Novel treatments in optic pathway gliomas.
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ABSTRACT:
SUBMITTER: Maheshwari A
PROVIDER: S-EPMC11182137 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Novel treatments in optic pathway gliomas.
Maheshwari Akash A Pakravan Mohammad M Charoenkijkajorn Chaow C Beres Shannon J SJ Lee Andrew G AG
Frontiers in ophthalmology 20220929
Optic pathway gliomas (OPG) are primary tumors of the optic nerve, chiasm, and/or tract that can be associated with neurofibromatosis type 1 (NF1). OPG generally have a benign histopathology, but a variable clinical course. Observation is generally recommended at initial diagnosis if vision is stable or normal for age, however, treatment may include chemotherapy, radiotherapy, or surgery in select cases. This manuscript reviews the literature on OPG with an emphasis on recent developments in tre ...[more]
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Project description:Neurofibromatosis type 1 (NF1) is one of the most common brain tumor predisposition syndromes, in which affected children are prone to the development of low-grade gliomas. While NF1-associated gliomas can be found in several brain regions, the majority arise in the optic nerves, chiasm, tracts, and radiations (optic pathway gliomas; OPGs). Owing to their location, 35-50% of affected children present with reduced visual acuity. Unfortunately, despite tumor stabilization following chemotherapy, vision does not improve in most children. For this reasons, more effective therapies are being sought that reflect a deeper understanding of the NF1 gene and the use of authenticated Nf1 genetically-engineered mouse strains. The implementation of these models for drug discovery and validation has galvanized molecularly-targeted clinical trials in children with NF1-OPG. Future research focused on defining the cellular and molecular factors that underlie optic glioma development and progression also has the potential to provide personalized risk assessment strategies for this pediatric population.
| S-EPMC5739070 | biostudies-literature
Project description:Optic pathway glioma (OPG), seen in 15% to 20% of individuals with neurofibromatosis type 1 (NF1), account for significant morbidity in young children with NF1. Overwhelmingly a tumor of children younger than 7 years, OPG may present in individuals with NF1 at any age. Although many OPG may remain indolent and never cause signs or symptoms, others lead to vision loss, proptosis, or precocious puberty. Because the natural history and treatment of NF1-associated OPG is different from that of sporadic OPG in individuals without NF1, a task force composed of basic scientists and clinical researchers was assembled in 1997 to propose a set of guidelines for the diagnosis and management of NF1-associated OPG. This new review highlights advances in our understanding of the pathophysiology and clinical behavior of these tumors made over the last 10 years. Controversies in both the diagnosis and management of these tumors are examined. Finally, specific evidence-based recommendations are proposed for clinicians caring for children with NF1.
| S-EPMC5908242 | biostudies-literature
Project description:BACKGROUND:Optic pathway gliomas (OPGs) are present in 20% of children with neurofibromatosis 1 (NF1) but are less frequently observed in adults. Our goal was to determine the natural history of OPGs in children and adults with NF1. RESULTS:We analyzed the features of OPGs and other intracranial lesions on 1775 head MRI scans of 562 unselected adults and children with NF1 collected between 2003 and 2015. 52 (9.3%) of 562 patients in this study had an OPG diagnosed on their MRI. The median age at first scan with an OPG present was 12.7 years. Of the 52 OPG patients, the intraorbital optic nerves were affected in 29 patients (56%), the prechiasmatic optic nerves were affected in 32 patients (62%), the optic chiasm was affected in 17 patients (33%) and the optic radiations were affected in 19 patients (37%). 29 patients had two or more areas affected. One patient had a newly-appearing OPG, and 1 patient showed progression. The rate of progression over 5 years was 2.4% (95% CI: 0.4% to 16%). Four patients showed partial regression of their OPGs, but we observed no case of complete regression during this study. The rate of regression over 5 years was 8.9% (95% confidence intervals: 2.8% to 26%). We found the presence of UBOs and the presence of OPGs in individual patients to be highly associated (p = 0.0061). CONCLUSION:OPGs are more common in older adults with NF1 than previously thought. The occurrences of unidentified bright objects (UBOs) and asymptomatic OPGs are associated with each other. This suggests the possibility that OPGs that remain asymptomatic may differ pathogenically from those that become symptomatic.
