Demographic and prognostic factors of optic nerve astrocytoma: a retrospective study of surveillance, epidemiology, and end results (SEER).

BACKGROUND: Optic nerve astrocytomas (ONAs) are neurological neoplasms in the central nervous system (CNS), and they have the highest incidence rate among all the tumor types in the visual pathway. In this study, we conducted a Surveillance, Epidemiology, and End Results (SEER) -based research to explore the demographic, survival, and prognostic factors of patients diagnosed with ONAs. METHODS: Utilizing the SEER database, we retrospectively evaluated data of patients diagnosed with ONAs of all ages from 1984 to 2016. We used the Student's t distribution to test variables of patients and various characteristics, and Kaplan-Meier curve to illustrate overall survival (OS) with 95.0% confidence intervals (CIs). We also performed univariate and multivariate analyses to evaluate various variables' validity on overall survival. RESULTS: A total of 1004 cases were analyzed, and revealed that age (P<0.001, hazard ratio (HR) = 8.830, 95% CI: 4.088-19.073), tumor grade (P<0.001, HR = 1.927, 95% CI: 1.516-2.450), diagnostic confirmation (P<0.001, HR = 2.444, 95% CI: 1.632-3.660), and histology type (P = 0.046, HR = 1.563, 95% CI: 1.008-2.424) of the tumor were associated with decreased survival. CONCLUSIONS: From this large, comparative study of ONAs, we found that younger age may be considered as a protective indicator, while high-grade astrocytic tumors have a worse prognosis. We also found that diagnostic confirmation and tumor grade were independent prognostic factors in this patient population.

Radiation Therapy for Optic Pathway and Hypothalamic Low-Grade Gliomas in Children.

PURPOSE: The long-term survival of pediatric patients with optic pathway or hypothalamic low-grade glioma (LGG) who receive radiation therapy (RT) has not been previously assessed. METHODS AND MATERIALS: A retrospective study was performed of all patients with optic-hypothalamic pediatric LGG treated with RT at a single institution. Eligible patients were aged ≤21 years at the time of RT and had localized LGG diagnosed by neuroimaging or histology. The median RT dose was 54 Gy, delivered in 30 fractions. Event-free survival (EFS) was defined as survival without progression or secondary high-grade glioma. Days were counted from the first day of RT. RESULTS: Eighty-nine patients were included in the study, with a median follow-up period of 12.5 years. Of the patients, 14 had neurofibromatosis type 1 (NF-1). The 10-year EFS rate was 61.9% (95% confidence interval [CI], 31.2%-82.1%) for patients with NF-1 and 67.5% (95% CI, 54.8%-77.3%) for those without NF-1. The 10-year overall survival rate was 92.3% (95% CI, 56.6%-98.9%) for patients with NF-1 and 98.4% (95% CI, 89.1%-99.8%) for those without NF-1. Pre-RT chemotherapy (which was more commonly given to younger patients) was associated with reduced EFS, whereas younger age was associated with reduced overall survival. Possible RT-induced neoplasms developed in 8 patients, including 4 with NF-1. The 10-year cumulative incidence of clinically significant vasculopathy was 7.1% (95% CI, 2.9%-13.9%); vasculopathy did not develop in any child aged >10 years at the commencement of RT. CONCLUSIONS: RT is an effective treatment for optic-hypothalamic LGG. Older children without NF-1 have a low risk of late toxicity. RT can be considered for selected younger patients or individuals with NF-1 as a salvage treatment after progression.

OPTIC NERVE INFILTRATION BY RETINOBLASTOMA: Predictive Clinical Features and Outcome.

