Chemotherapy effect on myocardial fibrosis markers in patients with gynecologic cancer and low cardiovascular risk

Lu Ye; Dan-Qing Wang; Meng-Xi Yang; Qing-Li Li; Hong Luo; Xiao-Juan Lin; Ke-Min Li; Liang Song; Yu Ma; Hui-Qiong Huang; Lan Zhong; Lu Yang; Jian-Jun Zhang; Feng-Ming Gong; Hua-Yan Xu; Lin-Jun Xie; Ru-Tie Yin; Ying-Kun Guo

doi:10.3389/fonc.2023.1173838

Chemotherapy effect on myocardial fibrosis markers in patients with gynecologic cancer and low cardiovascular risk

Front Oncol. 2023 Aug 8:13:1173838. doi: 10.3389/fonc.2023.1173838. eCollection 2023.

Authors

Lu Ye¹, Dan-Qing Wang², Meng-Xi Yang³, Qing-Li Li², Hong Luo¹, Xiao-Juan Lin², Ke-Min Li², Liang Song², Yu Ma², Hui-Qiong Huang², Lan Zhong², Lu Yang², Jian-Jun Zhang², Feng-Ming Gong², Hua-Yan Xu⁴, Lin-Jun Xie⁴, Ru-Tie Yin², Ying-Kun Guo⁴

Affiliations

¹ Department of Ultrasound, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
² Department of Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
³ Department of Radiology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
⁴ Department of Radiology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.

Abstract

Background: Patients with gynecologic cancers experience side effects of chemotherapy cardiotoxicity. We aimed to quantify cardiac magnetic resonance (CMR) markers of myocardial fibrosis in patients with gynecologic cancer and low cardiovascular risk who undergo chemotherapy.

Methods: This study is part of a registered clinical research. CMR T1 mapping was performed in patients with gynecologic cancer and low cardiovascular risk undergoing chemotherapy. The results were compared with those of age-matched healthy control subjects.

Results: 68 patients (median age = 50 years) and 30 control subjects were included. The median number of chemotherapy cycles of patients was 9.0 (interquartile range [IQR] 3.3-17.0). Extracellular volume fraction (ECV) (27.2% ± 2.7% vs. 24.5% ± 1.7%, P < 0.001) and global longitudinal strain (-16.2% ± 2.8% vs. -17.4% ± 2.0%, P = 0.040) were higher in patients compared with controls. Patients with higher chemotherapy cycles (>6 cycles) (n=41) had significantly lower intracellular mass indexed (ICMi) compared with both patients with lower chemotherapy cycles (≤6 cycles) (n=27) (median 27.44 g/m² [IQR 24.03-31.15 g/m²] vs. median 34.30 g/m² [IQR 29.93-39.79 g/m²]; P = 0.002) and the control group (median 27.44 g/m² [IQR 24.03-31.15 g/m²] vs. median 32.79 g/m² [IQR 27.74-35.76 g/m²]; P = 0.002). Patients with two or more chemotherapy regimens had significantly lower ICMi compared with both patients with one chemotherapy regimen (27.45 ± 5.16 g/m² vs. 33.32 ± 6.42 g/m²; P < 0.001) and the control group (27.45 ± 5.16 g/m² vs. 33.02 ± 5.52 g/m²; P < 0.001). The number of chemotherapy cycles was associated with an increase in the ECV (Standard regression coefficient [β] = 0.383, P = 0.014) and a decrease in the ICMi (β = -0.349, P = 0.009).

Conclusion: Patients with gynecologic cancer and low cardiovascular risk who undergo chemotherapy have diffuse extracellular volume expansion, which is obvious with the increase of chemotherapy cycles. Myocyte loss may be part of the mechanism in patients with a higher chemotherapy load.

Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR-DDD-17013450.

Keywords: T1 mapping; cardiac magnetic resonance; cardiotoxicity; myocardial fibrosis; neoplasms.

Grants and funding

This work was supported by the National Natural Science Foundation of China [82120108015, 82071874 and 81971586]; the Sichuan Science and Technology Program [2020YFS0050, 2020YJ0029, 2020YFS0131, 2019YFS0430 and 19ZDYF] and the Fundamental Research Funds for the Central Universities [SCU2020D4132].