Cutaneous neurofibromas (cNFs) are one of the hallmarks of neurofibromatosis type 1 (NF1) and are considered by patients to represent a major disease burden. A comprehensive strategy is needed to better characterize the natural history of cNFs, clarify the expected outcomes of current and future procedure-based therapies, and improve clinical trial design, with particular emphasis on identifying patient subgroups most likely to benefit from specific therapies. Ultimately, ending cNFs should be a priority.

Visible manifestations of NF1, from cutaneous to plexiform neurofibromas, affect almost every patient to differing extents. Drawing on the voices of the patient community, this talk shows how they shape daily life and self-image. NF1 must be understood as progressive, with prevention, not only removal, as our shared goal.

Background: Despite increasing clinical trials in cutaneous neurofibromas (cNFs), heterogeneity in outcome measures limits comparability. This study aimed to identify and evaluate patient- and clinician-reported outcome measures (PROMs and CROMs) for cNFs and develop an evidence-based framework for clinical trials.
Methods: Under the REiNS cNF Group and CHORD COUSIN Collaboration (C3), a 4-phase process was conducted: (i) systematic review (SR1) of cNF outcomes; (ii) SR (SR2) of validation studies of instruments (PROMs and CROMs); (iii) assessment of study quality using the COSMIN Risk of Bias tool, and evaluation of instrument quality using PRO-RATE and CRO-RATE systems; and (iv) expert and patient consensus. PubMed, Embase, and ClinicalTrials.gov were searched (inception–March 2024 for SR1; to November 2025 for SR2).
Results: A total of 55 studies in the SR1 and 78 in the SR2 led to the identification of 31 PROMs and 21 CROMs. Six PROMs were classified as high priority: pain (Visual Analog Scale, Numeric Rating Scale–10/11), pruritus (5-D Itch Scale and its modified version), quality of life (cNF-Skindex), and stigma (cNF-PUSH-D). Eighteen PROMs and 8 CROMs were rated as moderate priority, while 7 PROMs and 13 CROMs require further validation. No CROM reached the high-priority level, reflecting the need to adapt assessment tools to the developmental stage of these tumors.
Conclusions: This work provides a consensus-based set of outcome measures for cNF trials. Several PROMs are ready for standardized use, improving patient-centered assessment, while CROMs require further validation and stage-specific application.

Background: PAS-004 is a small molecule, allosteric inhibitor of MEK 1/2 and the first macrocyclic structure MEK inhibitor in clinical development.

Methods: Phase 1/1b clinical trial evaluate the safety, pharmacokinetic (PK), and preliminary efficacy of PAS-004 on target cutaneous neurofibromas (cNF) volume in adult patients with NF1. Up to seven measurable Target cNF per patient were assessed at baseline and after Cycle 1, 4, 6, 9, and 12. Target cNF were measured in triplicate using digital calipers. Length and width were used to calculate the cNF surface area. An intraclass correlation coefficient (ICC) was calculated for single and triplicate measurements of each lesion. Safety and tolerability are measured through a series of laboratory assessments and physical exams. A detailed PK profile was obtained after administration of PAS-004.

Results: As of 22 May 2026, 13 patients had cNFs that met criteria for Target cNFs. Median follow-up time of 8.4 months (range 5.8 – 10.8). PAS-004 PK analysis suggests linear PK with t1/2 of 60h, and Cmax/Cmin ratio below 2 at steady state. TRAEs were reported in 9 of 11 (82%) of these patients, and all but one were Gr1/Gr2. cNF evaluation demonstrated lesion regressions across all dosing cohorts, with 10 of 11 (91%) patients experiencing reduction in target cNF of at least 25%. ICC of 0.98 when triplicate measurements were used.

Conclusions: Preliminary results demonstrate clinical activity in patients with NF1-associated cNF. These findings provide a compelling rationale to continue to test PAS-004 in clinical trials for the treatment of NF1-associated cutaneous neurofibroma.

