ArticleOrphanet journal of rare diseases2018
Sirolimus is efficacious in treatment for extensive and/or complex slow-flow vascular malformations: a monocentric prospective phase II study.
Article in Orphanet journal of rare diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05983159 (A Modular Open Label, Signal Seeking, Phase II Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations), which is not on this map. Cited by 87 papers, 9 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Modular Open Label, Signal Seeking, Phase II Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations (TARGET-VM)
Who cites it
87 citing papers in PubMed, 9 syntheses or guidelines pooled it, 226 citations in OpenAlex.
- Japanese clinical practice guidelines for vascular tumors, vascular malformations, lymphatic malformations, and lymphangiomatosis 2022.Japanese journal of radiology · 2026Guideline
- Japanese clinical practice guidelines for vascular tumors, vascular malformations, lymphatic malformations, and lymphangiomatosis 2022.Surgery today · 2026Guideline
- Japanese Clinical Practice Guidelines for Vascular Tumors, Vascular Malformations, Lymphatic Malformations, and Lymphangiomatosis 2022.The Journal of dermatology · 2026Guideline
- Assessing the effectiveness of measurement scales in evaluating the health-related quality of life in rare disease patients after treatment: a systematic review.Health and quality of life outcomes · 2024Pooled it
- Sirolimus for vascular anomalies in the first year of life: a systematic review.Journal of perinatology : official journal of the California Perinatal Association · 2024Pooled it
- Sirolimus treatment for paediatric head and neck lymphatic malformations: a systematic review.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2023Pooled it
- Efficacy of sirolimus in children with lymphatic malformations of the head and neck.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2022Pooled it
- Medical Adjuvants in the Treatment of Surgically Refractory Arteriovenous Malformations of the Head and Face: Case Report and Review of Literature.Cerebrovascular diseases (Basel, Switzerland) · 2021Pooled it
- Japanese clinical practice guidelines for vascular tumors, vascular malformations, lymphatic malformations, and Lymphangiomatosis 2022.Pediatrics international : official journal of the Japan Pediatric SocietyGuideline
- A phase 2 randomized, double-blind trial of ART-001, a selective PI3Kα inhibitor, for the treatment of slow-flow vascular malformations.Orphanet journal of rare diseases · 2025Trial
- Preliminary results of the European multicentric phase III trial regarding sirolimus in slow-flow vascular malformations.JCI insight · 2023Trial
- A randomized, placebo-controlled study to evaluate safety and pharmacokinetics of ART-001 with a novel oral pediatric formulation in healthy subjects.Clinical and translational science · 2023Trial
- Clinical differences in sirolimus treatment with low target levels between children and adults with vascular malformations - A nationwide trial.Clinical and translational science · 2023Trial
- Constitutively active PIK3CA mutations are expressed by lymphatic and vascular endothelial cells in capillary lymphatic venous malformation.Angiogenesis · 2020Trial
- Prenatal Use of Sirolimus in Fetal Therapy: Current Evidence, Clinical Applications, and Future Directions.Cureus · 2026Review
- Review
- Sirolimus Treatment for Complex Fetal and Neonatal Vascular Anomalies: Emerging Evidence and Safety Considerations.Journal of clinical medicine · 2026Review
- TIE2 links MEKK3-KLF2/4 and PI3K signaling in cerebral cavernous malformation.The Journal of experimental medicine · 2026Article
- Japanese Clinical Practice Guidelines for Vascular Tumors, Vascular Malformations, Lymphatic Malformations, and Lymphangiomatosis 2022.Journal of plastic and reconstructive surgery · 2026Review
- KRAS-dependent glycolytic reprogramming of endothelial cells in sporadic arteriovenous malformations.EMBO molecular medicine · 2026Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundExtensive and complex vascular malformations often cause chronic pain and severe functional restraint. Conventional treatments, such as surgery and/or sclerotherapy, are rarely curative, underscoring the great need for new therapeutic modalities. Recent preclinical and clinical data demonstrated that sirolimus could offset the progression of vascular malformations and significantly improve quality of life of patients through inhibition of the Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian Target of Rapamycin (mTOR) pathway. The purpose of this prospective study was to assess the efficacy and safety of this treatment in patients with extensive or complex slow-flow vascular malformations.
methodsSirolimus was administered orally on a continuous dosing schedule with pharmacokinetic-guided target serum concentration level of 10 to 15 ng/ml. Patients were seen every month for the first three months and subsequently every three months. The primary endpoints were safety and efficacy, based on clinical, biological and radiological evaluations, as well as a quality of life questionnaire.
resultsNineteen patients, from 3 to 64 years old, with lymphatic (LM), venous (VM) or complex slow-flow malformations, refractory to standard care, were enrolled and received sirolimus continuously. After 12 months of follow-up, 16 patients were available for assessment of efficacy and safety: all had a significant and rapid improvement of their symptoms and quality of life. In two patients, sirolimus treatment permitted sclerotherapy and surgery, initially evaluated unfeasible. Sirolimus was well tolerated, with mucositis as the most common (10% of patients) grade 3 adverse event.
conclusionsSirolimus was efficient in extensive LM, VM and/or complex malformations that were refractory to conventional treatments and was well tolerated.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.