[Hypofractionated stereotactic irradiation for optic nerve glioma]. / Stereotaksicheskoe obluchenie gliom zritel'nogo nerva v rezhime gipofraktsionirovaniya.

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 cm3 (range 1.69-10.01 cm3). 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.

How can we consider variable RBE and LETd prediction during clinical practice? A pediatric case report at the Normandy Proton Therapy Centre using an independent dose engine.

BACKGROUND: To develop an auxiliary GPU-accelerated proton therapy (PT) dose and LETd 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 (DvRBE) and LETd 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 LETd 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 ∆D50,CTV and ∆D2,OAR both ⪅1%. The pediatric case report demonstrated implications of different beam arrangements on DvRBE and LETd distributions. From initial planning in RayStation sharing identical optimization constraints, FRoG analysis led to plan selection of the most conservative approach, i.e., minimized DvRBE,max and LETd,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 DvRBE and LETd implications to help clinical decision making, better understand unexpected toxicities and establish novel clinical procedures with metrics currently absent from the standard clinical TPS.

Regression and pseudoprogression of pediatric optic pathway glioma in patients treated with proton beam therapy.

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.

Early radiotherapy preserves vision in sporadic optic pathway glioma.

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.

Vision Outcomes for Pediatric Patients With Optic Pathway Gliomas Associated With Neurofibromatosis Type I: A Systematic Review of the Clinical Evidence.

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.

Long-term visual acuity outcomes after radiation therapy for sporadic optic pathway glioma.

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.

Moya-Moya syndrome after cranial radiation for optic glioma with NF1. Case report and literature review of syndromic cases.

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.

Long-term visual outcome after chemotherapy for optic pathway glioma in children: Site and age are strongly predictive.

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.

Cerebral peduncle tumor ablated by novel 3-mm laser tip.

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.

Optic pathway gliomas.

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.

Single agent vinorelbine in pediatric patients with progressive optic pathway glioma.

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.

The role of surgery in optic pathway/hypothalamic gliomas in children.

OBJECT: Optic pathway/hypothalamic gliomas (OPHGs) are generally benign tumors situated in an exquisitely sensitive brain region. The location and natural history of OPHGs has led to much debate about optimal treatment. This paper revisits the role of and optimal timing of debulking surgery in OPHG. METHODS: This paper presents a series of cases managed by the neuro-oncology team at Alder Hey Children's Hospital and a single surgeon. Data were collected retrospectively for periods prior to 2009 and prospectively thereafter. Tailored treatment strategies were used, including observation and combinations of surgery, chemotherapy, and radiotherapy. Tumor control rates and outcomes are reviewed. RESULTS: Forty-two patients were treated between 1998 and 2011. Their median age at diagnosis was 5 years 7 months. Nineteen patients were positive for neurofibromatosis Type 1 (NF1) and 23 patients were negative for NF1. The median duration of follow-up was 77 months (range 21.8-142.3 months). Presenting symptoms included visual impairment (in 50% of cases), headache (in 24%), and hypothalamic/pituitary dysfunction (in 29%). Twenty-two debulking procedures were performed in 21 patients. Four biopsies (3 open, 1 endoscopic) were also performed. The histological diagnosis was pilocytic astrocytoma in 21 patients and pilomyxoid astrocytoma in 2 patients. Ten patients (Group 1) had primary surgical debulking alone and were then observed. Four patients (Group 2) had surgical debulking, plus planned chemotherapy within 3 months. Seven patients (Group 3) required surgical debulking for progressive disease following a variety of treatments. Patient age had the greatest impact on subsequent tumor progression. In total, 13 patients received chemotherapy, 4 on initial presentation, 4 in combination with surgery, and 5 for further tumor progression. Five patients were treated with radiotherapy, 3 prior to referral to Alder Hey. Eleven patients required shunt insertion for hydrocephalus. Vision was stabilized for 74% of patients. The number of patients with hypothalamic/pituitary dysfunction increased from 12 at presentation to 16 by the end of treatment. The overall survival rate was 93%. Three patients died-1 from tumor progression, 1 from infective complications from tumor biopsy, and 1 from a spontaneous posterior fossa hemorrhage. NF1 was associated with improved outcome-fewer patients required active intervention and rates of visual impairment and/or or hypothalamic/pituitary dysfunction were lower. CONCLUSIONS: Good long-term survival and functional outcomes can be achieved in children with OPHG. Tumor control was achieved through an individualized approach using surgery, chemotherapy, or radiotherapy in varied combinations. The authors aim to limit radiotherapy to cases involving older children in whom other therapies have failed, due to the well-described and often devastating late effects associated with midline cranial irradiation. Surgery has a clear role for diagnosis, tumor control, and relief of mass effect. In particular, primary surgical debulking of tumor (without adjuvant therapy) is safe and effective. Recent advances in intraoperative MRI may add value and need further assessment.

