Treatment of Cardiac Rhabdomyomas with mTOR Inhibitors in Children with Tuberous Sclerosis Complex-A Systematic Review.

Monika Sugalska,Sergiusz Jóźwiak,Bożena Werner,Anna Tomik

doi:10.3390/ijerph18094907

Monika Sugalska, Sergiusz Jóźwiak + Show 2 more

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https://doi.org/10.3390/ijerph18094907

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Abstract

Background: Cardiac rhabdomyomas (CRs) are the earliest sign of tuberous sclerosis complex (TSC). Most of them spontaneously regress after birth. However, multiple and/or large tumors may result in heart failure or cardiac arrhythmia. Recently, the attempts to treat CRs with mTOR inhibitors (mTORi) have been undertaken. We reviewed the current data regarding the effectiveness and safety of mTORi in the treatment of CRs in children with TSC. Methods: The review was conducted according to the PRISMA guidelines. Medline, Embase, Cochrane library, and ClinicalTrial.gov databases were searched for original, full-text articles reporting the use of mTORi (everolimus or sirolimus) in the treatment of CRs in children with TSC. Results: Thirty articles describing 41 patients were identified (mostly case reports, no randomized or large cohort studies). Thirty-three children (80.5%) had symptomatic CRs and mTORi therapy resulted in clinical improvement in 30 of them (90.9%). CRs size reduction was reported in 95.1%. Some CRs regrew after mTORi withdrawal but usually without clinical symptoms recurrence. The observed side effects were mostly mild. Conclusions: mTORi may be considered as a temporary and safe treatment for symptomatic CRs in children with TSC, especially in high-risk or inoperable tumors. However, high-quality, randomized trials are still lacking.

Highlights

One child had a single Cardiac rhabdomyomas (CRs) (2.5%) and for eight children (19.5%) there was no data available considering the number of CRs
The largest or symptomatic CRs were mostly localized in ventricles and intraventricular septum (28 children, 63.3%)
Almost studies all included in this review reported significant CRs size reduction and clinical improvement under mechanistic target of rapamycin (mTOR) inhibitors (mTORi) therapy both in the everolimus and sirolimus group

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Only about 10% of cardiac tumors are malignant [1]. Cardiac rhabdomyomas (CRs) are the most common cardiac tumors in children [1]. CRs may occur as isolated lesions or be associated with tuberous sclerosis complex (TSC). TSC is a multiorgan genetic disease with an incidence rate of approximately 1:6000–1:13,000 live births [2]. The disease is caused by the mutation of TSC1 or TSC2 resulting in the overactivity of the mechanistic target of rapamycin (mTOR). Effect of mTORi on Clinical Symptoms Follow-Up Period after Withdrawal.

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