Provider News

The New, First-Ever Nonsurgical Option for Children With PROS Disorders: A Q&A With Dr. Jonathan Perkins

October 5, 2022

Jonathan Perkins, DOJonathan Perkins, DO, is clinic chief of Vascular Anomalies at Seattle Children’s.

Q: What is PROS?

PROS is PIK3CA-related overgrowth spectrum disorders. It is a group of rare overgrowth disorders caused by mutations in the PIK3CA gene that can lead to the overgrowth of various tissues throughout the body, as well as abnormal lymph vessels or blood vessels. CLOVES and Klippel-Trénaunay syndrome are two of the more common PROS conditions.

Q: The FDA has approved alpelisib (Vijoice) for PROS disorders. Why is this significant?

Alpelisib provides the first-ever nonsurgical option for PROS patients. In the past, many children with PROS have required multiple high-risk surgeries. Some children have lesions and symptoms that cannot be treated with surgery.

Q: Isn’t alpelisib already in use?

It’s a common breast cancer drug for adults but was not approved for pediatric use for PIK3CA-related conditions by the FDA until April of this year.

Q: Will every child with PROS benefit from apelisib?

It is too early to tell if all PROS patients will benefit from targeted medical therapy with alpelisib.

Unfortunately, many children with PROS aren’t diagnosed, which leaves them and their families unaware of the risks or treatment options. We want to take this opportunity to remind providers that Seattle Children’s is a national leader in caring for kids with PROS disorders, and we are available to evaluate and diagnose kids with suspected PROS.

Q: How will alpelisib change treatment for PROS?

It’s too soon to say for sure. But we think the use of alpelisib will reduce the numbers of surgeries PROS patients undergo and that these surgeries will be less extensive and more effective.

Because most PROS disorders are diagnosed in childhood, we anticipate a sharp increase in alpelisib use in the coming months and years. We hired a new full-time genetic counselor this summer for that reason.  We remain committed to shared decision making, offering treatments to improve symptoms, improve quality of life and decrease long-term risks. We recognize that treatment can sometimes cause more pain and issues than letting the anomaly be. While treatment options for PROS remain limited and specialized, alpelisib provides our patients with another option to consider.

Q: Who needs to know about alpelisib?

Dermatologists, interventional radiologists, hematologists and surgeons — the providers who most frequently encounter patients with PROS disorders — will want to be aware that alpelisib is a new option for these patients. Since it’s not uncommon for PROS disorders to go undiagnosed, now is a good time to remind all providers to be on the lookout for PROS disorders when evaluating patients with vascular or overgrowth concerns.

Q: When should I suspect PROS and refer the child to Seattle Children’s for evaluation and diagnosis?

Children with suspected vascular malformations, such as capillary malformation, lymphatic malformation, venous malformation and arteriovenous malformation with or without overgrowth should be evaluated. Overgrowth may include asymmetry as well as limb length discrepancy.

Q: What else is on the horizon for PROS?

Seattle Children’s is at the forefront of a lot of the new research on complex pediatric vascular anomalies. Ongoing research efforts include identification of malformation specific cell-free DNA (the newest — and a much less invasive — form of genetic testing), single-cell analysis of malformation tissue and fluid samples and quantitative measurements of change from targeted medical therapies using 3-D imaging, MRI scans and functional outcome questionnaires. This ongoing work bolsters the targeted “precision” therapy clinics we already have underway.

Q: What should providers know about our VAN program?

Seattle Children’s is the right place for pediatric patients with vascular anomalies to be cared for; as one of the largest centers on the West Coast for patients with these conditions, we have the unique expertise to diagnose their condition properly and recommend the safest and most appropriate treatments. Our strong multidisciplinary team includes specialists from Vascular Anomalies, Otolaryngology, Dermatology, Hematology, Interventional Radiology, Neurology, Gynecology, GI, Orthopedics, Cardiology and hospitalists who see the babies in the fetal surgery center and NICU. Our multidisciplinary conference meets regularly to review our patients and recommend a care plan to families.

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