OBJECTIVE: The surgical treatment of optic pathway gliomas (OPG) remains controversial, with visual outcomes often unpredictable. The present study explored surgical and clinical factors influencing visual acuity (VA) after OPG treatment and developed anatomical subtypes correlated with clinical symptoms.
METHODS: Children with OPG who underwent initial partial tumor resection at Beijing Tiantan Hospital from January 2011 to December 2022 were retrospectively analyzed. Multivariate logistic regression and random forest analyses were performed to identify risk factors for post-treatment VA deterioration and a decision tree model was created based on significant factors.
RESULTS: A total of 140 patients were enrolled. Multivariate logistic regression analysis identified surgical approach and initial VA as independent predictors of post-treatment VA deterioration (P < 0.05). Surgical approach, initial VA, and extent of tumor resection were the most significant factors for risk assessment and were included in the decision tree model, with surgical approach as the most important \"root\" node. The model demonstrated good predictive performance, with area under the curve values of 0.75 and 0.66 for the training and test datasets, respectively. A simple anatomical classification was developed, which revealed clinical characteristic differences among OPG types. Meanwhile, a correlation analysis of post-treatment visual deterioration was performed for each of the three anatomical types.
CONCLUSIONS: This study offers a predictive model for visual outcomes following initial tumor-reduction surgery in OPG patients, which may help in visual outcomes risk stratification. Additionally, the anatomical classification effectively indicates OPG growth direction, offering potential insights into clinical symptoms.

Photopic negative response (PhNR), an index of retinal ganglion cell (RGC) function, is impaired in patients with optic pathway gliomas (OPGs). The aim of this longitudinal study was to evaluate whether PhNR deteriorates over time in OPG patients. Fourteen pediatric patients affected by OPG (4 males and 10 females, mean age 12.4 ± 5.7 years, 8 with neurofibromatosis type 1 [NF1]) with ≥12 months of follow-up and ≥2 evaluations, were included in this retrospective study. All patients had received chemotherapy, with or without OPG surgical resection, at least 5 years prior to the study. At baseline, all patients underwent a complete ophthalmological examination. Follow-up included clinical examination and PhNR measurement as well as brain MRI (according to pediatric oncologist indications) every 6 or 12 months. Mean follow-up duration was 16.7 ± 7.5 months (range 12-36 months). Photopic electroretinograms were elicited by 2.0 cd-s/m2 Ganzfeld white flashes presented on a steady 20 cd/m2 white background. The PhNR amplitude was measured as the difference between baseline and the maximal negative amplitude (minimum) of the negative wave, following the photopic b-wave. Compared to baseline, mean PhNR amplitude was significantly decreased at the end of follow-up (p = 0.008). NF1-related OPGs exhibited a decline in PhNR amplitude (p = 0.005) and an increase in PhNR peak-time during the follow-up (p = 0.013), whereas sporadic OPGs showed no significant changes. Tumor size remained stable in all patients on MRI. PhNR amplitude decreased over the observation period, suggesting progressive RGC dysfunction in NF1-related pediatric OPGs, despite stable size on MRI imaging. PhNR could serve as a non-invasive objective tool for assessing longitudinal changes in RGC function in the clinical management of childhood OPG.

BACKGROUND: Pediatric low-grade glioma incidence has been rising in the U.S., mirroring the rising rates of pediatric and maternal obesity. Recently, children of obese mothers were demonstrated to develop brain tumors at higher rates. Importantly, obesity in the U.S. is largely driven by diet, given the prevalence of high fat and high sugar (HFHS) food choices. Since high-fat diet exposure can increase embryonic neuroglial progenitor cell (NPC) proliferation, the potential cells of origin for low-grade glioma, we hypothesized that in utero exposure to an obesogenic diet would modify pediatric brain penetrance and latency by affecting the tumor cell of origin.
METHODS: We employed several murine models of the Neurofibromatosis type 1 (NF1) pediatric brain tumor predisposition syndrome, in which optic pathway gliomas (Nf1-OPGs) arise from NPCs in the embryonic third ventricular zone (TVZ). We exposed dams and offspring to an obesogenic HFHS diet or control chow and analysed fetal neurodevelopment at E19.5 and tumor formation at 6w-3mo.
RESULTS: Progeny from HFHS diet-exposed dams demonstrated increased TVZ NPC proliferation and glial differentiation. Dietary switch cohorts confirmed that these effects were dependent upon maternal diet, rather than maternal weight. Obesogenic diet (Ob) similarly accelerated glioma formation in a high-penetrance Nf1-OPG strain and increased glioma penetrance in two low-penetrance Nf1-OPG strains. In contrast, Ob exposure in the postnatal period alone did not recapitulate these effects.
CONCLUSIONS: These findings establish maternal obesogenic diet as a risk factor for murine Nf1-OPG formation, acting in part through in utero effects on the tumor cell of origin.

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 treatment.

