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.

Phase II TPDCV protocol for pediatric low-grade hypothalamic/chiasmatic gliomas: 15-year update.

To report long-term results for children with low-grade hypothalamic/chiasmatic gliomas treated on a phase II chemotherapy protocol. Between 1984 and 1992, 33 children with hypothalamic/chiasmatic LGGs received TPDCV chemotherapy on a phase II prospective trial. Median age was 3.0 years (range 0.3-16.2). Twelve patients (36%) underwent STRs, 14 (42%) biopsy only, and seven (21%) no surgery. Twenty patients (61%) had pathologic JPAs, nine (27%) grade II gliomas, and four (12%) no surgical sampling. Median f/u for surviving patients was 15.2 years (range 5.3-20.7); 20 of the 23 surviving patients had 14 or more years of follow-up. Fifteen-year PFS and OS were 23.4 and 71.2%, respectively. Twenty-five patients progressed, of whom 13 are NED, two are AWD, and 10 have died. All children who died were diagnosed and first treated at age three or younger. Age at diagnosis was significantly associated with relapse and survival (P = 0.004 for PFS and P = 0.037 for OS). No PFS or OS benefit was seen with STR versus biopsy/no sampling (P = 0.58 for PFS, P = 0.59 for OS). For patients with JPAs and WHO grade II tumors, the 15-year PFS was 18.8 and 22.2% (P = 0.95) and 15-year OS was 73.7 and 55.6% (P = 0.17), respectively. Upfront TPDCV for children with hypothalamic/chiasmatic LGGs resulted in 15-year OS of 71.2% and 15-year PFS of 23.4%. No survival benefit is demonstrated for greater extent of resection. Age is a significant prognostic factor for progression and survival.

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.

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.

[Childhood diencephalic pilocytic astrocytoma. A review of seven observations]. / Les astrocytomes pilocytiques du diencephale de l'enfant. à propos de sept observations.

BACKGROUND AND PURPOSE: Pilocytic astrocytoma (PA) is a WHO grade I tumor of the central nervous system mostly arising in children and young adults. Management of diencephalic PA is a difficult challenge. Surgical treatment has to cope with both the difficulties of deep location and eloquent area tumors. MATERIALS AND METHODS: We retrospectively reviewed seven pediatric cases (female: 4, male: 3) of diencephalic PA. Opto-chiasmatic tumors were excluded from the series. Mean age at diagnosis was 108 months (9 years) (range: 4 month-18 years), median age was 111 months. Median follow-up for the series was 125 months. Tumor locations were as followed: right thalamus: 2, both thalami: 1, hypothalamus: 3, and right basal ganglia: 1. At the onset, the first symptom was mostly raised intracranial pressure. The delay in diagnosis ranged from 48 hours up to 6 years. TREATMENT: a shunting procedure was performed in 3 patients, a direct surgical approach in 5 patients (gross total removal: 2; partial removal: 3) and one patient had only a biopsy. Three children were re-operated. Three patients were treated by radiationtherapy (RT) after surgery. Chemotherapy was delivered for 4 children. RESULTS: The overall survival rate was 71.4 months (almost 6 years) (range: 3-184 months). Median survival rate was 42 months (3.5 years). Three children died, two by tumor progression and one death related to late side-effects of RT. Four patients have a good quality of life with GOS I (n = 3) or II (n = 1). We observed tumor regression in two patients at 1 and 17 years after the beginning of treatment. Correct diagnosis was only made for two cases at the initial pathological examination. CONCLUSION: The course of diencephalic PA is still unpredictable. The tumor can be controlled by a partial surgical removal, and a residual tumor can sometimes decrease in size after surgery. Gross total removal of these tumors, although difficult, may be performed. With cranial navigation systems, the risk is low. Pathological diagnosis is sometimes difficult to assess.

Risk factors for mortality caused by hypothalamic obesity in children with hypothalamic tumours.

