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Background: Progressive isolated optic nerve glioma (ONG) in children is a rare disease, treated with various modalities. A global treatment consensus is not available., Methods: We conducted a national retrospective multicenter cohort study (1995-2020) to investigate how different treatment strategies impact outcome for ONG in children, by assessing treatment responses to systemic anticancer therapy (SAT), surgery, and radiotherapy for ONG. The primary endpoints included changes in best-corrected visual acuity (BCVA) and tumor volume (TV) on MRI, both evaluated at the start and end of therapy and at long-term follow up., Results: A total of 21 ONGs (20 patients) received SAT (n = 14 (66.7%)), surgery (n = 4 (19.0%)), and radiotherapy (n = 3 (14.3%)). After SAT BCVA stabilized or improved in 66.6% (n = 4) and the TV decreased by a median of 45.1% (range: -88.6% to +31.5%) (n = 13). Before resection two eyes were already blind. After resection BCVA decreased to blindness in one eye. In total all four eyes were blind after resection. After first-line RT BCVA decreased in 66.7% of ONG to counting fingers or less, TV increased <3 months after RT by a median of 47.3% (range: -42.8% to +245.1%) (n = 3), followed by a long-term decrease of 94.4 and 13.8% (n = 2), respectively., Conclusion: SAT appears to be the preferred modality for progressive ONG in case of potential rescue of visual functions. Complete resection of ONG appears effective to reduce proptosis in case of preexisting blindness. The use of radiotherapy requires careful consideration due to the risk of severe visual impairment and secondary disease., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Optic pathway gliomas (OPG) are rare tumors in children. Lesion extent, visual functions, neurofibromatosis 1 (NF1), and age are factors that guide treatment. This study evaluates the clinical characteristics, treatment, and outcome of children and adolescents with OPG treated over a 31-year period in a single center., Methods: Ninety-five patients with OPG diagnosed between January 1990 and December 2021 were retrospectively evaluated. First-line chemotherapy regimen consisted of vincristine and carboplatinum for 1 year. Radiotherapy was not used as first-line treatment and tried to be avoided in the ones who progressed after first-line treatment., Results: Ninety-five children (44 male, 51 female) with a median age of 52 (1-216) months were evaluated. Sixty-three (66.3%) had NF1 and 10 (10,5%) diencephalic syndrome. The most common presenting symptoms were visual abnormalities and/or proptosis, nistagmus, and behavioral changes. Twenty-one (22.1%) patients with NF1 had stable disease throughout the follow-up period and received no treatment. Sixty-three of 74 patients received treatment at diagnosis and 11 due to progression during follow-up. Only one adolescent received radiotherapy at progression. Patients who progressed, received further line systemic treatment (vinblastine; bevacizumab; vincristine-cisplatinum-etoposide). Ten-year overall survival in all patients, in patients with NF1, and without NF1 were 97.2%, 98%, and 95.8% (p > .05), respectively; 10-year progression-free survival (PFS) in all patients, in patients with NF1, and without NF1 were 71.6%, 85.7%, and 54.2% (p = .001), respectively., Conclusions: In children with symptomatic/progressive OPG, chemotherapy consisting of vincristine-carboplatinum (VC) is effective. Radiotherapy may be avoided, especially in patients with NF1., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Purpose: We examined regression patterns in pediatric optic pathway gliomas (OPGs) after proton beam therapy (PBT) and evaluated local control and visual outcomes., Methods: A total of 42 brain magnetic resonance imaging (MRI) scans from seven consecutive sporadic OPGs that were initially treated with chemotherapy and received PBT between June 2007 and September 2016 at the National Cancer Center, Korea were analyzed. Patients underwent brain MRI regularly before and after PBT. Total tumor, cystic lesion, and solid enhancing lesion area delineation and volume calculations were performed on gadolinium-enhanced T1-weighted MRI using Eclipse version 13, Varian., Results: The median follow-up period after PBT was 70 months (range 47-88). The median age at the time of PBT was 7 years (range 4-16) and the median duration of chemotherapy before referral to PBT center was 25 months (range 3-70). The median time to the greatest increase in cystic volume was 32 months (range 12-43) after PBT. Solid enhancing lesion volume gradually decreased throughout the follow-up period. On an individual basis, total volume change was varied. However, on average, it regressed, although at a slower rate than solid enhancing lesion volume did. The local control rate was 85.7% (5-year progression-free survival rate, 80%; 5-year overall survival rate, 100%) and the rate of vision preservation was 71.4% (five of seven patients)., Conclusion: The regression patterns in pediatric OPGs after PBT involve significant cystic change. Therefore, total volume is not appropriate for evaluating response. Care by a multidisciplinary team is necessary to manage clinical symptoms related to radiologic changes., (© 2021 Wiley Periodicals LLC.)

