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Neuro-oncology Advances 2024Selumetinib is approved for the treatment of pediatric patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN) in...
BACKGROUND
Selumetinib is approved for the treatment of pediatric patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN) in multiple countries, including the USA (≥ 2 years). Until recently, individuals had to take selumetinib twice daily (BID) in a fasted state. This study evaluated the effect of a low-fat meal on selumetinib PK parameters and gastrointestinal (GI) tolerability in adolescent participants with NF1-PN.
METHODS
Eligible participants aged ≥ 12 to < 18 years took 25 mg/m selumetinib BID with a low-fat meal (T1) for 28 days, followed by a 7-day washout, and then administration in a fasted state (T2) for another 28 days. Primary objectives were to evaluate the effect of a low-fat meal on AUC and GI tolerability after multiple selumetinib doses in T1 versus T2. Key secondary objectives were additional PK parameters and adverse events (AEs).
RESULTS
At primary data cut-off, all 24 participants completed T1, and 23 participants completed T2. There were no significant differences in AUC between T1 and T2. In T1 and T2, 29.2% and 33.3% participants, respectively, reported ≥ 1 GI AE. No GI AEs Grade ≥ 3, or serious AEs, or GI AEs resulting in treatment interruptions, discontinuation, or dose reductions were reported in T1 and T2.
CONCLUSIONS
Dosing selumetinib with a low-fat meal had no clinically relevant impact on selumetinib AUC nor GI tolerability in adolescents with NF1-PN.
TRIAL REGISTRATION CLINICALTRIALSGOV ID
NCT05101148.
PubMed: 38721358
DOI: 10.1093/noajnl/vdae036 -
JMA Journal Apr 2024Even though an MEK inhibitor has been recently launched, neurofibroma still negatively affects the well-being of patients with neurofibromatosis type 1 (NF1). The...
INTRODUCTION
Even though an MEK inhibitor has been recently launched, neurofibroma still negatively affects the well-being of patients with neurofibromatosis type 1 (NF1). The coronavirus disease 2019 (COVID-19) pandemic resulted in restricted access to medical care. The present study was conducted to investigate the real-world settings of patients with NF1 who underwent surgery with or without restricted medical access during the COVID-19 pandemic.
METHODS
Based on data obtained from medical records, the present study examined 123 and 260 patients who underwent surgery for neurofibromas with and without restricted medical access, respectively.
RESULTS
The mean numbers of surgeries performed during the periods with and without restricted medical access were 5.8 and 9.8 per month, respectively, and there were 1.18- and 1.46-fold more female patients than male patients for each group, respectively. Regardless of whether medical access was restricted, the majority of patients who underwent surgery were middle-aged females with multiple or severe neurofibromas and mild extracutaneous symptoms. Tumor burden was the most common reason for surgery. However, cutaneous neurofibromas were more likely to be treated than plexiform neurofibromas under restricted medical access.
CONCLUSIONS
Patients with NF1, particularly middle-aged females with severe cutaneous manifestations and mild extracutaneous manifestations, still underwent surgery for neurofibromas regardless of whether medical access was restricted.
PubMed: 38721077
DOI: 10.31662/jmaj.2023-0161 -
American Society of Clinical Oncology... Jun 2024Most malignant peripheral nerve sheath tumors (MPNSTs) are clinically aggressive high-grade sarcomas, arising in individuals with neurofibromatosis type 1 (NF1) at a... (Review)
Review
Most malignant peripheral nerve sheath tumors (MPNSTs) are clinically aggressive high-grade sarcomas, arising in individuals with neurofibromatosis type 1 (NF1) at a significantly elevated estimated lifetime frequency of 8%-13%. In the setting of NF1, MPNSTs arise from malignant transformation of benign plexiform neurofibroma and borderline atypical neurofibromas. Composed of neoplastic cells from the Schwannian lineage, these cancers recur in approximately 50% of individuals, and most patients die within five years of diagnosis, despite surgical resection, radiation, and chemotherapy. Treatment for metastatic disease is limited to cytotoxic chemotherapy and investigational clinical trials. In this article, we review the pathophysiology of this aggressive cancer and current approaches to surveillance and treatment.
Topics: Humans; Neurofibromatosis 1; Nerve Sheath Neoplasms
PubMed: 38710002
DOI: 10.1200/EDBK_432242 -
The Pan African Medical Journal 2024
Topics: Humans; Female; Young Adult; Neurofibroma, Plexiform; Neurofibromatosis 1
PubMed: 38646135
DOI: 10.11604/pamj.2024.47.55.42510 -
Journal of Clinical and Experimental... Mar 2024Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited tumor predisposition disease with a highly variable phenotype. The influence of the characteristic NF1...
BACKGROUND
Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited tumor predisposition disease with a highly variable phenotype. The influence of the characteristic NF1 tumors (neurofibromas) on dentition has not yet been examined in detail. The aim of the study was to assess the dentition of NF1 children and adolescents, considering the symmetry of tooth development.