OBJECTIVE: The extent of resection of pediatric low-grade glioma mostly improves progression-free survival. In chiasmatic hypothalamic glioma (CHG), complete resections are limited due to the relevantly high risk of associated neurological and endocrinological deficits. Still, surgery might have its role in the framework of a multidisciplinary team (MDT) approach. We report our retrospective experience from two centers on surgical options and their impact on long-term outcomes.
METHODS: Medical records of surgically treated pediatric CHG patients between 2004 and 2022 were analyzed. Patient characteristics, surgical interventions, histology, and non-surgical therapy were retrieved together with outcome measures such as visual acuity, endocrine function, and survival.
RESULTS: A total of 63 patients (33 female, NF-1, n = 8) were included. Age at first diagnosis was 4.6 years (range 0.2-16.9) and cohort follow-up was 108 ± 72 months. Twenty patients were surgically treated with a biopsy and 43 patients with debulking at a median age of 6.5 years (range 0.16-16.9). Patients received a median of 2 tumor surgeries (range 1-5). Cyst drainage was accomplished in 15 patients, and 27 patients had ventriculoperitoneal shunt implantation. Non-surgical therapy was given in 69.8%. At the end of follow-up, 74.6% of patients had stable disease. The cohort had a median Karnofsky score of 90 (range 0-100). Four patients died. Hormone substitution was necessary in 30.2%, and visual acuity was impaired in 66% of patients.
CONCLUSIONS: Pediatric CHG is a chronic disease due to overall high survival with multiple progressions. Surgical therapy remains a key treatment option offering biopsy, limited tumor-debulking, cyst fenestration, and hydrocephalus management in the framework of MDT decision-making. Team experience contributes to reducing possible deficits in this challenging cohort.

Optic pathway gliomas (OPGs) represent a unique subset of brain tumours that primarily affect the paediatric population. Traditionally, these tumours are managed conservatively due to their location to and association with vital structures. This article explores the evolving role of surgery in the management of OPGs, particularly in the context of advancements in precision medicine. The advent of targeted therapy, especially for tumours with specific genetic alterations, such as BRAF V600E mutations, has revolutionized the treatment landscape, offering new avenues for patient-specific therapy. However, surgery still plays a crucial role, especially for debulking in cases of hydrocephalus or when standard therapies are ineffective. Advances in surgical techniques, including neuronavigation, endoscopic approaches, and intraoperative neurophysiological monitoring, have enhanced the safety and efficacy of operative interventions. Despite these developments, the complexity of OPGs necessitates a multidisciplinary approach, focusing on long-term outcomes and quality of life. Future research is needed to further elucidate the role of surgery in an era increasingly dominated by molecular genetics and targeted therapies.

Neurofibromatosis type 1 (NF1) is an autosomal dominant cancer predisposition syndrome characterized by the development of both central and peripheral nervous system tumors. Low-grade glioma (LGG) is the most prevalent central nervous system tumor occurring in children with NF1, arising most frequently within the optic pathway, followed by the brainstem. Historically, treatment of NF1-LGG has been limited to conventional cytotoxic chemotherapy and surgery. Despite treatment with chemotherapy, a subset of children with NF1-LGG fail initial therapy, have a continued decline in function, or recur. The recent development of several preclinical models has allowed for the identification of novel, molecularly targeted therapies. At present, exploration of these novel precision-based therapies is ongoing in the preclinical setting and through larger, collaborative clinical trials. Herein, we review the approach to surveillance and management of NF1-LGG in children and discuss upcoming novel therapies and treatment protocols.

Proton beam therapy (PBT) is increasingly used to treat cancers, especially in the paediatric and adolescent and young adult (AYA) population. As PBT becomes more accessible, determining when PBT should be used instead of photon irradiation can be difficult. There is a need to balance patient, tumour and treatment factors when making this decision. Comparing the dosimetry between these two modalities plays an important role in this process. PBT can reduce low to intermediate doses to organs at risk (OAR), but photon irradiation has its dosimetric advantages. We present two cases with brain tumours, one paediatric and one AYA, in which treatment plan comparison between photons and protons showed dosimetric advantages of photon irradiation. The first case was an 18-month-old child diagnosed with posterior fossa ependymoma requiring adjuvant radiotherapy. Photon irradiation using volumetric modulated arc therapy (VMAT) had lower doses to the hippocampi but higher doses to the pituitary gland. The second case was a 21-year-old with an optic pathway glioma. There was better sparing of the critical optic structures and pituitary gland using fractionated stereotactic radiation therapy over PBT. The dosimetric advantages of photon irradiation over PBT have been demonstrated in these cases. This highlights the role of proton-to-photon comparative treatment planning to better understand which patients might benefit from photon irradiation versus PBT.

BACKGROUND: Optic pathway gliomas (OPGs) represent 5% of childhood brain tumors. Successive relapses lead to multiple treatments exposing to late complications.
METHODS: We 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.
RESULTS: We 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.
CONCLUSIONS: Late 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.

UNASSIGNED: Patients with optic pathway gliomas (OPG) have good survival rates although their long-term quality of life can be affected by the tumor or treatment-related morbidity. This retrospective study sought to describe the clinical presentation and outcomes of children with OPG at a tertiary center in Mexico.
UNASSIGNED: Consecutive patients <18 years-of-age with newly diagnosed OPG between January 2002 and December 2020 at the Hospital Civil de Guadalajara Dr. Juan I. Menchaca in Guadalajara, Mexico were included.
UNASSIGNED: Thirty patients were identified with a median age of six years. The most frequent clinical manifestations were loss of visual acuity (40%) and headaches (23%). Neurofibromatosis-1 was found in 23.3% of the patients. Surgery, either biopsy or resection, was done in 20 of 30 patients. Two patients died shortly after initial surgery. The 5-year event-free survival (EFS) was 79.3% ± 10.8% and the 5-year overall survival was 89.5% ± 6.9%. Lower EFS was associated with age less than 3 years, intracranial hypertension at presentation, and diencephalic syndrome. Patients who received surgery as first-line treatment had a 3.1 times greater risk of achieving a performance score of less than 90 points at 6 months after diagnosis (p=0.006). Of 10 patients with vision testing, 5 had improvement in visual acuity, 4 had no changes, and one patient showed worsening.
UNASSIGNED: Our data suggests that favorable outcomes can be achieved with OPG in low- and middle-income countries, although a high rate of surgical complications was described leading to a lower overall survival. These data can be used prospectively to optimize treatment at this institute and other middle-income countries through a comprehensive, multidisciplinary approach.