| S-EPMC5913802 | biostudies-literature
Project description:IntroductionOptic pathway gliomas (OPGs), also known as Visual Pathway Gliomas, are insidious, debilitating tumours. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of OPGs within the optic pathway typically precludes complete resection or optimal radiation dosing, hence outcomes remain poor compared to many other low-grade gliomas. The aim of this systematic review was to formulate a comprehensive list of all current ongoing clinical trials that are specifically looking at clinical care of OPGs in order to identify trends in current research and provide an overview to guide future research efforts.MethodsThis systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The Cochrane Controlled Register of Trials (CENTRAL) and ClinicalTrials.gov were searched. Inclusion and exclusion criteria were applied and final results were reviewed.Results501 clinical trials were identified with the search strategy. All were screened and eligible studies extracted and reviewed. This yielded 36 ongoing clinical trials, 27 of which were pharmacological agents in phase I-III. The remaining trials were a mixture of biological agents, radiation optimisation, diagnostic imaging, surgical intervention, and a social function analysis.ConclusionOPG is a complex multifaceted disease, and advances in care require ongoing research efforts across a spectrum of different research fields. This review provides an update on the current state of research in OPG and summarises ongoing trials.
| S-EPMC7434789 | biostudies-literature
Project description:Optic pathway glioma (OPG) occurs in as many as one-fifth of individuals with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Generally considered low-grade and slow growing, many children with NF1-OPGs remain asymptomatic. However, due to their location within the optic pathway, ~20-30% of those harboring NF1-OPGs will experience symptoms, including progressive vision loss, proptosis, diplopia, and precocious puberty. While treatment with conventional chemotherapy is largely effective at attenuating tumor growth, it is not clear whether there is much long-term recovery of visual function. Additionally, because these tumors predominantly affect young children, there are unique challenges to NF1-OPG diagnosis, monitoring, and longitudinal management. Over the past two decades, the employment of authenticated genetically engineered Nf1-OPG mouse models have provided key insights into the function of the NF1 protein, neurofibromin, as well as the molecular and cellular pathways that contribute to optic gliomagenesis. Findings from these studies have resulted in the identification of new molecular targets whose inhibition blocks murine Nf1-OPG growth in preclinical studies. Some of these promising compounds have now entered into early clinical trials. Future research focused on defining the determinants that underlie optic glioma initiation, expansion, and tumor-induced optic nerve injury will pave the way to personalized risk assessment strategies, improved tumor monitoring, and optimized treatment plans for children with NF1-OPG.
| S-EPMC10351533 | biostudies-literature
Project description:In this paper, the authors present a clinical picture of the diagnosis and current treatment regimens of optic pathway glioma in the pediatric population, with an emphasis on the role of an ophthalmic diagnosis in the differentiation and monitoring of lesions. Glioma is the most common optic nerve tumor in children.MaterialArticles in PubMed, Scholar and Website were reviewed, taking into account current standards of management related to sporadic or NF1-related optic glioma, epidemiology, location, course of the disease, clinical manifestations, histological types of the tumor, genetic predisposition, diagnostic ophthalmic tests currently applicable in therapeutic monitoring of the tumor, neurological diagnosis, therapeutic management and prognosis. The importance of current screening recommendations, in line with standards, was emphasized.ResultsGlioma occurs in children most often in the first decade of life. Initially, they may be asymptomatic, and clinically ophthalmic changes are associated with the organ of vision or with systemic changes. Gliomas associated with the NF1 mutation have a better prognosis for sporadic gliomas. Diagnosis includes radiological imaging methods/MRI/ophthalmology/OCT and visual acuity log MAR assessment. The basis of treatment is clinical observation. In the case of disease progression, surgical treatment, chemotherapy and targeted therapy are used.ConclusionFurther research into novel techniques for detecting gliomas would allow for early monitoring of the disease.
| S-EPMC10649937 | biostudies-literature
Project description:BackgroundPediatric neurofibromatosis type 1 (NF1)-associated optic pathway gliomas (OPGs) exhibit different clinico-radiological features, treatment, and outcome compared with sporadic OPGs. While NF1-associated OPGs are caused by complete loss-of-function of the NF1 gene, other genetic alterations of the RAS-MAPK pathway are frequently described in the sporadic cases. We identified a group of patients who presented OPGs with typical radiological features of NF1-associated OPGs but without the NF1 diagnostic criteria. We aim to investigate into the possible molecular mechanisms underlying this "NF1-like" pediatric OPGs presentation.MethodsWe analyzed clinico-radiological features of 16 children with NF1-like OPGs and without NF1 diagnostic criteria. We performed targeted sequencing of the NF1 gene in constitutional samples (n = 16). The RAS-MAPK pathway major genes were sequenced in OPG tumor samples (n = 11); BRAF FISH and IHC analyses were also performed.ResultsIn one patient's blood and tumor samples, we identified a NF1 nonsense mutation (exon 50: c.7285C>T, p.Arg2429*) with ~8% and ~70% VAFs, respectively, suggesting a mosaic NF1 mutation limited to the brain (segmental NF1). This patient presented signs of neurodevelopmental disorder. We identified a somatic alteration of the RAS-MAPK pathway in eight tumors: four BRAF activating p.Val600Glu mutations, three BRAF:KIAA oncogenic fusions, and one putative gain-of-function complex KRAS indel inframe mutation.ConclusionsNF1-like OPGs can rarely be associated with mosaic NF1 that needs specific constitutional DNA analyses for diagnosis. Further studies are warranted to explore unknown predisposition condition leading to the NF1-like OPG presentation, particularly in patients with the association of a neurodevelopmental disorder.
