[Clinicopathological characteristics and prognosis of diffuse midline gliomas with histone H3K27M mutation: an analysis of 30 cases].

Objective: To analyze the clinicopathological characteristics and prognosis of diffuse midline glioma (DMG) with H3K27M mutation. Methods: Thirty cases of DMG were collected in Guangdong Sanjiu Brain Hospital from October 2016 to May 2018. The patients' clinicopathological data including age, tumor site and histological grade, treatment and follow-up data were collected and analyzed. Results: There were 21 males and 9 females, with a mean age of 26 years (range 5-53 years). Fourteen tumors were located in thalamus, 12 in brainstem (one involved both thalamus and brainstem), and one each in hypothalamus, fourth ventricle, and sellar region, respectively. Two cases presented as diffuse intracranial lesions. Three cases (10.0%) were of WHO grade Ⅰ, 10 cases (33.3%) were grade Ⅱ, eight cases (26.7%) were grade Ⅲ, and nine cases (30.0%) were grade Ⅳ.All patients with gradeⅠ tumors were older than 20 years. Histologically, all were pilocytic astrocytoma-like. Immunohistochemical staining demonstrated that all tumors were IDH1 negative. Twenty-eight tumors showed diffuse expression of H3K27M, and two showed focal expression. Twenty-one tumors(100.0%, 21/21) showed absent expression of H3K27me3. Sixteen tumors (57.1%, 16/28) showed strongly positive expression of p53, and ATRX was negative in eight tumors (38.1%, 8/21). The Ki-67 proliferation index ranged from 5% to 40%. Eight cases (including two cases of H3K27M expression of individual cells) showed K27M mutation in H3F3A gene. Intracranial and spinal cord dissemination occurred in six cases (20.0%, 6/30). Median progression-free survival (PFS) was 9.5 months and median overall survival (OS) was 34 months. Mean PFS was 11.2 months and mean OS was 24.3 months. Compared with adults (>20 years old), children/adolescents (no more than 20 years old) had significantly shorter median OS (8 months vs. 34 months, P=0.013). There was no significant difference in PFS and OS between DMGs located in the brain stem/thalamus and other sites within midline (P>0.05). There was no significant difference in PFS and OS between WHO grade ⅠDMGs and WHO grade Ⅱ-Ⅳ DMGs (P>0.05). Conclusions: DMGs occur more commonly in children and adolescents with male predominance. DMGs present with WHO Ⅰ-Ⅳ tumors morphologically, and pilocytic astrocytoma-like lesions with WHO Ⅰ are more common in adults. Expression of H3K27M but not H3K27me3 is helpful for diagnosis of DMG. The prognosis of children/adolescents is significantly worse than that of adults, whereas histological grade and tumor location do not affect prognosis.

Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas.

BACKGROUND: Activation of the RAS-RAF-MEK-ERK signaling pathway is thought to be the key driver of pediatric low-grade astrocytoma (PLGA) growth. Sorafenib is a multikinase inhibitor targeting BRAF, VEGFR, PDGFR, and c-kit. This multicenter phase II study was conducted to determine the response rate to sorafenib in patients with recurrent or progressive PLGA. METHODS: Key eligibility criteria included age ≥ 2 years, progressive PLGA evaluable on MRI, and at least one prior chemotherapy treatment. Sorafenib was administered twice daily at 200 mg/m(2)/dose (maximum of 400 mg/dose) in continuous 28-day cycles. MRI, including 3-dimensional volumetric tumor analysis, was performed every 12 weeks. BRAF molecular testing was performed on tumor tissue when available. RESULTS: Eleven patients, including 3 with neurofibromatosis type 1 (NF1), were evaluable for response; 5 tested positive for BRAF duplication. Nine patients (82%) came off trial due to radiological tumor progression after 2 or 3 cycles, including 3 patients with confirmed BRAF duplication. Median time to progression was 2.8 months (95% CI, 2.1-31.0 months). Enrollment was terminated early due to this rapid and unexpectedly high progression rate. Tumor tissue obtained from 4 patients after termination of the study showed viable pilocytic or pilomyxoid astrocytoma. CONCLUSIONS: Sorafenib produced unexpected and unprecedented acceleration of tumor growth in children with PLGA, irrespective of NF1 or tumor BRAF status. In vitro studies with sorafenib indicate that this effect is likely related to paradoxical ERK activation. Close monitoring for early tumor progression should be included in trials of novel agents that modulate signal transduction.

