Improving Prediction of Chemotherapy-Induced Nausea: Integrating Genes, Behavior, and the Microbiome

改善化疗引起恶心的预测：整合基因、行为和微生物组

基本信息

批准号：
10442417
负责人：
HEATHER S.L. JIM
金额：
$ 67.8万
依托单位：
H. LEE MOFFITT CANCER CTR & RES INST
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10442417
关键词：
Acute Adult Age Alcohol consumption Algorithms Antiemetics Anxiety Area Behavior Benefits and Risks Bioinformatics Biological Cancer Center Cancer Patient Characteristics Clinical Computerized Medical Record Data Data Collection Data Reporting Diarrhea Disease Evolution Fatigue Fright Functional disorder Future Genes Genetic Genetic Variation Goals Guidelines Heritability Hour Human Human Genome Human Microbiome Impaired cognition Infusion procedures International Intravenous Knowledge Malignant Neoplasms Medicine Metagenomics Methodological Studies Microbe Microbial Genetics Modeling Motion Sickness Mucositis Nausea Oncology Outcome Study Outpatients Participant Pathway Analysis Pathway interactions Patient risk Patients Peripheral Nervous System Diseases Protocols documentation Provider Quality of life Recording of previous events Reporting Research Risk Risk Factors Risk Management Role Sampling Serotonin Severities Time Toxic effect Toxicity due to chemotherapy Translating Treatment-related toxicity Update Variant base cancer care cancer therapy care costs care delivery chemotherapy clinical care clinical predictors clinical risk experience gastrointestinal genetic risk factor genetic testing genetic variant genome wide association study gut microbiome hangover health care service utilization high risk improved innovation insight microbial microbiome microbiome analysis microbiome composition novel strategies prediction algorithm prevent randomized trial recruit risk prediction sample collection sex side effect stool sample treatment risk

项目摘要

PROJECT SUMMARY Moderate to severe nausea is reported by up to 38% of cancer patients receiving moderately- or highly- emetogenic chemotherapy despite international antiemetic guidelines. Chemotherapy-induced nausea is associated with worse quality of life, increased healthcare utilization, and greater costs of care. Previous research has identified clinical and personal risk factors for nausea (e.g., disease stage, emetogenicity of chemotherapy, age, sex, history of motion sickness, anxiety, alcohol use), but risk-prediction algorithms based on these factors demonstrate room for improvement. Recent methodologies for studying the human genome and microbiome enable us for the first time to develop a more comprehensive understanding of the pathophysiology of chemotherapy-induced nausea and develop better algorithms. The goal of the current study is to improve understanding of risk of chemotherapy-induced nausea through integrated examination of genetic and microbiome variables with well-established clinical and personal risk factors. We will conduct the first GWAS of chemotherapy-induced nausea, then use pathway analysis to place results into functional context. Significant variants will be incorporated with clinical and personal factors into a clinical risk prediction algorithm. This study will also be among the first to examine the association of the gut microbiome with chemotherapy-induced nausea. Importantly, this study is one of the first to truly integrate biological, clinical, and patient-reported data to predict risk of treatment toxicity. This groundbreaking study will be a model for similar efforts in other side effects of chemotherapy such as cognitive impairment, fatigue, and peripheral neuropathy. Updated risk algorithms from the current study will be made publicly available and will inform a future randomized trial of risk-based antiemetic cancer care delivery. Positive results will spur integration of the risk algorithms into the electronic medical record with provider alerts to identify patients at risk of chemotherapy-induced nausea. Microbiome analyses conducted in the first two years of the study will provide rapid knowledge about its contributions to chemotherapy-induced nausea. Positive results will generate additional studies to determine whether microbial manipulation can prevent chemotherapy-induced nausea. Microbiome data are particularly exciting because they focus on an entirely new mechanism in chemotherapy-related toxicity. In summary, this rigorous, comprehensive study provides an integrated new approach to chemotherapy-induced nausea that is expected to significantly advance our understanding of pathophysiology and risk of this important clinical problem.

项目概要据报道，接受中度或高度恶心治疗的癌症患者中，高达 38% 的人会出现中度至重度恶心。尽管有国际止吐指南，但仍进行致吐化疗。化疗引起的恶心是与较差的生活质量、增加的医疗保健利用率和更高的护理成本相关。以前的研究已确定恶心的临床和个人危险因素（例如疾病阶段、呕吐物的致吐性）化疗、年龄、性别、晕动病史、焦虑、饮酒），但基于风险预测算法这些因素都表明有改进的空间。研究人类基因组的最新方法和微生物组使我们第一次能够更全面地了解化疗引起的恶心的病理生理学并开发更好的算法。当前的目标研究旨在通过综合检查来提高对化疗引起恶心风险的了解遗传和微生物组变量以及明确的临床和个人风险因素。我们将进行首先对化疗引起的恶心进行 GWAS，然后使用路径分析将结果放入功能分析中语境。显着变异将与临床和个人因素结合到临床风险预测中算法。这项研究也将是第一个研究肠道微生物组与化疗引起的恶心。重要的是，这项研究是第一个真正整合生物、临床和患者报告的数据来预测治疗毒性的风险。这项开创性的研究将成为治疗化疗其他副作用（如认知障碍、疲劳和周围神经病变。当前研究的更新风险算法将公开发布将为未来基于风险的止吐癌症护理服务的随机试验提供信息。积极的结果将促进将风险算法集成到电子病历中，并通过提供者警报来识别患者有化疗引起恶心的风险。研究头两年进行的微生物组分析将提供有关其对化疗引起的恶心的贡献的快速知识。积极的结果将开展更多研究以确定微生物操作是否可以预防化疗引起的恶心。微生物组数据特别令人兴奋，因为它们关注的是一种全新的机制化疗相关的毒性。总之，这项严谨、全面的研究提供了一个综合的新方法治疗化疗引起的恶心的方法有望显着增进我们对化疗引起的恶心的理解这一重要临床问题的病理生理学和风险。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Living with Metastatic Cancer: A Roadmap for Future Research.

DOI：
10.3390/cancers12123684
发表时间：
2020-12-08
期刊：
Cancers
影响因子：
5.2
作者：
Tometich DB;Hyland KA;Soliman H;Jim HSL;Oswald L
通讯作者：
Oswald L

Metagenomics and chemotherapy-induced nausea: A roadmap for future research.

DOI：
10.1002/cncr.33892
发表时间：
2022-02-01
期刊：
Cancer
影响因子：
6.2
作者：
Crowder SL;Hoogland AI;Welniak TL;LaFranchise EA;Carpenter KM;Li D;Rotroff DM;Mariam A;Pierce CM;Fischer SM;Kinney AY;Dong-Binh Tran T;Rastegari F;Berry DL;Extermann M;Kim RD;Tometich DB;Figueiredo JC;Muzaffar J;Bari S;Turner K;Weinstock GM;Jim HSL
通讯作者：
Jim HSL