PURPOSE: To identify the clinical features predictive of any optic nerve infiltration and postlaminar optic nerve infiltration by retinoblastoma on histopathology and to report the outcome (metastasis and death) in these patients. METHODS: Retrospective study. RESULTS: Of the 403 patients who underwent primary enucleation for retinoblastoma, 196 patients had optic nerve tumor infiltration (Group 1) and 207 patients had no evidence of optic nerve tumor infiltration (Group 2). Group 1 included patients with prelaminar (n = 47; 24%), laminar (n = 74; 38%), and postlaminar tumor infiltration with or without involving optic nerve transection (n = 74; 38%). Comparing Group 1 and Group 2, the patients in Group 1 had prolonged duration of symptoms (>6 months) (16% vs. 8%; P = 0.02) and were associated with no vision at presentation (23% vs. 10%; P = 0.01), higher rates of secondary glaucoma (42% vs. 12%; P < 0.0001), iris neovascularization (39% vs. 23%; P < 0.001), and larger tumors (mean tumor thickness, 12.8 mm vs. 12 mm; P = 0.0001). There was a higher prevalence of metastasis in Group 1 than in Group 2 (4% vs. 0%; P = 0.006). On multivariate analysis, clinical features predictive of any optic nerve tumor infiltration secondary glaucoma (hazard ratio = 5.38; P < 0.001) and those predictive of postlaminar optic nerve tumor infiltration included iris neovascularization (hazard ratio = 2.66; P = 0.001) and secondary glaucoma (hazard ratio = 3.13; P < 0.001). CONCLUSION: In this study, clinical features predictive of any optic nerve tumor infiltration included secondary glaucoma and those predictive of postlaminar optic nerve tumor infiltration included iris neovascularization and secondary glaucoma. Despite adjuvant treatment in those with postlaminar optic nerve tumor infiltration, metastasis occurred in 8% of patients.

Occurrence and distribution of pilomyxoid astrocytoma.

PURPOSE: To know the occurrence and distribution of Pilomyxoid Astrocytomas amongst tumours previously diagnosed histologically as Pilocytic Astrocytoma and to assess the clinical impact of this new entity. METHODS: Retrospective Diagnostic review of all cases histologically diagnosed as WHO Grade I Astrocytoma at a single Neurosurgical unit between 1990 and 2003. RESULTS: Of a total of 91 cases identified, 9 were found to have Pilomyxoid histology. Of these, 8 were children (mean age 3.33 years) and 1 adult. 6 tumours were hypothalamochiasmatic in location. The clinical course of Pilomyxoid tumours was aggressive marked by maturation, multiple recurrences and disease control was rarely achieved with single treatment modality as opposed to typical pilocytics. The overall survival of the pilomyxoid group was not statistically different from the pilocytic tumours. CONCLUSIONS: Encompassing all age-groups and locations, Pilomyxoid Astrocytomas constitute about 10% of all tumours previously diagnosed as Pilocytic Astrocytoma. Nearly two-thirds are hypothalamo-chiasmatic in location. Knowledge of this entity is essential for appropriate aggressive treatment and follow-up.

MRI findings at baseline and after neoadjuvant chemotherapy in orbital retinoblastoma (IRSS stage III).

BACKGROUND: Published findings on MRI results in retinoblastoma patients treated with neoadjuvant chemotherapy (NACT) are lacking. The present study evaluates the role of MRI in International Retinoblastoma Staging System (IRSS) stage III retinoblastoma treated with NACT. METHODS: 28 consecutive IRSS stage III retinoblastoma patients underwent MRI at baseline and after three cycles of NACT prior to enucleation. MRI films were reviewed retrospectively by an ophthalmic radiologist who was masked to patient outcome. Optic nerves were staged based on their thickness, contrast enhancement and length of involvement on MRI. Response evaluation criteria were based on optic nerve staging and changes in the size of the orbital mass on MRI after NACT. RESULTS: The proposed staging at baseline and after NACT was able to predict event-free-survival (EFS) (p=0.005 and p <0.001, respectively) and overall survival (OS) (p=0.002 and p=0.001, respectively) using the log-rank test for trends. Patients with complete or partial response according to the proposed response evaluation criteria had significantly better EFS (p<0.001) and OS (p=0.024) than those who had stable or progressive disease. CONCLUSIONS: The proposed MRI based optic nerve staging system and response evaluation criteria were able to predict EFS and OS at baseline and after NACT.

Postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin for the treatment of high-risk retinoblastoma.

