scholarly journals Retrospective Multicentric Study on Non-Optic CNS Tumors in Children and Adolescents with Neurofibromatosis Type 1

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1426
Author(s):  
Claudia Santoro ◽  
Stefania Picariello ◽  
Federica Palladino ◽  
Pietro Spennato ◽  
Daniela Melis ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Age At Onset ◽  
Young Patients ◽  
Progression Free Survival ◽  
Neurofibromatosis Type ◽  
Cns Tumors ◽  
Optic Pathway Glioma ◽  
Low Grade ◽  
Multicentric Study

The natural history of non-optic central nervous system (CNS) tumors in neurofibromatosis type 1 (NF1) is largely unknown. Here, we describe prevalence, clinical presentation, treatment, and outcome of 49 non-optic CNS tumors observed in 35 pediatric patients (0–18 years). Patient- and tumor-related data were recorded. Overall survival (OS) and progression-free survival (PFS) were evaluated. Eighteen patients (51%) harbored an optic pathway glioma (OPG) and eight (23%) had multiple non-optic CNS lesions. The majority of lesions (37/49) were managed with a wait-and-see strategy, with one regression and five reductions observed. Twenty-one lesions (42.9%) required surgical treatment. Five-year OS was 85.3%. Twenty-four patients progressed with a 5-year PFS of 41.4%. Patients with multiple low-grade gliomas progressed earlier and had a lower 5-year PFS than those with one lesion only (14.3% vs. 57.9%), irrespective of OPG co-presence. Non-optic CNS tumors are common in young patients with NF1. Neither age and symptoms at diagnosis nor tumor location influenced time to progression in our series. Patients with multiple lesions tended to have a lower age at onset and to progress earlier, but with a good OS.

scholarly journals Nonoptic pathway tumors in children with neurofibromatosis type 1

Neurology ◽  
2020 ◽  
Vol 95 (8) ◽  
pp. e1052-e1059 ◽  
Author(s):  
Jasia Mahdi ◽  
Manu S. Goyal ◽  
Jennifer Griffith ◽  
Stephanie M. Morris ◽  
David H. Gutmann
Keyword(s):  
Natural History ◽  
Neurofibromatosis Type 1 ◽  
Radiographic Progression ◽  
Progression Free Survival ◽  
Neurofibromatosis Type ◽  
Tumor Location ◽  
Age At Diagnosis ◽  
Optic Pathway Glioma ◽  
Cross Sectional

ObjectiveTo define the radiologic features and natural history of nonoptic pathway tumors (non-OPTs) in children with neurofibromatosis type 1 (NF1).MethodsWe performed a retrospective cross-sectional analysis of 64 children with NF1 harboring 100 probable non-OPTs. Age at diagnosis, sex, tumor location, number of tumors, symptomology, concurrent OPT, radiographic progression (defined as qualitative and quantitative increases in size), and treatment were assessed. Tumor volumes were measured from initial presentation until treatment or end of disease progression.ResultsSixty-three percent of probable non-OPTs progressed over time, where radiographic progression was concomitantly associated with clinical progression. Fifty-two percent of patients had incidentally identified probable non-OPTs. Twenty-five percent of patients were symptomatic at initial diagnosis, all of whom harbored tumors that grew on subsequent scans and required tumor-directed therapy. There were no clinical differences between probable non-OPTs localized to the brainstem vs other locations with respect to age, sex, concurrent optic pathway glioma, symptomology, and treatment. The average time from diagnosis to stabilization or decrease in tumor size was 2.34 years (SD, 2.15 years). Nineteen biopsied lesions were all histopathologically confirmed as tumor. Six children (9%) had deep extensive tumors, who presented earlier (mean age at diagnosis, 3.88 years), required multiple treatments, and had a shorter mean progression-free survival (48 months).ConclusionsOver half of children with NF1 in this study developed probable non-OPTs, the majority of which were clinically and radiographically progressive. While brainstem and nonbrainstem gliomas share similar clinical features and natural history, deep extensive tumors comprise a distinct aggressive group of tumors that warrant close attention.

scholarly journals RARE-54. MEK INHIBITION FOR AGGRESSIVE GLIOMAS IN ADULTS WITH NEUROFIBROMATOSIS TYPE 1

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi233-vi233
Author(s):  
Carlos Romo ◽  
Bronwyn Slobogean ◽  
Lindsay Blair ◽  
Jaishri O Blakeley
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Synergistic Effects ◽  
Single Agent ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Optimal Dose ◽  
Neurofibromatosis Type ◽  
Low Grade ◽  
Mek Inhibition

