Progressive Optic Pathway Glioma Research Articles

Antiseizure effect of MEK inhibitor in a child with neurofibromatosis type 1-Developmental and epileptic encephalopathy and optic pathway glioma.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder due to a mutation in NF1 gene, resulting in phenotypically heterogeneous systemic manifestations. Patients with NF1 are prone to develop neoplasms of the central nervous system (CNS) and are particularly at risk for optic pathway gliomas (OPG). Epilepsy is another recognized neurologic complication in patients with NF1, with a prevalence estimated between 4% and 14%. Several case reports and early phase clinical trials have demonstrated that the mitogen-activated protein kinase inhibitors (MEKi) are effective in NF1-low-grade gliomas (LGGs), but their influence on seizure activity in humans has not been established. Here, we report a patient with NF1 and developmental and epileptic encephalopathy (DEE) harboring pharmacoresistant tonic seizures, and progressive optic pathway glioma (OPG). By using a MEKi therapy for her OPG, we observed an end to epileptic seizures as well as a significant improvement of interictal EEG abnormalities, despite a lack of tumor reduction. MEK inhibitor therapy should be considered for patients with NF1 and refractory epilepsy.

Impact of Bevacizumab on Visual Function, Tumor Size, and Toxicity in Pediatric Progressive Optic Pathway Glioma: A Retrospective Nationwide Multicentre Study.

Bevacizumab (BVZ) is used as a subsequent line of treatment for pediatric optic pathway glioma (OPG) in the case of progression. Data on the treatment effect concerning tumor progression and visual function are scarce and nationwide studies are lacking. We performed a retrospective, nationwide, multicentre cohort study including all pediatric patients with OPG treated with BVZ in the Netherlands (2009-2021). Progression-free survival, change in visual acuity and visual field, MRI-based radiologic response, and toxicity were evaluated. In total, 33 pediatric patients with OPG were treated with BVZ (median 12 months). Visual acuity improved in 20.5%, remained stable in 74.4%, and decreased in 5.1% of 39 of all analysed eyes. The monocular visual field improved in 73.1%, remained stable in 15.4%, and decreased in 7.7% of 25 analysed eyes. Radiologic response at the end of therapy showed a partial response in 7 patients (21.9%), minor response in 7 (21.9%), stable disease in 15 (46.9%), and progressive disease in 3 (9.3%). Progression-free survival at 18 and 36 months after the start of BVZ reduced from 70.9% to 38.0%. Toxicity (≥grade 3 CTCAE) during treatment was observed in five patients (15.2%). Treatment of BVZ in pediatric patients with OPG revealed stabilisation in the majority of patients, but was followed by progression at a later time point in more than 60% of patients. This profile seems relatively acceptable given the benefits of visual field improvement in more than 70% of analysed eyes and visual acuity improvement in more than 20% of eyes at the cessation of BVZ.

Targeted Therapies for the Neurofibromatoses.

Simple SummaryThe neurofibromatoses—neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis—are genetic tumor predisposition syndromes in which affected patients are at risk for the development of nerve-associated central and peripheral tumors. Patients often develop multiple tumors which can result in significant symptoms and morbidity. Treatment of the tumors associated with these disorders has evolved over the past decade, including significant work focused on inhibition of the signaling dysregulation and symptom minimization. This review outlines the most common tumor types associated with each of these syndromes and the current progress in therapeutic options.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.

Single-Agent Oral Vinorelbine in the Treatment of Pediatric Progressive Optic Pathway Glioma: A Single Institutional Experience

Purpose: The vinca alkaloids’ activity against pediatric low-grade glioma (PLGG) is well established. The goal of the present study is to describe our experience with oral vinorelbine in patients with progressive optic pathway glioma (OPG), not only regarding the clinical response, but also the cost benefit using an oral medication. Methods: Patients under 21 years of age with unresectable and/or progressive OPG were eligible. Oral vinorelbine was administered at a dose of 90mg/m2 daily on days 0, 8 and 22, in a scheme of 4 weekly cycles for a total of 18 cycles (54 doses). Results: From 2013 to 2018, sixteen patients were enrolled onto the study, with a median age of 9,1 years (range 4,6-17,8y). The most common histology was pilocytic astrocytoma (88,8%). Best response to chemotherapy was reviewed with a response rate (complete, partial, or minor response) of 30% for the patients treated exclusively with the oral drug. Five-year event-free survival (EFS) rate was 43.4%. Six patients had to change to intravenous vinorelbine due to gastrointestinal toxicity, vomiting grade III. None of the patients showed neurotoxicity. The total cost including drug acquisition, administration and toxicity management was lower with the oral formulation comparing to IV one. Conclusion: Single-agent oral vinorelbine seems to have some clinical activity in the management of recurrent or refractory pediatric OPG, being an interesting and cost-effective option, minding that gastrointestinal toxicity may be limiting and a combination of antiemetics should be considered in this treatment regimen.

