The role of selumetinib in combined treatment of plexiform neurofibromas: postoperative strategy in adult patients with neurofibromatosis type 1

Introduction. Approximately 50 % of patients with neurofibromatosis type 1 (NF1) develop plexiform neurofibromas (PNs) which cause pain, functional abnormalities and disfigurement. In patients with NF1, vasculopathies and hemostasis disorders can occur, and surgical resection of PN can cause life-threatening hemorrhages. Standard treatment method of symptomatic PNs is surgical treatment but complete resection is often impossible. Additionally, renewal of PN growth is observed in 43 % of patients. Selumetinib, inhibitor of mitogen-activated protein kinase (MEK), allows to significantly control PNs in clinical trials and practice which confirms the possibility of its combination with surgical treatment.

Aim. To evaluate the results of surgical treatment of adult patients with symptomatic PNs, determine factors promoting development of complications and recurrences, and justify the use of selumetinib as a subsequent therapy.

Materials and methods. Retrospective analysis of treatment of adult patients with NF1 and symptomatic PNs who underwent symptomatic surgical treatment between July 2022 and September 2025. The study included 15 patients (11 women and 4 men); median PN volume was 1023 (14.56–74,800.00) mL. Some patients required multistage surgeries. Median follow-up was 10.5 months (95 % CI 3.75–23.00). PN sites: thoracic wall – 1 case, lower limb – 7, lumbar region – 3, back – 2, gluteal region – 2. In 3 cases, malignant tumor of the peripheral nerve sheath was reported; in 13 patients, mutation in the NF gene was identified.

Results. Surgical intervention relieved symptoms but led to significant complications. Median intraoperative blood loss volume was 700 (5–32,000 mL) mL. In 28 % of patients, complications associated with wound healing developed, in 5 (42 %) patients – clinical and/or radiological disease recurrence. Median disease-specific survival was 32 months (95 % CI 14–36). One patient died due to coagulopathy (blood loss volume was 32 L, operative time 9 h). Selumetinib in the postoperative period was prescribed to 3 (20 %) patients with residual or progressive disease. Significant differences were observed in PN volumes depending on sex (p = 0.009), as well as significant effect of PN volume on а operative time (p = 0.041), blood loss volume (p = 0.011), development of secondary wound healing (p = 0.016) and renewal of tumor growth (p = 0.028) was identified. There was no association between development of malignant tumor of the peripheral nerve and PN volume (p = 0.885).

Conclusion. Surgical treatment of PN is characterized by increased difficulty due to high rate of intraoperative complications, primarily blood loss, and leads only to temporary relief. The obtained dependencies (effect of PN volume on blood loss volume, operative time, development of secondary wound healing, and PN growth renewal) is statistically significantly confirms risks associated with high PN size. Correlation the volume of PN volume with female sex is also of interest. Notably, none of the patients receiving selumetinib after surgery had tumor growth, but follow-up is very short. A trend is observed towards selection of combination treatment where aggressive surgical techniques are accompanied by timely MEK prescription which prevents repeat PN growth and improves/preserves long-term clinical and radiological results.