Background: To develop an auxiliary GPU-accelerated proton therapy (PT) dose and LET d engine for the IBA Proteus®ONE PT system. A pediatric low-grade glioma case study is reported using FRoG during clinical practice, highlighting potential treatment planning insights using variable RBE dose (D vRBE ) and LET d as indicators for clinical decision making in PT., Methods: The physics engine for FRoG has been modified for compatibility with Proteus®ONE PT centers. Subsequently, FRoG was installed and commissioned at NPTC. Dosimetric validation was performed against measurements and the clinical TPS, RayStation (RS-MC). A head patient cohort previously treated at NPTC was collected and FRoG forward calculations were compared against RS-MC for evaluation of 3D-Γ analysis and dose volume histogram (DVH) results. Currently, treatment design at NPTC is supported with fast variable RBE and LET d calculation and is reported in a representative case for pediatric low-grade glioma., Results: Simple dosimetric tests against measurements of iso-energy layers and spread-out Bragg Peaks in water verified accuracy of FRoG and RS-MC. Among the patient cohort, average 3D-Γ applying 2%/2 mm, 3%/1.5 mm and 5%/1 mm were > 97%. DVH metrics for targets and OARs between FRoG and RayStation were in good agreement, with ∆D 50,CTV and ∆D 2,OAR both ⪅1%. The pediatric case report demonstrated implications of different beam arrangements on D vRBE  and LET d distributions. From initial planning in RayStation sharing identical optimization constraints, FRoG analysis led to plan selection of the most conservative approach, i.e., minimized D vRBE,max and LET d,max in OARs, to avoid optical system toxicity effects (i.e., vision loss)., Conclusion: An auxiliary dose calculation system was successfully integrated into the clinical workflow at a Proteus®ONE IBA facility, in excellent agreement with measurements and RS-MC. FRoG may lead to further insight on D vRBE and LET d implications to help clinical decision making, better understand unexpected toxicities and establish novel clinical procedures with metrics currently absent from the standard clinical TPS., (© 2021. The Author(s).)

Optic nerve glioma is a rather rare tumor. It predominantly arises in pediatric patients, including those with type I neurofibromatosis. This neoplasm is accompanied by decreased visual function and exophthalmos. Treatment strategy is individualized depending on age, volume and spread of tumor, as well as severity of clinical manifestations. Possible treatment options are surgical resection, chemotherapy, radiotherapy and their combination. Radiotherapy can be recommended for patients with intact visual functions, no severe proptosis and trophic lesions. Classic fractionation mode is used as a standard. Currently, the possibility of hypofractionated irradiation is being considered., Objective: To evaluate safety and efficacy of hypofractionated radiotherapy in patients with optic nerve glioma., Material and Methods: Sixteen patients with optic nerve gliomas underwent hypofractionated stereotactic irradiation (CyberKnife) between May 2014 and October 2019. Single focal dose was 5.5 Gy. There were 5 fractions up to total focal dose of 27.5 Gy. The sample enrolled 14 children with a median age of 4 years (range 23 months - 13 years) and 2 adults aged 47 and 66 years, respectively. Median of tumor volume was 2.77 cm 3 (range 1.69-10.01 cm 3 )., Results: Tumor growth control was achieved in all patients, partial remission was observed in 5 (32%) patients. None patient had deterioration of visual function. Improvement of visual acuity was noted in 3 (19%) cases. Visual field enlargement occurred in 4 (67%) out of 6 patients who were preoperatively examined. After irradiation, proptosis decreased by ≥ 1 mm in 9 (60%) out of 15 patients.