Prognostic Role of Conventional and Dynamic Contrast-Enhanced MRI in Optic Pathway Gliomas.

The natural history of optic pathway glioma (OPG) is highly variable and unpredictable. We present a pilot study of the prognostic role of conventional and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) in the evaluation of OPG. We retrospectively reviewed 17 patients with 20 pretreatment OPG lesions who underwent conventional and DCE MRI between January 2010 and December 2016. Conventional MRI was evaluated for enhancement pattern, cystic component, optic nerve tortuosity, optic nerve dural ectasia, and optic nerve perineural thickening. The DCE MRI data were analyzed for quantitative parameters using the two-compartment pharmacokinetic model (Ktrans , kep , and ve ) and for semiquantitative parameters based on time-signal intensity curve (AUC60 , peak, and wash-in). The results were compared with the clinically progressive or nonprogressive tumor. Five progressive OPGs and 15 nonprogressive OPGs were included. Conventional MRI findings of diffuse enhancement and cystic component were significantly correlated with progressive OPGs (both P = .01). Conventional MRI yielded sensitivity of 60%, specificity of 100%, and accuracy of 90%. Ktrans , kep , and ve as well as AUC60 , peak, and wash-in were significantly higher in progressive OPGs (P < .05). Using DCE MRI increased diagnostic performance up to a sensitivity of 100%, specificity of 93%, and accuracy of 95%. DCE MRI accurately distinguished progressive and nonprogressive OPGs, with high sensitivities and specificities. DCE MRI has a significant prognostic role in predicting progressive OPGs, thus making it useful for the identification of patients who need close clinical and imaging follow-up.

Complex Multidisciplinary Follow-Up Of Children With Neurofibromatosis Type 1

Abstract Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders with mainly mild cutaneous manifestations. Some patients with NF1, however, develop severe complications such as progressive optic pathway glioma, plexiform neurofibroma or malignant peripheral nerve sheath tumour. Due to potentially progressive and asymptomatic course of the disease, patients with NF1 require a regular multidisciplinary follow-up in coordination with various specialties and early intervention. In this article, we summarise our long-term experience with multidisciplinary follow-up of NF1 patients in the Centre for Neurofibromatosis Type 1 patients at the Children's University Hospital in Bratislava.

Low-Dose Cisplatin-Etoposide Regimen for Patients with Optic Pathway Glioma: A Report of Four Cases and Literature Review

Optic pathway gliomas (OPGs) account for 5% of all childhood brain tumors. For years it has been discussed which was the best method of examining tumor progression when the magnetic resonance imaging (MRI) scan does not change. The role of chemotherapy in their treatment still remains controversial. We treated four consecutive patients affected by progressive OPG with lower cumulative doses of cisplatin/etoposide. The extension of disease was assessed by brain MRI scan. A complete ophthalmologic examination was performed. Ototoxicity was monitored. Our OPG patients had reduced visual acuity (VA) and/or visual field (VF) regardless of the MRI evaluation. All patients showed rapid visual recovery with improvement both in VA and in VF. At the time of writing, after a median follow-up of 34 months, all patients were alive and free from disease progression. Our results confirm the effectiveness and the low-toxicity profile of the cisplatin/etoposide regimen for treatment of children affected by OPG. We suggest that VA and VF can be considered as the most accurate parameters for defining the start of chemotherapy and tumor response.

Visual outcome following chemotherapy for progressive optic pathway gliomas

Optic pathway gliomas (OPG) are relatively indolent tumors that may occur sporadically or in association with neurofibromatosis 1. Treatment is initiated only when a clear clinical or radiological deterioration is documented. Chemotherapy is the standard first line of treatment. Due to the indolent nature of this tumor, the most important challenge in OPG treatment is vision preservation. In this study we determined the visual outcome of 19 patients with progressive OPGs who received chemotherapy and correlated it with imaging. Mean neuro-ophthalmological follow-up is 4 years and 3 months. Indications for treatment were radiological tumor progression (6 patients), visual decline (6 patients), or both (7 patients). Fifteen patients (78%) had to change to 2nd line chemotherapy (7 due to allergies and 8 due to treatment failure). During the course of chemotherapy, 11 patients (57.8%) displayed radiological tumor progression, 4 (21.5%) demonstrated stable tumor, and 4 (21.5%) displayed tumor regression. During the follow-up period, 14 (73.6%) had an overall visual deterioration, 4 (21%) had stable vision, and 1 patient (5.2%) improved. Visual acuity was examined in 38 eyes. Seventeen eyes (47.2%) deteriorated, fourteen (38.8%) were stable, and five (13.8%) improved. Ten eyes (27.7%) deteriorated to legal blindness. There was no correlation between radiological tumor growth and visual deterioration. The majority of our patients, who received chemotherapy for progressive OPG, experienced a decline in their visual function. New, more effective treatments are needed in order to preserve vision in this group.

