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。标准治疗的强度（即对头颈癌的化学放疗）（HNC）在过去的二十年中一直在扩展，导致急性毒性增加了500％。这些苛刻的方案使90％的HNC冲浪者具有不良治疗效果。对于某些人，辐射引起的纤维化（RIF）是渐进的，导致与治疗相关的效应。最严重的后遗症是颈部残疾和吞咽困难，可降低质量和生存。我们的研究团队已经验描述了 HNC存活中颈部残疾和障碍的负担和影响。结果表明，HNC的54％幸存者报告颈部残疾，颈部残疾增加与后悔吞咽困难有关症状。但是，我们对RIF及其同时发生的对手的表征知之甚少治疗效果轨迹（即随时间变化的模式），因此禁止开发量身定制减轻发病率的干预措施。另外，虽然可靠的生物标志物来确定rif风险最大的生物标志物不存在，我们的初步工作表明特定的循环microRNA（miRNA）可能与 rif晚。迫切需要欣赏RIF的临床轨迹和随后的不良影响并阐明这些轨迹发展和可变性的因素以优化HNC 幸存者的福祉。这项研究的目的是确定RIF和同时存在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。我们的中心假设是1）RIF和同时发生的不良治疗效应的实质性变异性存在 HNC患者接受辐射，2）这种变异性将聚集成不同的轨迹，3）组会员资格将由个体因素，癌症/癌症治疗特征和miRNA解释变化。这项前瞻性研究（n = 334）使用纵向设计，并在辐射前进行评估（时间 0）和在1（时间1），6（时间2），12（时间3）和24个月（时间4，探索性）后的随访。目的1是表征RIF和同时发生的不良治疗效果的轨迹（即颈部疾病，吞咽困难）及其协会。在AIM 2中，我们将确定个人和癌症/治疗因素解释RIF的变异性和共发生的不良治疗效果。 AIM 3将探索在辐射后24个月内，RIF和同时发生的不良治疗效果。最后，AIM 4将探索与RIF轨迹和同时发生的不良治疗效果相关的循环miRNA。团体- 将聘请基于双重轨迹建模和多项式逻辑回归，并通过模型验证。这项研究对于制定减轻RIF的干预措施和随后的同时发生治疗效果至关重要。 HNC生存经验可降低发病率，增加QoL并提高生存率。而且，mirnas拥有作为承诺的生物标志物，可以更好地确定临床前RIF风险的生存的潜力发生RIF的表现并评估对抗RIF治疗的治疗反应。