Sirolimus Can Increase the Disappearance Rate of Cardiac Rhabdomyomas Associated with Tuberous Sclerosis: A Prospective Cohort and Self-Controlled Case Series Study

Abstract

Objectives To investigate the efficacy and safety of sirolimus in the treatment of cardiac rhabdomyomas associated with tuberous sclerosis complex and the specific benefits in different subgroups. Study designThe study was a prospective cohort and self-controlled case series study. Based on the prevalence of cardiac rhabdomyoma at different ages, we estimated the natural tumor disappearance rate. The subgroup analysis was done by Cox regression. Self-controlled case series method was used to assess the magnitude and duration of the drug effect. Adverse events were described.Results A total of 217 patients were included in the cohort study. Tumor disappearance rate was higher in younger age groups (hazard ratio = 0.99, P = .027) and female patients (hazard ratio = 2.08, P = .015). The age-adjusted incidence ratio showed that the disappearance of rhabdomyomas between 3 and 6 months was more related to sirolimus. Adverse events were observed 60 times in 42 of 217 children, mainly stomatitis.Conclusions Sirolimus can increase the disappearance rate of cardiac rhabdomyoma in the tuberous sclerosis complex population. Efficacy varies by sex and age: female and younger patients have higher tumor disappearance rate. Sirolimus is well-tolerated.

Patient With Dysphonia

“…8 Sirolimus, a mammalian target of rapamycin inhibitor, has been reported to be effective in treating cardiac rhabdomyomas associated with tuberous sclerosis and is well tolerated. 10 The present patient started taking sirolimus for graft-vs-host disease 10 weeks before the biopsy. During the biopsy, there was improvement in the vocal fold lesions, and a limited biopsy was performed.…”

“…Extralaryngeal extension requiring open hemilaryngectomy has also been reported . Sirolimus, a mammalian target of rapamycin inhibitor, has been reported to be effective in treating cardiac rhabdomyomas associated with tuberous sclerosis and is well tolerated . The present patient started taking sirolimus for graft-vs-host disease 10 weeks before the biopsy.…”

Safety Evaluation of Oral Sirolimus in the Treatment of Childhood Diseases: A Systematic Review

“…After a careful full-text review, 12 studies were eligible for the final data extraction and analysis. Finally, nine studies [ 22 , 23 , 24 , 25 , 29 , 30 , 31 , 32 , 33 ] were included in the analyses. The remaining three studies were excluded, including a prospective cohort study and two randomized controlled trials.…”

“…The characteristics of the subsumed studies are summarized in Table 1 . In total, the 9 studies consisted of 575 patients, and there were 7 prospective studies [ 22 , 23 , 24 , 29 , 30 , 31 , 32 ] and 2 randomized controlled trials [ 25 , 33 ]. Of these studies, four were related to tuberous sclerosis complex [ 25 , 31 , 32 , 35 ], two were related to lymphatic anomalies [ 31 , 32 ], two were related to vascular anomalies [ 22 , 25 ] and one was related to nephrotic syndrome [ 24 ].…”

Tuberous sclerosis complex with left ventricular noncompaction: a case description

“…Mutations in TSC 1 or TSC 2 genes cause overactivation of the mammalian target of rapamycin (mTOR), resulting in abnormal cell proliferation and cardiac rhabdomyoma formation. mTOR inhibitors such as sirolimus can treat cardiac rhabdomyoma associated with TSC (11). LVNC is a genetically heterogeneous disease caused by the cessation of normal myocardial compaction in the embryonic period.…”