RAND/UCLA Modified Delphi Panel on the Severity, Testing, and Medical Management of PIK3CA-Related Spectrum Disorders (PROS)

Abstract

Objective(s):. PIK3CA-related overgrowth spectrum (PROS) is a group of disorders caused by somatic variants in the PIK3CA gene. We aimed to update recommendations on the severity classification, testing, and medical management of patients with PROS. Methods:. Using validated consensus methodology, we convened a 13-member panel in 2020 and reviewed current evidence on how to diagnose and treat PROS. The panel was asked to rate the level of disease severity, and the appropriateness of whether to test for a mutation and medical therapy in 217 patient scenarios before a virtual meeting. Panelists discussed areas of disagreement and completed ratings following the meeting. Results:. The panel developed clinical presentations and endorsed the disease severity framework defined by functional impairment, a reduction in quality of life, and risk of death. Panelists agreed it is appropriate to test for a PIK3CA gene variant in every moderately/severely affected patient. Panelists agreed it may be appropriate to consider an mammalian (mechanistic) target of rapamycin inhibitor in some severely affected patients and some moderately affected patients with progressive disease. Although clinical trials have only recently begun and the evidence remains limited, panelists also agreed it may be appropriate to consider treatment with phosphoinositide 3-kinase/serine/threonine protein kinase inhibitors in severely affected patients with a confirmed PIK3CA variant or without a confirmed variant but with progressive disease. Conclusion:. These recommendations represent the consensus of experts informed by published literature and experience. Future research should validate this guidance using clinical data. Once validated, we hope these recommendations will improve outcomes for patients with PROS.