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Child's Nervous System : ChNS :... Aug 2022To assess clinical and humanistic burden among pediatric patients with neurofibromatosis type 1 (NF1) and plexiform neurofibroma (PN) in the USA.
PURPOSE
To assess clinical and humanistic burden among pediatric patients with neurofibromatosis type 1 (NF1) and plexiform neurofibroma (PN) in the USA.
METHODS
NF1-PN patients aged 8-18 years (treatment-naïve or ≤ 1 month of selumetinib treatment) and their caregivers and caregivers of similar patients aged 2-7 years were recruited through the Children's Tumor Foundation to participate in an online cross-sectional survey (December 2020-January 2021). Caregivers provided data on patients' demographic and clinical characteristics and burden of debulking surgeries. Patients and caregivers provided self-reported or proxy responses to health-related quality of life (HRQoL) questions using validated instruments.
RESULTS
Sixty-one patients and 82 caregivers responded to the survey. Median (range) age of patients was 11.5 (3-18) years, and 53.7% were female. Most were treatment-naïve (97.6%), with NF1-PN diagnosis for > 5 years (68.3%). Most patients (59.8%) had > 1 PN and 11.0% reporting > 5 PNs. Common NF1-PN symptoms included pain (64.6%), disfigurement (32.9%), and motor dysfunction (28.0%). Patients and caregiver proxies reported low overall HRQoL and reduced physical, emotional, social, and school functioning. Patients also reported considerable pain severity, interference, daily activity impairments, and movement difficulty. Few patients had received complete resections of their tumors (12.2%). 39.0% reported ≥ 1 debulking surgery, among whom, 15.6% had complications, and debulking surgery-related hospitalizations were common (53.1%).
CONCLUSIONS
The clinical and humanistic burden among pediatric NF1-PN patients is substantial. While debulking surgeries are used for symptom management, they are associated with considerable clinical sequelae. Results highlight a need for improved disease management strategies.
Topics: Child; Cross-Sectional Studies; Female; Humans; Male; Neurofibroma, Plexiform; Neurofibromatosis 1; Quality of Life; Surveys and Questionnaires
PubMed: 35579709
DOI: 10.1007/s00381-022-05513-8 -
Cancers Mar 2023The 2021 WHO classification of the CNS Tumors identifies as "Peripheral nerve sheath tumors" (PNST) some entities with specific clinical and anatomical characteristics,... (Review)
Review
The 2021 WHO classification of the CNS Tumors identifies as "Peripheral nerve sheath tumors" (PNST) some entities with specific clinical and anatomical characteristics, histological and molecular markers, imaging findings, and aggressiveness. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is particularly low due to the rarity, and drawn recommendations accordingly. Tumor diagnosis is primarily based on hematoxylin and eosin-stained sections and immunohistochemistry. Molecular analysis is not essential to establish the histological nature of these tumors, although genetic analyses on DNA extracted from PNST (neurofibromas/schwannomas) is required to diagnose mosaic forms of NF1 and SPS. MRI is the gold-standard to delineate the extension with respect to adjacent structures. Gross-total resection is the first choice, and can be curative in benign lesions; however, the extent of resection must be balanced with preservation of nerve functioning. Radiotherapy can be omitted in benign tumors after complete resection and in NF-related tumors, due to the theoretic risk of secondary malignancies in a tumor-suppressor syndrome. Systemic therapy should be considered in incomplete resected plexiform neurofibromas/MPNSTs. MEK inhibitor selumetinib can be used in NF1 children ≥2 years with inoperable/symptomatic plexiform neurofibromas, while anthracycline-based treatment is the first choice for unresectable/locally advanced/metastatic MPNST. Clinical trials on other MEK1-2 inhibitors alone or in combination with mTOR inhibitors are under investigation in plexiform neurofibromas and MPNST, respectively.