Nitrosourea-based chemotherapy in optic pathway glioma with progressive visual loss

Purpose: To report two patients with progressive optic pathway gliomas who had reversible visual loss after treatment with nitrosourea-based chemotherapy. Design: Retrospective case series. Results: Two patients with optic pathway gliomas and progressive visual field loss were treated with nitrosourea-based chemotherapy consisting of 6-thioguanine, procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine (TPCV). Both patients experienced dramatic and sustained visual improvement after treatment. Conclusion: Patients with progressive optic pathway gliomas may benefit from initial therapy with nitrosourea-based chemotherapy.This treatment might delay or avoid the need for radiation therapy and its associated side effects, especially in younger aged children.

Radiation therapy of optico–hypothalamic gliomas (OHG) – radiographic response, vision and late toxicity

Background: Management strategies for optic pathway gliomas include observation, surgery, irradiation, chemotherapy and a combination of these modalities. It has been the policy of our University Hospital to consider radiation as the standard treatment for progressive optic pathway gliomas. This report describes the clinical presentation, treatment patterns and outcome with special emphasis on the long term functional status of patients with optico–hypothalamic gliomas (OHG). Patients and methods: Between 1975 and 1997, 25 patients with OHG were treated by radiation therapy (RT) following surgery or biopsy. All patients received a local RT with a 0.5–1 cm margin around the lesions as depicted on CT or MRI scans. Age adjusted radiation doses ranged from 45 to 60 Gy with a single fraction size of 1.6–2 Gy. Endpoints of the study were: radiographic response, survival, progression-free survival and time to endocrinologic toxicity as well as the visual function during follow-up. The median follow-up time was 9 years (range, 1.5–23 years). Results: A partial response was noted in six (24%) of the patients, 13 (52%) patients had a stable tumour throughout the observation period and six (24%) patients had a tumour progression. Overall survival and progression-free survival rates were 94 and 69% at 10 years, respectively. A significant influence on progression-free survival was noted for age at diagnosis ( P=0.04) and total dose ( P=0.05). Nine out of 13 (69%) patients aged below 10 years compared with 3/12 (25%) patients aged above 10 years experienced hypothalamic–pituitary deficiency ( P=0.008) during follow-up. As for visual acuity, nine patients had an improvement, another 13 patients a stable situation and three patients a measurable deterioration. Visual field deficits improved in three, remained unchanged in 16 patients and worsened in only one patient. Conclusion: Postoperative RT with a total dose above 45 Gy should be considered as standard treatment in OHG with documented progression. Close radiographic monitoring and lifelong yearly evaluation for the need of possible hormone replacement are strongly recommended.

Carboplatin treatment of progressive optic pathway gliomas to delay radiotherapy

Six patients with optic pathway gliomas who were previously managed with surgery and/or chemotherapy were treated with carboplatin (560 mg/sq m) after radiographic evidence of disease progression. The median age at diagnosis was 2 years (range 4 months to 7 years), and the interval between diagnosis and carboplatin therapy ranged between 7 months and 6.5 years (median 1.8 years). Treatment was given at 4-week intervals and continued until unacceptable toxicity supervened, the disease progressed, or the disease was stable for 12 months. All patients demonstrated disease stability at the outset of the third cycle and continued to do so at the time of this writing. Two patients are 16 and 32 months from initial carboplatin therapy and have been off treatment for 5 and 14 months, respectively; two patients are still receiving therapy at 7 and 11 months after their initial treatment. During the study, two patients developed hypersensitivity to the drug, requiring its discontinuation. Toxicity was minimal, consisting mainly of thrombocytopenia, requiring a one-dose reduction in four of the six treated patients. No platelet transfusions were needed. These results suggest that carboplatin can arrest growth of progressive optic pathway gliomas in children and can allow delay of radiotherapy. A larger trial will be required to define the optimal use of carboplatin in the treatment of low-grade gliomas in children.