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Expert Opinion on Investigational Drugs Jan 2022Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic condition, which predisposes individuals to the development of plexiform neurofibromas (PN), benign nerve...
INTRODUCTION
Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic condition, which predisposes individuals to the development of plexiform neurofibromas (PN), benign nerve sheath tumors seen in 30-50% of patients with NF1. These tumors may cause significant pain and disfigurement or may compromise organ function. Given the morbidity associated with these tumors, therapeutic options for patients with NF1-related PN are necessary.
AREAS COVERED
We searched the www.clinicaltrials.gov database for 'plexiform neurofibroma.' This article summarizes completed and ongoing trials involving systemic therapies for PN.
EXPERT OPINION
Surgery is the mainstay treatment; however, complete resection is not possible in many cases. Numerous systemic therapies have been evaluated in patients with NF1, with MEK inhibitors (MEKi) showing the greatest efficacy for volumetric reduction and improvement in functional and patient-reported outcomes. The MEKi selumetinib is now FDA approved for the treatment of inoperable, symptomatic PN in pediatric NF1 patients. Questions remain regarding the use of this drug class in terms of when to initiate therapy, overall duration, reduced dosing schedules, and side effect management. Future studies are needed to fully understand the clinical application of MEKi and to evaluate other potential therapies through appropriate trial designs for this potentially devastating, manifestation in NF1.
Topics: Child; Humans; Neurofibroma, Plexiform; Neurofibromatosis 1; Pain; Protein Kinase Inhibitors
PubMed: 34932916
DOI: 10.1080/13543784.2022.2022120 -
ANZ Journal of Surgery Apr 2022
Topics: Abdominal Pain; Humans; Mesentery; Neurofibroma, Plexiform; Neurofibromatosis 1
PubMed: 34473877
DOI: 10.1111/ans.17186 -
Annual Review of Pathology 2012Neurofibromatosis type 1 (NF1) is a genetic disease that results from either heritable or spontaneous autosomal dominant mutations in the NF1 gene. A second-hit mutation... (Review)
Review
Neurofibromatosis type 1 (NF1) is a genetic disease that results from either heritable or spontaneous autosomal dominant mutations in the NF1 gene. A second-hit mutation precedes the predominant NF1 neoplasms, which include myeloid leukemia, optic glioma, and plexiform neurofibroma. Despite this requisite NF1 loss of heterozygosity in the tumor cell of origin, nontumorigenic cells contribute to both generalized and specific disease manifestations. In mouse models of plexiform neurofibroma formation, Nf1 haploinsufficient mast cells promote inflammation, accelerating tumor formation and growth. These recruited mast cells, hematopoietic effector cells long known to permeate neurofibroma tissue, mediate key mitogenic signals that contribute to vascular ingrowth, collagen deposition, and tumor growth. Thus, the plexiform neurofibroma microenvironment involves a tumor/stromal interaction with the hematopoietic system that depends, at the molecular level, on a stem cell factor/c-kit-mediated signaling axis. These observations parallel findings in other NF1 disease manifestations and are clearly relevant to medical management of these neurofibromas.
Topics: Animals; Antineoplastic Agents; Benzamides; Hematopoietic System; Humans; Imatinib Mesylate; Mast Cells; Neurofibroma, Plexiform; Neurofibromatosis 1; Neurofibromin 1; Piperazines; Proto-Oncogene Proteins c-kit; Pyrimidines; Signal Transduction; Stem Cell Factor; Tumor Microenvironment
PubMed: 22077553
DOI: 10.1146/annurev-pathol-011811-132441 -
Fetal and Pediatric Pathology Feb 2023The perineal presentation of plexiform neurofibroma is exceptional, with only two cases reported to date. We present an 8-year-old African male with a large perineal...
The perineal presentation of plexiform neurofibroma is exceptional, with only two cases reported to date. We present an 8-year-old African male with a large perineal tumor of years of evolution. He had no associated symptoms. Café au lait stains were observed on examination, without other findings of relevance. The patient had no preoperative radiological studies. Partial excision of the lesion was performed. Histopathological study of the specimen revealed a plexiform neurofibroma. The lack of diagnostic suspicion due to the atypical nature of the location, the anatomical complexity of surgical resection and the potential urological and rectal involvement make this lesion a diagnostic-therapeutic challenge. Among the differential diagnoses, schwannoma, congenital lipoma, hamartoma and lipoblastoma should be considered.
