Individuals & Families

TSC Research Summaries: Heart

Prenatal diagnosis of a gigantic cardiac rhabdomyoma in Tuberous Sclerosis Complex a new therapeutic option with everolimus

Author(s): Elisabeth Mlczoch M.D., Andreas Hanslik M.D., Doris Luckner M.D., Erwin Kitzmüller M.D., Daniela Prayer M.D., Ina Michel-Behnke M.D.
Ultrasound Obstet Gynecol 2014 Jun 10 [Epub ahead of print]
DOI: 10.1002/uog.13434

What is the topic?

About 50% of tuberous sclerosis complex (TSC) patients are thought to have cardiac rhabdomyomas. These are non-cancerous tumors that grow in the heart. Rhabdomyomas mainly grow before birth, between the second and third trimesters, and slightly after birth. Most of the tumors then partially or completely regress (shrink) during the first year of life. This article describes a case of an infant diagnosed prenatally (before birth) with TSC and found to have a giant cardiac rhabdomyoma in her heart. The rhabdomyoma was in a position to severely impact the infant’s health, and required intervention after birth. Treatment with the drug everolimus (an mTOR inhibitor) was given and the tumor shrank significantly so that the child did not have to have the tumor surgically removed.  This is a case report of one infant with TSC.

What did the authors hope to learn?

The authors hoped that the medication would shrink the rhabdomyoma enough that the infant’s heart could function normally. They monitored the child for any adverse effects of the medication that would require treatment or stopping the medication. While several studies have been published proving the effectiveness of mTOR inhibitor medications such as sirolimus (rapamycin) and everolimus for treatment of brain tumors (SEGA), kidney tumors (angiomyolipomas), and facial tumors (angiofibromas), few have been conducted on rhabdomyomas. The authors hoped to demonstrate that everolimus was a reasonable alternative to surgery in infants whose rhabdomyomas require treatment.

What was the background of this case?

Monitoring began at 23 weeks of gestation (pregnancy), and the baby was delivered at 37 weeks of gestation. She had a giant rhabdomyoma tumor mass filling the majority of the right ventricle of her heart, and impairing the flow of blood. Some measures were taken to keep blood flowing, however she was expected to suffer heart failure without more aggressive treatment. The family was presented options for heart surgery or treatment with the mTOR inhibitor everolimus.

What was the treatment?

At three weeks of age, the infant began receiving the oral medication everolimus, as an off-label use of the drug. Her blood serum was monitored for everolimus levels, blood count, and electrolyte levels. The size of the large rhabdomyoma was monitored by echocardiogram. A few small rhabdomyomas, which were not considered a threat to the infant’s health, were followed as well.

What were the results of the treatment?

After three weeks of treatment, the large rhabdomyoma had gotten smaller, and by age three months the size had decreased dramatically. The treatment was considered so successful that the medication was stopped. However, two weeks after stopping medication the rhabdomyoma got significantly larger and medication was restarted. Again there was a rapid response to the drug and the rhabdomyoma shrunk. The researchers plan to continue treatment throughout the child’s first year of life. The only adverse side effect seen was hyponatremia (low blood sodium), which required continuous supplementing.

This article was submitted for publication before the child’s rhabdomyomas were known to be resolved, so she was still taking the medication at the time it was written. It is unknown how long treatment with everolimus is required in this case. The authors believe that treatment can eventually be stopped and the tumor will not regrow, because most rhabdomyomas regress with age.  However it is not yet known if this will happen. There currently are no established guidelines for this treatment.

What do the results mean for you?

Most rhabdomyomas seen in TSC children partially or completely regress during the first year of life.  Since they seldom cause problems, they are just monitored. For those that cause serious life-threatening complications, surgery is the standard treatment. However more treatment options are needed for children who are not good surgical candidates. This is one of the first reports of the use of everolimus specifically to treat infant cardiac rhabdomyomas, so it may serve as a guide to future physicians considering this off-label drug use. The success of the treatment in this child should prompt more research in this area.

This summary was written by Cristy Wade, MS, parent of child with TSC, and consumer reviewer for the Tuberous Sclerosis Complex Research Program (August 2014).