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Rationale Objectives Methods Results Conclusion Sirolimus is a treatment for slow‐flow vascular malformations (SFVMs). However, the long‐term management remains challenging.The SIROLO study assessed the long‐term effects and real‐life management of oral sirolimus for SFVMs by investigating data from 15 French tertiary centres for vascular anomalies.Participants were retrospectively included if they had a SFVM that was being/had been treated with sirolimus for at least 3 years in total. Data were collected on treatment goals when initiating sirolimus, investigator‐reported efficacy, safety, dosages and treatment withdrawal.The cohort involved 67 patients with various SFVM entities (mean [±SD] age 19.6 ± 12.5 years, 35 children, 52.2%). We found a heterogeneity of predefined treatment goals, the most frequent being cessation of pain. The investigators considered that sirolimus had persistent efficacy for bleeding, ulceration and pain but only slight efficacy for reducing volume. It was reported to be well‐tolerated, although serious adverse events (mainly infections and also two ovarian cysts) were reported in 6 patients (9.0%) and required definitive sirolimus discontinuation for one. Overall, 11 patients (16.4%) had at least one temporary withdrawal period, leading to symptom recurrence and sirolimus resumption at a mean of 6.4 ± 9.6 months. The mean sirolimus concentration was 6.4 ± 3.7 ng/mL during the first 6 months and decreased over time (mean concentration during the last 6 months: 4.2 ± 3.2 ng/mL), probably to target the minimal efficient dosage. Eight patients (11.9%) switched to alpelisib because of insufficient efficacy of sirolimus.This real‐life study gives answers to frequent questions patients and parents ask before sirolimus initiation for SFVMs, such as persistence of efficacy over time, long‐term side effects and time to recurrence in case of withdrawal. [ABSTRACT FROM AUTHOR]

Background and Aim: Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare congenital vascular entity, mainly characterized by cutaneous and gastrointestinal venous malformations. BRBNS remains relatively unexplored and only limited descriptive data is available. The aim of this study was to evaluate the clinical features, diagnostic work-up and therapeutic management in current practice., Methods: A multicenter, European, cohort study was performed to investigate the BRBNS population. Patient demographics, clinical presentation and management data were collected., Results: In this multicenter cohort study including 44 patients, BRBNS is diagnosed at a median age of 12 years, mainly based on clinical presentation (65.9 %). The majority of patients present cutaneous (68.2 %) and digestive (79.5 %) lesions, mainly in the colon and small bowel. d-dimer and fibrinogen levels are checked in <50 % of patients at diagnosis. Tie2/TEK mutation testing is rarely performed. Gastrointestinal bleeding is the most common complication (54.3 %), requiring endoscopic treatment (36.4 %) by various techniques., Conclusions: This is the largest cohort study on BRBNS. Diagnosis is mainly based on clinical presentation. d-dimer, fibrinogen and Tie2/TEK mutation testing should be performed in case of suspected BRBNS as it could help confirm the diagnosis., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

KRAS gain-of-function mutations are frequently observed in sporadic arteriovenous malformations. The mechanisms underlying the progression of such KRAS -driven malformations are still incompletely understood, and no treatments for the condition are approved. Here, we show the effectiveness of sotorasib, a specific KRAS G12C inhibitor, in reducing the volume of vascular malformations and improving survival in two mouse models carrying a mosaic Kras G12C mutation. We then administered sotorasib to two adult patients with severe KRAS G12C-related arteriovenous malformations. Both patients had rapid reductions in symptoms and arteriovenous malformation size. Targeting KRAS G12C appears to be a promising therapeutic approach for patients with KRAS G12C-related vascular malformations. (Funded by the European Research Council and others.)., (Copyright © 2024 Massachusetts Medical Society.)