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: 10641877
• 负责人: ZHONGXING LIAO
• 金额: $ 76.42万
• 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/10641877
• 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; Categories; Chest; Clinical; Complication; DNA Repair; Data; Data Set; Decision Making; Disease; Disease Outcome; Dose; Event; Functional disorder; Genes; Genetic; Genetic Predisposition to Disease; Goals; 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; 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; participant enrollment; patient population; personalized risk prediction; 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.

项目摘要/摘要 非小细胞肺癌（NSCLC）是肺癌最普遍的形式，约为 在所有肺癌中，有85％是最致命的癌症之一。标准NSCLC治疗包括 手术，免疫疗法，化学疗法和放射治疗。放射疗法可以通过任何一个 照片或质子；但是，两种类型的放射治疗对胸部都可能导致心脏损伤。迄今为止， 根据 个体辐射介导的心脏损伤的风险。为了计划放射治疗，正常组织并发症 通常使用概率（NTCP）模型，并考虑到几何形状或 肿瘤和非肿瘤组织之间的体积以及组织剂量的约束。但是，这些患者 人口依赖的模型仅基于光子放射疗法数据（不是质子），不要考虑 器官子结构的辐射脆弱性差异，并且不考虑单个NSCLC患者 特定毒性的风险（例如心脏毒性）。因此，该提案检验了化学放疗的假设 相关心脏毒性可以通过优化剂量优化和个体现有的心血管风险 - 选择适当的射击方式的分层。现有的心血管危险因素，例如 个体遗传易感性，心脏损伤血液生物标志物和血管钙化程度将是 与AIM 1中的化学放疗相关性心脏毒性和总生存率（OS）相关。 现有的心血管危险因素将回顾性地从两个前瞻性，随机分析 照片与质子的比较和注册表试验，其中包括未入学的质子处理的患者 进入随机试验。预先存在的心血管事件与放射疗法之间的关联 - 介导的心脏事件和OS将用作生成一种独一无二的NTCP模型的参数 （目标2）。在AIM 3中，将制定一项前瞻性队列注册试验，以纵向评估心脏功能， 心脏健身和模型实施。在模型实施过程中，两个最大优化的辐射 将制定为每个入学的患者的治疗计划：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约束。预定义的NTCP目标将设置为 评估这两个计划。如果个性化计划将NTCP目标提高15％，则将使用 个性化计划。模型性能将通过数据连续评估和改进 从试验中积累。该拟议项目的长期目标是最大程度地减少心血管 受伤的同时优化NSCLC患者的结果，基于同时发生的个体患者对心脏损伤的风险 通过多变量模型选择放射治疗方式和技术的化学放疗治疗。预防 癌症患者的心血管损伤，使个人可以寿命更长，而更充实的生活正处于直接状态 与国家癌症研究所和国家心脏，肺和血液研究所的任务保持一致。

项目成果

Can We Mitigate Coronary Heart Disease Risk in Patients with Cancer?

• DOI: 10.1007/s11883-022-01035-5
• 发表时间: 2022-05-28
• 期刊: CURRENT ATHEROSCLEROSIS REPORTS
• 影响因子: 5.8
• 作者: Manohar, Hasitha;Potter, Adam S.;Palaskas, Nicolas L.
• 通讯作者: Palaskas, Nicolas L.

Correcting CT misregistration in data-driven gated (DDG) PET with PET self-gating and deformable image registration.

通过 PET 自门控和可变形图像配准，纠正数据驱动门控 (DDG) PET 中的 CT 重合失调。

• DOI: 10.1002/mp.16958
• 发表时间: 2024
• 期刊: Medical physics
• 影响因子: 3.8
• 作者: Sun,Peng;Thomas,MAllan;Luo,Dershan;Pan,Tinsu
• 通讯作者: Pan,Tinsu

Geometric and dosimetric accuracy of deformable image registration between average-intensity images for 4DCT-based adaptive radiotherapy for non-small cell lung cancer.

• DOI: 10.1002/acm2.13341
• 发表时间: 2021-08
• 期刊: Journal of applied clinical medical physics
• 影响因子: 2.1
• 作者: He Y;Cazoulat G;Wu C;Peterson C;McCulloch M;Anderson B;Pollard-Larkin J;Balter P;Liao Z;Mohan R;Brock K
• 通讯作者: Brock K