BACKGROUND: Analysis of 52 eyes with high-risk retinoblastoma managed with postenucleation adjuvant chemotherapy using vincristine sulfate, etoposide phosphate, and carboplatin showed no evidence of systemic metastasis in any case during a mean (range) follow-up of 66 (12-202) months. PURPOSE: To determine the efficacy of postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin in the prevention of metastasis for patients with high-risk retinoblastoma. METHODS: Retrospective, nonrandomized, interventional case series of 52 eyes in 51 patients with high-risk retinoblastoma consisting of tumor invasion into the anterior segment, posterior uvea 3 mm or greater, postlaminar optic nerve, or any combination of posterior uvea and optic nerve involvement. RESULTS: Of 51 consecutive patients with high-risk retinoblastoma, there were 30 males (59%) and 21 females (41%), with a median age of 28 months at diagnosis. All 52 eyes were classified as group E. The main histopathologic risk factors included anterior segment invasion (7 [13%]), isolated massive posterior uveal invasion of 3 mm or greater (6 [12%]), isolated postlaminar optic nerve invasion (15 [29%]), or any posterior uveal invasion with any optic nerve involvement (24 [46%]). There was additional invasion into the sclera (3 [6%]) and extrascleral structures, including the orbit (1 [2%]). A single histopathologic high-risk factor was present in 32 eyes (62%), whereas 20 eyes (38%) manifested 2 or more high-risk characteristics. Based on previously published series, untreated high-risk retinoblastoma carries at least a 24% risk for metastatic disease. In the present series, using vincristine, etoposide, and carboplatin in all cases, there was no metastasis during a mean follow-up of 66 months (median [range], 55 [12-202] months). CONCLUSIONS: Retinoblastoma with invasion into the postlaminar optic nerve and/or posterior uvea is at high risk for metastasis and death. In this study, postenucleation chemotherapy using vincristine, etoposide, and carboplatin was effective in preventing metastasis in every case (100%).

Proton irradiation for peripapillary and parapapillary melanomas.

OBJECTIVE: To examine ocular outcomes and survival after proton irradiation in patients with peripapillary and parapapillary melanomas ineligible for the Collaborative Ocular Melanoma Study. METHODS: A total of 573 patients who received proton irradiation from January 4, 1985, through December 24, 1997, for tumors located within 1 disc diameter of the optic nerve, and therefore ineligible for the Collaborative Ocular Melanoma Study, were evaluated. Cumulative rates of vision loss in the treated eye, eye loss, melanoma-related mortality, and tumor recurrence were estimated using the Kaplan-Meier method. RESULTS: Most (53.4%) tumors abutted the optic disc; median distance from the tumor to the macula was 0.5 disc diameters. By 5 years after proton therapy, radiation papillopathy had developed in 56.8% and maculopathy in 60.4% of patients. Of 450 patients with a baseline visual acuity of 20/200 or better in the treated eye, vision was retained in 54.9% at 2 years after irradiation. This decreased to 20.3% by 5 years after treatment, although 56.2% had visual acuity of counting fingers or better. Five- and 10-year rates of local recurrence were 3.3% and 6.0%, respectively. Enucleation rates were 13.3% at 5 years and 17.1% at 10 years after treatment. Melanoma-related mortality rates were similar to those in our larger cohort of patients (24.0% at 15 years). CONCLUSIONS: Proton irradiation should be considered for treating patients with tumors contiguous to the optic disc. Although visual acuity is compromised, some preservation is possible (counting fingers or better in many patients). Eye conservation is likely, with low rates of tumor recurrence and no increased risk of metastasis.

Outcomes of multidisciplinary management in pediatric low-grade gliomas.

PURPOSE: To evaluate the outcomes in pediatric low-grade gliomas managed in a multidisciplinary setting. METHODS AND MATERIALS: We conducted a single-institution retrospective study of 181 children with Grade I-II gliomas. Log-rank and stepwise Cox proportional hazards models were used to analyze freedom from progression (FFP) and overall survival (OS). RESULTS: Median follow-up was 6.4 years. Thirty-four (19%) of patients had neurofibromatosis Type 1 (NF1) and because of their favorable prognosis were evaluated separately. In the 147 (81%) of patients without NF1, actuarial 7-year FFP and OS were 67 ± 4% (standard error) and 94 ± 2%, respectively. In this population, tumor location in the optic pathway/hypothalamus was associated with worse FFP (39% vs. 76%, p < 0.0003), but there was no difference in OS. Age ≤5 years was associated with worse FFP (52% vs. 75%, p < 0.02) but improved OS (97% vs. 92%, p < 0.05). In those with tissue diagnosis, gross total resection (GTR) was associated with improved 7-year FFP (81% vs. 56%, p < 0.02) and OS (100% vs. 90%, p < 0.03). In a multivariate model, only location in the optic pathway/hypothalamus predicted worse FFP (p < 0.01). Fifty patients received radiation therapy (RT). For those with less than GTR, adjuvant RT improved FFP (89% vs. 49%, p < 0.003) but not OS. There was no difference in OS between patient groups given RT as adjuvant vs. salvage therapy. In NF1 patients, 94% of tumors were located in the optic pathway/hypothalamus. With a conservative treatment strategy in this population, actuarial 7-year FFP and OS were 73 ± 9% and 100%, respectively. CONCLUSIONS: Low-grade gliomas in children ≤5 years old with tumors in the optic pathway/hypothalamus are more likely to progress, but this does not confer worse OS because of the success of salvage therapy. When GTR is not achieved, adjuvant RT improves FFP but not OS. Routine adjuvant RT can be avoided and instead reserved as salvage.

