Early evaluation of subclinical cardiotoxicity in patients with lung cancer receiving immune checkpoint inhibitors by cardiovascular magnetic resonance: a prospective observational study

Jia Liu; Yukun Cao; Kuikui Zhu; Sheng Yao; Mei Yuan; Xiangchuang Kong; Xiaoming Liu; Yumin Li; Yue Cui; Xiaoyu Han; Xiaoyue Zhou; Rui Meng; Heshui Shi

doi:10.21037/qims-22-41

Early evaluation of subclinical cardiotoxicity in patients with lung cancer receiving immune checkpoint inhibitors by cardiovascular magnetic resonance: a prospective observational study

Quant Imaging Med Surg. 2022 Oct;12(10):4771-4785. doi: 10.21037/qims-22-41.

Authors

Jia Liu^{1

2}, Yukun Cao^{1

2}, Kuikui Zhu³, Sheng Yao⁴, Mei Yuan^{1

2}, Xiangchuang Kong^{1

2}, Xiaoming Liu^{1

2}, Yumin Li^{1

2}, Yue Cui^{1

2}, Xiaoyu Han^{1

2}, Xiaoyue Zhou⁵, Rui Meng^#³, Heshui Shi^#^{1

2}

Affiliations

¹ Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
³ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁵ MR Collaboration, Siemens Healthineers Ltd., Shanghai, China.

^# Contributed equally.

Abstract

Background: Few studies have focused on the subclinical cardiotoxicity of immune checkpoint inhibitors (ICIs) in cancer patients. This study aimed to evaluate the manifestations of subclinical cardiotoxicity of ICI therapy using cardiovascular magnetic resonance (CMR) and to explore whether CMR parameters can help predict cardiotoxicity at the early stage of ICI therapy.

Methods: A prospective, longitudinal study was conducted among patients with lung cancer. The patients were planned to undergo serial CMRs before (baseline), 3 weeks after (1st follow-up), and 3 months after (2nd follow-up) the initiation of ICI therapy, respectively. Patients with 3 CMRs were included in the analysis. Serial quantitative measurements based on CMR were compared using one-way repeated measures analysis of variance (RM-ANOVA). On the basis of cancer therapy-related cardiac dysfunction (CTRCD) observed at the second follow-up, patients were categorized into a CTRCD group and a non-CTRCD group. Baseline clinical and CMR parameters and the relative reduction of left ventricular global strain at the second follow-up was compared between the CTRCD group and the non-CTRCD group. Receiver operating characteristic (ROC) analysis was used to identify CTRCD that developed 3 months after ICI therapy.

Results: A total of 36 patients with 3 CMRs (60.7±9.2 years old, 77.8% male) were included in the analysis. Left ventricular-global radial strain (LV-GRS) decreased significantly at the second follow-up (37.9%±8.5% vs. 33.1%±1.0%; P=0.014), but left ventricular ejection fraction (LVEF) did not change significantly (51.5%±6.0% vs. 49.2%±6.5%; P>0.05). A total of 7 patients (19.4%) had developed CTRCD by the second follow-up. Baseline clinical and CMR parameters did not differ between the CTRCD group and the non-CTRCD group (P>0.05 for all). In the CTRCD group, the left ventricular-global circumferential strains (LV-GCSs) showed significant reductions at both the first and second follow-up (P=0.008 and 0.035, respectively), but the LVEF only showed a significant reduction at the second follow-up (P<0.001). The relative reduction of LV-GRS at the second follow-up was significantly higher in the CTRCD group than in the non-CTRCD group (29.8%±25.8% vs. 6.8%±20.4%; P=0.036) and was used to predict CTRCD developed at the 3-month timepoint after ICI therapy [area under the curve (AUC) =0.759; P=0.036].

Conclusions: In the early stage of ICI therapy, assessment of myocardial strain can be used to detect subclinical left ventricular systolic dysfunction in patients with lung cancer earlier than LVEF. The relative reduction of LV-GRS can be used to predict CTRCD 3 months after ICI therapy.

Keywords: Immune checkpoint inhibitor (ICI); cancer therapy-related cardiac dysfunction (CTRCD); cardiotoxicity; cardiovascular magnetic resonance (CMR); myocardial strain.