Nygård Lotte, Vogelius Ivan Richter, Kofoed Klaus F, Bentzen Søren, Specht Lena
Department of Oncology, Section of Radiotherapy, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Faculty of Health and Medical Sciences, Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Hematol Oncol. 2025 Sep;43(5):e70134. doi: 10.1002/hon.70134.
Late cardiac toxicity after radiation therapy and/or systemic therapy with anthracyclines for lymphomas is a serious concern. To estimate the risks with different treatment combinations, reliable estimates of the dose-response relationships are needed. We performed a literature-based regression analysis of long-term cardiac events after lymphoma treatment. The objective was to identify dose-response relationships for anthracycline and radiotherapy regarding congestive heart failure (CHF), ischemic heart disease (IHD), and valvular heart disease (VHD). We included papers published January 2000-December 2022 with data on long term cardiac outcomes in lymphoma patients, radiation doses to the heart, and anthracycline doses. Papers without dose/response information were excluded. We identified six eligible papers including 22,916 patients. The excess relative risk (ERR) of CHF for anthracyclines per 100 mg/m2 (corresponding to 2 cycles of ABVD or CHOP chemotherapy) was 92% (CI: 74%-101%), and for radiotherapy per Gray (Gy) of mean heart dose it was 6.1% (CI: 4.4%-7.6%). Corresponding numbers for the other endpoints were: IHD: No effect of anthracyclines, ERR = 4.4%/Gy (CI: 2.7%-6.1%) and VHD: ERR = 25%/100 mg/m2 (CI: 13%-37%) and ERR = 10%/Gy (CI: 6%-13%). Data agree with a linear no threshold dose-response relationship for related endpoints, that is, there are no "safe" lower doses of either anthracyclines or radiotherapy. Late cardiac toxicity risks for all three endpoints can be assessed in each patient by a combined estimate from the cumulative doses of anthracyclines and radiation to the heart. This estimate can guide future treatment allocation in lymphoma patients.
放射治疗和/或使用蒽环类药物进行全身治疗后，淋巴瘤患者出现的晚期心脏毒性是一个严重问题。为了评估不同治疗组合的风险，需要对剂量反应关系进行可靠估计。我们对淋巴瘤治疗后的长期心脏事件进行了基于文献的回归分析。目的是确定蒽环类药物和放射治疗在充血性心力衰竭（CHF）、缺血性心脏病（IHD）和瓣膜性心脏病（VHD）方面的剂量反应关系。我们纳入了2000年1月至2022年12月发表的有关淋巴瘤患者长期心脏结局、心脏放射剂量和蒽环类药物剂量的数据。没有剂量/反应信息的论文被排除。我们确定了6篇符合条件的论文，共涉及22916例患者。每100mg/m²蒽环类药物（相当于2个周期的ABVD或CHOP化疗）导致CHF的超额相对风险（ERR）为92%（CI：74%-101%），平均心脏剂量每格雷（Gy）放射治疗导致CHF的ERR为6.1%（CI：4.4%-7.6%）。其他终点的相应数字为：IHD：蒽环类药物无影响，ERR = 4.4%/Gy（CI：2.7%-6.1%）；VHD：ERR = 25%/100mg/m²（CI：13%-37%），ERR = 10%/Gy（CI：6%-13%）。数据表明相关终点存在线性无阈值剂量反应关系，即蒽环类药物或放射治疗不存在“安全”的低剂量。通过对心脏蒽环类药物累积剂量和放射剂量的综合估计，可以评估每位患者所有三个终点的晚期心脏毒性风险。这一估计可为淋巴瘤患者未来的治疗分配提供指导。
