Department of Population Sciences, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Rd, Duarte, CA 91010, United States.
Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Rd, Duarte, CA 91010, United States.
Int J Cardiol. 2023 Jun 1;380:40-46. doi: 10.1016/j.ijcard.2023.03.040. Epub 2023 Mar 21.
Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). Emerging data suggest that these agents can result in clinically significant cardiotoxicity, compromising the care.
We conducted a prospective longitudinal study to evaluate the incidence of de novo cardiac dysfunction as assessed by echocardiography and blood biomarkers in mRCC patients receiving TKI with or without ICI followed at baseline, 3-month and 6-month. We recruited consecutive newly diagnosed mRCC patients treated at our institution between 2015 and 2018 as well as patients with localized RCC not treated with systemic therapies and healthy control (HC) subjects for comparison.
Twenty-eight patients were enrolled in the mRCC group (a mean age of 65.2 ± 7.5 years), 29 patients in the localized RCC group (63.6 ± 8.9 years), and 20 volunteers in the HC group (52.9 ± 9.6 years). At baseline, patients from all three groups had normal cardiac function as measured by left ventricular ejection fraction (LVEF), although patients with mRCC or localized RCC had significantly lower mean LVEF compared to HC (61.9%, 62.4%, and 68.1% respectively). Otherwise, there were no statistically significant changes in echocardiographic parameters or incidence of clinical heart failure from baseline to 6-months in patients with mRCC. Cardiac blood biomarkers including troponin I, brain natriuretic peptide, and galectin-3 remained stable over time.
Our findings suggest that contemporary treatment strategies of mRCC at this single institution are well tolerated without clinically meaningful overt declines in cardiac function over time. Further studies are warranted to include a larger number of patients to better assess the overall cardiovascular safety associated with contemporary treatments of mRCC.
酪氨酸激酶抑制剂(TKIs)和免疫检查点抑制剂(ICIs)彻底改变了转移性肾细胞癌(mRCC)的治疗方法。新出现的数据表明,这些药物可导致临床上显著的心脏毒性,从而影响治疗。
我们进行了一项前瞻性纵向研究,以评估接受 TKI 联合或不联合 ICI 治疗的 mRCC 患者在基线、3 个月和 6 个月时通过超声心动图和血液生物标志物评估新发心功能障碍的发生率。我们招募了 2015 年至 2018 年期间在我院接受治疗的新诊断为 mRCC 的连续患者以及未接受全身治疗的局限性 RCC 患者,并与健康对照组(HC)进行比较。
共纳入 28 例 mRCC 患者(平均年龄 65.2±7.5 岁)、29 例局限性 RCC 患者(63.6±8.9 岁)和 20 例 HC 志愿者(52.9±9.6 岁)。尽管 mRCC 或局限性 RCC 患者的平均 LVEF 明显低于 HC(分别为 61.9%、62.4%和 68.1%),但所有三组患者在基线时的左心室射血分数(LVEF)均正常。除此之外,mRCC 患者在 6 个月时,超声心动图参数或临床心力衰竭的发生率与基线相比没有统计学上的显著变化。心脏血液生物标志物,包括肌钙蛋白 I、脑利钠肽和半乳糖凝集素-3,随时间推移保持稳定。
我们的研究结果表明,在该单中心,mRCC 的当代治疗策略具有良好的耐受性,不会随时间推移导致心脏功能出现有临床意义的明显下降。需要进一步的研究来纳入更多的患者,以更好地评估与 mRCC 当代治疗相关的整体心血管安全性。