MATERIAL AND METHODS
The panoramic radiographs of 59 patients with a confirmed NF1 diagnosis were compared with 59 age-and-sex-matched controls. The stages of tooth development on the sides of the jaw, added to a score, were assessed. In addition, the number of filled or decayed teeth, and the number of retained or missing teeth were assessed.
RESULTS
The tooth development of both study groups is symmetrical for almost all parameters and in the same developmental stage according to the sum score of the tooth development stages. Discrete developmental delays of teeth, in particular in the oral area of facial plexiform neurofibroma (PNF) are noticeable. NF1 patients' teeth showed less decay and more restorations than that of the control group. The facial PNF (FPNF) does not impair emergence of deciduous teeth.
CONCLUSIONS
Development of dentition of NF1 patients does not differ from the general population. However, FPNF with oral tumor components often prevent mesial movement of permanent molars and premolars, so these teeth do not develop contact (spacing), hardly emerge or may stay retained in bone. Oral PNF may have a low-retarding effect on some tooth root development (e.g., wisdom teeth). This effect is negligible when comparing the affected and unaffected sides of the jaw and is probably non-specific. Neurofibromatosis type 1, plexiform neurofibroma, dentition, mixed dentition, symmetry, oral health, tooth development.
PubMed: 38600934
DOI: 10.4317/jced.61363 -
Cureus Feb 2024Plexiform neurofibroma is a benign peripheral nerve sheath tumor known to be pathognomonic for neurofibromatosis type 1. However, solitary plexiform neurofibroma in the...
Plexiform neurofibroma is a benign peripheral nerve sheath tumor known to be pathognomonic for neurofibromatosis type 1. However, solitary plexiform neurofibroma in the oral cavity is extremely rare. Herein, we presented a 73-year-old Saudi male with solitary plexiform neurofibroma located on the maxillary alveolar ridge, which was excised successfully using a 940 nm diode laser. Microscopic examination revealed a multinodular arrangement of benign spindle cells in a haphazard pattern. Immunohistochemical analysis showed positive staining for S100 and CD34 in the tumor cells.
PubMed: 38562267
DOI: 10.7759/cureus.55277 -
Pharmaceutics Mar 2024Neurofibromatosis Type 1 (NF1) is a common neurogenic condition characterized by heterozygous loss of function mutations in the neurofibromin gene. NF1 patients are...
Neurofibromatosis Type 1 (NF1) is a common neurogenic condition characterized by heterozygous loss of function mutations in the neurofibromin gene. NF1 patients are susceptible to the development of neurofibromas, including plexiform neurofibromas (pNFs), which occurs in about half of all cases. Plexiform neurofibroma are benign peripheral nerve sheath tumors originating from Schwann cells after complete loss of neurofibromin; they can be debilitating and also transform into deadly malignant peripheral nerve sheath tumors (MPNSTs). Here, our data indicates that silver nanoparticles (AgNPs) may be useful in the treatment of pNFs. We assessed the cytotoxicity of AgNPs using pNF cells and Schwann cells derived from the same NF1 patient. We found that AgNPs are selectively cytotoxic to pNF cells relative to isogenic Schwann cells. We then examined the role of neurofibromin expression on AgNP-mediated cytotoxicity; restoration of neurofibromin expression in pNF cells decreased sensitivity to AgNP, and knockdown of neurofibromin in isogenic Schwann cells increased sensitivity to AgNP, outlining a correlation between neurofibromin expression and AgNP-mediated cytotoxicity. AgNP was able to selectively remove pNF cells from a co-culture with patient-matched Schwann cells. Therefore, AgNPs represent a new approach for clinical management of NF1-associated pNF to address significant clinical need.
PubMed: 38543265
DOI: 10.3390/pharmaceutics16030371 -
Journal of Multidisciplinary Healthcare 2024The aim of this manuscript was to assess the epidemiology and clinical features of Neurofibromatosis type 1 (NF-1) based on the newly published revised NF-1 diagnostic...
PURPOSE
The aim of this manuscript was to assess the epidemiology and clinical features of Neurofibromatosis type 1 (NF-1) based on the newly published revised NF-1 diagnostic criteria and to evaluate complications of NF-1 including neurodevelopmental disorders.
PATIENTS AND METHODS
A retrospective cross-sectional observational study was conducted in the Ministry of National Guard Health Affairs (MNGHA) healthcare organization branches including four tertiary hospitals and 51 primary health care centers in different regions in Saudi Arabia. This study included all patients diagnosed with NF1 using the revised NIH diagnostic criteria published in 2021 that were registered at the electronic medical records (EMR) from 2015 to 2021.