PubMed: 37046591
DOI: 10.3390/cancers15071930 -
American Journal of Medical Genetics.... Jun 2022We report on the location, symptoms, and management of plexiform neurofibroma (PN) in children with Neurofibromatosis Type 1 (NF1) attending the 2 National Complex... (Review)
Review
Location, symptoms, and management of plexiform neurofibromas in 127 children with neurofibromatosis 1, attending the National Complex Neurofibromatosis 1 service, 2018-2019.
We report on the location, symptoms, and management of plexiform neurofibroma (PN) in children with Neurofibromatosis Type 1 (NF1) attending the 2 National Complex Neurofibromatosis 1 Services at Guy's and St. Thomas' NHS Foundation Trust, London and St Mary's Hospital, Manchester. Retrospective data collection was performed from patient chart reviews from April 2018 to April 2019. There were 127 NF1 patients with PN, age range 0.8-17.0, mean age was 9.9 years (SD ± 4.2 years). The main location of the PN was craniofacial in 35%, and limb in 19%. Disfigurement was present in 57%, pain in 28%, impairment of function in 23%, and threat to function in 9% of children. Fifty-four percent of patients were managed conservatively, 28% surgically, and 19% are either taking or due to start a mitogen-activated protein kinase kinase (MEK) inhibitor (selumetinib or trametinib), either through a clinical trial or compassionate usage scheme. This national study provides a comprehensive overview of the management of children with PN in an era where new therapies (MEK inhibitors) are becoming more widely available. We anticipate that there will be a shift to more patients receiving MEK inhibitor therapy and combination therapy (surgery and MEK inhibitor) in the future.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Mitogen-Activated Protein Kinase Kinases; Neurofibroma, Plexiform; Neurofibromatosis 1; Protein Kinase Inhibitors; Retrospective Studies
PubMed: 35178860
DOI: 10.1002/ajmg.a.62691 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Jun 2022Neurofibromatosis type 1(NF1) is an autosomal dominant genetic disease in which a mutation in the NF1 gene on chromosome 17q11.2 results in inactivation or... (Review)
Review
Neurofibromatosis type 1(NF1) is an autosomal dominant genetic disease in which a mutation in the NF1 gene on chromosome 17q11.2 results in inactivation or down-regulation of neurofibromin. This results in a series of neurocutaneous lesions characterized by neurofibromatosis. Patients with plexiform neurofibromas(PN), as one of the main manifestations of NF1, often experience pain, dysfunction, skeletal deformities, changes in appearance and other symptoms. In severe cases, compression of the airways and vital organs occurs, and the PN is at risk of malignancy progression. At present, its treatment is still challenging. Surgery is the primary treatment for PN, but complete resection is often difficult. In recent years, chemotherapy for PN has become a hot topic. This article reviews the research progress in the pathogenesis, diagnosis and treatment of PN in recent years.
Topics: Child; Genes, Neurofibromatosis 1; Humans; Mutation; Neurofibroma, Plexiform; Neurofibromatosis 1
PubMed: 35822370
DOI: 10.13201/j.issn.2096-7993.2022.06.015 -
Diagnostics (Basel, Switzerland) Feb 2021We present a case demonstrating the performance of different radiographical imaging modalities in the diagnostic work-up of a patient with neurofibromatosis type 1 (NF1)...
We present a case demonstrating the performance of different radiographical imaging modalities in the diagnostic work-up of a patient with neurofibromatosis type 1 (NF1) and plexiform neurofibroma (PN). The newborn boy showed an expansive-infiltrative cervical and facial mass presented with macrocrania, craniofacial disfigurement, exophthalmos and glaucoma. A computer tomography (CT) and a magnetic resonance imaging (MRI) were performed. The CT was fundamental to evaluate the bone dysmorphisms and the MRI was crucial to estimate the mass extension. The biopsy of the lesion confirmed the suspicion of PN, thus allowing the diagnosis of NF1. PN is a variant of neurofibromas, a peripheral nerves sheath tumor typically associated with NF1. Even through currently available improved detection techniques, NF1 diagnosis at birth remains a challenge due to a lack of pathognomonic signs; therefore congenital PN are recognized in 20% of cases. This case highlights the importance of using different radiological methods both for the correct diagnosis and the follow-up of the patient with PN. Thanks to MRI evaluation, it was possible to identify earlier the progressive increasing size of the PN and the possible life threatening evolution in order to perform a tracheostomy to avoid airways compression.
