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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 -
Progress in Brain Research 2022GKNS for uveal melanoma has become a recognized valued treatment which avoids enucleation of the eye. In the early days, the eccentric location of these tumors made...
GKNS for uveal melanoma has become a recognized valued treatment which avoids enucleation of the eye. In the early days, the eccentric location of these tumors made treatment difficult, but Gamma Knife Perfexion has solved that problem. It is known that larger tumors and tumors with an anterior location have a worse prognosis. GKNS has also been of rather unexpected benefit in optic nerve gliomas that require treatment. Choroidal hemangiomas may benefit from treatment as can secondary glaucoma. It has also been found to be beneficial in the treatment of thyrotoxic ophthalmopathy.
Topics: Choroid Neoplasms; Glaucoma; Humans; Melanoma; Uveal Neoplasms
PubMed: 35074088
DOI: 10.1016/bs.pbr.2021.10.039 -
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 -
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 -
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 -
The Lancet. Oncology Jun 2020Paediatric low-grade gliomas (also known as pLGG) are the most common type of CNS tumours in children. In general, paediatric low-grade gliomas show clinical and... (Review)
Review
Paediatric low-grade gliomas (also known as pLGG) are the most common type of CNS tumours in children. In general, paediatric low-grade gliomas show clinical and biological features that are distinct from adult low-grade gliomas, and the developing paediatric brain is more susceptible to toxic late effects of the tumour and its treatment. Therefore, response assessment in children requires additional considerations compared with the adult Response Assessment in Neuro-Oncology criteria. There are no standardised response criteria in paediatric clinical trials, which makes it more difficult to compare responses across studies. The Response Assessment in Pediatric Neuro-Oncology working group, consisting of an international panel of paediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address issues and unique challenges in assessing response in children with CNS tumours. We established a subcommittee to develop consensus recommendations for response assessment in paediatric low-grade gliomas. Final recommendations were based on literature review, current practice, and expert opinion of working group members. Consensus recommendations include imaging response assessments, with additional guidelines for visual functional outcomes in patients with optic pathway tumours. As with previous consensus recommendations, these recommendations will need to be validated in prospective clinical trials.
Topics: Age of Onset; Central Nervous System Neoplasms; Child; Consensus; Endpoint Determination; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Neoplasm Grading; Neuroimaging; Perfusion Imaging; Positron-Emission Tomography; Predictive Value of Tests; Time Factors; Treatment Outcome; Tumor Burden
PubMed: 32502457
DOI: 10.1016/S1470-2045(20)30064-4 -
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 -
Annual Review of Vision Science Sep 2020The damage or loss of retinal ganglion cells (RGCs) and their axons accounts for the visual functional defects observed after traumatic injury, in degenerative diseases... (Review)
Review
The damage or loss of retinal ganglion cells (RGCs) and their axons accounts for the visual functional defects observed after traumatic injury, in degenerative diseases such as glaucoma, or in compressive optic neuropathies such as from optic glioma. By using optic nerve crush injury models, recent studies have revealed the cellular and molecular logic behind the regenerative failure of injured RGC axons in adult mammals and suggested several strategies with translational potential. This review summarizes these findings and discusses challenges for developing clinically applicable neural repair strategies.
Topics: Animals; Cell Survival; Disease Models, Animal; Humans; Nerve Crush; Nerve Regeneration; Optic Nerve Diseases; Optic Nerve Injuries; Retinal Ganglion Cells
PubMed: 32936739
DOI: 10.1146/annurev-vision-022720-094953 -
Radiologie (Heidelberg, Germany) Mar 2024Orbital tumours include a variety of orbital diseases of different origins. In the case of malignant orbital tumours, early detection is important so that treatment can... (Review)
Review
Orbital tumours include a variety of orbital diseases of different origins. In the case of malignant orbital tumours, early detection is important so that treatment can be initiated promptly. Neuroradiological imaging, in particular magnetic resonance imaging (MRI), plays an important role in the diagnostic of orbital tumours. In adults, lymphoproliferative diseases, inflammations and secondary orbital tumours are most frequently found, whereas in children mostly dermoid cysts, optic gliomas and capillary haemangiomas are found. Optic glioma is a pilocytic astrocytoma and accounts for two thirds of all primary optic tumours. Optic nerve sheath meningiomas mostly affect middle-aged women. In childhood, retinoblastoma is the most common intraocular tumour. This is an aggressive malignant tumour which can occur unilaterally or bilaterally. Based on the imaging findings, differential diagnoses can usually be easily narrowed down using criteria such as age of manifestation, frequency, localisation and imaging characteristics.
Topics: Adult; Child; Middle Aged; Humans; Female; Orbital Neoplasms; Orbital Diseases; Optic Nerve Neoplasms; Optic Nerve Glioma; Meningeal Neoplasms; Retinal Neoplasms
PubMed: 38194103
DOI: 10.1007/s00117-023-01257-x