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Current Opinion in Ophthalmology Sep 2019Optic pathway gliomas are low-grade neoplasms that affect the precortical visual pathway of children and adolescents. They can affect the optic nerve, optic chiasm,... (Review)
Review
PURPOSE OF REVIEW
Optic pathway gliomas are low-grade neoplasms that affect the precortical visual pathway of children and adolescents. They can affect the optic nerve, optic chiasm, optic tracts and radiations and can either be sporadic or associated with neurofibromatosis type one. Gliomas isolated to the optic nerve (ONG) represent a subgroup of optic pathway gliomas, and their treatment remains controversial. New developments in ONG treatment have emerged in recent years, and it is necessary for clinicians to have a current understanding of available therapies.
RECENT FINDINGS
The current review of the literature covers the background of and recent developments in ONG treatment, with a focus on standard chemotherapy, new molecularly targeted therapies, radiation therapy and surgical resection and debulking.
SUMMARY
Although standard chemotherapy remains the mainstay of ONG treatment, newer molecularly targeted therapies such as mitogen-activated protein kinase kinase inhibitors and bevacizumab represent a promising new treatment modality, and clinical studies are ongoing.
Topics: Adolescent; Antineoplastic Agents; Child; Female; Humans; Male; Molecular Targeted Therapy; Ophthalmologic Surgical Procedures; Optic Chiasm; Optic Nerve Glioma; Optic Nerve Neoplasms; Optic Tract; Radiotherapy
PubMed: 31246635
DOI: 10.1097/ICU.0000000000000587 -
Nature Jun 2021Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse...
Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours. Although the role of neurons in tumour progression has previously been demonstrated, the importance of neuronal activity to tumour initiation is less clear-particularly in the setting of cancer predisposition syndromes. Fifteen per cent of individuals with the neurofibromatosis 1 (NF1) cancer predisposition syndrome (in which tumours arise in close association with nerves) develop low-grade neoplasms of the optic pathway (known as optic pathway gliomas (OPGs)) during early childhood, raising the possibility that postnatal light-induced activity of the optic nerve drives tumour initiation. Here we use an authenticated mouse model of OPG driven by mutations in the neurofibromatosis 1 tumour suppressor gene (Nf1) to demonstrate that stimulation of optic nerve activity increases optic glioma growth, and that decreasing visual experience via light deprivation prevents tumour formation and maintenance. We show that the initiation of Nf1-driven OPGs (Nf1-OPGs) depends on visual experience during a developmental period in which Nf1-mutant mice are susceptible to tumorigenesis. Germline Nf1 mutation in retinal neurons results in aberrantly increased shedding of neuroligin 3 (NLGN3) within the optic nerve in response to retinal neuronal activity. Moreover, genetic Nlgn3 loss or pharmacological inhibition of NLGN3 shedding blocks the formation and progression of Nf1-OPGs. Collectively, our studies establish an obligate role for neuronal activity in the development of some types of brain tumours, elucidate a therapeutic strategy to reduce OPG incidence or mitigate tumour progression, and underscore the role of Nf1mutation-mediated dysregulation of neuronal signalling pathways in mouse models of the NF1 cancer predisposition syndrome.
Topics: Animals; Astrocytoma; Cell Adhesion Molecules, Neuronal; Cell Transformation, Neoplastic; Female; Genes, Neurofibromatosis 1; Germ-Line Mutation; Humans; Male; Membrane Proteins; Mice; Mutation; Nerve Tissue Proteins; Neurofibromin 1; Neurons; Optic Nerve; Optic Nerve Glioma; Photic Stimulation; Retina
PubMed: 34040258
DOI: 10.1038/s41586-021-03580-6 -
Journal of Neurological Surgery. Part... Feb 2021To describe the diagnostic and management features of optic nerve gliomas. Literature review. Optic nerve gliomas are generally benign in the pediatric age...
To describe the diagnostic and management features of optic nerve gliomas. Literature review. Optic nerve gliomas are generally benign in the pediatric age group although they are usually malignant and aggressive in adults. As such, the mechanisms by which these lesions are diagnosed, the systemic implications, the goals of intervention, and the nature of therapeutic management all differ between these tumors. This article addresses these lesions and discusses the diagnostic and therapeutic paradigms by which they may be approached.
PubMed: 33777621
DOI: 10.1055/s-0040-1722634 -
Neuro-oncology Oct 2021Pediatric low-grade gliomas (pLGGs) are the most common childhood brain tumor. Progression-free survival (PFS) is much lower than overall survival, emphasizing the need...