PubMed: 33540839
DOI: 10.3390/diagnostics11020218 -
Journal of Clinical Oncology : Official... Jul 2022The NCI-COG Pediatric MATCH trial assigns patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II studies of...
Phase II Study of Selumetinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Genetic Alterations: Arm E of the NCI-COG Pediatric MATCH Trial.
PURPOSE
The NCI-COG Pediatric MATCH trial assigns patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II studies of molecularly targeted therapies on the basis of detection of predefined genetic alterations. Patients with tumors harboring mutations or fusions driving activation of the mitogen-activated protein kinase (MAPK) pathway were treated with the MEK inhibitor selumetinib.
METHODS
Patients received selumetinib twice daily for 28-day cycles until disease progression or intolerable toxicity. The primary end point was objective response rate; secondary end points included progression-free survival and tolerability of selumetinib.
RESULTS
Twenty patients (median age: 14 years) were treated. All were evaluable for response and toxicities. The most frequent diagnoses were high-grade glioma (HGG; n = 7) and rhabdomyosarcoma (n = 7). Twenty-one actionable mutations were detected: hotspot mutations in (n = 8), (n = 3), and (n = 1), inactivating mutations in (n = 7), and V600E (n = 2). No objective responses were observed. Three patients had a best response of stable disease including two patients with HGG ( mutation, six cycles; mutation, 12 cycles). Six-month progression-free survival was 15% (95% CI, 4 to 34). Five patients (25%) experienced a grade 3 or higher adverse event that was possibly or probably attributable to study drug.
CONCLUSION
A national histology-agnostic molecular screening strategy was effective at identifying children and young adults eligible for treatment with selumetinib in the first Pediatric MATCH treatment arm to be completed. MEK inhibitors have demonstrated promising responses in some pediatric tumors (eg, low-grade glioma and plexiform neurofibroma). However, selumetinib in this cohort with treatment-refractory tumors harboring MAPK alterations demonstrated limited efficacy, indicating that pathway mutation status alone is insufficient to predict response to selumetinib monotherapy for pediatric cancers.
Topics: Adolescent; Benzimidazoles; Child; Child, Preschool; Glioma; Humans; Infant; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins p21(ras); Young Adult
PubMed: 35363510
DOI: 10.1200/JCO.21.02840 -
Journal of Clinical Neuroscience :... Nov 2021Multinodular/plexiform schwannomas and neurofibromas of major nerves are rare: before surgery, differential diagnosis among these two uncommon variants is challenging....
BACKGROUND AND AIMS
Multinodular/plexiform schwannomas and neurofibromas of major nerves are rare: before surgery, differential diagnosis among these two uncommon variants is challenging. For both forms, surgical removal is recommended in case of progressive growth and worsening of neurological symptoms. Surgery has a higher risk of neurological damage than conventional schwannomas or neurofibromas. In literature, a comparison among these rare tumors is usually limited to the pathological aspect while specific surgical and clinical management indications are lacking. Cutaneous tumors of both forms arising from terminal peripheral nerves' branches might be treated by plastic surgeons while tumors of major nerves remain under neurosurgical competence. Here we report our recent neurosurgical experience on the matter, to furnish useful suggestions for the management of these tumors.
METHOD
We analyzed the clinical, radiological, and pathological data in a consecutive case series of plexiform/multinodular nerve tumors operated at our institution in the last five years.