The alternative lengthening of telomere phenotype is significantly associated with loss of ATRX expression in high-grade pediatric and adult astrocytomas: a multi-institutional study of 214 astrocytomas.

Loss-of-function of alpha thalassemia/mental retardation syndrome X-linked (ATRX) protein leads to a phenotype called alternative lengthening of telomeres (ALT) in some tumors. High-grade astrocytomas comprise a heterogeneous group of central nervous system tumors. We examined a large cohort of adult (91) and pediatric (n=88) high-grade astrocytomas as well as lower grade forms (n=35) for immunohistochemical loss of ATRX protein expression and the presence of ALT using telomere-specific fluorescence in situ hybridization, with further correlation to other known genetic alterations. We found that in pediatric high-grade astrocytomas, 29.6% of tumors were positive for ALT and 24.5% were immunonegative for the ATRX protein, these two alterations being highly associated with one another (P<0.0001). In adult high-grade astrocytomas, 26.4% of tumors were similarly positive for ALT, including 80% of ATRX protein immunonegative cases (P<0.0001). Similar frequencies were found in 11 adult low-grade astrocytomas, whereas all 24 pilocytic astrocytomas were negative for ALT. We did not find any significant correlations between isocitrate dehydrogenase status and either ALT positivity or ATRX protein expression in our adult high-grade astrocytomas. In both cohorts, however, the ALT positive high-grade astrocytomas showed more frequent amplification of the platelet-derived growth factor receptor alpha gene (PDGFRA; 45% and 50%, respectively) than the ALT negative counterparts (18% and 26%; P=0.03 for each). In summary, our data show that the ALT and ATRX protein alterations are common in both pediatric and adult high-grade astrocytomas, often with associated PDGFRA gene amplification.

Phase II trial of radiotherapy after hyperbaric oxygenation with multiagent chemotherapy (procarbazine, nimustine, and vincristine) for high-grade gliomas: long-term results.

PURPOSE: To analyze the long-term results of a Phase II trial of radiotherapy given immediately after hyperbaric oxygenation (HBO) with multiagent chemotherapy in adults with high-grade gliomas. METHODS AND MATERIALS: Patients with histologically confirmed high-grade gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive days per week up to a total dose of 60 Gy. Each fraction was administered immediately after HBO, with the time interval from completion of decompression to start of irradiation being less than 15 minutes. Chemotherapy consisting of procarbazine, nimustine, and vincristine and was administered during and after radiotherapy. RESULTS: A total of 57 patients (39 patients with glioblastoma and 18 patients with Grade 3 gliomas) were enrolled from 2000 to 2006, and the median follow-up of 12 surviving patients was 62.0 months (range, 43.2-119.1 months). All 57 patients were able to complete a total radiotherapy dose of 60 Gy immediately after HBO with one course of concurrent chemotherapy. The median overall survival times in all 57 patients, 39 patients with glioblastoma and 18 patients with Grade 3 gliomas, were 20.2 months, 17.2 months, and 113.4 months, respectively. On multivariate analysis, histologic grade alone was a significant prognostic factor for overall survival (p < 0.001). During treatments, no patients had neutropenic fever or intracranial hemorrhage, and no serious nonhematologic or late toxicities were seen in any of the 57 patients. CONCLUSIONS: Radiotherapy delivered immediately after HBO with multiagent chemotherapy was safe, with virtually no late toxicities, and seemed to be effective in patients with high-grade gliomas.

Tyrosine kinase expression in pediatric high grade astrocytoma.