BACKGROUND
Pediatric low-grade gliomas (pLGGs) are the most common childhood brain tumor. Progression-free survival (PFS) is much lower than overall survival, emphasizing the need for alternative treatments. Sporadic (without neurofibromatosis type 1) optic pathway and hypothalamic gliomas (OPHGs) are often multiply recurrent and cause significant visual deficits. Recently, there has been a prioritization of functional outcomes.
METHODS
We present results from children with recurrent/progressive OPHGs treated on a PBTC (Pediatric Brain Tumor Consortium) phase II trial evaluating efficacy of selumetinib (AZD6244, ARRY-142886) a MEK-1/2 inhibitor. Stratum 4 of PBTC-029 included patients with sporadic recurrent/progressive OPHGs treated with selumetinib at the recommended phase II dose (25mg/m2/dose BID) for a maximum of 26 courses.
RESULTS
Twenty-five eligible and evaluable patients were enrolled with a median of 4 (1-11) previous therapies. Six of 25 (24%) had partial response, 14/25 (56%) had stable disease, and 5 (20%) had progressive disease while on treatment. The median treatment courses were 26 (2-26); 14/25 patients completed all 26 courses. Two-year PFS was 78 ± 8.5%. Nineteen of 25 patients were evaluable for visual acuity which improved in 4/19 patients (21%), was stable in 13/19 (68%), and worsened in 2/19 (11%). Five of 19 patients (26%) had improved visual fields and 14/19 (74%) were stable. The most common toxicities were grade 1/2 CPK elevation, anemia, diarrhea, headache, nausea/emesis, fatigue, AST and ALT increase, hypoalbuminemia, and rash.
CONCLUSIONS
Selumetinib was tolerable and led to responses and prolonged disease stability in children with recurrent/progressive OPHGs based upon radiographic response, PFS, and visual outcomes.
Topics: Benzimidazoles; Brain Neoplasms; Child; Humans; Neurofibromatosis 1; Optic Nerve Glioma
PubMed: 33631016
DOI: 10.1093/neuonc/noab047 -
Nature Communications May 2022Neuronal activity is emerging as a driver of central and peripheral nervous system cancers. Here, we examined neuronal physiology in mouse models of the tumor...
Neuronal activity is emerging as a driver of central and peripheral nervous system cancers. Here, we examined neuronal physiology in mouse models of the tumor predisposition syndrome Neurofibromatosis-1 (NF1), with different propensities to develop nervous system cancers. We show that central and peripheral nervous system neurons from mice with tumor-causing Nf1 gene mutations exhibit hyperexcitability and increased secretion of activity-dependent tumor-promoting paracrine factors. We discovered a neurofibroma mitogen (COL1A2) produced by peripheral neurons in an activity-regulated manner, which increases NF1-deficient Schwann cell proliferation, establishing that neurofibromas are regulated by neuronal activity. In contrast, mice with the Arg1809Cys Nf1 mutation, found in NF1 patients lacking neurofibromas or optic gliomas, do not exhibit neuronal hyperexcitability or develop these NF1-associated tumors. The hyperexcitability of tumor-prone Nf1-mutant neurons results from reduced NF1-regulated hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function, such that neuronal excitability, activity-regulated paracrine factor production, and tumor progression are attenuated by HCN channel activation. Collectively, these findings reveal that NF1 mutations act at the level of neurons to modify tumor predisposition by increasing neuronal excitability and activity-regulated paracrine factor production.
Topics: Animals; Humans; Mice; Neurofibroma; Neurofibromatosis 1; Neurofibromin 1; Neurons; Optic Nerve Glioma; Peripheral Nervous System; Schwann Cells
PubMed: 35589737
DOI: 10.1038/s41467-022-30466-6 -
Journal of Korean Neurosurgical Society May 2018Gliomas are the most common pediatric tumors of the central nervous system. In this review, we discuss the clinical features, treatment paradigms, and evolving concepts... (Review)
Review
Gliomas are the most common pediatric tumors of the central nervous system. In this review, we discuss the clinical features, treatment paradigms, and evolving concepts related to two types of pediatric gliomas affecting two main locations: the optic pathway and thalamus. In particular, we discuss recently revised pathologic classification, which adopting molecular parameter. We believe that our review contribute to the readers' better understanding of pediatric glioma because pediatric glioma differs in many ways from adult glioma according to the newest advances in molecular characterization of this tumor. A better understanding of current and evolving issues in pediatric glioma is needed to ensure effective management decision.