Radiation therapy: orbital tumors.

Orbital tumors are rare overall, comprising 0.1% of all tumors and less than 20% of all orbital diseases. Tumors may be benign, locally aggressive, or malignant. Of the malignant tumors, lymphomas and metastases are the most common and are primarily seen in the elderly population. While surgery and chemotherapeutic agents are often employed in the management of these lesions, not all patients are candidates for these therapies. Radiation therapy offers a noninvasive, well-tolerated primary treatment modality, whereby vision-sparing is feasible in many cases. In this chapter, we review an array of non-neoplastic entities and orbital tumors, for which there exists a role for radiation, and the radiotherapeutic techniques and applications in their management.

Optic nerve glioma treatment with fractionated stereotactic radiotherapy.

In the current report, the authors present a case of optic nerve glioma treated with fractionated stereotactic radiotherapy (FSRT). An 11-year-old girl was referred to our clinic with increasing proptosis over a 1-year period. At that time orbital MRI revealed a 20 × 17-mm mass in the right retroorbital lipomatous tissue, and FSRT was delivered to the tumor using the CyberKnife. During the 1.5-year follow-up, ophthalmological examinations did not indicate any treatment-related severe toxicity, and posttreatment MRI demonstrated marked regression of the lesion to 13 × 10 mm. Given the scarcity of reports on this subject, the authors support more extended studies of the CyberKnife for the effective treatment of this relatively common childhood tumor.

Long-term response in high-grade optic glioma treated with medically induced hypothyroidism and carboplatin: a case report and review of the literature.

Glioblastoma multiforme (GBM) is the most malignant and frequent brain tumor, with an aggressive growth pattern and poor prognosis despite best treatment modalities. Long-term survival of patients with GBM is rare. Optic glioma represents 0.6-1.2% of all brain tumors. Unlike low-grade optic gliomas in children, optic gliomas in adults are highly aggressive and death usually occurs in less than a year. Prolonged progression-free survival and survival rates have been reported in association with induced hypothyroidism in two clinical trials for recurrent GBM. We present the clinical, radiological, and pathological findings in a patient with inoperable GBM of the optic chiasm. Following failure of initial, standard radiation and temozolomide therapy, chemical hypothyroidism was induced using the antithyroid thioamide, propylthiouracil, followed by carboplatin chemotherapy. Initial thyroid stimulating hormone, free T4, and free T3 analysis was carried out and then monthly. This patient responded rapidly to treatment (clinically and with tumor regression within 4 weeks) on two separate occasions with an extended remission period (2.5 years) and prolonged overall survival (4.5 years). We report the successful long-term tumor response to medically induced chemical hypothyroidism in conjunction with carboplatinum chemotherapy of an adult patient with grade IV GBM of the optic chiasm. These clinical observations find mechanistic support from the recent identification of potent mitogenic actions of the thyroid hormone, L-thyroxine, in malignant glioma through binding to a cognate thyroid hormone receptor on the αvß3 integrin. Approaches to block its activity are now explored in preclinical studies.

Management options for visual pathway compression from optic gliomas.

Optic pathway gliomas (OPGs) manifest with neuro-ophthalmic symptoms and signs; however, presentation can vary as their location and growth patterns are highly variable. An exophytic expansion of an OPG within the intracranial cavity can cause compression on neurological structures, warranting intervention. However, management guidelines are limited and the treatment itself may also cause neuro-ophthalmic complications. Therefore, clinical decision-making must include input from a multidisciplinary team that includes ophthalmology, neurosurgery, radiation oncology and neuroradiology.

Assessment of radiation-induced second cancer risks in proton therapy and IMRT for organs inside the primary radiation field.

