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CLINICAL RESPONSE TO SELUMETINIB: CASE REPORT

RESUMO

Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis are tumor suppressor syndromes characterized by multiple nervous system tumors, which manifest in different locations depending on their genetic etiology. NF1 affects approximately 1:3000 individuals and is a tumor caused by mutations of the NF1 gene on chromosome 17q11.2. The treatment of NF1 consists of surgical excision of cutaneous neurofibromas (CNFs) when symptomatic. Surgical removal of plexiform neurofibromas (PNFs) are not always possible due their diffuse and multiple nerve roots involvement. The recent advance is the FDA approval of the MEK inhibitor selumetinib (Koselugo™) for the treatment of children with symptomatic, inoperable PNF based on a trial that demonstrated 72% response rate in tumor volume shrinkage by ≥ 20% in NF1 children with PNFs. However, this is not curative as no subjects had complete tumor disappearance and tumors regrew particularly after dose reduction or cessation due to toxic effects, such as diarrhea, weight gain, paronychia, skin ulceration, and elevated creatinine level. This case report is about a patient with NF1 diagnosed at 14 years old in 2008 who started compassionate use of Selumetinib 80 mg/day (divided into two doses a day) in august 2020 due to clinical and functional worsening at this time. He had difficulty swallowing due to neurofibromas in cervical region, also had inability to walk, was able to move only on a wheelchair, and difficulty in evacuating and urinating, using a urinary catheter and laxative medications continuously. Neuroaxis resonance showed countless nodular images in the subcutaneous tissue of the scalp, compatible with neurofibroma, sometimes confluent, predominance in the occipital regions. Other similar lesions can be seen in the deep cervical spaces. Countless PNFs involving all intervertebral foramina evaluated, confluent in the paravertebral regions, sometimes forming masses. Intradural and extramedullary lesions within the vertebral canal stand out, the largest at the level of C1 and C2, compressing the spinal cord, without altering its signal. After starting Selumetinib the patient had a significant reduction in neurofibromas, and significant clinical improvement. At the moment, the patient is able to walk with the help of a walker, has sphincter control and improved dysphagia. The case is maintaining follow-up in the neuro-oncology sector at UNIFESP, with stable clinical status.

Palavras Chave

Neurofibromatosis type 1 (NF1), Selumetinib, Neurofibroma