Topics: Male; Humans; Child; Neurofibroma, Plexiform; Neurofibromatosis 1; Diagnosis, Differential
PubMed: 35234555
DOI: 10.1080/15513815.2022.2045404 -
Orbit (Amsterdam, Netherlands) Oct 2023Neurofibromatosis type 1 (NF1) affects cell growth in neural tissues, resulting in neurofibromas of the internal organs, peripheral nerves and/or autonomic nerves. We... (Review)
Review
Neurofibromatosis type 1 (NF1) affects cell growth in neural tissues, resulting in neurofibromas of the internal organs, peripheral nerves and/or autonomic nerves. We describe a highly unusual case of plexiform neurofibroma presenting with lacrimal gland enlargement in an 18 year old male, which led to a diagnosis of NF1.
Topics: Male; Humans; Adolescent; Neurofibroma, Plexiform; Lacrimal Apparatus; Neurofibromatosis 1; Neurofibroma; Peripheral Nerves
PubMed: 35312416
DOI: 10.1080/01676830.2022.2052112 -
Clinical Cancer Research : An Official... Aug 2021On April 10, 2020, the FDA approved selumetinib (KOSELUGO, AstraZeneca) for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1...
On April 10, 2020, the FDA approved selumetinib (KOSELUGO, AstraZeneca) for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. Approval was based on demonstration of a durable overall response rate per Response Evaluation in Neurofibromatosis and Schwannomatosis criteria and supported by observed clinical improvements in plexiform neurofibroma-related symptoms and functional impairments in 50 pediatric patients with inoperable plexiform neurofibromas in a single-arm, multicenter trial. The overall reponse rate per NCI investigator assessment was 66% (95% confidence interval, 51-79) with at least 12 months of follow-up. The median duration of response was not reached, and 82% of responding patients experienced duration of response ≥12 months. Clinical outcome assessment endpoints provided supportive efficacy data. Risks of selumetinib are consistent with MAPK (MEK) inhibitor class effects, including ocular, cardiac, musculoskeletal, gastrointestinal, and dermatologic toxicities. Safety was assessed across a pooled database of 74 pediatric patients with plexiform neurofibromas and supported by adult and pediatric selumetinib clinical trial data in cancer indications. The benefit-risk assessment for selumetinib in patients with inoperable plexiform neurofibromas was considered favorable.
Topics: Adolescent; Benzimidazoles; Child; Child, Preschool; Drug Approval; Female; Humans; Male; Neurofibroma, Plexiform; United States
PubMed: 33712511
DOI: 10.1158/1078-0432.CCR-20-5032 -
The Annals of Pharmacotherapy Jun 2022To evaluate the safety and efficacy of selumetinib, a novel MEK inhibitor, for the treatment of plexiform neurofibromas (PN) in patients with neurofibromatosis type 1... (Review)
Review
OBJECTIVE
To evaluate the safety and efficacy of selumetinib, a novel MEK inhibitor, for the treatment of plexiform neurofibromas (PN) in patients with neurofibromatosis type 1 (NF1).
DATA SOURCES
An English-based literature search of PubMed, EMBASE, and ClinicalTrials.gov was conducted using the terms AND from inception to August 1, 2021.
STUDY SELECTION AND DATA EXTRACTION
Relevant prescribing information, abstracts, and articles identified through the search were considered for inclusion in this review.
DATA SYNTHESIS
The open-label, multicenter, single-arm, phase II SPRINT trial demonstrated clinically significant improvements in PN-related complications. Of 50 symptomatic patients, 68% experienced a partial response, with a median change in tumor volume of -27.9% from baseline. Estimated progression-free survival at 3 years was 84%. Additionally, clinically meaningful improvements were seen on patient- and parent-reported assessments evaluating pain, range of motion, disfigurement, and quality of life. Overall, the adverse effect profile for selumetinib appears mild and manageable.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Selumetinib is the first FDA-approved treatment for inoperable PN in patients with NF1, demonstrating that MEK inhibition is a promising therapeutic strategy. Studies are ongoing to assess the effect of selumetinib on other NF1-associated tumor types and to determine the optimal dosing schedule and treatment duration. Cost and treatment burden must be considered when selecting selumetinib therapy.
