Cardiac rhabdomoyomas and TSC
Cardiac rhabdomyomas (CRs) are non-cancerous tumours in the heart. Both single and multiple CRs are a major diagnostic criteria for TSC, with the likelihood of TSC diagnosis varying depending on the number of CRs. Multiple CRs are associated with 95% risk of TSC diagnosis. A single CR is associated with TSC in 23–73% of cases.
Most CRs spontaneously regress after birth. In a small number of cases however multiple and/or large tumours may result in heart failure or cardiac arrhythmia. Until recently surgery or treatments with anti-arrhythmic drugs were the only therapies available to treat the small number of CRs that required intervention. In more recent times our understanding of the mTOR pathway in TSC and the development of mTOR inhibitor medicines, has offered further opportunities in the management of CRs. This review evaluated the data regarding the effectiveness and safety of mTOR inhibitors in the treatment of CRs in children with TSC.
How was the review conducted?
The review looked at clinical research publications that discussed CRs, TSC and mTOR inhibitors in children aged 0-18 with the aim of evaluating the size of CRs before and after treatment with mTOR inhibitors and any associated side effects. As CRs requiring treatment are not common, there were only 30 studies available which were able to be evaluated and in total these studies included just 41 children.
What did the review find?
The majority of the children included in this review had multiple CRs (78%) and most were treated in the neonatal period (70%) or infancy (19.5%). The types of mTOR inhibitors included either everolimus or sirolimus, but the doses used differed between the studies, making direct comparison between trials impossible.
Almost all the studies reported significant reduction in CRs and clinical improvement after treatment with mTOR inhibitors. However, the authors suggest caution in interpretating this significantly positive result due to the small number of children and lack of control groups in the trials, and also the fact that CRs have a natural tendency to spontaneously regress with age. The authors suggest that the reduction in the size of CRs was relatively quick after treatment with mTOR inhibitors and that it is reasonable to think that treatment accelerated this reduction, however larger scale studies are needed to support this finding.
In regard to side effects, most were mild and were easily managed and included changes in blood lipid levels, stomatitis (mouth ulcers) and infections.
Should mTOR inhibitors be used to treat CRs?
The authors conclude that although there is evidence for the effectiveness and safety of mTOR inhibitors in the treatment of CRs, currently, due to the lack of high-quality studies, the evidence is not sufficiently robust to unequivocally recommend this therapy in every patient. However, mTOR inhibitors may be considered as a temporary option for symptomatic CRs in children with TSC, especially when the risk of surgery is significant. It is hoped that further randomised control trials will provide more information on the effectiveness of mTOR inhibitors in the treatment of CRs in children with TSC.
Sugalska, M., Tomik, A., Jóźwiak, S., & Werner, B. (2021). Treatment of Cardiac Rhabdomyomas with mTOR Inhibitors in Children with Tuberous Sclerosis Complex-A Systematic Review. International journal of environmental research and public health, 18(9), 4907.
Full paper available at: https://doi.org/10.3390/ijerph18094907
This information is intended to provide some insights into recent TSC-related research. It is not intended to, and it should not, constitute medical or other advice. Readers are warned not to take any action without first seeking medical advice.