A single-center case study series assessing the effect of selumetinib use in patients with neurofibromatosis-related plexiform neurofibromas

Abstract

Background: Neurofibromatosis type 1 (NF1) is a common genetic disorder of phenotypic variability with age-dependent penetrance. This study describes the diagnosis, clinical characterization, management, and outcomes of a large patient cohort with plexiform neurofibroma (PN) treated with selumetinib in a real-world clinical setting.

Methods: This single-center observational study consecutively enrolled patients with NF1-PN treated with selumetinib from April 2018 to 2023. Data on clinical features, tumor types and locations, and results from genetic tests were recorded at baseline; details of disease management with selumetinib and surgical intervention and disease evolution including imaging data and evaluations of pain and function were documented.

Results: Overall, 54 patients with a median age (range) of 16.4 (4.5-58.0) years were enrolled. Most had cutaneous manifestations (88.9%), including cutaneous neurofibromas and PN. Patients underwent [18F]fluorodeoxyglucose (FDG)-PET/CT imaging before treatment to rule out malignant lesions. Initial evaluations included directed magnetic resonance imaging (MRI), which facilitated future comparisons and allowed for the assessment of PN resectability. Pharmacological treatment with selumetinib (with surgery, without surgery) resulted in the following proportion of patients achieving stable disease (58.8%, 54.3%), partial response (29.4%, 28.6%), and improved pain (58.8%, 37.1%), deformity (17.6%, 20.0%), and functional (17.6%, 20.0%) outcomes, respectively.

Conclusions: Results from this study demonstrate that NF1-PN can be managed effectively with selumetinib with surgical intervention in some patients. Most patients achieved tumor stability and improved symptom control, and the majority of patients continue under treatment. Effective diagnosis and management were achieved through individualized utility of FDG-PET/CT and MRI imaging and targeted resource allocation.

Keywords: neurofibromatosis type 1; plexiform neurofibroma; selumetinib.

Figure 1.

Age of patients at diagnosis. Data included for patients with available data (n = 28, NF1 diagnosis; n = 54, PN diagnosis). Abbreviations: NF1, neurofibromatosis type 1; PN, plexiform neurofibroma.

Figure 2.

Percentage of neurofibromin variant categories. Data included for patients with available data (n = 33). Categories of genetic variants were grouped. The categories of 21 variants were unknown. One variant was found in NF2 (Supplementary Table 1).

Figure 3.

Treatment effects. (A) Observed tumor activity based on subjective evaluation of imaging data according to use and sequencing of surgery alongside treatment with selumetinib;^a (B) Observed symptom improvements according to use and sequencing of surgery alongside treatment with selumetinib.^{b a}Imaging data based on final MRI evaluation and neuroradiological assessment. ^bSymptom categories are not mutually exclusive per patient. ^cFor pain, improvement is defined as a ≥2-point reduction in the numerical pain scale over 2 consecutive visits, resolution of the absence of pain. ^dIncontinence improvement (3 instances, 2 resolved), stability (2 instances), respiratory function improvement (2 instances), aesthetic improvement (2 instances), dysphagia improvement (2 instances), dysarthria improvement (2 instances), exercise tolerance improvement (2 instances), sensory symptom resolution, discomfort improvement, decrease of lower limb diameter, improved social interaction, scoliosis improvement, muscular strength improvement, neurofibroma growth, functional paresis decline.