Revisiting the role of angiotensin-converting enzyme inhibitors in preventing chemotherapy cancer related cardiac disease in paediatric malignant bone tumours patients

Children with malignant bone tumours (MBT), including osteosarcoma (OS) and Ewing sarcoma (ES), receive anthracycline-based chemotherapy, which poses a significant cardiotoxicity risk. While cardioprotective strategies such as ACE inhibitors (ACEIs) have been explored, their efficacy in paediatric oncology remains unclear. Integrating these strategies is for safeguarding cardiac health and enhancing long-term survivorship for MBT.

The aim of this trial to evaluate the cardioprotective role of ACEIs in preventing or mitigating chemotherapy-induced cardiotoxicity in paediatric MBT patients, aiming to support their incorporation into standard treatment protocols.

A prospective randomised clinical trial (RCT) included 111 newly diagnosed MBT patients (55 ES, 56 OS) were randomised to control or intervention arm, receiving prophylactic ACEIs from day one of chemotherapy. The primary endpoint was ≥10% reduction in left ventricular ejection fraction (LVEF) or ≥15% decrease in global longitudinal strain (GLS) within 12 months post-treatment. Secondary endpoints included death or hospitalisation due to cardiac events.

The study comprised 111 participants, with 61 controls and 50 interventions, balanced by tumour type and gender. Intervention arm had a higher median age at diagnosis (13.2 vs. 10.6 years) and larger body surface area (BSA) (1.45m² vs. 1.20m²). The intervention group demonstrated better outcomes, including lower EF reduction (50% vs. 67%), improved EF-based Event-Free Survival (EFS) with a longer median survival (13.80 vs. 7.82 months), and a higher 12-month survival probability (54% vs. 34%, P=0.03). Cumulative incidence analysis yielded a similar p-value (0.03). However, after adjustment for age and BSA the difference was not statistically significant (HR = 0.60, 95% CI: 0.36–1.00, P=0.051). GLS showed no significant differences in EFS and cumulative incidence, with 12-month survival probabilities of (54% vs. 47%) and incidence of (45.5% vs. 52.9%) in control and intervention arm, respectively. Results showed a potential benefit of the intervention in reducing EF-related cardiac events and improving EFS. Only one intervention patient required ICU admission for cardiogenic shock, with no cardiac life-threatening events in either group.

Anthracycline-induced cardiotoxicity remains a major concern in paediatric cancer treatment. While ACEIs have demonstrated potential benefits in reducing EF-related cardiac events and improving EFS, statistical significance was not achieved, aligning with adult studies. Further research should focus on identifying novel cardioprotective agents for paediatric oncology.