Background: Sporadic optic pathway/hypothalamic gliomas represent a unique entity within pediatric low-grade glioma. Despite favorable survival, location makes treatment difficult and local progression debilitating. This study is a longitudinal assessment of visual acuity (VA) among children treated within the last 2 decades., Methods: Clinical characteristics were abstracted for patients treated from 2000 to 2018 at Texas Children's Cancer Center in Houston. Ophthalmologic data taken at 3- to 6-month intervals were examined with age-appropriate VA metrics converted to the LogMAR (logarithm of the minimum angle of resolution) scale. Kaplan-Meier blindness-free survival (BFS) curves, calculated as time-to-bilateral functional blindness (LogMAR ≥0.8 in both eyes), were calculated for patients receiving early radiation therapy (RT; upfront or as first-line salvage treatment) or chemotherapy (CT) and evaluated using the log-rank test., Results: Thirty-eight patients with a median follow-up of 8.5 years (range, 2-17 years) were identified. Median age at diagnosis was 3 years (interquartile range, <1-6 years). Early RT was administered in 11 patients (29%). Twenty-seven patients (71%) were treated primarily with CT, initiated at a median age of 3.5 years (range, <1-11 years). Eight patients in the CT group did eventually require RT secondary to VA loss and following multiple lines of CT. Median age at RT for all patients was 11 years (range, 3-17 years). BFS rates were 81% at 5 years and 60% at 8 years for CT and 100% at 5 and 8 years for early RT (P = .017)., Conclusions: In a contemporary cohort, early RT, defined as initial or first-line salvage therapy, was found to have superior BFS for appropriately selected patients with sporadic optic pathway/hypothalamic gliomas., Lay Summary: Children with low-grade brain tumors of the optic pathway generally have excellent long-term survival; however, given the location of these tumors, there can commonly be threatened vision if the tumor grows. Although radiation is generally deferred in children on the basis of legitimate concerns regarding the effects on the developing brain, it may represent a vision-preserving therapy for well-selected older patients., (© 2021 American Cancer Society.)

Children with neurofibromatosis type I (NF1) have a higher predisposition for low-grade astrocytomas of the optic pathway, commonly referred to as optic pathway gliomas (OPGs). OPGs can result in visual deterioration. Treatment outcomes in OPG-NF1 management are often reported around tumor stabilization. We sought to compare vision outcomes associated with different OPG treatment strategies to inform about this important functional metric. A meta-analysis exploring the different modalities to treat children with OPG-NF1 was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using multiple databases. Of the 113 articles identified in the search, 23 full text articles, representing 564 patients, were included for review. These articles included retrospective, prospective, and randomized controlled studies on observation (n=9), chemotherapy (n=19), radiation therapy (n=6), and surgery (n=7). Of the patients undergoing observation, 87% (60/69) demonstrated stable acuity. In the chemotherapy studies, 27.3% (72/264) demonstrated improved acuity/visual field and/or visual-evoked potential amplitudes, 39.4% (104/264) stable acuity, and 33.3% (88/264) deterioration. Both the radiation and surgical treatments reported worsening acuity at 90.9% (10/11) and 73.3% (11/15), respectively. Causal associations are not known. Indications for and timing of treatment choice warrant larger scale study to provide further understanding., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Children with sporadic optic pathway glioma (OPG) commonly experience a decline in visual acuity (VA). This study aimed to quantify long-term VA outcomes after definitive radiation therapy (RT)., Methods: From 1997 to 2017, 41 patients underwent RT for OPG and had baseline VA testing. All patients underwent serial VA testing every 3-6 months during the first 5 years and annually thereafter. The cumulative incidence of VA decline or improvement (per eye) was estimated using death as a competing risk., Results: Mean follow-up was 5 years. Most tumors (93%) involved the postchiasmatic optic tracts and/or hypothalamus. Of the tumors tested for BRAF alterations (n = 15), 67% had a BRAF fusion. Median time to VA decline was 20 months in the eye with worse vision and 22 months in the better eye. For the worse eye, the 5-year cumulative incidences of VA decline and improvement were 17.9% [95% confidence interval (CI) 7-32.8%] and 13.5% (95% CI 4.7-26.7%), respectively. For the better eye, the 5-year cumulative incidences of VA decline and improvement were 11.5% (95% CI 3.5-30.7%) and 10.6% (95% CI 2.6-25.2%), respectively. Visual outcomes did not correlate with radiographic evidence of tumor progression., Conclusions: The 5-year cumulative incidence of VA decline was low. VA decline is most likely to occur within the first 2 years after RT and is not associated with radiographic progression of disease, highlighting the need for frequent ophthalmologic exams during this period.