Clinicopathological features and global genomic copy number alterations of pilomyxoid astrocytoma in the hypothalamus/optic pathway: comparative analysis with pilocytic astrocytoma using array-based comparative genomic hybridization.

Pilomyxoid astrocytoma is a recently identified variant of pilocytic astrocytoma. We studied 11 circumscribed astrocytomas with focal (n=5) or diffuse (n=6) pilomyxoid features and compared them with 17 pilocytic astrocytomas from the hypothalamic/chiasmatic region in children. In one patient, a tumor that recurred after initial surgery had changed from pure-form pilomyxoid astrocytoma to the mixed form. The presence of a pilomyxoid area was associated with shorter survival. Next, we compared the comprehensive genome copy number changes in the pilomyxoid astrocytoma (n=4) with those in pilocytic astrocytoma (n=6) cases by array-based comparative genomic hybridization. The number of lost clones was larger in pilomyxoid astrocytoma than in pilocytic astrocytoma. Clones located in chromosome 8q24.3 were frequently gained in pilocytic astrocytoma (four of six) and in pilomyxoid astrocytoma (one of four). Clones located in 9p24.3 and 15q26.3 were lost in all of the pilomyxoid astrocytomas and in five of the pilocytic astrocytomas. Those in 8p23.3 showed a copy number loss in three of the pilomyxoid astrocytomas and four of the pilocytic astrocytomas. The frequency of copy number changes was significantly different between pilomyxoid astrocytoma and pilocytic astrocytoma in 47 (3.6%) clones, 20 of them having been located in 2p, 10 in 2q, and 11 in 3q. An unsupervised hierarchical clustering analysis classified the cases into three clusters: one pilomyxoid astrocytoma patient into one cluster, two pilomyxoid astrocytoma patients into another cluster, and six pilocytic astrocytoma patients and one pilomyxoid astrocytoma patient into the third cluster. In conclusion, the presence of mixed-form pilomyxoid astrocytoma, the acquisition of pilocytic astrocytoma features in a recurrent tumor in pure-form pilomyxoid astrocytoma, and the above results of the genome-wide gene copy number analysis suggest that pilomyxoid astrocytoma might be a pathologically and genetically related, aggressive variant of pilocytic astrocytoma with partially different genetic alterations.

Outcome of patients with retinoblastoma and postlaminar optic nerve invasion.

PURPOSE: To evaluate the outcome of patients with retinoblastoma and postlaminar optic nerve invasion (PLONI). DESIGN: Retrospective interventional case series. PARTICIPANTS: Sixty-one consecutive patients included in 3 successive protocols were analyzed. METHODS: Pathologic review was done in each case. Patients were stratified into 2 risk groups: the high-risk group included those with concomitant full choroidal and/or scleral invasion and were given adjuvant chemotherapy. Those without these features were considered low risk and chemotherapy was withheld after 1994. MAIN OUTCOME MEASURES: Extraocular relapse and survival according to stratification. RESULTS: The probability of event-free survival (pEFS) was 0.91 and the probability of overall survival (pOS) was 0.94 at 5 years. Patients in the high-risk group (n = 22) had pEFS of 0.86. Three had extraocular relapse (involving the central nervous system; all died of disease). Microscopic scleral invasion was associated to extraocular relapse (P = 0.05). Lower risk patients (n = 39) had a pEFS of 0.94 and pOS of 1. Eighteen received postenucleation chemotherapy and none relapsed. Twenty-one received no adjuvant therapy and 2 had a systemic relapse but were successfully retrieved. Relapsing patients had a higher ratio of affected optic nerve (>25% of it overall length; P = 0.02). CONCLUSIONS: Patients with PLONI have an excellent outcome with current therapy. Risk stratification according to the presence of concomitant choroidal and/or scleral invasion may help in the decision of giving adjuvant therapy.

