Understanding the path to diagnosis and clinical presentation of patients with PIK3CA-related overgrowth spectrum (PROS) through an innovative patient-centered data platform.
Authors: Adams Denise , Pace Nelson D. , Rego Shannon , Wang Steven , Ankrah Nii , Turner Stuart , Paul Mary Lisha , Navid Fariba 
Published: June 2022

e18707

Background: PROS is a group of rare disorders driven by activating mutations in PIK3CA. Overactivation of the PI3K pathway, which regulates growth and proliferation, results in asymmetric malformations/overgrowths. Localized interventions are often not curative and no medical therapy for PROS is approved; however, mTOR inhibitors (ie sirolimus) are used off-label with modest success. Using a patient (pt)-focused approach, we seek to better understand the current path to diagnosis (dx), course of disease, interventions, and pt outcomes to optimize future therapies. Methods: Pts treated in the US are being actively recruited via interactions with pt advocacy groups, pt communities, social media, and allstripes.com. Following research and HIPAA authorization from each pt/guardian, AllStripes’ proprietary real-world evidence (RWE) platform collects pt medical records into a master medical record from which study data are abstracted. All activities are covered under AllStripes’ IRB-approved protocol. To enroll in the PROS cohort, pts must have a confirmed PROS dx via PIK3CA genetic testing. Data completeness and nomenclature are dependent on physician documentation. Results: To date 14 pts (7 female, 7 male) have enrolled; median age at enrollment was 10.5 y (range, 1-38). Of the 14 pts, 71.4% of pts (n = 10) had congenital onset. PIK3CA genetic testing was primarily (n = 12, 85.7%) completed as a part of a multigene panel. The most frequent specialties involved in dx were medical genetics (n = 4, 28.6%) and pediatric heme-oncology (n = 3, 21.4%). Clinical presentation commonly included vascular malformations (n = 8, 57.1%). Most pts were diagnosed with CLOVES (n = 12, 85.7%). Seven pts (50.0%) had documented lesions at dx, median of 2 (range, 1-13) lesions per pt, increasing after dx to 3 (range, 1-14). All pts reported PROS-related complications; 50.0% (n = 7) required hospitalization/ER visit. Musculoskeletal, neurological, and gastrointestinal related complications were each reported by ≥50% of pts. All pts required ≥1 surgery; ≥50% of pts had diagnostic, debulking, vascular, or other procedures. Median number of surgeries per pt was 7 (range, 1-28), corresponding to a median of 0.76 surgeries per pt per year. Eight pts (57.1%) received PROS related medications: 6 (42.9%) received alpelisib, 5 (35.7%) received sirolimus. Conclusions: While each pt is unique, similarities in the path to dx (eg, specialties involved) and disease history (eg, clinical presentation, symptoms experienced) exist. RWE abstracted from medical records rapidly provides data in an otherwise limited field, helping to address key questions. Preliminary results highlight the burden of PROS and the reliance on repetitive surgical interventions for management, suggesting there remains a high unmet medical need for effective therapeutic strategies.