Glen Claire, Adam Sarah, McDowell Kirsty, Waterston Ashita, Tan Yun Yi, Petrie Mark C, Coats Caroline J, Lang Ninian N
School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom.
Queen Elizabeth University Hospital, National Health Service Greater Glasgow and Clyde, Glasgow, United Kingdom.
JACC CardioOncol. 2023 Jun 6;5(5):628-637. doi: 10.1016/j.jaccao.2023.04.004. eCollection 2023 Oct.
Rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors have revolutionized treatment for patients with BRAF-mutated melanoma. Although left ventricular systolic dysfunction associated with these therapies has been reported in clinical trials, the real-world incidence is poorly defined, as are risk factors for its development.
This study sought to characterize the incidence, time course, and risk factors for cancer therapy-related cardiac dysfunction (CTRCD) in patients with melanoma receiving BRAF and MEK inhibitors.
Patients with melanoma treated with BRAF and MEK inhibitors at a cancer hospital network between June 1, 2017, and June 30, 2020, were included retrospectively. CTRCD was defined as mild, moderate, or severe according to International Cardio-Oncology Society (ICOS) definitions. Baseline cardiotoxicity risk stratification was performed using the Heart Failure Association/ICOS tool.
Of the 63 patients included, 27% developed CTRCD (17% mild and 10% moderate). No patients developed severe CTRCD or symptomatic heart failure. CTRCD occurred most frequently in patients considered to be at "low" and "medium" baseline risk of cardiotoxicity (82%). The baseline left ventricular ejection fraction and global longitudinal strain were not different in patients who developed moderate CTRCD vs those who did not. Left ventricular internal diameters in diastole and systole were larger in patients who developed moderate CTRCD compared with those who did not (left ventricular internal diameter in diastole: 4.9 ± 0.6 cm vs 4.3 ± 0.6 cm; 0.023; left ventricular internal diameter in systole: 3.3 ± 0.4 cm vs 2.8 ± 0.5 cm; 0.039).
BRAF and MEK inhibitor-associated CTRCD is common. The utility of the Heart Failure Association/ICOS risk stratification tool appears limited in this group, and better risk prediction tools are needed. The long-term consequences of CTRCD, particularly mild CTRCD, warrant evaluation in larger prospective studies.
快速加速型纤维肉瘤B型（BRAF）和丝裂原活化细胞外信号调节激酶（MEK）抑制剂彻底改变了BRAF突变型黑色素瘤患者的治疗方式。尽管在临床试验中已报道了与这些疗法相关的左心室收缩功能障碍，但实际发生率尚不明确，其发生的危险因素也不清楚。
本研究旨在描述接受BRAF和MEK抑制剂治疗的黑色素瘤患者中癌症治疗相关心脏功能障碍（CTRCD）的发生率、时间进程和危险因素。
回顾性纳入2017年6月1日至2020年6月30日期间在一家癌症医院网络接受BRAF和MEK抑制剂治疗的黑色素瘤患者。根据国际心脏肿瘤学会（ICOS）的定义，CTRCD被定义为轻度、中度或重度。使用心力衰竭协会/ICOS工具进行基线心脏毒性风险分层。
在纳入的63例患者中，27%发生了CTRCD（17%为轻度，10%为中度）。没有患者发生严重CTRCD或有症状性心力衰竭。CTRCD最常发生在被认为心脏毒性基线风险为“低”和“中”的患者中（82%）。发生中度CTRCD的患者与未发生的患者相比，基线左心室射血分数和整体纵向应变无差异。发生中度CTRCD的患者与未发生的患者相比，舒张末期和收缩末期左心室内径更大（舒张末期左心室内径：4.9±0.6 cm对4.3±0.6 cm；P = 0.023；收缩末期左心室内径：3.3±0.4 cm对2.8±0.5 cm；P = 0.039）。
BRAF和MEK抑制剂相关的CTRCD很常见。心力衰竭协会/ICOS风险分层工具在该组中的效用似乎有限，需要更好的风险预测工具。CTRCD的长期后果，尤其是轻度CTRCD，值得在更大规模的前瞻性研究中进行评估。