Abstract BACKGROUND Neurofibromatosis type 1 (NF1) is caused by mutations of the tumor suppressor gene NF1 resulting in decreased levels of neurofibromin and dysregulation of the RAS pathway, including MEK/ERK upregulation. Central nervous system malignancies have an overall standardized incidence ratio of 37.5 in population studies, with higher rates of aggressive gliomas in adults with NF1. Further, the response to standard glioma therapies in this population is mixed in published series. MEK1/2 inhibitors have shown activity in both NF1 driven plexiform neurofibromas and low grade gliomas, however, data is lacking about their optimal dose or sequencing relative to standard glioma therapies for adults with NF1 associated aggressive gliomas. We present recent experiences with the MEK1/2 inhibitor trametinib in adults with NF1 and newly diagnosed aggressive gliomas. METHODS A retrospective chart review was conducted on all adult patients with NF1 and astrocytoma treated with trametinib at the Johns Hopkins Brain Cancer Program from 2016 to 2018. RESULTS Four patients met selection criteria. Median age at diagnosis was 37 years [25–43]. Histologic diagnoses were: pilocytic astrocytoma (1), diffuse astrocytomas (2), and anaplastic astrocytoma (1). All tumors were IDH1 wild-type. Three received trametinib as frontline therapy (2 mg daily), one as second line treatment. All achieved a partial radiographic response within 2 months from the start of trametinib. Median overall survival was 15 months [4–19]; three patients are alive at publication, with a median of 12 months from diagnosis. Median progression-free survival was 2.5 months [1–11]. CONCLUSIONS Astrocytomas in adults with NF1, including histologically low-grade tumors, often have a more aggressive course than suggested by histology. These cases demonstrate clinical benefit from single agent MEK inhibition as well as possible synergistic effects with conventional therapies for gliomas in people with NF1, however, prospective investigation is needed.

Visual outcomes after chemotherapy for optic pathway glioma in children with and without neurofibromatosis type 1: results of the International Society of Paediatric Oncology (SIOP) Low-Grade Glioma 2004 trial UK cohort

2018 ◽  
Vol 102 (10) ◽  
pp. 1367-1371 ◽  
Author(s):  
Kevin Falzon ◽  
Evangelos Drimtzias ◽  
Susan Picton ◽  
Ian Simmons
Keyword(s):  
Risk Factors ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Paediatric Oncology ◽  
Optic Pathway Glioma ◽  
Final Visit ◽  
Low Grade ◽  
Optic Pathway ◽  
Associated Risk Factors

AimsTo report visual acuity (VA) outcomes following chemotherapy for optic pathway glioma (OPG) in children with or without neurofibromatosis type-1 (NF1) and to analyse associated risk factors.MethodsA prospective, multicentre, cohort study involving 155 children treated between September 2004 and December 2012. Initial and final VA was used for per-eye and per-subject analysis. Correlation tests were performed to determine whether initial VA predicted final VA. Logistic regression was used to determine whether age and tumour location were associated risk factors.Results90 children had complete ophthalmological data. At initiation of chemotherapy, 26% and 49% of eyes with NF1-OPG and sporadic OPG, respectively, had VA of ≥0.7 log of the minimum angle of resolution (logMAR). At final visit, per eye, 49% had ≤0.2, 23% had 0.30–0.60 and 28% had VA≥0.70 logMAR in the NF1-OPG group. In the sporadic OPG group, per eye, 32% had ≤0.2, 11% had VA 0.30–0.60 and 57% had ≥0.70 logMAR. Children with sporadic OPG, per eye, were significantly less likely to have VA outcomes ≤0.60 logMAR compared with children with NF1-OPG (OR=0.30; 95% CI 0.16 to 0.56; P<0.0001). Per subject, VA improved in 24%, remained stable in 35% and worsened in 41% of children with NF1-OPG and improved in 18%, remained stable in 43% and worsened in 39% of children with sporadic OPG.ConclusionsChildren with and without NF1 demonstrated the same rate of VA improvement, stabilisation or worsening; however, children with sporadic OPG had a poorer VA outcome. Better initial VA, older age, absence of postchiasm tumour and presence of NF1 were associated with improved or stable VA outcomes.