Optic nerve invasion of uveal melanoma.

The aim of the study was to identify the histopathological characteristics associated with the invasion of the optic nerve of uveal melanoma and to evaluate the association between invasion of the optic nerve and survival. In order to achieve this, all uveal melanomas with optic nerve invasion in Denmark between 1942 and 2001 were reviewed (n=157). Histopathological characteristics and depth of optic nerve invasion were recorded. The material was compared with a control material from the same period consisting of 85 cases randomly drawn from all choroidal/ciliary body melanomas without optic nerve invasion. Prelaminar/laminar optic nerve invasion was in multivariate analysis associated with focal retinal invasion, neovascularization of the chamber angle, and scleral invasion. Postlaminar invasion was further associated with non-spindle cell type and rupture of the inner limiting membrane of the retina. The optic nerve was invaded in four different ways: 1) by tumor extension from the neuroretina through the lamina cribrosa; 2) by direct extension into the optic nerve head between Bruch's membrane and the border tissue of Elschnig; 3) by direct invasion through the border tissue of Elschnig; and 4) in one case a tumor spread along the inner limiting membrane to the optic nerve through the lamina cribrosa. Invasion of the optic nerve had no impact on all-cause mortality or melanoma-related mortality in multivariate analyses. The majority of melanomas invading the optic nerve are large juxtapapillary tumors invading the optic nerve because of simple proximity to the nerve. A neurotropic subtype invades the optic nerve and retina in a diffuse fashion unrelated to tumor size or location.

Optic nerve invasion of uveal melanoma: clinical characteristics and metastatic pattern.

PURPOSE: To determine the frequency of optic nerve invasion in uveal melanoma, to identify clinical factors associated with optic nerve invasion, and to analyze the metastatic pattern and the association with survival. METHODS: All iris, ciliary body, and choroidal melanomas (N = 2758) examined between 1942 and 2001 at the Eye Pathology Institute, University of Copenhagen, Denmark, and the Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark, were reviewed. Cases with optic nerve invasion were identified and subdivided into prelaminar or laminar invasion and postlaminar invasion. Clinical characteristics were compared with those from 85 cases randomly drawn from all ciliary body and choroidal melanomas without optic nerve invasion from the same period. Survival data were obtained by the Kaplan-Meier method, and the Mantel-Cox log-rank test was used to test differences in survival among the three patient groups. RESULTS: Optic nerve invasion was found in 157 uveal melanomas (5.7%; 95% confidence interval [CI], 4.8%-6.6%). Frequency varied during the observation period between 5% and 7%. Only choroidal and ciliary body melanomas were found to invade the optic nerve. Eighty-five (54%) were confined to the prelaminar or laminar part, and 72 (46%) were confined to the postlaminar part. Increased intraocular pressure (IOP) and juxtapapillary location were associated with prelaminar or laminar invasion and postlaminar invasion. Age older than 70 years, reduced vision to light perception or worse, nonvisible fundus, and large (>15 mm) tumor size were associated with postlaminar spread. In univariate analysis, patients with postlaminar invasion had significantly higher all-cause and melanoma-related mortality than the other patients. CONCLUSIONS: Optic nerve invasion in uveal melanoma is found in 1 in 20 patients. Visible juxtapapillary melanoma or loss of light perception should make the clinician suspicious of melanoma with optic nerve invasion, and special awareness of postlaminar spread should be addressed when increased IOP is present independently of decreased visual acuity and tumor location.

Metastatic retinoblastoma clinical features, treatment, and prognosis.

