effects (i.e., neck disability, dysphagia) and their associations. In Aim 2, we will determine the individual and cancer/treatment factors that explain variability in RIF and the co-occurring adverse treatment effects. Aim 3 will explore the trajectories of RIF and co-occurring adverse treatment effects through 24 months post-radiation. Finally, Aim 4 will explore circulating miRNAs associated with trajectories of RIF and co-occurring adverse treatment effects. Group- based and dual trajectory modeling and multinomial logistic regression with model validation will be employed. This study is essential to develop interventions to mitigate RIF and subsequent co-occurring treatment effects HNC survivors experience to reduce morbidity, increase QOL and improve survival. Moreover, miRNAs have the potential to serve as promising biomarkers to better determine survivors at risk for RIF before the clinical manifestations of RIF occur and to assess therapeutic response to anti-RIF treatments.

项目摘要。头颈癌标准治疗（即放化疗）的强度 (HNC) 在过去二十年中不断扩大，导致急性毒性增加了 500%。严格的治疗方案使 90% 的 HNC 幸存者出现不良治疗效果，其中一些是由放射引起的。纤维化（RIF）是进行性的，导致治疗相关的衰弱效应，最严重的后遗症是。我们的研究团队根据经验描述了颈部残疾和吞咽困难，这会降低生活质量和生存率。颈部残疾和损伤对 HNC 幸存者的负担和影响结果显示，54% 的 HNC 幸存者。幸存者报告颈部残疾，颈部残疾的增加与吞咽困难恶化有关然而，我们对 RIF 的特征及其同时发生的不良反应知之甚少。治疗效果轨迹（即随时间变化的模式），从而阻碍了定制治疗的开发此外，可靠的生物标志物可以确定 RIF 风险最大的人群。不存在，我们的初步工作表明特定的循环 microRNA (miRNA) 可能与晚期 RIF 迫切需要了解 RIF 的临床轨迹和随后的不良反应。并阐明这些轨迹的发展和变化背后的因素，以优化 HNC 本研究的目的是确定 RIF 和同时发生的不同轨迹。不良治疗效果（即颈部残疾、吞咽困难）以及影响这些轨迹的因素。中心假设是 1) RIF 的显着变异性和同时发生的不良治疗效应存在于接受放射治疗的 HNC 患者，2) 这种变异性将聚集成不同的轨迹，以及 3) 组成员资格将通过个体因素、癌症/癌症治疗特征和 miRNA 来解释这项前瞻性研究（n=334）采用纵向设计，并在辐射前（时间）进行评估。 0）以及辐射后 1（时间 1）、6（时间 2）、12（时间 3）和 24 个月（时间 4，探索性）的随访。目标 1 是描述 RIF 的轨迹和同时发生的不良治疗反应（即颈部残疾、在目标 2 中，我们将确定个体和癌症/治疗因素。解释 RIF 的变异性和同时发生的不良治疗效应，目标 3 将探讨 RIF 的变化轨迹。最后，目标 4 将探讨放射后 24 个月内的 RIF 和同时发生的不良治疗效应。循环 miRNA 与 RIF 轨迹和同时发生的不良治疗效果相关。将采用基于双轨迹建模和带有模型验证的多项逻辑回归。这项研究对于制定干预措施以减轻 RIF 和随后同时发生的治疗效果至关重要 HNC 幸存者可以降低发病率、提高生活质量并提高生存率。作为有前途的生物标志物的潜力，可以在临床前更好地确定有 RIF 风险的幸存者 RIF 的表现并评估抗 RIF 治疗的治疗反应。