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Cancer Therapy-Related Cardiac Dysfunction in Patients Treated with a Combination of an Immune Checkpoint Inhibitor and Doxorubicin

Authors
 Seon-Hwa Lee  ;  Iksung Cho  ;  Seng-Chan You  ;  Min-Jae Cha  ;  Jee-Suk Chang  ;  William D Kim  ;  Kyu-Yong Go  ;  Dae-Young Kim  ;  Jiwon Seo  ;  Chi-Young Shim  ;  Geu-Ru Hong  ;  Seok-Min Kang  ;  Jong-Won Ha  ;  Sun-Young Rha  ;  Hyo-Song Kim 
Citation
 CANCERS, Vol.14(9) : 2320, 2022-05 
Journal Title
CANCERS
Issue Date
2022-05
Keywords
cancer therapy-related cardiac dysfunction ; doxorubicin ; immune checkpoint inhibitor ; sarcoma
Abstract
Backgrounds: There are scarce data on whether immune checkpoint inhibitors (ICIs) increase the risk of cardiac dysfunction when used with cardiotoxic agents. Thus, we evaluated cardiac dysfunction in patients with sarcoma receiving doxorubicin with or without ICI using echocardiography and left ventricular global longitudinal strain (LVGLS).

Methods: A total of 95 patients were included in this study. Echocardiography and LVGLS were evaluated at baseline and follow-up (at 3 and 6 months of chemotherapy) and compared with the doxorubicin (Dox; n = 73) and concomitant ICI with doxorubicin (Dox-ICI; n = 22) groups. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a left ventricular ejection fraction (LVEF) drop of >10% and LVEF of <50% (definite CTRCD), LVEF drop of >10%, LVEF of ≥50%, and LVGLS relative reduction of >15% (probable CTRCD) at six months.

Results: There were no significant differences in age, cumulative dose of doxorubicin, and cardiovascular risk factors between the two groups. At baseline, the LVEF was similar in the Dox and Dox-ICI groups (p = 0.493). In the Dox group, LVEF decreased to 59 ± 6% (Δ -7 ± 1.3%, p < 0.001) and LVGLS decreased from -17.3 ± 3.2% to -15.4 ± 3.2% (Δ -10.1 ± -1.9%, p < 0.001) at six months. In the Dox-ICI group, LVEF decreased to 55 ± 9% (Δ -9 ± 2.1%, p < 0.001), along with a significant decrease in LVGLS (from -18.6 ± 1.9% to -15.3 ± 3.6%, Δ -12.4 ± -2.4%, p < 0.001). Over a median follow-up of 192 days, there were no cases with clinical manifestations of fulminant myocarditis. In the Dox group, definite and probable CTRCD were observed in seven (10.1%) and five (7.4%) patients, respectively. In the Dox-ICI group, definite and probable CTRCD were observed in four (19%) and four (19%) patients, respectively. The total number of patients who developed CTRCD was significantly higher in the Dox-ICI group than in the Dox group (38.1% vs. 17.4%, p = 0.042). Serum troponin-T level was significantly higher in the Dox-ICI group than in the Dox group (53.3 vs. 27.5 pg/mL, p = 0.023).

Conclusions: ICIs may increase the risk of CTRCD when used with cardiotoxic agents. CTRCD should be monitored in patients treated with ICIs by cardiac biomarkers and echocardiography, including LV-GLS.
Files in This Item:
T202202042.pdf Download
DOI
10.3390/cancers14092320
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Min(강석민) ORCID logo https://orcid.org/0000-0001-9856-9227
Go, Kyu-Yong(고규용)
Kim, Dae-Young(김대영)
Kim, Hyo Song(김효송) ORCID logo https://orcid.org/0000-0002-0625-9828
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Seo, Jiwon(서지원) ORCID logo https://orcid.org/0000-0002-7641-3739
Shim, Chi Young(심지영) ORCID logo https://orcid.org/0000-0002-6136-0136
You, Seng Chan(유승찬) ORCID logo https://orcid.org/0000-0002-5052-6399
Lee, Seonhwa(이선화)
Chang, Jee Suk(장지석) ORCID logo https://orcid.org/0000-0001-7685-3382
Cho, Ik Sung(조익성)
Ha, Jong Won(하종원) ORCID logo https://orcid.org/0000-0002-8260-2958
Hong, Geu Ru(홍그루) ORCID logo https://orcid.org/0000-0003-4981-3304
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188629
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