PURPOSE: To evaluate the clinical features, treatment, and prognosis in patients with metastatic retinoblastoma. DESIGN: Retrospective interventional case series. PARTICIPANTS: Eighteen consecutive patients with metastatic retinoblastoma who were diagnosed and managed at the Oncology Service of Ankara University, Turkey, between January 1999 and January 2005. METHODS: All patients underwent magnetic resonance imaging (MRI) of the orbit and brain, lumbar puncture, bone marrow aspiration, and bone scintigraphy for metastatic evaluation. Histopathologic confirmation of retinoblastoma via enucleation, exenteration, or orbital biopsy was obtained in each patient. The status of extraocular spread (optic nerve, extrascleral extension, or both) was assessed based on histopathologic or MRI results. Systemic treatment for metastatic retinoblastoma consisted of chemotherapy and radiotherapy (craniospinal, orbital, or both), if necessary. MAIN OUTCOME MEASURES: Status of extraocular spread, site of metastasis, and survival from metastatic retinoblastoma. RESULTS: At presentation, the mean patient age was 45 months (range, 13-86). Ten patients had unilateral retinoblastoma, 7 had bilateral retinoblastoma, and 1 had trilateral retinoblastoma. All patients with metastatic retinoblastoma had histopathologic or MRI evidence of unilateral extraocular disease characterized by optic nerve involvement, extrascleral extension, or both. Nine of 18 patients experienced central nervous system (CNS) involvement, 5 patients had distant and CNS metastasis, and 4 patients had distant metastasis only. Fourteen patients underwent craniospinal irradiation and 12 had orbital irradiation. At a mean follow-up of 24 months (range, 4-62), all patients with CNS and concurrent distant and CNS metastasis were deceased. Four patients who had distant metastasis only were alive at a follow-up ranging from 9 to 62 months. CONCLUSIONS: The prognosis for metastatic retinoblastoma is dismal and the presence of CNS involvement may portend an even worse outcome.

Low grade chiasmatic-hypothalamic glioma-carboplatin and vincristin chemotherapy effectively defers radiotherapy within a comprehensive treatment strategy -- report from the multicenter treatment study for children and adolescents with a low grade glioma -- HIT-LGG 1996 -- of the Society of Pediatric Oncology and Hematology (GPOH).

BACKGROUND: Low grade gliomas arise in all CNS-locations and age groups, chiasmatic-hypothalamic tumors occur especially in young children. Early radiotherapy (RT) shall be deferred by chemotherapy (CT) within the concept of the HIT-LGG 1996 study, offering a comprehensive treatment strategy for all age groups. PATIENTS: 198 of 905 protocol patients (21.9 %) had a chiasmatic (34), chiasmatic-hypothalamic (144) or hypothalamic (20) primary tumor, median age at diagnosis 3.6 years (0.2-16.3 y.), 54 had neurofibromatosis (27.3 %), 108 female (54.5 %). 98 children had severe visual impairment as their first symptom. The initial neurosurgical intervention resulted in 5 complete, 26 subtotal, 45 partial resections, 67 biopsies; 55 children had a diagnosis on the basis of neuroradiologic findings. Histology showed 132 pilocytic astrocytoma I degrees , 6 astrocytoma II degrees /nos and 2 DIGG/DIA I degrees (3 not known). RESULTS: 82 children were treated at diagnosis, 68 upon clinical or radiological progression following observation times of 3.0 to 115.0 months. RT: 27 children received conventional (18) or interstitial (8) RT (1 not documented) at a median age of 7.3 years; 7 tumors went into further progression. At a median observation time of 50.1 months 21 tumors are stable, 3 regressive (2 not evaluable, 1 death). CT: 123 children received vincristin/carboplatin at a median age of 3.7 years. 105/123 achieved CR/PR/SD. 44/123 tumors were progressive after median 22.5 months, 37 with a chiasmatic-hypothalamic primary, 16/44 were irradiated. At a median observation time of 44.7 months 2 children are in complete remission, 92 tumors are stable, 8 regressive, 9 progressive. 4 children died, 8 are not evaluable. At 60 months overall survival of the cohort is 0.93; PFS of the CT-group is 0.61, the RT-free survival 0.83. Within the CT-group children with an age at diagnosis < 1 year and non-pilocytic histology are at increased risk for early progression. Causative factors cannot be defined, yet. CONCLUSION: Within the comprehensive treatment strategy for low grade glioma HIT-LGG 1996 chemotherapy is effective to delay the need for early radiotherapy in chiasmatic-hypothalamic glioma. More effective reduction of the risk for progression has to be sought for young children < 1 year.

Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part I: Treatment modalities of radiation therapy.