RESULTS
A total of 184 patients fulfilled the diagnostic criteria and were included in this study. The median age at diagnosis was 11 years (IQR: 4.00-20.25). The most encountered diagnostic criteria in this study were Café-au-lait macules (85.3%), and (42.9%) were found to have two or more neurofibromas with plexiform neurofibroma being the most common subtype (23.36%), approximately (36.4%) of the patient with optic pathway glioma. Nearby (26.6%) of the patients displayed different type of tumors. Iris Lisch nodules were presented in 36.4% of patients at a median age of 12 years (IQR: 9.0-21.8). Cardiovascular abnormality was encountered in 9.8% of the patients. Around 27.7% of the patients reported headache and 11.4% of the patient suffered from different type of epilepsy. Besides, 10.5% of the patients had intellectual disability, 33.8% suffered from communication disorders, and 4.9% patients had ADHD.
CONCLUSION
The results of this study will enable practitioners to adopt a more holistic approach and prioritize numerous attributes, which they can subsequently incorporate into their therapeutic methodologies. Furthermore, the identification of these attributes will facilitate an expeditious and accurate diagnosis. Hence, the implementation of intervention during its nascent phase may result in a more advantageous consequence.
PubMed: 38533410
DOI: 10.2147/JMDH.S454921 -
Journal of Patient-reported Outcomes Mar 2024Half of the patients with Neurofibromatosis type 1 (NF1) develop one or more tumours called plexiform neurofibromas, which can have a significant impact on Quality of...
The PlexiQoL, a patient-reported outcome measure on quality of life in neurofibromatosis type 1-associated plexiform neurofibroma: translation, cultural adaptation and validation into the Dutch language for the Netherlands.
BACKGROUND
Half of the patients with Neurofibromatosis type 1 (NF1) develop one or more tumours called plexiform neurofibromas, which can have a significant impact on Quality of Life (QoL). The PlexiQoL questionnaire is a disease-specific QoL measure for adults with NF1-associated plexiform neurofibromas. The aim of this study was to adapt and validate a Dutch version of the PlexiQoL for the Netherlands.
METHODS
The PlexiQoL was translated using the dual-panel methodology, followed by cognitive debriefing interviews to assess face and content validity. The psychometric properties were evaluated by administering the questionnaire on two separate occasions to a sample of adults with NF1 and plexiform neurofibromas. Feasibility was evaluated by the presence of floor/ceiling effects. Reliability was assessed by evaluating Cronbach's alpha coefficient and test-retest reliability, using Spearman's rank correlation coefficients. Mann-Whitney U tests were used to check for known group validity. The Nottingham Health Profile (NHP) questionnaire was used as comparator questionnaire to evaluate convergent validity.
RESULTS
The translation and cognitive debriefing interviews resulted in a Dutch version of the PlexiQoL that reflected the original concept and underlying semantic meanings of the UK English version. Forty participants completed the validation survey. The Dutch PlexiQoL demonstrated excellent internal consistency (Cronbach's α 0.825) and test-retest reliability (Spearman correlation coefficient 0.928). The questionnaire detected differences in PlexiQoL scores between participants based on self-reported general health and disease severity. Convergent validity was confirmed for relevant NHP subsections.
CONCLUSIONS
The Dutch PlexiQoL demonstrated excellent psychometric properties and can be reliably used to measure plexiform neurofibroma-related QoL in adults with NF1 in the Netherlands.
Topics: Adult; Humans; Quality of Life; Neurofibroma, Plexiform; Neurofibromatosis 1; Netherlands; Reproducibility of Results; Language; Patient Reported Outcome Measures
PubMed: 38499890
DOI: 10.1186/s41687-024-00714-y -
Cancers Feb 2024Neurofibromatosis type 1 (NF1) is a common genetic disorder resulting in the development of both benign and malignant tumors of the peripheral nervous system. NF1 is... (Review)
Review
Neurofibromatosis type 1 (NF1) is a common genetic disorder resulting in the development of both benign and malignant tumors of the peripheral nervous system. NF1 is caused by germline pathogenic variants or deletions of the tumor suppressor gene, which encodes the protein neurofibromin that functions as negative regulator of p21 RAS. Loss of heterozygosity in Schwann cells (SCs), the cells of origin for these nerve sheath-derived tumors, leads to the formation of plexiform neurofibromas (PNF)-benign yet complex neoplasms involving multiple nerve fascicles and comprised of a myriad of infiltrating stromal and immune cells. PNF development and progression are shaped by dynamic interactions between SCs and immune cells, including mast cells, macrophages, and T cells. In this review, we explore the current state of the field and critical knowledge gaps regarding the role of haploinsufficiency on immune cell function, as well as the putative impact of Schwann cell lineage states on immune cell recruitment and function within the tumor field. Furthermore, we review emerging evidence suggesting a dueling role of immune cells along the neurofibroma to MPNST continuum, on one hand propitiating PNF initiation, while on the other, potentially impeding the malignant transformation of plexiform and atypical neurofibroma precursor lesions. Finally, we underscore the potential implications of these discoveries and advocate for further research directed at illuminating the contributions of various immune cells subsets in discrete stages of tumor initiation, progression, and malignant transformation to facilitate the discovery and translation of innovative diagnostic and therapeutic approaches to transform risk-adapted care.
PubMed: 38473354
DOI: 10.3390/cancers16050994