Markers of Cardiotoxicity with Radiation Therapy in Breast Cancer

乳腺癌放射治疗的心脏毒性标志物

基本信息

批准号：
10249141
负责人：
Justin Bekelman
金额：
$ 40.55万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-28 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10249141
关键词：
Address Affect Ancillary Study Anterior Biological Biological Markers Blood Vessels Breast Cancer Patient Breast Cancer Treatment Cancer Control Cancer Patient Cancer Survivor Cardiac Cardiomyopathies Cardiotoxicity Cardiovascular Physiology Cardiovascular system Clinical Cohort Studies Collaborations Coronary heart disease Data Development Disease Dose Drug toxicity Echocardiography Enrollment Event Exposure to Female Functional disorder Healthcare Heart Heart failure Image Injury Internal Mammary Lymph Node Left Ventricular Ejection Fraction Malignant Neoplasms Measures Medicine Memorial Sloan-Kettering Cancer Center Modernization Morbidity - disease rate National Heart, Lung, and Blood Institute Oncology Outcome PGF gene Parents Participant Pennsylvania Phenotype Photons Pragmatic clinical trial Prospective cohort study Proton Radiation Protons Quality of life Radiation Radiation Dose Unit Radiation Oncology Radiation therapy Radiobiology Randomized Research Research Priority Resources Risk Secondary to Site Stress Structure Subgroup Time Toxic effect Universities Vascular Diseases Vision Woman advanced breast cancer base cancer survival cancer therapy cardiovascular effects cardiovascular injury cardiovascular risk factor clinical care comorbidity comparative effectiveness coronary event curative treatments effective therapy imaging biomarker malignant breast neoplasm mortality multidisciplinary multimodality personalized strategies pro-brain natriuretic peptide (1-76)proton therapy radiation effect repository standard care symptom management

项目摘要

Abstract Radiation therapy (RT) is a highly effective and widely used treatment for breast cancer, the most common female cancer worldwide. However, RT carries a significant risk of cardiovascular (CV) toxicity, limiting important gains in cancer control and survival. There are a number of fundamental questions related to the CV effects of modern-day proton and photon RT. Do changes in CV biomarkers and imaging markers with RT support the hypothesis that proton therapy is less cardiotoxic than photon therapy? Which RT dose-volume parameters are most strongly associated with changes in these markers? Can we use biologic and imaging markers to identify high CV risk subgroups? In order to address these questions, we propose a time-sensitive biomarker and imaging ancillary study to the ongoing Radiotherapy Comparative Effectiveness (RadComp) pragmatic clinical trial of breast cancer patients randomized to proton versus photon therapy (PCORI PCS-1403-12804; NCT02603341). The overall objectives of our proposal are to determine how early, subclinical measures of CV injury and dysfunction as detected by imaging (Aim 1) and biologic (Aim 2) markers differ according to RT type (proton versus photon); and which RT cardiac dose-volume parameters are most strongly associated with changes in these markers (Aim 3). To accomplish these objectives, we will build a longitudinal prospective cohort study of 150 RadComp participants from the 3 highest enrolling sites: Memorial Sloan Kettering Cancer Center (MSKCC), the University of Pennsylvania (Penn), and Northwestern Memorial HealthCare (NW). Our proposal addresses a research priority within the NHLBI Strategic Vision, NCI Symptom Management and Quality of Life Steering Committee, and NCI Radiation Research Branch.

抽象的放射疗法（RT）是一种高效且广泛使用的乳腺癌治疗方法，是最常见的全球女性癌症。但是，RT具有心血管（CV）毒性的重大风险，限制了重要的癌症控制和生存的增长。有许多与简历效应有关的基本问题现代质子和光子RT。使用RT支持CV生物标志物和成像标记的更改假设质子疗法比光子疗法少的心毒性？哪个rt剂量 - 体积参数为与这些标记的变化最密切相关？我们可以使用生物学和成像标记来识别高CV风险亚组？为了解决这些问题，我们提出了一个时间敏感的生物标志物，对正在进行的放射疗法比较有效性（RADCOMP）实用临床的成像辅助研究乳腺癌患者与质子与光子疗法的随机试验（PCORI PCS-1403-12804； NCT02603341）。我们提案的总体目标是确定简历的早期，亚临床措施成像（AIM 1）和生物学（AIM 2）标记所检测到的损伤和功能障碍因RT类型而异（质子与光子）；以及哪些RT心脏剂量 - 体积参数与这些标记的变化（AIM 3）。为了实现这些目标，我们将建立一个纵向前瞻性队列研究来自3个最高入学地点的150名RADCOMP参与者：纪念Sloan Kettering Cancer Center （MSKCC），宾夕法尼亚大学（宾夕法尼亚大学）和西北纪念医疗保健（NW）。我们的建议解决NHLBI战略愿景，NCI症状管理和生活质量中的研究优先事项指导委员会和NCI辐射研究部。