BACKGROUND: Hypothalamic obesity (HyOb) is a common complication of childhood hypothalamic tumours. Patients with HyOb probably have a higher mortality rate than those with other types of obesity due in many cases to obstructive sleep apnoea/hypoventilation. OBJECTIVES: To identify predictive factors for mortality caused by HyOb in children. METHODS: Twenty children with HyOb secondary to hypothalamic tumours that were followed-up for ≥3 years and aged <15 years at diagnosis, and received supraphysiological glucocorticoid treatment for ≤1 month. RESULTS: Mean age at diagnosis was 6.36 ± 3.60 years. Mean body mass index (BMI) Standard deviation of the samples (SDS) increased from 0.77 ± 1.26 to 2.66 ± 1.45 during the first 6 months, but slowed from month 6-12 (2.73 ± 1.35). ΔBMI SDS at 0-6 months was significantly higher in patients aged <6 years at diagnosis than in those aged >6 years at diagnosis (3.71 ± 1.96 vs. 0.83 ± 0.73, P < 0.001). Maximum BMI SDS was also significantly higher in the younger group (3.88 ± 1.39 vs. 2.79 ± 0.64, P < 0.05). In all, four patients died and the mortality rate was significantly higher in the patients with a further increase in BMI SDS > 1 SDS after 6 months of therapy (RR: 8.4, P < 0.05). Both overall mortality and obesity-related mortality rates were higher in the patients aged <6 years at diagnosis (4.5-fold, 7.2-fold higher, respectively, P > 0.05). The mortality rate was also 3.7-fold higher in the patients with a maximum BMI SDS ≥ 3 at any time during the first 3 years after therapy(P > 0.05). CONCLUSIONS: An increase in BMI SDS after 6 months of therapy was observed to be a risk factor for mortality caused by HyOb. In addition, age <6 years at diagnosis and a maximum BMI SDS ≥ 3 were associated with a higher mortality rate, indicating that earlier and more aggressive treatment of obesity is required.

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

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

Management of optic pathway and chiasmatic-hypothalamic gliomas in children with radiation therapy.

BACKGROUND AND PURPOSE: Optic pathway and chiasmatic-hypothalamic gliomas are rare childhood tumors. This study presents the experience in management of these tumors with radiation therapy. MATERIALS AND METHODS: Thirty-three children with the diagnosis of optic pathway and chiasmatic-hypothalamic gliomas were treated with radiation therapy from 1973 through 1994 in the Department of Radiation Oncology at Ankara University Faculty of Medicine. Twenty-four children had optic pathway gliomas and nine had chiasmatic-hypothalamic gliomas. Evidence of neurofibromatosis was present in six children. Subtotal resection was performed in 22 children and a biopsy in seven. The most common prescription for total tumor dose was 50 Gy, delivered in 2 Gy daily fractions. Follow-up ranged from 0.5 to 16.1 years (mean, 13.6 years). RESULTS: Overall, progression-free and cause-specific survival probabilities for the entire group were 93%, 82% and 93%, respectively, at 5 years and 79%, 77% and 88%, respectively, at 10 years. Differences in overall, progression-free and cause-specific survival probabilities between optic pathway and chiasmatic-hypothalamic gliomas were not statistically significant. Absence of evidence of neurofibromatosis correlated with significantly better progression-free and cause-specific survival probabilities. CONCLUSION: Radiation therapy is effective in stabilization or improvement of vision and prevention of tumor progression in both optic pathway and chiasmatic-hypothalamic gliomas.

Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas.

OBJECTIVE: Pilocytic astrocytoma (PA) is a common type of pediatric brain tumor that can arise within the hypothalamic/chiasmatic region and typically has an excellent outcome. We identified a group of tumors, previously classified as PAs, with unique histological features and aggressive behavior. This article describes the clinicopathological features of these unusual neoplasms, which are currently known as pilomyxoid astrocytomas (PMAs), to better differentiate them from typical PAs. METHODS: Medical information and surgical specimens were obtained for 42 PA cases and 21 PMA cases. Patient demographic features, treatment modalities, progression-free survival (PFS) times, overall survival (OS) times, and outcomes were compared between the groups with nonparametric tests. RESULTS: The PMA group included 12 male and 9 female patients. The PA group included 27 male and 15 female patients. The mean ages at diagnosis for the PMA and PA groups were 18 months (range, 2-84 mo) and 58 months (range, 4-189 mo), respectively (P < 0.01). The mean PFS times for the PMA and PA groups were 26 and 147 months, respectively (P < 0.001). The mean OS times for the PMA and PA groups were 63 and 213 months, respectively (P < 0.001). Sixteen patients with PMAs (76%) experienced local recurrence, and three of those patients demonstrated evidence of cerebrospinal fluid dissemination. Twenty-one patients with PAs (50%) experienced local recurrence, none with evidence of cerebrospinal fluid dissemination. Within the follow-up period, seven patients with PMAs (33%) and seven patients with PAs (17%) died as a result of their disease. In an age-matched set, the mean PFS times for the PMA and PA groups were 25 and 163 months, respectively (P < 0.01), and the mean OS times for the PMA and PA groups were 60 and 233 months, respectively (P < 0.001). CONCLUSION: Hypothalamic/chiasmatic PMAs occurred in a significantly younger population and were associated with substantially shorter PFS and OS times than were typical PAs. Increased recognition of these lesions could affect the prognosis and treatment of pediatric astrocytomas.

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.

Long-term outcome in children with gliomas of the anterior visual pathway.