scholarly journals Optic pathway glioma and the sex association in neurofibromatosis type 1: a single-center study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Anne Munk Henning ◽  
Mette Møller Handrup ◽  
Sia Mariann Kjeldsen ◽  
Dorte Ancher Larsen ◽  
Cecilie Ejerskov
Keyword(s):  
Risk Factor ◽  
Visual Impairment ◽  
Neurofibromatosis Type 1 ◽  
Protective Factor ◽  
Neurofibromatosis Type ◽  
University Hospital ◽  
Optic Pathway Glioma ◽  
Low Grade ◽  
Optic Pathway

Abstract Background Low-grade optic pathway glioma (OPG) develops in 15–20% of children with neurofibromatosis type 1 (NF1). OPGs are symptomatic in 30–50% and one-third of these require treatment. A few studies have suggested female sex as a risk factor for visual impairment associated with NF1-OPG. This descriptive study investigated the correlation between NF1-OPG growth, sex and visual impairment. Method We based our cross-sectional study on a systematic, retrospective data collection in a NF1 cohort of children and adolescents below 21 years of age followed at Center for Rare Diseases, Aarhus University Hospital, Denmark. For each patient with OPG a medical chart review was performed including demographics, ophthalmological examinations and magnetic resonance imaging (MRI) of OPG. Results Of 176 patients with NF1 (85 females, 91 males), we identified 21 patients with OPG (11.9%) with a preponderance of females, p = 0.184. Eight females (62%) and one male (13%) had visual impairment at the last ophthalmological evaluation. Five out of 21 children with OPG (24%) underwent diagnostic MRI because of clinical findings at the ophthalmological screening. Nine children (43%) had symptoms suggestive of OPG and seven (33%) experienced no OPG-related symptoms before the diagnostic MRI. Of eight children diagnosed with OPG ≤ two years of age, one had visual impairment. Of 13 children diagnosed > two years of age, eight had visual impairment; in each group, four of the children were treated with chemotherapy. The study suggested no correlation between NF1-OPG growth and sex. Conclusion Our data suggest sex as a risk factor for visual impairment, while an OPG diagnose ≤ two years of age was a protective factor for visual impairment. Females with NF1-OPG had a higher prevalence of visual impairment outcome compared to males. Interestingly, our data also suggest a better response to treatment in children with OPG diagnosed ≤ two years of age compared to older children. The findings in our study suggest sex as a potential prognostic factor for visual impairment.

Optic pathway glioma with intraocular extension in a child with neurofibromatosis type-1

2020 ◽  
Vol 43 (5) ◽  
pp. e179-e181
Author(s):  
F. Palma-Carvajal ◽  
H. González-Valdivia ◽  
J.P. Figueroa-Vercellino ◽  
C. Saavedra-Gutiérrez ◽  
C. Rovira-Zurriaga ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Optic Pathway Glioma ◽  
Optic Pathway

scholarly journals High-Dose Intravenous Vitamin C Treatment of a Child with Neurofibromatosis Type 1 and Optic Pathway Glioma: A Case Report

2016 ◽  
Vol 17 ◽  
pp. 774-781 ◽  
Author(s):  
Nina Mikirova ◽  
Ronald Hunnunghake ◽  
Ruth C. Scimeca ◽  
Charles Chinshaw ◽  
Faryal Ali ◽  
...  
Keyword(s):  
Case Report ◽  
Vitamin C ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Optic Pathway Glioma ◽  
High Dose ◽  
Optic Pathway ◽  
Intravenous Vitamin

Macrocephaly Is Not a Predictor of Optic Pathway Glioma Development or Treatment in Neurofibromatosis Type 1

2016 ◽  
Vol 31 (14) ◽  
pp. 1540-1545 ◽  
Author(s):  
Stephanie M. Morris ◽  
Courtney L. Monroe ◽  
David H. Gutmann
Keyword(s):  
Prognostic Factor ◽  
Brain Tumors ◽  
Clinical Features ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Optic Pathway Glioma ◽  
Optic Pathway ◽  
Clinical Progression ◽  
Clinical Biomarkers

Neurofibromatosis type 1 is a common neurogenetic disorder characterized by significant clinical variability. As such, numerous studies have focused on identifying clinical, radiographic, or molecular biomarkers that predict the occurrence or progression of specific clinical features in individuals with neurofibromatosis type 1. One of these clinical biomarkers, macrocephaly, has been proposed as a prognostic factor for optic pathway glioma development. In the current study, the authors demonstrate that macrocephaly is not associated with the development of these brain tumors or the need to institute treatment for clinical progression. These findings suggest that macrocephaly is not a robust biomarker of optic pathway glioma formation or progression in children with neurofibromatosis type 1.