PubMed: 29742884
DOI: 10.3340/jkns.2018.0040 -
Cells Sep 2023Optic pathway gliomas (OPGs) encompass two distinct categories: benign pediatric gliomas, which are characterized by favorable prognosis, and malignant adult gliomas,... (Review)
Review
Optic pathway gliomas (OPGs) encompass two distinct categories: benign pediatric gliomas, which are characterized by favorable prognosis, and malignant adult gliomas, which are aggressive cancers associated with a poor outcome. Our review aims to explore the established standards of care for both types of tumors, highlight the emerging therapeutic strategies for OPG treatment, and propose potential alternative therapies that, while originally studied in a broader glioma context, may hold promise for OPGs pending further investigation. These potential therapies encompass immunotherapy approaches, molecular-targeted therapy, modulation of the tumor microenvironment, nanotechnologies, magnetic hyperthermia therapy, cyberKnife, cannabinoids, and the ketogenic diet. Restoring visual function is a significant challenge in cases where optic nerve damage has occurred due to the tumor or its therapeutic interventions. Numerous approaches, particularly those involving stem cells, are currently being investigated as potential facilitators of visual recovery in these patients.
Topics: Adult; Humans; Child; Neurofibromatosis 1; Optic Nerve Glioma; Brain Neoplasms; Hyperthermia, Induced; Immunotherapy; Tumor Microenvironment
PubMed: 37830595
DOI: 10.3390/cells12192380 -
Cancers Nov 2021Over the past several years, management of the tumors associated with the neurofibromatoses has been recognized to often require approaches that are distinct from their... (Review)
Review
Over the past several years, management of the tumors associated with the neurofibromatoses has been recognized to often require approaches that are distinct from their spontaneous counterparts. Focus has shifted to therapy aimed at minimizing symptoms given the risks of persistent, multiple tumors and new tumor growth. In this review, we will highlight the translation of preclinical data to therapeutic trials for patients with neurofibromatosis, particularly neurofibromatosis type 1 and neurofibromatosis type 2. Successful inhibition of MEK for patients with neurofibromatosis type 1 and progressive optic pathway gliomas or plexiform neurofibromas has been a significant advancement in patient care. Similar success for the malignant NF1 tumors, such as high-grade gliomas and malignant peripheral nerve sheath tumors, has not yet been achieved; nor has significant progress been made for patients with either neurofibromatosis type 2 or schwannomatosis, although efforts are ongoing.
PubMed: 34885143
DOI: 10.3390/cancers13236032 -
Neurologia Medico-chirurgica Jan 2018Optic pathway/hypothalamic gliomas (OP/HGs) are rare astrocytic tumors that appear more commonly among young children and often are unresectable. They comprise... (Review)
Review
Optic pathway/hypothalamic gliomas (OP/HGs) are rare astrocytic tumors that appear more commonly among young children and often are unresectable. They comprise approximately 2% of all central nervous system tumors and account for 3-5% of pediatric intracranial tumors. Initial manifestations are often visual disturbances, endocrinopathies and hypothalamic dysfunction such as the diencephalic syndrome, and sometimes hydrocephalus due to cerebrospinal fluid (CSF) outflow obstruction. In many cases, the tumors are diagnosed late in the clinical course because they silently enlarge. These tumors consist mostly of histologically benign, World Health Organization (WHO) grade I tumors represented by pilocytic astrocytomas (PA), the rest being pilomyxoid astrocytomas (PXA) - WHO grade II tumors. In young pediatric patients, however, can be seen PXA that show aggressive clinical course such as CSF dissemination. Our small series of 14 non-Neurofibromatosis type 1 (NF-1) OP/HGs PA patients underwent extended resection without any adjuvant treatments. The median age at initial treatment was 11.5 ± 6.90 years (range, 1-25 years) and median follow up 85.5 ± 25.0 months. Surgical resection for OP/HGs results in acceptable middle-term survival, tumor control and functional outcome equivalent to chemotherapy. There is, however, no longer doubt that chemotherapy with or without biopsy and as-needed debulking surgery remains the golden standard in management of OP/H. Clinical conditions and treatment plans for OP/HGs vary depending on their structure of origin.
Topics: Adolescent; Brain Neoplasms; Child; Child, Preschool; Female; Glioma; Humans; Hypothalamus; Infant; Male; Optic Chiasm; Optic Tract; Young Adult
PubMed: 29118304
DOI: 10.2176/nmc.ra.2017-0081