The over-expression of several receptor tyrosine kinases in adult high grade astrocytomas (HGA) led to trials of tyrosine kinase inhibitors in these patients. Similar molecular genetic analysis of pediatric HGA is only beginning to be published. Thus it is unclear to what degree these pathways are also involved in the pediatric age group and whether they may also serve as useful therapeutic targets for children with HGAs. Here we investigated the protein expression profile of a series of pediatric HGAs. Following institutional ethical approval, clinical information and tumor samples were obtained for 42 HGA patients. Mean age at presentation was 10.1 years (range 0.13-19.3 years). OS was 12% and PFS was 3.7%. Extent of resection was associated with improved PFS (P = 0.0015) with a trend towards improved OS (P = 0.08). There was no significant effect of age or adjuvant therapy use on PFS or OS. Immunopositivity for each of the markers was as follows: p53 35%; PDGFR-alpha 45%; PDGFR-beta 31%; PTEN 67%; EGFR wild type 58%; EGFRvIII 2%. No significant effect on OS or PFS was found for any of the markers by log rank analysis. However, all long-term survivors expressed PTEN and were EGFRvIII negative. Further, there were distinct differences in protein expression between pediatric and adult HGAs suggesting that EGFR kinase inhibitors may not be beneficial for treatment of HGA in the pediatric age group and pointing to the need to study pediatric astrocytomas as distinct entities from adult astrocytomas.

[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.

A population-based study of the incidence and survival rates in patients with pilocytic astrocytoma.

OBJECT: The incidence of pilocytic astrocytomas and the rate of patient survival were analyzed in a population-based study in the canton of Zürich, Switzerland. METHODS: Between 1980 and 1994, 987 astrocytic and oligodendroglial tumors were diagnosed, of which 55 (5.5%) were pilocytic astrocytomas. The incidence rate, adjusted to the World Standard Population, was 4.8 per 1 million per year. The mean age at clinical diagnosis was 19.6 +/- 12.7 years, and the male/female ratio was 1.12. The most frequent tumor sites were the cerebellum (40%), followed by supratentorial locations (35%), the optic pathway and hypothalamus (11%), and the brainstem (9%). The mean follow-up period was 12 years. Observed survival rates were 100% at 5 years and 95.8% at 10 years after diagnosis (relative survival rate at 10 years: 96.8%). Seven patients (13%) received postoperative radiotherapy, but this did not significantly affect survival. In all patients the tumors were histologically classified as WHO Grade I, except in two patients who had anaplastic pilocytic astrocytoma (Grade III), one of whom died after 7 years, whereas the other was still alive after 10 years. CONCLUSIONS: This population-based study shows that, because of the benign biological behavior of pilocytic astrocytomas and advances in microneurosurgery, the survival rates for patients with these tumors are excellent, regardless of postoperative radiotherapy.

Stereotactic guided laser-induced interstitial thermotherapy (SLITT) in gliomas with intraoperative morphologic monitoring in an open MR: clinical expierence.

Stereotactic guided laser-induced interstitial thermotherapy (SLITT) is a minimal invasive method to produce thermonecrosis in cerebral tumour tissue. Clinical data are sparse due to its limited application until now and the value of this approach for tumour control and survival time remain to be defined. Twenty-four patients (7 low-grade gliomas, 11 anaplastic gliomas, 6 glioblastomas) with brain tumours, most recurrences, were treated with SLITT, in total 30 laser procedures were performed. Under local anaesthesia a 600 micro m laser-fiber was inserted by the stereotactic-guided technique. In open low-field MR the denaturation of the tumour by a Nd-YAG-laser (1064 nm) was monitored using T 1 -weighted 3-D turbo FLASH sequences. The ablation procedure had to be stopped twice because of neurological deficit, one major infection occurred. In two cases neurological improvement was observed. Mean survival times for low grade astrocytomas, anaplastic gliomas and glioblastomas were 144 months, 39 months, 17 months, respectively. Mean survival times after SLITT were 34 months, 30 months and 9 months, respectively. Mean times to progression after SLITT for the 3 histological subgroups were 16 months, 10 months and 4 months, respectively. Five patients with low grade astrocytoma and a KI greater or equal 70 maintained a high quality functional status for 11, 20, 21, 33 and 43 months. In anaplastic tumours patients maintained a KI of 70 for a median time of 15 months and for those with glioblastoma the respective high quality duration was 7.5 months after SLITT. SLITT for selected patients with glioma could have a clinical value in a multimodality treatment schedule maintaining quality of live. Due to the minimal invasive technique, the method is a therapy of choice and may be favoured to reoperation. Major indications of this treatment are small tumours, in eloquent regions and deep seated, as well as in older patients or patients in poor functional status.