We performed a retrospective assessment of the long-term visual, neurologic, and systemic outcomes of 47 patients with anterior visual pathway gliomas seen at the Johns Hopkins Hospital. All of the patients had follow-up of at least 10 years or died during the follow-up period. Two patients died before 10 years of follow-up were achieved. The remaining 45 patients (including three patients who subsequently died) had follow-up of 10-28 years (mean, 15.3 years; median, 15 years). Sixteen of the patients in this study, most of whom had neurofibromatosis type 1 (NF1), received no treatment. None of these patients died or developed neurologic morbidity as a result of their tumor. Thirty-one of the patients, most of whom did not have evidence of NF1, received treatment. Many of these patients subsequently developed neurologic, endocrine, or visual morbidity. However, although patients with anterior visual pathway gliomas who were not treated fared better visually, neurologically, and systemically than patients who were treated, patients who required treatment for progression generally had a good overall prognosis, particularly patients with tumors that did not involve the hypothalamus. Most of these patients survived and maintained useful vision in at least one eye. We believe that patients with anterior visual pathway gliomas, particularly those with NF1, should not be treated unless there is clear clinical or neuroimaging evidence of progression.

[A clinicopathological study of 16 cases with optico-hypothalamic glioma].

Although gliomas of the optic nerve pathways, optico-hypothalamic gliomas, have been considered to be benign neoplasms, some recurrent, malignant gliomas especially at the optic chiasm and hypothalamus have also been reported. It is crucial to know the factors that influence the prognosis of these tumor entities. In order to address this question, we analyzed 16 cases of optico-hypothalamic gliomas treated in our institute with emphasis especially upon the age, location of tumor, histological subtype and treatment modality. Eleven patients younger than 20 years and five older than 20 years were included in this study. In two patients the gliomas were accompanied by neurofibromatosis 1. The male to female ratio was 9:7. Anatomical locations of the tumors were categorized from T1 to T4, and visual symptoms were V0 to V4. Patients with tumors located within the optic nerve, chiasm (T1-3) mainly presented visual symptoms, but those with hypothalamus (T4) showed neuroendocrine signs but not visual ones. Twelve out of 16 cases represented isodense mass lesions on plain CT scans, which were homogenously enhanced by contrast media. Among 15 cases verified pathologically, 10 cases were pilocytic astrocytomas, 4 were astrocytomas and one was anaplastic astrocytoma. The survival rate was measured by Kaplan-Meier method and overall 5-year survival rate was 70.5%. Patients younger than 20 years could survive longer than those older than 20 years (87.5% and 40.0% respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Optic pathway gliomas in adolescence--time to challenge treatment choices?

BACKGROUND: Optimal management of optic pathway/hypothalamic glioma (OPHG) remains an ongoing challenge. Little is known about the natural history, management strategies, and outcomes in adolescents. Carboplatin-based chemotherapy is a useful modality in younger children, delaying radiation to their immature brains. National trials have focused on younger children and excluded adolescents from studies evaluating the role of chemotherapy. METHODS: This retrospective study describes clinical characteristics, treatment regimens, and outcomes in adolescents (aged ≥ 10 years) with OPHG (diagnosis during 1990-2006). Progression-free survival was compared with that in a cohort of younger children (aged <10 years). RESULTS: Thirty-three adolescents (19 females, 6 with neurofibromatosis type 1) with OPHG were identified within 2 Canadian pediatric oncology institutions. The majority presented with visual symptoms (82%). More than 55% (18 of 33) involved the posterior tract and/or hypothalamus (modified Dodge classification 3/4). Seventeen were initially observed; 8 remained progression free. Of the 25 of 33 adolescents who required active treatment, 9 (36%) needed second-line therapy. The progression-free survival for any first active treatment at age <10 years (52 of 102) or ≥ 10 years (25 of 33) was similar (46.9 vs 46.8 months; P = .60). In those who received chemotherapy as first-line treatment or after prior nonchemotherapy treatment failure, the progression-free survival trend was superior (62.9 vs 38.9 months) in those aged ≥ 10 years although not statistically significant (P = .16). CONCLUSIONS: Chemotherapy is a valuable treatment modality for the achievement of disease control even in adolescents; their progression-free survival compares favorably with that in younger children. We propose that chemotherapy be considered as a first-line modality in adolescents, avoiding potential radiation-associated morbidities.

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.

Optico-hypothalamic glioma: an analysis of 16 cases.

