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Pharmaceuticals (Basel, Switzerland) Jul 2022Trametinib has been used in neurofibromatosis type 1 (NF1) patients, especially those with unresectable nerve tumors, but no systematic review based on the latest... (Review)
Review
Trametinib has been used in neurofibromatosis type 1 (NF1) patients, especially those with unresectable nerve tumors, but no systematic review based on the latest studies has been published. We conducted this meta-analysis to evaluate the effectiveness and safety of trametinib in treating NF1-related nerve tumors. Original articles reporting the efficacy and safety of trametinib in NF1 patents were identified in PubMed, EMBASE, and Web of Science up to 1 June 2022. Using R software and the 'meta' package, the objective response rates (ORRs) and disease control rates (DCRs) were calculated to evaluate the efficacy, and the pooled proportion of adverse events (AEs) was calculated. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. Eight studies involving 92 patients were included, which had a very low to moderate quality of evidence. The pooled ORR was 45.3% (95% CI: 28.9-62.1%, I = 0%), and the DCR was 99.8% (95% CI: 95.5-100%, I = 0%). The most common AEs was paronychia, with a pooled rate of 60.7% (95% CI: 48.8-72.7%, I = 0%). Our results indicate the satisfactory ability to stabilize tumor progression but a more limited ability to shrink tumors of trametinib in NF1-related nerve tumors. The safety profile of trametinib is satisfactory.
PubMed: 36015104
DOI: 10.3390/ph15080956 -
Pediatric Neurology Sep 2022The neurofibromatoses comprise three different genetic conditions causing considerable morbidity and mortality: neurofibromatosis type 1 (NF1), neurofibromatosis type 2... (Review)
Review
INTRODUCTION
The neurofibromatoses comprise three different genetic conditions causing considerable morbidity and mortality: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN). This review summarizes recent and ongoing clinical trials involving patients with neurofibromatoses to better understand the current state of clinical trial research centered around these conditions and inform areas of need.
METHODS
A search was conducted using the Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases. Inclusion and exclusion criteria were designed to identify clinical trials focused on patients with NF1, NF2, or SWN completed in or after 2010 and in process as of December 31, 2021. Information was collected using standardized guidelines.
RESULTS
A total of 134 clinical trials were included, with 75 (56%) completed and 59 (44%) in process. For completed trials, 74% (n = 56) involved patients with NF1, and of those based on specific tumors (n = 26, 46%), the majority focused on plexiform neurofibromas (PNs) (n = 12, 46%). For ongoing trials, 79% (n = 47) involve patients with NF1, and of those based on specific tumors (n = 29, 61%), the majority are focused on PNs (n = 13, 45%).
CONCLUSION
Both recent and ongoing clinical trials have primarily focused on patients with NF1 and the treatment of PNs. This research has led to the first FDA-approved drug for NF1-PN and has changed management of these tumors, allowing for systemic therapy rather than reliance on only a surgical modality. Trials evaluating comorbid psychiatric conditions and quality of life among patients with any of the neurofibromatoses appear less common. These areas may warrant focus in future studies to improve clinical management.
Topics: Humans; Neurilemmoma; Neurofibroma, Plexiform; Neurofibromatoses; Neurofibromatosis 1; Neurofibromatosis 2; Quality of Life; Skin Neoplasms
PubMed: 35759947
DOI: 10.1016/j.pediatrneurol.2022.06.003 -
Neurological Sciences : Official... Feb 2022Patients with neurofibromatosis type-1 (NF-1) and associated plexiform neurofibromas (PNs) often have a high burden of illness owing to debilitating symptoms of these...
PURPOSE
Patients with neurofibromatosis type-1 (NF-1) and associated plexiform neurofibromas (PNs) often have a high burden of illness owing to debilitating symptoms of these tumors and limited management options. To investigate this complex disease, a systematic literature review (SLR) was conducted on the epidemiology of pediatric NF-1 and associated PNs, the burden of illness, and outcomes of surgical resection of these tumors.
METHODS
Searches of MEDLINE and Embase (from database inception to October 2019) and conference proceedings (2017-2019) were performed to identify relevant studies. The review methodology was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
Twenty studies were identified. Evidence confirmed NF-1 is rare but that occurrence may differ geographically. Only limited data on the birth incidence of NF-1 were identified. Prevalence estimates for pediatric NF-1 varied from one per 960 individuals (aged 17 years) to one per 5681 children (aged < 16 years) across five large registry/surveillance studies (each involving > 19,000 individuals). The prevalence of associated PNs was 0-29.6%. PNs carried increased mortality risk in pediatric NF-1 in both studies that explored this potential association. Patients with PNs reported high use of analgesics. The complication rate post-surgery for PNs was around 17-19%. The recurrence rate (18-68%) was dependent on the extent of excision achieved during surgery.
CONCLUSIONS
Data suggest NF-1 is a rare disease with increased morbidity and mortality in children with associated PNs. Surgical outcomes for PNs are often poor. These findings suggest significant unmet needs in patients with NF-1-associated PNs.
Topics: Child; Humans; Neurofibroma, Plexiform; Neurofibromatosis 1
PubMed: 34143343
DOI: 10.1007/s10072-021-05361-5 -
International Journal of Surgical... 2016. Malignant peripheral nerve sheath tumours (MPNSTs) are difficult to diagnose and treat and contribute to significant morbidity and mortality for patients with... (Review)
Review
. Malignant peripheral nerve sheath tumours (MPNSTs) are difficult to diagnose and treat and contribute to significant morbidity and mortality for patients with Neurofibromatosis-1 (NF-1). FDG-PET/CT is being increasingly used as an imaging modality to discriminate between benign and malignant plexiform neurofibromas. . To assess the value of FDG-PET/CT in differentiating between benign and malignant peripheral nerve lesions for patients with Neurofibromatosis-1. . A systematic review of the literature was performed prior to application of stringent selection criteria. Ultimately 13 articles with 796 tumours were deemed eligible for inclusion into the review. . There was a significant difference between mean SUV of benign and malignant lesions (1.93 versus 7.48, resp.). Sensitivity ranged from 89 to 100% and specificity from 72 to 94%. ROC analysis was performed to maximise sensitivity and specificity of SUV cut-off; however no clear value was identified (range 3.1-6.1). Significant overlap was found between the SUV of benign and malignant lesions making differentiation of lesions difficult. Many of the studies suffered from having a small cohort and from not providing histological data on all lesions which underwent FDG-PET/CT. . This systematic review is able to demonstrate that FDG-PET/CT is a useful noninvasive test for discriminating between benign and malignant lesions but has limitations and requires further prospective trials.
Topics: Cell Transformation, Neoplastic; Diagnosis, Differential; Fluorodeoxyglucose F18; Humans; Neurofibroma, Plexiform; Neurofibromatosis 1; Positron Emission Tomography Computed Tomography; ROC Curve; Radiopharmaceuticals; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 28058117
DOI: 10.1155/2016/6162182