Conformal proton radiation therapy for pediatric low-grade astrocytomas.

BACKGROUND: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). PATIENTS AND METHOD: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.7 years). Tumors were located centrally (diencephalic) in 15 patients, in the cerebral and cerebellar hemispheres in seven patients, and in the brainstem in five patients. 25/27 patients (92%) were treated for progressive, unresectable, or residual disease following subtotal resection. Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic pathway tumors were treated without histologic confirmation. Target doses between 50.4 and 63.0 CGE (Cobalt Gray Equivalent, mean: 55.2 CGE) were prescribed at 1.8 CGE per fraction, five treatments per week. RESULTS: At a mean follow-up period of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all located within the irradiated field), and 4/27 patients had died. By anatomic site these data translated into rates of local control and survival of 87% (13/15 patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86% (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5 patients) for tumors located in the brainstem. Proton radiation therapy was generally well tolerated. All children with local control maintained their performance status. One child with associated neurofibromatosis, Type 1, developed Moyamoya disease. All six patients with optic pathway tumors and useful vision maintained or improved their visual status. CONCLUSIONS: This report on pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and efficacious 3-D conformal treatment modality. Results are encouraging for central tumors as well as large optic pathway tumors, where dose conformity is of particular importance; yet it is difficult to achieve. Longer follow-up time is needed to fully evaluate the benefits of normal tissue sparing.

Treatment of malignant astrocytomas with repetitive resections: a longitudinal study.

BACKGROUND: The impact of repeated surgical resection on the survivorship of patients with malignant astrocytomas is an issue of some controversy in the medical literature. OBJECTIVES: To clarify this issue through a retrospective analysis of treatment outcomes in a brain tumor clinic. METHODS: The patient records from the Brain Tumor Clinic at Hahnemann University Hospital for the period 1988 to 2000 were reviewed. From these, 112 cases of glioblastoma multiforme and 50 cases of anaplastic astrocytoma were chosen for analysis. RESULTS: The group of patients with glioblastomas showed a median survival of 415 days. When analyzed as subgroups based on the number of surgical resections, the median survival was 393 days in the group with biopsy only, 380 days in the group with one surgical resection, and 548 days in the group with two or three resections. Using the Kaplan-Meier method to generate survival plots and the log rank test to compare groups, repeat debulking was found to be a significant predictor of survival (P = 0.173). The group of patients with anaplastic astrocytomas showed a median survival of 1,311 days. When analyzed by subgroups, the patients with biopsy only had a median survival of 544 days, those with one debulking 1,589 days and those with two or three debulkings 1,421 days. There was a trend toward increased survival with debulking and the log rank test again showed statistical significance (P = 0.1998). CONCLUSIONS: This study indicates that repeated surgical resections offer increased survival for both glioblastomas and anaplastic astrocytomas.

X-ray phototherapy for canine brain masses.

Brain masses diagnosed in 47 pet dogs as tumors by CT scans, and confirmed in 12 dogs by necropsies, were injected with iodinated contrast media and treated by a modified CT scanner, the CTRx. Twenty-six dogs that received six or more weekly treatments of about 5.6 Gy per fraction, of which about 25% was contributed by radiation from the iodine, for a median total dose of 39 Gy, had a median survival of 230 days. This compares well with the 150 days reported for 25 dogs given 46-48 Gy of cobalt-60 radiation to the whole brain, and is significantly greater than the 6 to 13 days in untreated historic controls.

Infiltrative astrocytomas of the thalamus.