BACKGROUND: Treatment of childhood low-grade gliomas is a challenging issue owing to their low incidence and the lack of consensus about "optimal" treatment approach. MATERIAL AND METHODS: Reports in the literature spanning 60 years of radiation therapy, including orthovoltage, megavoltage and recently modern high-precision treatments, were reviewed with respect to visual function, survival, prognostic factors, dose prescriptions, target volumes, and treatment techniques. Based on these experiences, future strategies in the management of childhood low-grade glioma are presented. RESULTS: Evaluation of published reports is difficult because of inconsistencies in data presentation, relatively short follow-up in some series and failure to present findings and results in a comparable way. Even with the shortcomings of the reports available in the literature, primarily concerning indications, age at treatment, dose response, timing and use of "optimal" treatment fields, radiation therapy continues to play an important role in the management of these tumors achieving long-term survival rates up to 80% or more. Particularly in gliomas of the visual pathway, high local tumor control and improved or stable visual function is achieved in approximately 90% of cases. Data on dose-response relationships recommend dose prescriptions between 45 and 54 Gy with standard fractionation. There is consensus now to employ radiation therapy in older children in case of progressive disease only, regardless of tumor location and histologic subtype. In younger children, the role of radiotherapy is unclear. Recent advances in treatment techniques, such as 3-D treatment planning and various "high-precision" treatments achieved promising initial outcome, however with limited patient numbers and short follow-ups. CONCLUSIONS: Radiation therapy is an effective treatment modality in children with low-grade glioma regarding tumor control and improvement and/or preservation of neurologic function or vision, respectively. More prospective studies are needed to address the impact of modern radiation therapy technologies (including intensity-modulated radiotherapy) on outcome especially in the very young and to define the role of radiation therapy as a part of a comprehensive treatment approach. The forthcoming prospective trial SIOP/GPOH LGG RT 2003 is addressing this issue.

Pilocytic astrocytomas in children: prognostic factors--a retrospective study of 80 cases.

OBJECTIVE: Pilocytic astrocytomas (PA) are Grade I brain tumors characterized by an excellent prognosis. In some cases, however, the patient has a bad outcome. The aim of our study was to search for the clinicopathological factors underlying the prognosis for patients with this disease. METHODS: We reviewed the clinical, neuroradiological, and histopathological features of 80 PAs (33 cerebellar, 18 optochiasmatic, 16 brainstem, 7 spinal cord, 3 thalamic, 2 optic nerve, and 1 hemispheric) in pediatric patients. RESULTS: Pathological examination revealed 58 classic PAs and 20 pilomyxoid astrocytomas, which are a histological variant of PAs. Two cases remained unclassified. The mean overall follow-up period was 58 months, the 5-year progression-free survival rate was 75%, and the 5-year survival rates were 100 and 92% after total and partial removal. Univariate statistical analysis revealed that partial resection, optochiasmatic PA localization, and pilomyxoid variant were associated with a worse prognosis, but the latter two parameters were too closely related to the extent of resection to be independent prognostic factors in multivariate analysis. Among the patients who underwent partial surgical removal, only invasion of the surrounding structures was related to prognosis. CONCLUSION: PAs are benign tumors, but some clinicopathological factors, such as partial resection, optochiasmatic location, invasion of surrounding structures, and the pilomyxoid variant, have a worse prognosis.

Management of optic chiasmatic/hypothalamic astrocytomas in children.

OBJECTIVE: The management of optic chiasmatic gliomas is controversial, partly related to failure to separate out those tumors involving the optic chiasm only (chiasmatic tumors) from those also involving the hypothalamus (chiasmatic/hypothalamic tumors). The purpose of this study was: (i) to analyze the outcomes of chiasmatic and chiasmatic/hypothalamic tumors separately; and (ii) to determine the appropriateness of recommending radical surgical resection for the chiasmatic/hypothalamic tumors. METHODS: A retrospective chart review of all newly diagnosed tumors involving the optic chiasm from 1982-1996 at British Columbia's Children's Hospital was performed. RESULTS: There were 32 patients less than 16 years of age, 14 with chiasmatic and 18 with chiasmatic/hypothalamic astrocytomas, with an average duration of follow-up of 5.8 years and 6.3 years, respectively. Ten of the patients with chiasmatic tumors and none with chiasmatic/hypothalamic tumors had neurofibromatosis I. Thirteen of the 14 chiasmatic tumors were managed with observation only, and none had progression requiring active intervention. For the chiasmatic/hypothalamic tumors, eight patients had subtotal resections (>95% resection), six had partial resections (50-95%), three had limited resections (<50%), and one had no surgery. There were fewer complications associated with the limited resections, especially with respect to hypothalamic dysfunction. There was no correlation between the extent of resection (subtotal, partial, or limited) and the time to tumor progression (average 18 months). CONCLUSIONS: In conclusion, chiasmatic and chiasmatic/hypothalamic tumors are different entities, which should be separated out for the purposes of any study. For the chiasmatic/hypothalamic tumors, there was more morbidity and no prolongation of time to progression when radical resections were compared to more limited resections. Therefore, if surgery is performed, it may be appropriate to do a surgical procedure that strives only to provide a tissue diagnosis and to decompress the optic apparatus and/or ventricular system.