| S-EPMC7317061 | biostudies-literature
Project description:BackgroundOptic pathway gliomas (OPGs) represent 5% of childhood brain tumors. Successive relapses lead to multiple treatments exposing to late complications.MethodsWe included patients treated at Gustave Roussy (GR) between January 1980 and December 2015 for OPG, before 18 years old and alive at 5 years from diagnosis. Mortality and physical health conditions data were extracted from medical data files and updated, thanks to the GR long-term follow-up program and French national mortality registry for patients included in the French Childhood Cancer Survivor Study.ResultsWe included 182 5-year OPG-childhood survivors in the analysis (sex ratio M/F 0.8, 35% with neurofibromatosis type 1 [NF1]). With a median follow-up of 17.2 years (range = 5-41), we registered 82 relapses, 9 second malignancies, and 15 deaths as first events after 5 years, resulting in 20-year conditional overall survival (C-OS) and late events-free survival of 79.9% (95% confidence interval [CI] = 71-86) and 43.5% (95% CI = 36-51), respectively. Radiotherapy exposure in NF1 patients (hazard ratio [HR] = 6, 95% CI = 1.7-21.2) and hypothalamic involvement (HR = 3.2, 95% CI = 1.4-7.3) were significantly associated with C-OS in multivariable analyses. Ninety-five percent of 5-year OPG survivors suffered from any health condition, especially visual acuity "<1/10" (n = 109), pituitary deficiency (n = 106), and neurocognitive impairment (n = 89). NF1 (HR 2.1) was associated with precocious puberty. With a median time post-diagnosis of 4.2 years, 33 cerebrovascular events were observed in 21 patients.ConclusionsLate relapses, second malignancies, and cerebrovascular diseases are severe late events resulting in premature mortality. Morbidity is high and needs after-cancer care to improve quality of life. Risk factors could be considered to better stratify long-term follow-up.
| S-EPMC11226872 | biostudies-literature
Project description:This study investigates whether optical coherence tomography (OCT) could add useful information in the examination of children with optic pathway glioma (OPG) at high risk of developing vision loss. For this purpose, the relationship between ganglion cell-inner plexiform layer (GC-IPL) thickness and visual function, evaluated with tests of visual acuity (VA) and visual field (VF), as well as tumor site according to magnetic resonance imaging (MRI), were examined in a geographically defined group of children with OPG. Children aged <18 years with OPG underwent ophthalmic examination including VA, VF (Zeiss HFA perimetry) and OCT imaging (Zeiss Cirrus HD-OCT). Out of 51 patients included, 45 provided 77 eyes with MRI-verified OPG, and 19 patients provided 25 eyes without OPG. Significant correlations were found between GC-IPL, VF and VA (p < 0.001). The GC-IPL pattern loss corresponded in 95% to VF defects and in 92% to MRI findings. Our study indicates that GC-IPL measures could serve as an early marker of vision-threatening changes related to OPG and as a valuable link between MRI and visual function tests. Thinning of GC-IPL and differences in topography between eyes are strong indicators of and predictive of vision loss related to OPG.
| S-EPMC8774215 | biostudies-literature
Project description:BackgroundChemotherapy plays an important role in the treatment of optic pathway hypothalamic gliomas (OPHGs). Commonly used regimens include carboplatin and vincristine and monotherapy with vinblastine weekly. In this retrospective study, we used a monthly regimen of carboplatin and vinblastine to treat progressive/recurrent OPHGs and evaluated their effectiveness, visual preservation, and toxicity.MethodsThe study involved patients with OPGH who were treated with carboplatin and vinblastine once per month. The response, disease progression, overall survival, vision changes, and toxicity were recorded according to their medical charts at our institute, and survival was analyzed.ResultsA total of 25 patients were included, including 15 males (60%) and 10 females (40%). The response rate was 11/25 (44%), and the stabilization rate (complete response rate + partial response rate + minor response rate + and stable disease rate) was 21/25 (84%). The 3-year progression-free survival (PFS) rate was 54.6%, and the 5-year PFS rate was 46.8%. The 5-year overall survival rate was 100%. There were 6 patients who showed improved visual acuity (28.6%). Stable vision was found in 52.4% of patients. Only 2 patients experienced severe allergic reactions to carboplatin.ConclusionsThe results showed that extending the dosing interval of carboplatin and vinblastine to every month can be seen as a similar response compared with previous regimens. The toxicity of this regimen is milder, and patients benefit from a lower frequency of hospital visits. The regimen can be considered as a choice of the first line of chemotherapy for OPHG patients.
| S-EPMC11883347 | biostudies-literature