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The Journal of Pediatrics Sep 2023To assess the hypothesis that plexiform neurofibroma (PN) growth rates increase during puberty.
OBJECTIVE
To assess the hypothesis that plexiform neurofibroma (PN) growth rates increase during puberty.
STUDY DESIGN
PN growth rates before and during puberty were compared in a retrospective cohort of children with neurofibromatosis type 1 with puberty defined by Tanner staging. Of 33 potentially eligible patients, 25 had adequate quality magnetic resonance imaging for volumetric analysis and were included in ≥1 anchor cohort. Volumetric analysis was performed for all available imaging studies within the 4 years before and after puberty, and before and after 9- and 11-year-old anchor scans. Linear regression was performed to estimate the slope of change (PN growth rate); growth rates were compared with paired t test or Wilcoxon matched-pairs signed rank test.
RESULTS
There were no significant difference in rates of PN growth in milliliters per month or milliliters per kilogram per month in the prepubertal vs pubertal periods (mean, 1.33 ± 1.67 vs 1.15 ± 1.38 [P = .139] and -0.003 ± 0.015 vs -0.002 ± 0.02 [P = .568]). Percent increases of PN volumes from baseline per month were significantly higher prepubertally (1.8% vs 0.84%; P = .041) and seemed to be related inversely to advancing age.
CONCLUSIONS
Puberty and its associated hormonal changes do not seem to influence PN growth rate. These findings support those previously reported, but from a typical population of children with neurofibromatosis type 1 with puberty confirmed by Tanner staging.
Topics: Child; Humans; Neurofibroma, Plexiform; Neurofibromatosis 1; Retrospective Studies; Cohort Studies; Puberty
PubMed: 37244583
DOI: 10.1016/j.jpeds.2023.113513 -
Acta Medica Portuguesa Dec 2023
Topics: Humans; Neurofibroma, Plexiform; Neurofibromatosis 1
PubMed: 37205744
DOI: 10.20344/amp.19477 -
Cureus Apr 2023Background Neurofibromatosis type 1 (NF1) is a complex disorder. Genetics and environment might be attributed as the leading cause of NF1, which is characterized by...
Background Neurofibromatosis type 1 (NF1) is a complex disorder. Genetics and environment might be attributed as the leading cause of NF1, which is characterized by multisystemic involvement. We aim to elaborate on Saudi children's NF1 phenotypes and genotypes. Methods This study was conducted in the Ministry of National Guard Health Affairs (MNGHA), Saudi Arabia including three tertiary hospitals, using a retrospective cohort method. Electronic charts were reviewed to extract the variables. All Saudi pediatric patients aged less than 18 with NF1 were included. Consecutive sampling was used due to the limited number of patients. Results The study included 160 patients (81 males) with an average age of 8.08 years. Also, 33 (20.6%) patients had cutaneous neurofibroma while 31 (19.4%) patients had plexiform neurofibromas. Iris lisch nodules were seen in 33.75%. Optic pathway glioma was seen in 29 (18%) cases while non-optic pathway glioma was seen in 27 (17%) cases. Skeletal abnormalities were seen in 27 (17%) of cases. A first-degree relative with NF1 was seen in 83 (52%) of cases. Epilepsy was the presenting feature of 27 (17%) cases. Cognitive impairment was found in 15 (9.4%) patients. Genetic mutation was seen in 82/100 cases, the rest were negative. The types of mutations were as follows: nonsense 30 (36.6%); missense 20 (24.4%); splicing site mutation 12 (14.6%); frameshift 10 (12.2%); microdeletion 7 (8.5%); and whole gene deletion 3 (3.75%) patients. No phenotype-genotype correlation was seen. Conclusion In this cohort of Saudi pediatric patients with NF1, optic pathway glioma and other brain tumors were prevalent. The most common mutation is the nonsense mutation.
PubMed: 37181996
DOI: 10.7759/cureus.37385 -
Cancers May 2023Limited therapies exist for neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN). For this reason, the activity of vinblastine (VBL) and methotrexate...