Variations in the presentation of primary intraocular lymphoma: case reports and a review.

Primary intraocular lymphoma is a distinct subset of primary non-Hodgkin's lymphoma of the central nervous system (CNS). Diagnosis can be difficult and is often delayed, as the clinical presentation can mimic a number of other ocular conditions. This report describes four different presentations of intraocular lymphoma and focuses on its modes of clinical presentation. Primary intraocular lymphoma can present with a wide variety of manifestations frequently mimicking diffuse uveitis that is refractory to corticosteroids. Subretinal pigment epithelium tumors may be seen. However, other presentations may include multiple deep white dots in the retina secondary to tumor infiltration; retinal infiltration, causing a necrotizing retinitis; or infiltration of the retinal vasculature, causing arterial or venous obstruction. Finally, optic nerve invasion may be seen. CNS lymphoma develops in the majority of patients before, in conjunction with, or after the development of eye disease. Intraocular lymphoma often has a fatal outcome, but recognition of its modes of presentation facilitates early diagnosis and treatment that may improve prognosis.

Carboplatin is effective therapy for young children with progressive optic pathway tumors: a Pediatric Oncology Group phase II study.

The Pediatric Oncology Group conducted a phase II study to evaluate the activity of carboplatin in children 5 years or younger with progressive optic pathway tumors (OPTs). Of the 51 patients accrued to this study, 1 was not eligible because the child was older than 6 years. Fifty patients were eligible and had either neuro-imaging or symptomatic evidence of progressive OPTs. Twenty-one of 50 had evidence of neurofibromatosis type I (NF-1). Therapy consisted of carboplatin 560 mg/m2 at 4-week intervals. Patients with stable disease or better after two courses were continued on therapy for 18 months or until progressive disease. Of the 50 eligible children, 39 had stable disease or better, and 34 completed the 18-month therapy. Our data are sufficient to conclude that the proportion of objective responses (complete, partial, or minor response or stable disease) exceeded 30% (P < 0.00001), and the approximate 95% confidence interval estimate of the objective response rate was 0.665 to 0.895. Twenty-one patients went off protocol because of progressive disease. Fifteen patients progressed during the 18-month therapy, and 6 patients progressed after completing therapy. Six children died with progressive disease. Major toxicities were neutropenia and thrombocytopenia, and 3 children experienced allergic reactions. Carboplatin is active and safe for the treatment of young children with progressive OPTs. The addition of other potentially active drugs may further increase the event-free survival for these children.

Long-term follow up of 69 patients treated for optic pathway tumours before the chemotherapy era.

AIM: To analyse the long-term results of conservative management with radiotherapy in patients with optic pathway tumours. DESIGN: All 69 patients were symptomatic at diagnosis and most neoplasms involved the optic chiasm and hypothalamus. RESULTS: At 10 years, overall survival and progression free survival were 83% and 65.5%, respectively. After radiotherapy, vision improved in 18 patients and remained stable in 29 other patients. Cerebrovascular complications occurred in nine of 53 patients treated with radiotherapy after a median interval of two and a half years. These complications were five times more frequent in patients with neurofibromatosis type 1 (NF1). Severe intellectual disabilities were present in 18 children, most of whom underwent irradiation at a very young age (median age, 4 years). IMPLICATIONS: Radiotherapy is a valuable treatment in terms of tumour response, visual outcome, and progression free survival. However, in young children and in patients with NF1, major sequelae are encountered and new treatment strategies should be proposed for these patients.