We reviewed our experience of 16 patients with histologically proven optico-hypothalamic gliomas. They ranged in age from 0.3 to 15 years at the time of diagnosis. Fifteen tumors were located in the optic chiasm, optic nerve, optic tract and/or hypothalamus, while one tumor was confined to one optic nerve. All tumors were classified as low-grade astrocytomas, which were mainly composed of pilocytic astrocytes. No patient had associated neurofibromatosis. The initial treatment for tumors included surgery in 12, radiotherapy in 7, and chemotherapy in 4 patients. After treatment, visual function improved in 3 out of 14, and endocrine function improved in 1 out of 4 evaluable patients. The 5-year actuarial survival rate was 84.0%, and that at 10 years 71.1%. Our experience and the literature indicate that: (1) patients with disease limited to the optic nerve are adequately managed by resection alone; (2) chiasmal-hypothalamic gliomas behave variably, and progressive disease may occur late in the course of the illness; (3) gliomas that arise in patients under 2 years of age and involve the optic chiasm may act aggressively despite their histological benignity; (4) the beneficial effects of radiotherapy occur in about half of the patients; (5) although chemotherapy may be an effective adjuvant treatment modality, it is not an alternative to radiation therapy at present. Both surgery and irradiation therefore offer the best treatment now available for patients with progressive disease.

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.

Optic pathway and hypothalamic/chiasmatic gliomas in children younger than age 5 years with a 6-year follow-up.

BACKGROUND: Gliomas of the hypothalamus and optic pathways (H/OPG) comprise 5% of pediatric intracranial tumors, present most frequently in patients younger than age 5 years, and may have a more aggressive course in younger children. This study examined clinical characteristics and consequences of treatment of young children diagnosed with H/OPG: METHODS: The authors reviewed the course, treatment, and outcomes of 46 children diagnosed with H/OPG younger than age 5 years; the median follow-up was 72 months. The median age at diagnosis was 27 months. RESULTS: Fifteen (33%) of 46 patients had neurofibromatosis-1 (NF-1). Forty children (87%) had tumor progression in the follow-up period, and tumor growth was less common in children with NF-1. Initial therapy was limited to surgical resection in three and radiation in five children. To postpone radiation until after the age of 5 years, initial therapy was limited to chemotherapy in 32 patients. Radiation was not required in 9 of these patients and was postponed for 40 months (mean) in 17. Of the 46 children, 5 died of tumor progression, 4 became blind, and 20 of 34 evaluable patients had endocrine abnormalities. Endocrinopathy did not correlate with therapy. Ten of 17 children evaluated by questionnaire required special education. There was a trend for educational problems to occur in children who were irradiated before the age of 5 years. CONCLUSIONS: Gliomas of the hypothalamus and optic pathways and their treatment cause long term morbidity in young children. Chemotherapy postpones radiation effectively, and this delay may reduce neurologic morbidity; however, 60% of children eventually relapse. By contrast, patients with NF-1 have indolent disease.

Germ cell tumor in the hypothalamo-neurohypophysial region: clinical features and treatment.

Twenty-one patients with germ cell tumors (17 germinomas and 4 teratomas) involving the hypothalamic-neurohypophysial (HN) region were reviewed retrospectively. Eleven patients were males and 10 females, and their ages ranged from 7 to 45 years (average 18.5 years). Diabetes insipidus was the initial and the most prominent symptom in most germinomas; in teratomas the most prominent symptom was visual disturbance. Fifteen patients with germinomas were treated by radiotherapy, and 4 with teratomas were treated by surgical resection alone. Two recent germinoma patients with extensive CSF dissemination were treated with systemic chemotherapy consisting of anticancer platinum drugs and etoposide, which resulted in a complete disappearance of the tumors. Patients with germinoma treated after the introduction of CT scanning had a greatly improved mortality rate, and their actual survival rate was 87.5% over 10 years. On the basis of this review, the authors consider that diagnosis at an early stage of the disease and chemotherapy, which can be an effective therapeutic alternative to radiation therapy, may improve not only the mortality rate but also the quality of life of patients with HN germ cell tumors.

Surgery of giant gliomas of chiasma and IIIrd ventricle.

During a period of 17 years (from 1976 till now) 45 patients with giant gliomas of the chiasma and the IIIrd ventricle out of a total amount of 120 patients with hypothalamic gliomas were operated. The following classification of tumours was used: I) tumours with predominant anterior growth; II) tumours which infiltrate chiasma and penetrate into the IIIrd ventricle; III) gliomas of the floor of the IIIrd ventricle and the chiasma, growing into the ventricle cavity; IV) tumours of the chiasma, optic tract and thalamus. The authors come to the conclusion, that surgical removal of giant tumours of the chiasma and the IIIrd ventricle, though risk, may result in an improvement or stabilisation of visual functions (77%) and a long period free from recurrencies (9.5%). The postoperative period is relatively favourable and the mortality is low (6%). The main contraindication in our opinion is a wide infiltration of adjacent brain structures by the tumour and spreading along both optical tracts. We consider the giant size of a tumour in itself a sufficient indication for surgery.