Risk prediction and longitudinal assessment of cardiotoxicity and functional capacity trajectory in NSCLC patients

NSCLC 患者心脏毒性和功能能力轨迹的风险预测和纵向评估

• 批准号: 10181792
• 负责人: ZHONGXING LIAO
• 金额: $ 78.87万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10181792
• 关键词: 3-Dimensional; Accounting; Activities of Daily Living; Aftercare; Apoptosis; Biological Markers; Blood; Blood specimen; Brain natriuretic peptide; C-reactive protein; Cancer Patient; Cardiac; Cardiotoxicity; Cardiovascular system; Chemotherapy and/or radiation; Chest; Clinical; Complication; DNA Repair; Data; Data Set; Decision Making; Disease; Disease Outcome; Dose; Enrollment; Event; Functional disorder; Genes; Genetic; Genetic Markers; Genetic Predisposition to Disease; Goals; Gold; Heart; Heart Injuries; Immunotherapy; Incidence; Individual; Inflammation; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Mediating; Mission; Modality; Modeling; Multivariate Analysis; National Cancer Institute; National Heart, Lung, and Blood Institute; Non-Small-Cell Lung Carcinoma; Normal tissue morphology; Operative Surgical Procedures; Organ; Outcome; Patient Outcomes Assessments; Patient Selection; Patient risk; Patient-Focused Outcomes; Patients; Pattern; Performance; Pharmaceutical Preparations; Photons; Physicians; Population Study; Probability; Process; Prospective cohort; Prospective cohort study; Protons; Radiation; Radiation Dose Unit; Radiation therapy; Randomized; Registries; Reporting; Risk; Risk Factors; Selection for Treatments; Shapes; Single Nucleotide Polymorphism; Statistical Models; Structure; Techniques; Testing; Tissues; Toxic effect; Troponin T; Validation; Vascular calcification; base; cancer survival; cancer therapy; cancer type; cardiovascular injury; cardiovascular risk factor; chemoradiation; chemotherapy; clinical practice; clinical risk; cohort; comorbidity; coronary calcium scoring; demographics; fitness; heart damage; heart function; high risk; improved; individual patient; optimal treatments; patient population; personalized predictions; population based; predictive modeling; prevent; prospective; proton therapy; radiation risk; randomized trial; response; risk prediction; risk stratification; tool; treatment planning; trial comparing; tumor

Project Summary/Abstract Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, accounting for approximately 85% of all lung cancers, which is one of the deadliest types of cancers. Standard NSCLC treatments include surgery, immunotherapy, chemotherapy, and radiation therapy. Radiation therapy can be delivered by either photons or protons; however, both types of radiation therapy to the chest can result in cardiac injury. To date, no available clinical tool exists to guide physicians in choosing the best type of radiation therapy according to an individual’s risk for radiation-mediated cardiac injury. To plan radiation therapy, normal tissue complication probability (NTCP) models are commonly used and take into consideration differences in geometric shape or volumes between tumor and non-tumor tissue, as well as tissue dose constraints. However, these patient population-reliant models are based only on photon radiation therapy data (not proton), do not consider the differences in radiation vulnerability of organ substructures, and do not consider the individual NSCLC patient’s risk for a specific toxicity (e.g., cardiac toxicity). Hence, this proposal tests the hypothesis that chemoradiation- related cardiac toxicity can be minimized by dose optimization and individual pre-existing cardiovascular risk- stratification for choosing appropriate radiation modality. Pre-existing cardiovascular risk factors, such as individual genetic predisposition, cardiac injury blood biomarkers, and extent of vascular calcification will be correlated with chemoradiation-associated cardiac toxicity and overall survival (OS) in Aim 1. Data on pre- existing cardiovascular risk factors will be retrospectively collected from two prospective, randomized comparisons of photons vs. protons and from a registry trial, which included proton-treated patients not enrolled into the randomized trial. Associations between pre-existing cardiovascular events and radiation therapy- mediated cardiac events as well as OS will be used as parameters to generate a one-of-a-kind NTCP model (Aim 2). In Aim 3, a prospective cohort registration trial will be developed to longitudinally assess cardiac function, cardiac fitness, and model implementation. During model implementation, two maximally optimized radiation therapy plans for each enrolled patient will be developed: 1) using standard population-based dose constraints; and 2) using personalized dose constraints based on individual risk. A predefined NTCP goal will be set to evaluate both plans. If the personalized plan improves the NTCP goal by 15%, the patient will be treated using the personalized plan. The model performance will be continuously assessed and improved using the data accumulated from the trial. The long-term objectives of this proposed project are to minimize cardiovascular injury while optimizing NSCLC patient outcomes, based on individual patient risk to cardiac injury after concurrent chemoradiation therapy by multivariable model selection of radiation therapy modality and technique. Preventing cardiovascular injury in cancer patients so that individuals can live longer, and more fulfilling lives is in direct alignment with the mission of both the National Cancer Institute and the National Heart, Lung, and Blood Institute.

项目概要/摘要 非小细胞肺癌 (NSCLC) 是最常见的肺癌形式，约占肺癌的 85% 的肺癌是最致命的癌症类型之一，标准非小细胞肺癌治疗包括。 手术、免疫治疗、化疗和放射治疗均可通过其中任意一种进行。 光子或质子；然而，迄今为止，这两种类型的胸部放射治疗都会导致心脏损伤。 没有可用的临床工具来指导医生根据情况选择最佳的放射治疗类型 个人发生辐射介导的心脏损伤的风险，以计划放射治疗、正常组织并发症。 概率（NTCP）模型是常用的，并且考虑了几何形状或形状的差异 然而，肿瘤和非肿瘤组织之间的体积以及组织剂量受到限制。 人口相关模型仅基于光子放射治疗数据（而非质子），不考虑 器官亚结构的辐射易损性差异，并且不考虑个体 NSCLC 患者的 因此，该提案检验了放化疗的假设。 通过剂量优化和个体预先存在的心血管风险可以最大限度地减少相关的心脏毒性 分层以选择适当的放射方式。 个体遗传倾向、心脏损伤血液生物标志物和血管钙化程度将被 与目标 1 中放化疗相关的心脏毒性和总生存期 (OS) 相关。 现有的心血管危险因素将从两个前瞻性、随机 光子与质子的比较以及注册试验的比较，其中包括未入组的接受质子治疗的患者 纳入随机试验。先前存在的心血管事件与放射治疗之间的关联。 介导的心脏事件以及 OS 将用作参数来生成独一无二的 NTCP 模型 （目标 2）在目标 3 中，将开发一项前瞻性队列注册试验来纵向评估心脏功能， 心脏健康和模型实施 在模型实施期间，两个最大优化的辐射。 将为每位入组患者制定治疗计划：1）使用基于人群的标准剂量限制； 2) 根据个人风险使用个性化剂量限制，将设定预定义的 NTCP 目标。 评估这两个计划，如果个性化计划将 NTCP 目标提高 15%，则患者将接受治疗。 个性化计划将使用数据不断评估和改进。 该项目的长期目标是尽量减少心血管疾病。 根据并发治疗后个体患者心脏损伤的风险，优化 NSCLC 患者的预后 通过放射治疗方式和技术的多变量模型选择进行放化疗。 癌症患者的心血管损伤，使个人能够活得更长，生活更充实，这直接关系到 与国家癌症研究所和国家心肺血液研究所的使命保持一致。