Impact of Age at Diagnosis on Cardiotoxicity in High-Grade Osteosarcoma and Ewing Sarcoma Patients

Julius C Heemelaar; Frank M Speetjens; Ahmed A M Al Jaff; Richard E Evenhuis; Elissa A S Polomski; Bart J A Mertens; J Wouter Jukema; Hans Gelderblom; Michiel A J van de Sande; M Louisa Antoni

doi:10.1016/j.jaccao.2022.11.016

Impact of Age at Diagnosis on Cardiotoxicity in High-Grade Osteosarcoma and Ewing Sarcoma Patients

JACC CardioOncol. 2023 Feb 21;5(1):117-127. doi: 10.1016/j.jaccao.2022.11.016. eCollection 2023 Feb.

Affiliations

¹ Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
² Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
³ Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, the Netherlands.
⁴ Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.
⁵ Netherlands Heart Institute, Utrecht, the Netherlands.

Abstract

Background: Osteosarcoma and Ewing sarcoma patients face a significant risk of cardiotoxicity as defined by left ventricular dysfunction and heart failure (HF).

Objectives: This study sought to evaluate the association between age at sarcoma diagnosis and incident HF.

Methods: A retrospective cohort study was performed at the largest sarcoma center in the Netherlands among patients with an osteosarcoma or Ewing sarcoma. All patients were diagnosed and treated over a 36-year period (1982-2018) and followed until August 2021. Incident HF was adjudicated through the universal definition of heart failure. Determinants including age at diagnosis, doxorubicin dose, and cardiovascular risk factors were entered as fixed or time-dependent covariates into a cause-specific Cox model to assess their impact on incident HF.

Results: The study population consisted of 528 patients with a median age at diagnosis of 19 years (Q1-Q3: 15-30 years). Over a median follow-up time of 13.2 years (Q1-Q3: 12.5-14.9 years), 18 patients developed HF with an estimated cumulative incidence of 5.9% (95% CI: 2.8%-9.1%). In a multivariable model, age at diagnosis (HR: 1.23; 95% CI: 1.06-1.43) per 5-year increase, doxorubicin dose per 10-mg/m² increase (HR: 1.13; 95% CI: 1.03-1.24), and female sex (HR: 3.17; 95% CI: 1.11-9.10) were associated with HF.

Conclusions: In a large cohort of sarcoma patients, we found that patients diagnosed at an older age are more prone to develop HF.

Keywords: AYA, adolescent and young adult; CTX, cardiotoxicity; HF, heart failure; age; anthracyclines; cancer; cardio-oncology; heart failure; sarcoma.