Introduction: Moya-Moya angiopathy is a neurovascular disease that predisposes to ischemic or hemorrhagic strokes. It is generated by a steno-occlusion of the terminal portion of the internal carotid arteries, which induces the development of abnormal neovessels in the deep regions of the brain. Some pathologies such as sickle cell disease, Down syndrome or Graves' disease may be associated with Moya-Moya angiopathy. These syndromic forms harbor several differences compared with idiopathic Moya-Moya disease., Case Report: We report the case of a young patient who presented with a syndromic form of Moya-Moya angiopathy after cranial radiation therapy for an optic glioma associated with type 1 neurofibromatosis treated by combined revascularization. We discuss the particularities of syndromic forms, in their presentation and management based on a review of the literature., Conclusion: Many diseases can be associated with Moya-Moya syndrome. Symptomatic patients should undergo surgery, but the risk of postoperative complications appears to be greater than that encountered in patients with non-syndromic Moya-Moya angiopathy., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Optic pathway gliomas (OPGs) are commonly noted in pediatric oncology services. Radiotherapy is effective at controlling tumors, but has many undesirable late effects, especially in patients with neurofibromatosis. Chemotherapy is commonly used to preserve vision and delay or eliminate the need for radiotherapy. Despite visual threat being a common reason to initiate chemotherapy in patients with OPG, reports of visual outcome after chemotherapy are not common and reports of long-term visual outcome are even scarcer., Methods: In a single institution, all patients with OPG who had received chemotherapy or radiotherapy between 1996 and 2013 were identified from hospital databases. Visual, treatment, and radiological data were recorded. Categorized visual acuity was the primary outcome measure., Results: Of 43 patients identified, visual data were available for 42 patients. Approximately 14% of patients experienced an improvement in visual acuity during therapy, 9% of patients experienced a deterioration, and the remainder were stable. At a mean follow-up of 78 months, 26% of patients were legally blind. Children aged <2 years and patients with a chiasmatic/hypothalamic tumor site were overrepresented in this category. An intraconal location was predictive of poor visual outcome for that eye but was unilateral with normal vision in the contralateral eye., Conclusions: Risk factors for long-term visual deterioration are young age, chiasmatic/hypothalamic tumor site, and intraconal tumor site for the involved eye. The most common visual outcome for children with OPG after treatment with chemotherapy is stability. This stability is maintained over the long term for >90% of children without these risk factors., (© 2015 American Cancer Society.)

Background/objective: Decisions to use open surgery or radiotherapy in pediatric patients with familial neoplastic syndromes must consider not only the symptomatic benefits of treatment, but also future limitations these treatments may impose. Specifically, open surgical resection of noncurable tumors may preclude or encumber future lesion resections, while radiotherapy has detrimental effects on pediatric cognitive development and increases the risk of future malignancy development. We provide the first report of using a novel 3.0-mm diffusing laser tip with laser-induced thermal therapy (LiTT) to treat a pediatric patient with neurofibromatosis type 1 (NF-1)., Methods: A 12-year-old boy with NF-1 presented with a progressively enlarging lesion in the right midbrain. A stereotactic biopsy was performed, followed by LiTT with a novel 3.0-mm laser applicator., Results: MRI 1 week after LiTT showed stable gross total ablation of the lesion with reduction in fluid-attenuated inversion recovery signal. The patient remained neurologically intact 6 months after his procedure, and follow-up MRI showed no evidence of recurrence., Conclusion: LiTT is a powerful adjunct to conventional open surgical and radiotherapy modalities in the treatment of patients with familial neoplastic syndromes or incurable lesions. The novel laser applicator tip described expands the treatment scope of this technique., (© 2015 S. Karger AG, Basel.)

The management of progressive unresectable low-grade glioma remains controversial. Treatment options have included radiotherapy, and more recently chemotherapy, usually following an initial period of observation. Within this context, we evaluated vinorelbine, a semi-synthetic vinca alkaloid that has shown evidence of activity against glioma. From July 2007 an institutional protocol with vinorelbine (30 mg/m(2) days 0, 8, 22) for a total of 18 cycles, has been conducted at IOP/GRAACC/UNIFESP for children with optic pathway glioma (OPG). The main objectives were clinical and radiological response, as well as toxicity profile. Twenty-three patients with progressive OPG with a mean age of 69 months (4-179) were enrolled. Three patients had a diagnosis of neurofibromatosis type 1. Twenty-two patients were assessable for response with an overall objective response rate of 63 %, with eight patients showing stable disease. The most important toxicity was hematologic (grade III/IV neutropenia) observed in four patients. Gastrointestinal toxicity (grade I/II vomiting) was observed in seven patients and only 1 patient showed grade I peripheral neuropathy. The median progression-free survival (PFS) was 33 months (6.9-69) with a 3 and 5 year PFS of 64 ± 19 and 37 ± 20 %, respectively, for an overall 3 and 5 year-survival of 95 ± 10 %. This study suggests that vinorelbine may be an interesting option for pediatric low-grade gliomas, showing low toxicity profile and providing a good quality of life for patients with such chronic disease.

Optic pathway gliomas (OPGs) are among the most challenging neoplasms in modern pediatric neuro-oncology. Recent technological advances in imaging, surgery, and chemotherapy may lead to better understanding of the pathophysiology and better clinical results. This chapter reviews these advances and the current treatment paradigms.