What is the diagnosis and treatment of Neurofibroma in Oncology (Oncology)?

From the Guidelines

Neurofibromas are benign tumors that develop from the cells that surround and support nerve cells, and their management depends on the location, size, and symptoms, with observation, surgical removal, and targeted therapies such as the MEK inhibitor selumetinib (Koselugo) being treatment options. The diagnosis of neurofibromas involves a combination of clinical examinations, imaging studies (MRI or CT scans), and genetic counseling, particularly for patients with neurofibromatosis type 1 (NF1) [ 1 ].

Key Considerations

• Asymptomatic neurofibromas are often managed with observation and regular monitoring [ 2 ].
• Surgical removal is the primary treatment for symptomatic or rapidly growing neurofibromas, particularly if they cause pain, neurological deficits, or cosmetic concerns [ 3 ].
• For patients with NF1-associated neurofibromas, comprehensive care includes regular clinical examinations, imaging studies, and genetic counseling [ 4 ].
• Malignant transformation to malignant peripheral nerve sheath tumors occurs in approximately 2-5% of patients with NF1, necessitating vigilance for rapid growth, new pain, or neurological changes [ 5 ].

Treatment Options

• The MEK inhibitor selumetinib (Koselugo) is FDA-approved for children with NF1 at a dose based on body surface area, and clinical trials are exploring additional targeted therapies [ 6 ].
• Pain management may include standard analgesics, gabapentin, or pregabalin for neuropathic pain.
• Multidisciplinary care involving neurosurgeons, oncologists, geneticists, and pain specialists offers the best outcomes for patients with complex or numerous neurofibromas.

Recent Updates

• Updated consensus cancer surveillance recommendations for pediatric patients with NF1, NS, CS, and other RASopathies emphasize the importance of early tumor detection and intervention while minimizing the risks of surveillance [ 6 ].
• Whole-body magnetic resonance imaging (WB-MRI) has proven its efficacy in detecting number, volume, and distribution of neurofibromas, and may be a useful tool for cancer screening in patients with NF1 [ 1 ].

From the FDA Drug Label

1 INDICATIONS AND USAGE

KOSELUGO is indicated for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).

14 CLINICAL STUDIES

14. 1 Neurofibromatosis Type 1 (NF1) with Inoperable Plexiform Neurofibromas (PN) The efficacy of KOSELUGO was evaluated in SPRINT Phase II Stratum 1, an open-label, multicenter, single arm trial (NCT01362803) Eligible patients were required to have NF1 with inoperable PN, defined as a PN that could not be completely removed without risk for substantial morbidity due to encasement of, or close proximity to, vital structures, invasiveness, or high vascularity of the PN.

The diagnosis of Neurofibroma in Oncology is based on the presence of symptomatic, inoperable plexiform neurofibromas (PN) in patients with neurofibromatosis type 1 (NF1). The treatment of Neurofibroma in Oncology is selumetinib (KOSELUGO), which is indicated for pediatric patients 2 years of age and older with NF1 who have symptomatic, inoperable PN [7] [8]. Key points about the treatment include:

• Age: 2 years of age and older
• Condition: neurofibromatosis type 1 (NF1) with symptomatic, inoperable plexiform neurofibromas (PN)
• Medication: selumetinib (KOSELUGO)

From the Research

Diagnosis of Neurofibroma

• The diagnosis of neurofibroma in patients with neurofibromatosis type 1 (NF1) can be challenging, as these tumors can be benign or malignant 9.
• Histopathologic evaluation of atypical neurofibromatous tumors is crucial in predicting transformation into malignant peripheral nerve sheath tumor (MPNST) 9.
• Features such as nuclear atypia, loss of neurofibroma architecture, high cellularity, and/or mitotic activity can indicate malignancy 9.
• The term "atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP)" has been proposed for lesions displaying at least two of these features 9.

Treatment of Neurofibroma

• Treatment options for neurofibromas in NF1 patients have historically been limited to surgery, but recent advances have led to the development of new therapies 10, 11.
• The MEK inhibitor selumetinib has been approved for the treatment of plexiform neurofibromas, offering a new option for patients with NF1 10.
• Other potential treatments for peripheral nerve sheath tumors (PNSTs) in NF1 patients include Ras/MAPK pathway inhibitors, immunotherapy, chemotherapy, and radiation therapy 11.
• Early diagnosis and surgery are still considered the most effective treatment for MPNST, but new insights into pathogenesis offer hope for the development of specific methods of treatment with reduced toxicity and more precise molecular targeting 12.