Academic Journal

Targeted treatment of severe vascular malformations harboring PIK3CA and TEK mutations with alpelisib is highly effective with limited toxicity

Bibliographic Details
Title: Targeted treatment of severe vascular malformations harboring PIK3CA and TEK mutations with alpelisib is highly effective with limited toxicity
Authors: Martin Sterba, Petra Pokorna, Renata Faberova, Blanka Pinkova, Jarmila Skotakova, Anna Seehofnerova, Jan Blatny, Lucia Janigova, Olga Koskova, Hana Palova, Michal Mahdal, Lukas Pazourek, Petr Jabandziev, Ondrej Slaby, Peter Mudry, Jaroslav Sterba
Source: Scientific Reports, Vol 13, Iss 1, Pp 1-9 (2023)
Subject Terms: Medicine, Science
Publisher Information: Nature Portfolio, 2023.
Publication Year: 2023
Collection: LCC:Medicine
LCC:Science
Description: Abstract This was a prospective cohort study of eighteen patients with large and debilitating vascular malformations with one or more major systemic complications. In all patients, we discovered activating alterations in either TEK or PIK3CA. Based on these findings, targeted treatment using the PI3K inhibitor alpelisib was started with regular check-ups, therapy duration varied from 6 to 31 months. In all patients, marked improvement in quality of life was observed. We observed radiological improvement in fourteen patients (two of them being on combination with either propranolol or sirolimus), stable disease in 2 patients. For 2 patients, an MRI scan was not available as they were shortly on treatment, however, a clinically visible response in size reduction or structure regression, together with pain relief was observed. In patients with elevated D-dimer levels before alpelisib administration, a major improvement was noted, suggesting its biomarker role. We observed overall very good tolerance of the treatment, documenting a single patient with grade 3 hyperglycemia. Patients with size reduction were offered local therapies wherever possible. Our report presents a promising approach for the treatment of VMs harboring different targetable TEK and PIK3CA gene mutations with a low toxicity profile and high efficacy.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-023-37468-4
Access URL: https://doaj.org/article/a577de5101bc4a5b9cfe353e1382fac2
Accession Number: edsdoj.577de5101bc4a5b9cfe353e1382fac2
ISSN: 20452322
DOI: 10.1038/s41598-023-37468-4
Database: Directory of Open Access Journals