Limited therapies exist for neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN). For this reason, the activity of vinblastine (VBL) and methotrexate (MTX) was evaluated in children and young adults with NF1 and PN. Patients ≤ 25 years of age with progressive and/or inoperable NF1-PN received VBL 6 mg/m and MTX 30 mg/m weekly for 26 weeks, followed by every 2 weeks for 26 weeks. Objective response rate was the primary endpoint. Of 25 participants enrolled, 23 were evaluable. The median age of participants was 6.6 years (range 0.3-20.7). The most frequent toxicities were neutropenia and elevation of transaminases. On two-dimensional (2D) imaging, 20 participants (87%) had stable tumor, with a median time to progression of 41.5 months (95% confidence interval 16.9, 64.9). Two of eight participants (25%) with airway involvement demonstrated functional improvements including decreased positive pressure requirements and apnea-hypopnea index. A post hoc three-dimensional (3D) analysis of PN volumes was completed on 15 participants with amenable imaging; 7 participants (46%) had progressive disease on or by the end of therapy. VBL/MTX was well-tolerated but did not result in objective volumetric response. Furthermore, 3D volumetric analysis highlighted the lack of sensitivity of 2D imaging for PN response evaluation.
PubMed: 37174087
DOI: 10.3390/cancers15092621 -
Oral and Maxillofacial Surgery Mar 2024Plexiform neurofibromas (PNF) are rare tumors arising from peripheral nerve sheath cells. PNF are a hallmark in patients with neurofibromatosis type 1 (NF1), a tumor...
PURPOSE
Plexiform neurofibromas (PNF) are rare tumors arising from peripheral nerve sheath cells. PNF are a hallmark in patients with neurofibromatosis type 1 (NF1), a tumor predisposition syndrome. PNF often grow invasively and destructively, what may complicate surgical treatment. Data on frequency, location, and surgical procedures of patients with NF1-associated FPNF are scarce. This study provides treatment data of NF1 patients.
METHODS
Localization and treatment data of 69 NF1 patients with neck PNF were analyzed. Frequency of lesions was recorded in coded colors on schematic neck drawings.
RESULTS
The tumors showed no side preference, were located in the entire area under investigation, and did not respect anatomical units/dermatomes. However, the sternocleidomastoid region was particularly frequently affected. The mean number of surgical measures per patient was 1.33. Complications were extensive swelling, hematoma, and bleeding. Histological assessment usually confirmed the clinical assessment of neoplasm. However, histologic differentiation of PNST reveals differences in between tumors that have been unified in clinical assessment as PNF.
CONCLUSION
The color-coded, schematic overview of the frequency distribution of surgical neck interventions in NF1 patients with PNF proved a useful tool to gain assessment of preferred treatment needs. The imaging procedure may be suitable for controlling the external aspect of natural tumor development (growth, effects of aging) in the same way as the documentation of the post-surgical course. Treatment plans for patients with these tumors should consider that repeated interventions may be necessary to achieve a longer-term stable result.
Topics: Humans; Neurofibroma, Plexiform; Neurofibromatosis 1
PubMed: 37173460
DOI: 10.1007/s10006-023-01155-5 -
The Journal of Clinical Investigation Jun 2023Neurofibromatosis type 1 (NF1) is one of the most common tumor-predisposing genetic disorders. Neurofibromas are NF1-associated benign tumors. A hallmark feature of...
