Bernhard, Sarah MaikeSarah MaikeBernhardAdam, Luise LeonoreLuise LeonoreAdamAtef, HadyHadyAtefHäberli, DarioDarioHäberliBramer, Wichor MWichor MBramerMinder, BeatriceBeatriceMinder0000-0003-1345-2594Döring, YvonneYvonneDöringLaine Carmeli, Jessica EvelynJessica EvelynLaine CarmeliMuka, TaulantTaulantMukaRössler, Jochen KarlJochen KarlRössler0000-0003-4022-4917Baumgartner, IrisIrisBaumgartner2024-10-052024-10-052022-03https://boris-portal.unibe.ch/handle/20.500.12422/57083BACKGROUND PIK3CA-related overgrowth syndromes (PROS) include a variety of clinical presentations that are associated with hypertrophy of different parts of the body. AIM Perform a systematic literature review to assess the current treatment options and their efficacy and safety in PROS. METHODS A literature search was performed in EMBASE, MEDLINE (Ovid), Web of Science Core Collection, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and Google Scholar to retrieve publications on the treatment for hypertrophy in PROS and randomized controlled trials, cohort studies or case series including ≥10 patients reporting were included in the review. Titles, abstracts and full texts were assessed by two reviewers independently. The Risk of Bias (RoB) was assessed using the Newcastle Ottawa Scale. RESULTS 16 articles for the treatment of hypertrophy in PROS patients were included, 13 (81.3%) from clinical retrospective studies and 3 (13.7%) from prospective cohort studies. The ROB grade was low for 2, medium for 12 and high for 2 studies. 13 articles reported surgical treatment, while 3 reported pharmacological treatment using PIK3/mTOR pathway inhibitors in PROS patients. In 3 studies, PROS was defined by a mutation in the PIK3CA gene, while the other studies relied on a clinical definition of PROS. Surgical therapy was beneficial for a specific subgroup of PROS (macrodactyly), but little was reported concerning surgery and potential benefits in other PROS entities. Reported side effects in surgical therapy were mostly prolonged wound healing or scarring. PIK3/mTOR pathway inhibition was beneficial in patients with PROS reducing hypertrophy as well as systemic symptoms. Adverse effects reported included infection, changes in blood count, liver enzymes and metabolic measures. CONCLUSION Surgery is a locally limited treatment option in specific types of PROS. A promising treatment option in PROS is the pharmacological PIK3CA inhibition. However, the level of evidence on treatment of overgrowth in PROS patients is limited.enPhosphatidylinositol 3-Kinase Phosphoinositide-3 Kinase Inhibitors TOR Serine-Threonine Kinases000 - Computer science, knowledge & systems::020 - Library & information sciences600 - Technology::610 - Medicine & health300 - Social sciences, sociology & anthropology::360 - Social problems & social servicesarticle10.48350/1580083435867210.1016/j.jvsv.2021.07.008