Background: Cutaneous neurofibromas(cNFs) are a major source of morbidity and reduced quality of life for individuals with Neurofibromatosis Type 1(NF1). Traditional treatment commonly involves serial excision or laser ablation of symptomatic lesions under local anaesthetic(LA) as day-case procedures. Electrodessication offers the potential to treat hundreds of lesions during a single session and has been associated with high patient satisfaction and low complication rates. The economic impact of these treatment approaches remains poorly defined.
Methods: A retrospective cost analysis was performed comparing electrodessication with conventional LA day-case surgical excision for cNFs at a tertiary NF service between 2010 and 2026. Direct hospital costs including theatre time, staffing, consumables, recovery, and follow-up were evaluated.
Results: From 2010 to 2026, 364 individual patients with NF1 were cared for by the service. This accounted for 595 individual surgical encounters. Median age at operation was 35 years(range 4-80yrs). Electrodessication comprised of a day case general anaesthetic procedure targeting a large number of cutaneous neurofibromata whereas symptomatic lesions were excised under local anaesthetic. Number of individual procedures ranged from 1-11 per patient. Median cost of electrodessication was £2,710(€3,145) compared to £1866(€2188) for LA surgery. Time interval between procedures was collected.
Conclusions: Electrodessication is a cost-efficient strategy for managing multiple cNFs in NF1. By enabling treatment of large numbers of lesions during a single episode of care, it reduces procedural burden and lowers cost per lesion compared with conventional LA day-case surgery. These findings support consideration of electrodessication within specialised NF services and provide evidence for future health-economic evaluation.

Background: Beyond cardinal diagnostic features, NF1 is associated with a broad spectrum of potentially severe complications including plexiform neurofibromas (PN), optic pathway gliomas (OPG), neurodevelopmental delays, cognitive impairment, epilepsy, and chronic pain. Real-world data on the prevalence of these manifestations in large unselected national cohorts remain limited, as does evidence on access to and long-term adherence to MEK inhibitor therapy.
Methods: Prospective data from a national multidisciplinary NF1 registry were analysed using standardized electronic case report forms across all age groups. National MEK inhibitor prescription volume was obtained from the national NF1 patient organization.
Results: Among 4,230 registered patients (71% aged ≤18 years, median age 14 years), phenotypic data were available for 3,115 (74%). PN were documented in 34%, with the highest proportion at ages 17–18 years (36%); OPG were documented in 12%. Among patients with phenotype data, pain syndrome was present in 10.9% (n=340), speech delay in 9.9% (n=308), intellectual disability in 7.6% (n=238), and epilepsy in 3.2% (n=100). Registry data and national patient organization data captured 730 patients receiving selumetinib. Among documented cases, median starting age was 12 years (IQR 8–15) and median treatment duration 34 months, suggesting prolonged real-world treatment duration.
Conclusion: This large national cohort demonstrates the real-world burden of non-cutaneous NF1 complications and highlights a significant gap between registry-documented and actual MEK inhibitor use, underscoring the need for improved registry coverage to enable comprehensive monitoring of targeted therapy outcomes.

Background: Between 30-50% of patients with neurofibromatosis type 1 are postulated to develop plexiform neurofibromas (PNFs). These can cause significant functional and cosmetic sequelae. We describe the indications for pre-operative embolization of PNFs and compare the cost to simple excision alone.

Methods: Retrospective case note review between 2014-2022 with PNFs who had pre-operative embolisation. Data were also collected on total overall cost to the hospital as well as time between embolization and surgery, use of cell saver, autologous transfusion and post-operative transfusion.

Results: Eleven patients with a median age of 45 years (range 25-60 years) underwent pre-operative embolization of their PNF compared to eight patients with a median age of 30 years (range 22-37 years) were not embolised. Pre-operative imaging (CT or MR angiography) was performed to identify feeding arteries and discussed in both the complex type 1 neurofibromatosis and vascular intervention MDTs. Median length of procedure in the intervention group was 360 minutes (197-435minutes) compared to 396 minutes (120-480minutes) in the non-intervention group. The total surgical time in the intervention group was 250 minutes (140-195 minutes). The median cost of embolisation was £27,778 (€32,058) compared to £20,726 (€23,920) in the non-intervention group.

Conclusions: While the overall cost of pre-operative embolization is higher, our experience suggests that it reduces the chance of significant intraoperative and post operative bleeding in patients with PNFs. Pre-operative embolisation in combination cell salvage, local anaesthetic with adrenaline and the use of tranexamic acid can reduce surgical time and reduce morbidity.