There is clinical evidence that second malignancies in radiation therapy occur mainly within the beam path, i.e. in the medium or high-dose region. The purpose of this study was to assess the risk for developing a radiation-induced tumor within the treated volume and to compare this risk for proton therapy and intensity-modulated photon therapy (IMRT). Instead of using data for specific patients we have created a representative scenario. Fully contoured age- and gender-specific whole body phantoms (4 year and 14 year old) were uploaded into a treatment planning system and tumor volumes were contoured based on patients treated for optic glioma and vertebral body Ewing's sarcoma. Treatment plans for IMRT and proton therapy treatments were generated. Lifetime attributable risks (LARs) for developing a second malignancy were calculated using a risk model considering cell kill, mutation, repopulation, as well as inhomogeneous organ doses. For standard fractionation schemes, the LAR for developing a second malignancy from radiation therapy alone was found to be up to 2.7% for a 4 year old optic glioma patient treated with IMRT considering a soft-tissue carcinoma risk model only. Sarcoma risks were found to be below 1% in all cases. For a 14 year old, risks were found to be about a factor of 2 lower. For Ewing's sarcoma cases the risks based on a sarcoma model were typically higher than the carcinoma risks, i.e. LAR up to 1.3% for soft-tissue sarcoma. In all cases, the risk from proton therapy turned out to be lower by at least a factor of 2 and up to a factor of 10. This is mainly due to lower total energy deposited in the patient when using proton beams. However, the comparison of a three-field and four-field proton plan also shows that the distribution of the dose, i.e. the particular treatment plan, plays a role. When using different fractionation schemes, the estimated risks roughly scale with the total dose difference in%. In conclusion, proton therapy can significantly reduce the risk for developing an in-field second malignancy. The risk depends on treatment planning parameters, i.e. an analysis based on our formalism could be applied within treatment planning programs to guide treatment plans for pediatric patients.

Visual outcomes in pediatric optic pathway glioma after conformal radiation therapy.

PURPOSE: To assess visual outcome prospectively after conformal radiation therapy (CRT) in children with optic pathway glioma. METHODS AND MATERIALS: We used CRT to treat optic pathway glioma in 20 children (median age 9.3 years) between July 1997 and January 2002. We assessed changes in visual acuity using the logarithm of the minimal angle of resolution after CRT (54 Gy) with a median follow-up of 24 months. We included in the study children who underwent chemotherapy (8 patients) or resection (9 patients) before CRT. RESULTS: Surgery played a major role in determining baseline (pre-CRT) visual acuity (better eye: P=.0431; worse eye: P=.0032). The visual acuity in the worse eye was diminished at baseline (borderline significant) with administration of chemotherapy before CRT (P=.0726) and progression of disease prior to receiving CRT (P=.0220). In the worse eye, improvement in visual acuity was observed in patients who did not receive chemotherapy before CRT (P=.0289). CONCLUSIONS: Children with optic pathway glioma initially treated with chemotherapy prior to receiving radiation therapy have decreased visual acuity compared with those who receive primary radiation therapy. Limited surgery before radiation therapy may have a role in preserving visual acuity.

Longitudinal measures of visual function, tumor volume, and prediction of visual outcomes after treatment of optic pathway gliomas.

PURPOSE: To examine longitudinal changes in visual acuity, tumor volume, and visual evoked potentials (VEP) before and after treatment in children with optic pathway gliomas. DESIGN: Retrospective cohort study. PARTICIPANTS: Twenty-one patients (0.7-9 years of age). METHODS: Patients initially were treated either by chemotherapy (n = 18) or radiotherapy (n = 3). Patients were followed up with serial magnetic resonance imaging, age-corrected visual acuity measurements in logarithm of the minimum angle of resolution (logMAR) units, and pattern VEP. Longitudinal visual outcome data were obtained on average for 9 years (range, 4-16 years). Tumor volumes before and after treatment were estimated in 15 patients. Multivariate regression was used to predict visual outcomes. MAIN OUTCOME MEASURES: Visual acuity, relative tumor volumes, and VEP. RESULTS: Before treatment, 81% of patients had reduced visual acuity and 81% had optic nerve pallor, whereas all had a reduced VEP in 1 or both eyes. After initial treatment, tumor volume decreased in 53%, stabilized in 27%, and progressively increased in 20%. Treatment arrested the rapid decline in visual acuity loss and stabilized visual acuity for 4 to 5 years. The rate of visual acuity decline was not correlated with tumor shrinkage. Sixty-two percent of patients required additional treatment with either chemotherapy or radiation because of tumor growth or progressive loss of visual function. Visual acuity at last examination was stable or improved in 33% of patients, but on average declined 0.4 logMAR units. Visual acuity was 20/200 or better in 1 eye of 62% of patients. The rate of visual acuity decline was predicted weakly by tumor volume at presentation (R(2) = 0.19; P<0.009). Visual acuity at last examination was predicted best by visual acuity and tumor volume at presentation (R(2) = 0.66; P<0.001). CONCLUSIONS: Systemic chemotherapy arrested the decline in visual acuity and stabilized vision on average for 5 years. At presentation, VEPs were a more sensitive indicator of optic pathway damage than visual acuity or optic nerve appearance. Although tumor reduction or stabilization was achieved in 80% of patients, pre-existing visual damage, indexed by objective measures of tumor volume and visual function, limited visual outcomes. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.