Markers of Cardiotoxicity with Radiation Therapy in Breast Cancer

摘要 放射治疗(RT)是一种高效和广泛使用的治疗乳腺癌的方法，是最常见的 世界范围内的女性癌症。然而，RT具有心血管(CV)毒性的显著风险，限制了重要的 癌症控制和存活率方面的进展。有许多与简历效果相关的基本问题 现代质子和光子RT。心血管生物标记物和影像标记物的变化是否支持RT 假设质子疗法比光子疗法对心脏的毒性小？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是什么？我们能否使用生物和成像标记物来识别 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记物和 影像辅助研究对正在进行的放射治疗疗效比较(RadComp)的实用临床 乳腺癌患者随机接受质子和光子治疗的试验(PCORI PCS-1403-12804； NCT02603341)。我们建议的总体目标是确定CV的早期、亚临床测量 影像(目标1)和生物(目标2)标记物检测的损伤和功能障碍根据RT类型的不同而不同 (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(目标3)。为了实现这些目标，我们将建立一个纵向的前瞻性队列 来自3个登记人数最多的地点：纪念斯隆·凯特琳癌症中心的150名RadComp参与者的研究 (MSKCC)、宾夕法尼亚大学(Penn)和西北纪念医疗保健(NW)。我们的建议 阐述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辐射研究处。

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.