Considerations for development of therapies for cutaneous neurofibroma.

OBJECTIVE: The only therapies currently available for cutaneous neurofibromas (cNF) are procedural. The goals of the Therapies Development Working Group were to (1) summarize currently available treatment options for cNF, (2) define key considerations for drug discovery and development generally, and specifically for cNF, and (3) outline recommendations for the successful development of medical therapies for cNF. METHODS: The subgroup reviewed published and unpublished data on procedural, drug/device, and medical treatment approaches utilized for cNFs via literature search. The team defined disease- and patient-specific factors to consider for therapies development in a series of consensus meetings. RESULTS: The team identified 5 approaches entailing procedural and drug/device methods currently under study. There have been 4 clinical studies exploring various interventional therapies, from which outcomes were highly variable. The team identified 4 key factors to prioritize during the development of products for the treatment for cNF: safety, anatomic distribution of cNF, numbers of tumors to be treated, and route of administration. CONCLUSIONS: The number, size, and distribution of cNF is highly variable among patients with NF1 and it is possible that different phenotypes will require different drug development paths. The nonfatal nature of the disease and relatively limited patient numbers suggest that for any product to have a higher likelihood of acceptance, it will have to (1) demonstrate an effect that is clinically meaningful, (2) have a safety profile conducive to long-term dosing, and (3) have a low manufacturing cost.

A high-throughput molecular data resource for cutaneous neurofibromas.

Neurofibromatosis type 1 (NF1) is a genetic disorder with a range of clinical manifestations such as widespread growth of benign tumours called neurofibromas, pain, learning disorders, bone deformities, vascular abnormalities and even malignant tumours. With the establishment of the Children's Tumour Foundation biobank, neurofibroma samples can now be collected directly from patients to be analysed by the larger scientific community. This work describes a pilot study to characterize one class of neurofibroma, cutaneous neurofibromas, by molecularly profiling of ~40 cutaneous neurofibromas collected from 11 individual patients. Data collected from each tumour includes (1) SNP Arrays, (2) Whole genome sequencing (WGS) and (3) RNA-Sequencing. These data are now freely available for further analysis at http://www.synapse.org/cutaneousNF.

Tratamento de lesões cutâneas múltiplas na neurofibromatose tipo 1: nova técnica de excisão eletrocirúrgica / Treatment of multiple cutaneous lesions in neurofibromatosis type 1: new excision electrosurgical technique

A neurofibromatose tipo 1 (NF1) é um distúrbio autossômico dominante que apresenta lesões cutâneas múltiplas, frequentemente chegando à faixa de 500 a 1.000 lesões. Além das implicações psicológicas, as lesões apresentam um difícil dilema cirúrgico pela existência de limitadas opções. Os autores apresentam uma série de 175 pacientes com inúmeras lesões cutâneas tratadas com uma nova abordagem, utilizando a excisão por eletrocautério. A técnica resulta na remoção de grandes números de lesões com uma discreta cicatriz, um mínimo de desconforto e uma significativa satisfação do paciente.

Electrosurgical excision technique for the treatment of multiple cutaneous lesions in neurofibromatosis type I.

Neurofibromatosis I (NF1) is an autosomal dominant disease that presents with multiple cutaneous lesions often numbering into the 500-1000 range. In addition to the psychosocial implications, there are limited surgical options for this condition. A series of 97 consecutive patients with NF1 presented with numerous cutaneous lesions. Treatment involved electrocautery excision of the lesions using a handheld device in one or more stages. This technique resulted in the removal of large numbers of lesions in limited stages, with minimal scarring, minor discomfort and high patient acceptance. For patients with NF1, single or multistage excision of cutaneous lesions using electrocautery produces an acceptable aesthetic result with high patient satisfaction.