RESULTS
In our series, neurofibroma type of plexiform tumors was more frequent than schwannoma type: two sporadic plexiform-multinodular schwannomas (patients 1, and 5) and three multinodular/plexiform Neurofibromatosis familial (Neurofibromatosis 1 / NF-1) (patients 2, 3, and 4). Surgery was complex when major nerves were involved. The early outcome appeared mostly related to the pre-surgical neurological conditions and histological grading.
INTERPRETATION
Although sharing some features, multinodular-plexiform schwannomas and neurofibromas have consistent differences from the clinical, surgical and pathological points of view.
Topics: Humans; Neurilemmoma; Neurofibroma; Neurofibromatoses; Neurofibromatosis 1; Peripheral Nerves
PubMed: 34656232
DOI: 10.1016/j.jocn.2021.09.022 -
World Journal of Clinical Cases Jul 2022Peripheral nerve sheath tumors (PNSTs), a rare group of neoplasms in the orbit, comprise only 4% of all orbital tumors. At present, there are very few studies detailing...
BACKGROUND
Peripheral nerve sheath tumors (PNSTs), a rare group of neoplasms in the orbit, comprise only 4% of all orbital tumors. At present, there are very few studies detailing the features of these tumors identified using imaging technology.
AIM
To compare the differences in location, morphology, magnetic resonance imaging (MRI) signal intensity/computed tomography (CT) value, and enhancement degree of tumors of different pathological PNSTs types.
METHODS
Clinical, pathological, CT, and MRI data were analyzed retrospectively in 34 patients with periorbital sheath tumors diagnosed using histopathology from January 2013 to August 2021.
RESULTS
Among 34 cases of orbital peripheral nerve sheath tumors, 21 were schwannomas, 12 were neurofibromas, and 1 was a plexiform neurofibroma. Common clinical symptoms presented by patients with these types of tumors include eyelid swelling, exophthalmos, and limited eye movement. Schwannomas mostly occur in the intramuscular space with small tumor volume and rare bone involvement. Neurofibromas develop in the extrapyramidal space with larger tumor volume and more bone involvement. Radiologically, schwannomas and neurofibromas are characterized by regular morphology and uneven density and signal. One case of plexiform neurofibroma showed tortuous and diffuse growth along the nerve, with a worm-like appearance on imaging.
CONCLUSION
Different pathological types of orbital peripheral nerve sheath tumors have unique imaging characteristics. Comprehensive consideration of the patient's clinical and imaging manifestations is of great value in the diagnosis of orbital peripheral nerve sheath tumors.
PubMed: 36158022
DOI: 10.12998/wjcc.v10.i21.7356 -
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 -
Radiologie (Heidelberg, Germany) Dec 2022Neurofibromatosis type 1 (NF1) is a tumor predisposition syndrome and is one of the most common genetic diseases. It is therefore a condition encountered by... (Review)
Review
BACKGROUND
Neurofibromatosis type 1 (NF1) is a tumor predisposition syndrome and is one of the most common genetic diseases. It is therefore a condition encountered by radiologists in clinical routine. Since the variability of the clinical expression is very high and several organ systems are affected, we present a standardized diagnostic approach in this article.
METHODS
Evaluation of the literature on neurofibromatosis type 1 in the context of radiological examination methods.
RESULTS
In addition to the frequently known changes in the central and peripheral nervous system such as optic gliomas and plexiform neurofibromas, lesions from the orthopedic spectrum and vascular changes must also be included in the radiological diagnosis.
CONCLUSIONS
Due to the diversity of the clinical picture of NF1, it is reasonable to define an examination strategy which takes into account the needs of radiological routine and also reliably detects the most frequent and prognostically significant pathologies accompanying this disease. In this article, the current recommendations for diagnosis of neurofibromatosis-associated tumors and skeletal changes are summarized, and examination protocols and time intervals are suggested.
Topics: Humans; Neurofibromatosis 1; Follow-Up Studies; Optic Nerve Glioma; Neurofibroma, Plexiform
PubMed: 36070094
DOI: 10.1007/s00117-022-01059-7