Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

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

M. Sterba, P. Pokorna, R. Faberova, B. Pinkova, J. Skotakova, A. Seehofnerova, J. Blatny, L. Janigova, O. Koskova, H. Palova, M. Mahdal, L. Pazourek, P. Jabandziev, O. Slaby, P. Mudry, J. Sterba

. 2023 ; 13 (1) : 10499. [pub] 20230628

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc23010979

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc23010979
003      
CZ-PrNML
005      
20230801132738.0
007      
ta
008      
230718s2023 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1038/s41598-023-37468-4 $2 doi
035    __
$a (PubMed)37380669
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Sterba, Martin $u Department of Paediatrics, Faculty of Medicine, University Hospital Brno, Masaryk University, Brno, Czech Republic $u Department of Paediatric Oncology, Faculty of Medicine, University Hospital Brno, Masaryk University, Cernopolni 212/9, 613 00, Brno, Czech Republic
245    10
$a Targeted treatment of severe vascular malformations harboring PIK3CA and TEK mutations with alpelisib is highly effective with limited toxicity / $c M. Sterba, P. Pokorna, R. Faberova, B. Pinkova, J. Skotakova, A. Seehofnerova, J. Blatny, L. Janigova, O. Koskova, H. Palova, M. Mahdal, L. Pazourek, P. Jabandziev, O. Slaby, P. Mudry, J. Sterba
520    9_
$a 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.
650    _2
$a lidé $7 D006801
650    12
$a fosfatidylinositol-3-kinasy $x genetika $7 D019869
650    _2
$a prospektivní studie $7 D011446
650    12
$a kvalita života $7 D011788
650    _2
$a fosfatidylinositol-3-kinasy třídy I $x genetika $7 D058534
650    _2
$a mutace $7 D009154
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Pokorna, Petra $u Department of Biology, Faculty of Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic
700    1_
$a Faberova, Renata $u Department of Paediatrics, Faculty of Medicine, University Hospital Brno, Masaryk University, Brno, Czech Republic
700    1_
$a Pinkova, Blanka $u Department of Paediatrics, Faculty of Medicine, University Hospital Brno, Masaryk University, Brno, Czech Republic
700    1_
$a Skotakova, Jarmila $u Department of Paediatric Radiology, Faculty of Medicine, University Hospital Brno, Masaryk University, Brno, Czech Republic
700    1_
$a Seehofnerova, Anna $u Department of Paediatric Radiology, Faculty of Medicine, University Hospital Brno, Masaryk University, Brno, Czech Republic
700    1_
$a Blatny, Jan $u Department of Paediatrics, Faculty of Medicine, University Hospital Brno, Masaryk University, Brno, Czech Republic
700    1_
$a Janigova, Lucia $u Department of Paediatric Oncology, Faculty of Medicine, University Hospital Brno, Masaryk University, Cernopolni 212/9, 613 00, Brno, Czech Republic
700    1_
$a Koskova, Olga $u Department of Paediatric Surgery, Orthopaedics and Traumatology, Faculty of Medicine, University Hospital Brno, Masaryk University, Brno, Czech Republic
700    1_
$a Palova, Hana $u Department of Biology, Faculty of Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic
700    1_
$a Mahdal, Michal $u 1st Department of Orthopaedics, Faculty of Medicine, St. Anne's University Hospital Brno, Masaryk University, Brno, Czech Republic
700    1_
$a Pazourek, Lukas $u 1st Department of Orthopaedics, Faculty of Medicine, St. Anne's University Hospital Brno, Masaryk University, Brno, Czech Republic
700    1_
$a Jabandziev, Petr $u Department of Paediatrics, Faculty of Medicine, University Hospital Brno, Masaryk University, Brno, Czech Republic $u Department of Biology, Faculty of Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic
700    1_
$a Slaby, Ondrej $u Department of Biology, Faculty of Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic
700    1_
$a Mudry, Peter $u Department of Paediatric Oncology, Faculty of Medicine, University Hospital Brno, Masaryk University, Cernopolni 212/9, 613 00, Brno, Czech Republic. mudry.peter@fnbrno.cz $u International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic. mudry.peter@fnbrno.cz $1 https://orcid.org/0000000334347937
700    1_
$a Sterba, Jaroslav $u Department of Paediatric Oncology, Faculty of Medicine, University Hospital Brno, Masaryk University, Cernopolni 212/9, 613 00, Brno, Czech Republic $u International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic
773    0_
$w MED00182195 $t Scientific reports $x 2045-2322 $g Roč. 13, č. 1 (2023), s. 10499
856    41
$u https://pubmed.ncbi.nlm.nih.gov/37380669 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20230718 $b ABA008
991    __
$a 20230801132734 $b ABA008
999    __
$a ok $b bmc $g 1963417 $s 1197244
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2023 $b 13 $c 1 $d 10499 $e 20230628 $i 2045-2322 $m Scientific reports $n Sci Rep $x MED00182195
LZP    __
$a Pubmed-20230718

Find record

Citation metrics

Archiving options