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Background/aims: More than 99% of individuals with neurofibromatosis 1 develop cutaneous neurofibromas, benign nerve sheath tumors that manifest as nodules on the skin. These cutaneous neurofibromas emerge with age, appearing most commonly in adolescence. Nevertheless, few data have been published on how adolescents with neurofibromatosis 1 feel about cutaneous neurofibromas. The purpose of this study was to assess the perspectives of adolescents with neurofibromatosis 1 and their caregivers regarding cutaneous neurofibroma morbidity, treatment options, and acceptable risks-benefits of treatment., Methods: An online survey was distributed through the world's largest NF registry. Eligibility criteria included self-reported neurofibromatosis 1 diagnosis, adolescent child ages 12-17 years, ≥1 cutaneous neurofibroma, and ability to read English. The survey was designed to collect details about the adolescent's cutaneous neurofibromas, views on morbidity related to cutaneous neurofibromas, social and emotional impact of cutaneous neurofibromas, communication regarding cutaneous neurofibromas, and views regarding current and potential future cutaneous neurofibroma treatment., Results: Survey respondents included 28 adolescents and 32 caregivers. Adolescents reported having several negative feelings about cutaneous neurofibromas, particularly feeling worried about the potential progression of their cutaneous neurofibromas (50%). Pruritus (34%), location (34%), appearance (31%), and number (31%) were the most bothersome cutaneous neurofibroma features. Topical medication (77%-96%), followed by oral medication (54%-93%), was the most preferred treatment modality. Adolescents and caregivers most often replied that cutaneous neurofibroma treatment should be initiated when cutaneous neurofibromas become bothersome. The majority of respondents were willing to treat cutaneous neurofibromas for at least 1 year (64%-75%). Adolescent and caregivers were least willing to risk pain (72%-78%) and nausea/vomiting (59%-81%) as a cutaneous neurofibroma treatment side effect., Conclusions: These data indicate that adolescents with neurofibromatosis 1 are negatively impacted by their cutaneous neurofibromas, and that both adolescents and their caregivers would be willing to try longer-term experimental treatments., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: K.Y.S. is on the scientific advisory board for NFlection Therapeutics. S.R.P. is co-founder of NFlection Therapeutics and NF2 Therapeutics; serves on the scientific advisory board of SonALAsense; and consults for Akouos. The other authors have no conflicts of interest to disclose.

Cutaneous neurofibromas (cNFs) are a hallmark of patients with the neurofibromatosis type 1 (NF1) genetic disorder. These benign nerve sheath tumors, which can amount to thousands, develop from puberty onward, often cause pain and are considered by patients to be the primary burden of the disease. Mutations of NF1, encoding a negative regulator of the RAS signaling pathway, in the Schwann cell (SCs) lineage are considered to be at the origin of cNFs. The mechanisms governing cNFs development are poorly understood, and therapeutics to reduce cNFs are missing, mainly due to the lack of appropriate animal models. To address this, we designed the Nf1-KO mouse model that develops cNFs. Using this model, we found that cNFs development is a singular event and goes through 3 successive stages: initiation, progression, and stabilization characterized by changes in the proliferative and MAPK activities of tumor SCs. We found that skin trauma accelerated the development of cNFs and further used this model to explore the efficacy of the MEK inhibitor binimetinib to cure these tumors. We showed that while topically delivered binimetinib has a selective and minor effect on mature cNFs, the same drug prevents their development over long periods., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Neurofibromatosis type 1 is an inherited condition with variable phenotypic expression and a high medical and social burden. The objectives of this patient survey were to better understand the real-world experiences of patients living with cutaneous neurofibromas (cNF), to perceive their satisfaction and feelings about cNF current management (only laser and surgery are currently available), and to highlight their expectations of new therapeutic modalities., Results: One hundred seventy patients from 4 European countries took part in the study, 65% (n = 110) were women and mean age was 39 years old. 96% (n = 164) of respondents have cNF on visible parts of the body and the survey confirmed that total number of cNF and visibility increase with age. Patients reported that cNF mainly impacts everyday mood, general daily life and social life. The visibility of cNF had a higher impact than their number. 92% (n = 156) of patients have a regular and multidisciplinary medical follow-up. The dermatologist is one of the most consulted healthcare professionals. 76% (n = 130) of respondents have treated their cNF: 65% (n = 111) had surgery and 38% (n = 64) had multiple laser sessions. Frequency of operations and regrowth of cNF were the two most unsatisfactory aspects with both treatments for patients. Indeed, after removal, new cNF appear in more than 75% (n = 128) of cases. As a future treatment, patients expected a topical (30%, n = 51) or oral medication (29%, n = 50). Around 2 out of 3 patients would agree to take it at least once a day or more for life but they would like a well-tolerated treatment. According to patients, the most important effectiveness criteria of a new treatment are to block cNF growth and reduce their number. 70% (n = 119) of patients would consider a future treatment moderately effective to very effective if it could clear 30% of cNF., Conclusions: This first cNF European patient community survey confirmed that the visible stigma and unaesthetic aspect of cNF have an important impact on patients' quality of life. The survey highlighted that patients were not entirely satisfied with the actual surgery and laser treatments and revealed their clear and realistic expectations for future treatment of cNF.

Background: Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by a predisposition to develop multiple benign tumors. A major feature of NF1 is the development of localized cutaneous neurofibromas. Cutaneous neurofibromas manifest in > 99% of adults with NF1 and are responsible for major negative effects on quality of life. Previous reports have correlated increased burden of cutaneous neurofibromas with age and pregnancy, but longitudinal data are not available to establish a quantitative natural history of these lesions. The purpose of this study is to conduct a prospective natural history study of 22 adults with NF1 over an 8-year period to quantify cutaneous neurofibroma number and size., Results: The average monthly increase in volume for cutaneous neurofibromas was 0.37 mm 3 in the back region (95% CI (0.23, 0.51), p < 0.0001), 0.28 mm 3 in the abdominal region (95% CI (0.16, 0.41), p < 0.0001), and 0.21 mm 3 in the arm/leg region (95% CI (0.08, 0.34), p = 0.0022). The number of cutaneous neurofibromas significantly increased in the back (slope = 0.032, p = 0.011) and abdominal (slope = 0.018, p = 0.026) regions, while the leg/arm regions retained a positive trend (slope = 0.004, p = 0.055)., Conclusions: The number and volume of cutaneous neurofibromas significantly increased over an 8-year timespan; however, the rate of increase is variable by individual and body region. These findings may provide insight into cutaneous neurofibroma development and benefit researchers considering clinical trials targeting cutaneous neurofibromas.