Frederika A. van Nimwegen, Michael Schaapveld, Michael Hauptmann, Karen Kooijman, Berthe M.P. Aleman, and Flora E. van Leeuwen, Netherlands Cancer Institute, Amsterdam; Michael Schaapveld, Netherlands Comprehensive Cancer Organization; Judith Roesink, University Medical Center Utrecht, Utrecht; Cècile P.M. Janus, Erasmus MC Cancer Institute, Rotterdam; Augustinus D.G. Krol, Leiden University Medical Center, Leiden; Richard van der Maazen, Radboud University Medical Center, Nijmegen, Netherlands; David J. Cutter, and Sarah C. Darby, University of Oxford; and David J. Cutter, Oxford University Hospitals NHS Trust, Oxford, United Kingdom.
J Clin Oncol. 2016 Jan 20;34(3):235-43. doi: 10.1200/JCO.2015.63.4444. Epub 2015 Nov 16.
Cardiovascular diseases are increasingly recognized as late effects of Hodgkin lymphoma (HL) treatment. The purpose of this study was to identify the risk factors for coronary heart disease (CHD) and to quantify the effects of radiation dose to the heart, chemotherapy, and other cardiovascular risk factors.
We conducted a nested case-control study in a cohort of 2,617 5-year HL survivors, treated between 1965 and 1995. Cases were patients diagnosed with CHD as their first cardiovascular event after HL. Detailed treatment information was collected from medical records of 325 cases and 1,204 matched controls. Radiation charts and simulation radiographs were used to estimate in-field heart volume and mean heart dose (MHD). A risk factor questionnaire was sent to patients still alive.
The median interval between HL and CHD was 19.0 years. Risk of CHD increased linearly with increasing MHD (excess relative risk [ERR]) per Gray, 7.4%; 95% CI, 3.3% to 14.8%). This results in a 2.5-fold increased risk of CHD for patients receiving a MHD of 20 Gy from mediastinal radiotherapy, compared with patients not treated with mediastinal radiotherapy. ERRs seemed to decrease with each tertile of age at treatment (ERR/Gy(<27.5years), 20.0%; ERR/Gy(27.5-36.4years), 8.8%; ERR/Gy(36.5-50.9years), 4.2%; P(interaction) = .149). Having ≥ 1 classic CHD risk factor (diabetes mellitus, hypertension, or hypercholesterolemia) independently increased CHD risk (rate ratio, 1.5; 95% CI, 1.1 to 2.1). A high level of physical activity was associated with decreased CHD risk (rate ratio, 0.5; 95% CI, 0.3 to 0.8).
The linear radiation dose-response relationship identified can be used to predict CHD risk for future HL patients and survivors. Appropriate early management of CHD risk factors and stimulation of physical activity may reduce CHD risk in HL survivors.
心血管疾病日益被认为是霍奇金淋巴瘤（HL）治疗的晚期效应。本研究旨在确定冠心病（CHD）的危险因素，并定量评估心脏辐射剂量、化疗和其他心血管危险因素的影响。
我们对 1965 年至 1995 年期间接受治疗的 2617 例 5 年 HL 幸存者队列进行了嵌套病例对照研究。病例为 HL 后首次心血管事件诊断为 CHD 的患者。从 325 例病例和 1204 例匹配对照的病历中收集详细的治疗信息。使用辐射图表和模拟射线照片来估计场内心脏体积和平均心脏剂量（MHD）。向仍存活的患者发送了一份危险因素调查问卷。
HL 与 CHD 的中位间隔时间为 19.0 年。CHD 的风险随每格雷增加的 MHD 呈线性增加（超额相对风险 [ERR]），为 7.4%；95%置信区间为 3.3%至 14.8%）。与未接受纵隔放疗的患者相比，接受纵隔放疗 MHD 为 20Gy 的患者 CHD 风险增加了 2.5 倍。ERR 似乎随治疗时年龄的每三分位降低（ERR/Gy（<27.5 岁），20.0%；ERR/Gy（27.5-36.4 岁），8.8%；ERR/Gy（36.5-50.9 岁），4.2%；P（交互）=0.149）。存在≥1 个经典 CHD 危险因素（糖尿病、高血压或高胆固醇血症）会独立增加 CHD 风险（比率比，1.5；95%置信区间，1.1 至 2.1）。高水平的身体活动与 CHD 风险降低相关（比率比，0.5；95%置信区间，0.3 至 0.8）。
确定的线性辐射剂量-反应关系可用于预测未来 HL 患者和幸存者的 CHD 风险。适当的早期 CHD 危险因素管理和身体活动刺激可能会降低 HL 幸存者的 CHD 风险。
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