Markers of Cardiotoxicity with Radiation Therapy in Breast Cancer

摘要 放射治疗（RT）是一种非常有效和广泛使用的乳腺癌治疗方法， 全球女性癌症然而，RT具有显著的心血管（CV）毒性风险，限制了重要的治疗。 在癌症控制和生存方面的进展。有一些基本问题与CV效应有关， 现代质子和光子RT。RT治疗后CV生物标志物和成像标志物的变化是否支持 质子治疗比光子治疗心脏毒性小的假设？哪些RT剂量体积参数是 与这些标志物的变化最密切相关的？我们能不能用生物学和影像学标记 高CV风险亚组？为了解决这些问题，我们提出了一种时间敏感的生物标志物， 正在进行的放射治疗比较有效性（RadComp）实用临床的成像辅助研究 乳腺癌患者随机接受质子与光子治疗的试验（PCORIPCS-1403-12804; NCT02603341）。我们提案的总体目标是确定CV的早期亚临床指标 根据RT类型，通过成像（Aim 1）和生物学（Aim 2）标记检测的损伤和功能障碍不同 （质子与光子）;以及哪些RT心脏剂量-体积参数与 这些标志物的变化（目标3）。为了实现这些目标，我们将建立一个纵向前瞻性队列 来自3个最高招募中心的150名RadComp参与者的研究：纪念斯隆凯特琳癌症中心 （MSKCC），宾夕法尼亚大学（Penn）和西北纪念医疗保健（NW）。我们的建议 解决了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辐射研究分支。

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.