Management Landscape

Current management approaches are limited and may not address the underlying cause of disease

To date, there are no approved therapies for PROS (PIK3CA-Related Overgrowth Spectrum) that aim to affect its root cause: PIK3CA mutation.

 

 

Surgical and radiologic embolization procedures are currently the most common approaches to managing PROS. These procedures, however, may be unsuitable for some patients based on the risk-benefit profile.1,2

 

Nonetheless, surgery is common in childhood. Patients, however, may experience recurrence following surgery, and repeat surgeries are frequently required. In one study of 35 patients (median age, 7 years), 83% had undergone surgery, with more than half requiring multiple surgeries.3

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Surgical and radiologic embolization procedures are currently the most common approaches to managing PROS. These procedures, however, may be unsuitable for some patients based on the risk-benefit profile.1,2

 

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Nonetheless, surgery is common in childhood. Patients, however, may experience recurrence following surgery, and repeat surgeries are frequently required. In one study of 35 patients (median age, 7 years), 83% had undergone surgery, with more than half requiring multiple surgeries.3

 

 

PROS management may require continued assessment of various symptoms to assess the progression of symptoms and overgrowths.4

PROS management may require continued assessment of various symptoms to assess the progression of symptoms and overgrowths.4

 

 

Patients may temporarily manage their vascular issues, such as bleeding, venous insufficiency, and lymphedema, with applied pressure and the raising of limbs to manage inflammation and swelling.2

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Patients may temporarily manage their vascular issues, such as bleeding, venous insufficiency, and lymphedema, with applied pressure and the raising of limbs to manage inflammation and swelling.2

 

There is a need for treatment options that diminish overgrowth, reduce symptoms, and improve quality of life.5-7

Due to the heterogenous nature of PROS, patients may present with diverse manifestations and require different medical intervention that is focused on addressing symptoms. As a result, multiple specialists may be involved in a patient’s care.8

 

Partners in PROS Flashcard

Download the Partners in PROS flashcard to learn about specialists who may help support your patients with PROS at every step of their journey.

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Investigational approaches look to address the root cause of PROS

 

The potential for PI3K inhibition to affect the root cause of PROS provides a rationale for research into this therapeutic approach. To learn more about how PIK3CA mutations are at the root of PROS, watch the Mechanism of Disease video.

In preclinical murine models of PIK3CA mutation-induced vascular malformations, PI3K inhibition reduced vascular malformation volume, reduced proliferation, and increased apoptosis. However, the clinical significance has not been established. Ongoing clinical research is clarifying the potential role of PI3K inhibition for patients across the spectrum of PROS disorders.6

 

References:
  1. Bertino F, Braithwaite KA, Hawkins CM, et al. Congenital limb overgrowth syndromes associated with vascular anomalies. Radiographics. 2019;39(2):491-515.
  2. Bessis D, Vernhet H, Bigorre M, Quéré I, Rössler J. JAMA Dermatol. 2016;152(9):1058-1059.
  3. Keppler-Noreuil KM, Sapp JC, Lindhurst MJ, et al. Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum. Am J Med Genet A. 2014;164A(7):1713-1733.
  4. Keppler-Noreuil KM, Rios JJ, Parker VER, et al. PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. Am J Med Genet A. 2015;167A(2):287-295.
  5. Harvey JA, Nguyen H, Anderson KR, et al. Pain, psychiatric comorbidities, and psychosocial stressors associated with Klippel-Trenaunay syndrome. J Am Acad Dermatol. 2018;79(5):899-903.
  6. Castel P, Carmona FJ, Grego-Bessa J, et al. Somatic PIK3CA mutations as a driver of sporadic venous malformations. Sci Transl Med. 2016;8(332):1-10.
  7. Driscoll DJ, Gloviczki P. Combined slow-flow vascular malformation of the lower limb: Klippel-Trenaunay syndrome. In: Mulliken JB, Burrows PE, Fishman SJ, eds. Mulliken and Young's Vascular Anomalies: Hemangiomas and Malformations. 2nd ed. New York, NY: Oxford University Press; 2013:1027-1040.
  8. Kang HC, Baek ST, Song S, Gleeson JG. Clinical and genetic aspects of the segmental overgrowth spectrum due to somatic mutations in PIK3CA. J Pediatr. 2015;167(5):957-962.