CONCLUSION
Selumetinib exhibits impressive antitumor activity and sustained clinical benefit in patients lacking other viable treatment options. Further studies are warranted to determine the optimal age of initiation, treatment duration, and overall cost-effectiveness of selumetinib.
Topics: Benzimidazoles; Humans; Mitogen-Activated Protein Kinase Kinases; Multicenter Studies as Topic; Neurofibroma, Plexiform; Neurofibromatosis 1; Quality of Life
PubMed: 34541874
DOI: 10.1177/10600280211046298 -
International Journal of Gynecological... Jan 2021The female genital tract system is rarely affected by neurofibromatosis type 1 (NF1). Plexiform neurofibromas are congenital lesions that occur in patients with NF1. The...
The female genital tract system is rarely affected by neurofibromatosis type 1 (NF1). Plexiform neurofibromas are congenital lesions that occur in patients with NF1. The vulva is the most frequent genital location but vaginal, cervical, uterine, and ovarian neurofibromas have rarely been reported. We describe a case of plexiform neurofibromas involving the uterine cervix in a patient with known NF1 that presented with chronic pelvic pain and heavy menstrual bleeding.
Topics: Adult; Cervix Uteri; Female; Humans; Menorrhagia; Neurofibroma, Plexiform; Neurofibromatosis 1; Pelvic Pain; Uterine Neoplasms; Uterus
PubMed: 31688245
DOI: 10.1097/PGP.0000000000000647 -
Journal of Clinical Neuroscience :... Oct 2020Neurofibromatosis Type 1 (NF1) is a neurocutaneous tumour syndrome characterised by mutations in the NF1 gene and resultant neurofibromin protein. The condition is... (Review)
Review
Neurofibromatosis Type 1 (NF1) is a neurocutaneous tumour syndrome characterised by mutations in the NF1 gene and resultant neurofibromin protein. The condition is associated with several stigmata of variable penetrance, including various tumours. Massive and fatal haemorrhage arising from plexiform neurofibromas has been described in NF1 patients, though it is a rare clinical entity. The aetiology of massive haemorrhage in NF1 patients appears to be related to vasculopathy, including aneurysms and pseudoaneurysms, often arising within plexiform neurofibromas. There is currently no evidence-based consensus for managing this rare clinical emergency, likely as a result of its low incidence. We describe a case of massive haemorrhage in an NF1 patient managed via embolisation and discuss the literature.
Topics: Hemorrhage; Humans; Male; Middle Aged; Neck Pain; Neurofibroma, Plexiform; Pharyngeal Muscles
PubMed: 33099350
DOI: 10.1016/j.jocn.2020.08.024 -
The Turkish Journal of Pediatrics 2006A three-year-old girl with a lingual plexiform neurofibroma treated by total excision is presented. Despite their occurrence in the head and neck region, neural sheath... (Review)
Review
A three-year-old girl with a lingual plexiform neurofibroma treated by total excision is presented. Despite their occurrence in the head and neck region, neural sheath tumors are rarely encountered in the oral cavity. It is reported that 4-7% of patients affected by neurofibromatosis display oral manifestations. Neurofibromatosis is characterized by café-au-lait spots and cutaneous neurofibromas. Plexiform neurofibroma is said to be indicative of von Recklinghausen's disease (VRD) even though it may be the only manifestation of the disease. Generally, surgical resection represents the treatment of choice and the diagnosis can only be confirmed after histological examination. Affected patients need regular follow-up to detect malignant degeneration, an early recurrence or appearance of other manifestations of VRD.
Topics: Cafe-au-Lait Spots; Child, Preschool; Diagnosis, Differential; Female; Humans; Neurilemmoma; Neurofibroma, Plexiform; Neurofibromatosis 1; Tongue Neoplasms
PubMed: 16848118
DOI: No ID Found