Identifying challenges in neurofibromatosis: a modified Delphi procedure.

Area of Science:

• Neuro-oncology
• Rare diseases
• Clinical trial development

Background:

• Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are rare genetic disorders with highly variable clinical presentations.
• Identifying key manifestations is crucial for guiding the development of targeted drug therapies and clinical trials.

Purpose of the Study:

• To achieve expert and patient consensus on the most significant manifestations of NF1, NF2, and SWN that warrant the development of new drug trials.
• To prioritize specific disease aspects for future therapeutic interventions.

Main Methods:

• A five-stage modified Delphi procedure involving two questionnaires, a consensus meeting with 40 NF experts, a survey of 63 patient representatives, and a final workshop.
• Manifestations were scored using a 4-point Likert scale to assess the 'need for new treatment'.

Main Results:

• Experts prioritized malignant peripheral nerve sheath tumors (MPNST) and high-grade gliomas (HGG) for NF1; meningiomas for NF2; and pain for SWN.
• Patient representatives highlighted plexiform neurofibromas for NF1, vestibular schwannomas for NF2, and pain for SWN.
• Consensus meeting ranked MPNST highest for NF1, tumors for NF2, and pain for SWN.

Conclusions:

• NF experts and patient representatives reached a consensus on prioritizing drug trial development for specific NF1 manifestations, including MPNST, benign peripheral nerve sheath tumors, cutaneous manifestations, and HGG.
• Tumor development is the priority for NF2, while pain management is the key focus for SWN.
• This consensus provides a clear roadmap for directing research and therapeutic development in neurofibromatosis and schwannomatosis.