Neurofibromatosis type 1 (NF1) is one of the most common tumor-predisposing genetic disorders. Neurofibromas are NF1-associated benign tumors. A hallmark feature of neurofibromas is an abundant collagen-rich extracellular matrix (ECM) that constitutes more than 50% of the tumor dry weight. However, little is known about the mechanism underlying ECM deposition during neurofibroma development and treatment response. We performed a systematic investigation of ECM enrichment during plexiform neurofibroma (pNF) development and identified basement membrane (BM) proteins, rather than major collagen isoforms, as the most upregulated ECM component. Following MEK inhibitor treatment, the ECM profile displayed an overall downregulation signature, suggesting ECM reduction as a therapeutic benefit of MEK inhibition. Through these proteomic studies, TGF-β1 signaling was identified as playing a role in ECM dynamics. Indeed, TGF-β1 overexpression promoted pNF progression in vivo. Furthermore, by integrating single-cell RNA sequencing, we found that immune cells including macrophages and T cells produce TGF-β1 to induce Schwann cells to produce and deposit BM proteins for ECM remodeling. Following Nf1 loss, neoplastic Schwann cells further increased BM protein deposition in response to TGF-β1. Our data delineate the regulation governing ECM dynamics in pNF and suggest that BM proteins could serve as biomarkers for disease diagnosis and treatment response.
Topics: Humans; Neurofibromatosis 1; Transforming Growth Factor beta1; Membrane Proteins; Proteomics; Neurofibroma; Protein Kinase Inhibitors; Collagen; Basement Membrane; Extracellular Matrix; Mitogen-Activated Protein Kinase Kinases; Schwann Cells
PubMed: 37140985
DOI: 10.1172/JCI168227 -
Neuro-oncology Oct 2023Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many in our...
BACKGROUND
Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many in our previously published phase 1/2 clinical trials (SPRINT, NCT01362803). At the data cutoff (DCO) of the prior publications, 65% of participants were still receiving treatment. This report presents up to 5 years of additional safety and efficacy data from these studies.
METHODS
This manuscript includes data from the phase 1 and phase 2, stratum 1 study which included participants with clinically significant PN-related morbidity. Participants received continuous selumetinib dosing (1 cycle = 28 days). Safety and efficacy data through February 27, 2021 are included. PN response assessed by volumetric magnetic resonance imaging analysis: Confirmed partial response (cPR) ≥20% decrease from baseline on 2 consecutive evaluations. Phase 2 participants completed patient-reported outcome measures assessing tumor pain intensity (Numeric Rating Scale-11) and interference of pain in daily life (pain interference index).
RESULTS
For the 74 children (median age 10.3 years; range 3-18.5) enrolled, overall cPR rate was 70% (52/74); median duration of treatment was 57.5 cycles (range 1-100). Responses were generally sustained with 59% (44) lasting ≥ 12 cycles. Tumor pain intensity (n = 19, P = .015) and pain interference (n = 18, P = .0059) showed durable improvement from baseline to 48 cycles. No new safety signals were identified; however, some developed known selumetinib-related adverse events (AEs) for the first time after several years of treatment.
CONCLUSIONS
With up to 5 years of additional selumetinib treatment, most children with NF1-related PN had durable tumor shrinkage and sustained improvement in pain beyond that previously reported at 1 year. No new safety signals were identified; however, ongoing monitoring for known selumetinib-related AEs is needed while treatment continues.
Topics: Child; Humans; Neurofibromatosis 1; Neurofibroma, Plexiform; Benzimidazoles; Pain
PubMed: 37115514
DOI: 10.1093/neuonc/noad086 -
Cureus Mar 2023Teratomas are a type of germ cell tumor that may contain several different types of tissue. Neurofibroma is a benign peripheral nerve sheath tumor with the plexiform...
Teratomas are a type of germ cell tumor that may contain several different types of tissue. Neurofibroma is a benign peripheral nerve sheath tumor with the plexiform type being pathognomonic for neurofibromatosis type 1. We report a case of a 33-year-old woman with a background of Neurofibromatosis type 1 who presented with left-sided chest pain and shortness of breath. She was diagnosed with a large mediastinal mass which was confirmed from a CT-guided biopsy as neurofibroma. Following a multidisciplinary team discussion, she underwent mediastinal mass resection and the final histopathology report revealed mediastinal mature teratoma.
PubMed: 37095824
DOI: 10.7759/cureus.36562 -
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 -
The Pan African Medical Journal 2023
Topics: Humans; Neurofibromatoses; Face; Neurofibroma, Plexiform; Neurofibromatosis 1
PubMed: 37013203
DOI: 10.11604/pamj.2023.44.25.37895