scholarly journals A phase II study of continuous oral mTOR inhibitor everolimus for recurrent, radiographic-progressive neurofibromatosis type 1–associated pediatric low-grade glioma: a Neurofibromatosis Clinical Trials Consortium study

2020 ◽  
Vol 22 (10) ◽  
pp. 1527-1535 ◽  
Author(s):  
Nicole J Ullrich ◽  
Sanjay P Prabhu ◽  
Alyssa T Reddy ◽  
Michael J Fisher ◽  
Roger Packer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Neurofibromatosis Type 1 ◽  
Mtor Inhibitor ◽  
Neurofibromatosis Type ◽  
Mtor Pathway ◽  
Pharmacokinetic Parameters ◽  
Low Grade ◽  
Nerve Sheath Tumor ◽  
Pathway Inhibition

Abstract Background Activation of the mammalian target of rapamycin (mTOR) pathway is observed in neurofibromatosis type 1 (NF1) associated low-grade gliomas (LGGs), but agents that inhibit this pathway, including mTOR inhibitors, have not been studied in this population. We evaluate the efficacy of the orally administered mTOR inhibitor everolimus for radiographically progressive NF1-associated pediatric LGGs. Methods Children with radiologic-progressive, NF1-associated LGG and prior treatment with a carboplatin-containing chemotherapy were prospectively enrolled on this phase II clinical trial to receive daily everolimus. Whole blood was analyzed for everolimus and markers of phosphatidylinositol-3 kinase (PI3K)/mTOR pathway inhibition. Serial MRIs were obtained during treatment. The primary endpoint was progression-free survival at 48 weeks. Results Twenty-three participants (median age, 9.4 y; range, 3.2–21.6 y) were enrolled. All participants were initially evaluable for response; 1 patient was removed from study after development of a malignant peripheral nerve sheath tumor. Fifteen of 22 participants (68%) demonstrated a response, defined as either shrinkage (1 complete response, 2 partial response) or arrest of tumor growth (12 stable disease). Of these, 10/15 remained free of progression (median follow-up, 33 mo). All remaining 22 participants were alive at completion of therapy. Treatment was well tolerated; no patient discontinued therapy due to toxicity. Pharmacokinetic parameters and pre-dose concentrations showed substantial between-subject variability. PI3K/mTOR pathway inhibition markers demonstrating blood mononuclear cell mTOR pathway inactivation was achieved in most participants. Conclusion Individuals with recurrent/progressive NF1-associated LGG demonstrate significant disease stability/shrinkage during treatment with oral everolimus with a well-tolerated toxicity profile. Everolimus is well suited for future consideration as upfront or combination therapy in this patient population.

scholarly journals Secondary Knee Osteoarthritis due to Neurofibromatosis Type 1 Treated with above the Knee Amputation: A Case Report

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Jay Patel ◽  
Jeffrey Whiting ◽  
Daniel Jones
Keyword(s):  
Knee Osteoarthritis ◽  
Neurofibromatosis Type 1 ◽  
Young Patients ◽  
Neurofibromatosis Type ◽  
Functional Improvement ◽  
Poor Bone Quality ◽  
Knee Amputation ◽  
Device Use ◽  
Severe Grade

Background. Neurofibromatosis Type 1 (NF-1) has a variety of associated orthopaedic manifestations that have been previously reported. We report a case of severe, grade 4 knee osteoarthritis (OA) with recurrent subluxation and joint laxity due to multiple extra-articular neurofibromas ultimately treated with Above the Knee Amputation (AKA).Case Description. A 39-year-old man presented with multiple neurofibromas and lymphedema leading to degenerative changes of the knee. Conservative treatment failed due to the severity of the knee degeneration and patient discomfort. Likewise, arthroplasty was not possible due to poor bone quality and joint instability. Therefore, AKA was selected to relieve symptoms and provide functional improvement. six months after the procedure the patient has increased functional capacity for ambulation and activities of daily living, as well as significant decrease in pain and discomfort.Clinical Relevance. Extra-articular neurofibromas causing severe secondary OA in relatively young patients can be functionally improved with AKA and prosthetic device use.

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