Clinical characteristics and outcome in 57 patients with infiltrative thalamic astrocytomas were analyzed retrospectively. The median patient age was 22 years (range 1 to 69 years). Fourteen patients had no surgery, 37 had biopsy, and six had subtotal resection. The histological diagnosis was astrocytoma in 14 patients, anaplastic astrocytoma in 25, and glioblastoma multiforme in two; two specimens were nondiagnostic. The initial treatment was conventional radiation therapy (RT) in 20 patients (one also received interstitial brachytherapy), RT followed by chemotherapy in 18, hyperfractionated RT in 17 (one also received chemotherapy), and chemotherapy alone in two. The median time to tumor progression was 47 weeks (range 5 to 388 weeks); median survival was 73 weeks (range 11 to 502 weeks). Actuarial 1-, 2-, 3-, and 5-year survival rates were 67%, 35%, 24%, and 20%, respectively. Tumor progression was usually treated with chemotherapy. The assessed treatment failure was within 2 months after RT in 12 patients in whom the findings of the neurological and radiological examinations did not correspond. This assessment showed false-negative diagnosis of radiation-induced changes in five patients (42%); false-positive diagnosis of tumor progression could not be ascertained. In univariate Cox proportional-hazards analysis, histological diagnosis of astrocytoma, age under 18 years, and open biopsy were prognostically favorable features; in multivariate analysis, only open biopsy was favorable. Infiltrative astrocytomas of the thalamus carry a dismal prognosis, regardless of the type of treatment. Hyperfractionated RT does not increase toxicity but its benefit over conventional RT remains unproven.

Low-grade glial tumors in basal ganglia and thalamus: natural history and biological reappraisal.

The natural history of 70 patients affected by low-grade astrocytomas was recorded after the histological diagnosis was obtained by serial stereotactic biopsy. Forty-three percent of these patients died within 3 years. The value of cell kinetics assessment at the time of stereotactic biopsy was investigated, and the labeling index percent may be considered the most accurate prognostic factor in these histologically homogeneous astrocytomas. It has been confirmed that the young age of patients predicts a more favorable course, but the value of this also seems to be linked to and dependent on cell kinetics. These data are discussed in view of the opportunity to perform more aggressive "cytoreductive" treatments in deep brain tumors when these indices support an expected poor prognosis.

Management and outcome of low-grade astrocytomas of the midline in children: a retrospective review.

Low-grade astrocytomas of the midline of the brain can be difficult to manage because of their location. To evaluate treatment and outcome, we performed a retrospective study of children with midline low-grade astrocytomas admitted to The Hospital for Sick Children between 1976 and 1991. Eighty-eight children with biopsy-proven low-grade astrocytomas were identified. Forty-three tumors occurred in the optic pathways or hypothalamus, 13 in the thalamus, 7 in the pineal region, 14 in the midbrain, and 11 in the medulla. Patient follow-up ranged from 6 months to 15 years, with a mean of 4 years, 9 months. Overall outcome was related to the extent of resection, histological type, and location. Partial resections were often associated with involution of the tumor. Response to radiation was variable, and serious sequelae were observed. Thirty-three patients experienced recurrence, often with a good response to subsequent surgery; however, 12 of these patients died. The probability of survival was calculated to be 96% at 1 year, 91% at 5, and 80% at 10 years. Our study suggests that resection should be considered in all patients, both at presentation and recurrence.

Supratentorial pilocytic astrocytomas. A clinicopathologic, prognostic, and flow cytometric study of 51 patients.

BACKGROUND: Supratentorial pilocytic astrocytomas are uncommon tumors, the prognosis and management of which have been controversial. METHODS: The authors retrospectively studied the clinical and pathologic aspects of 51 patients with supratentorial pilocytic astrocytomas, with particular reference to their response to treatment. RESULTS: The study group consisted of 25 male and 26 female patients (median age, 15 years). The extent of surgical removal was gross total or radical subtotal in 16 patients and subtotal removal or biopsy in 35. At a median follow-up of 14.9 years, 41 patients were alive. Overall survival was 82% at 10 and 20 years; 89% of surviving patients were fully active. Survival at 10 years was 100% for the 16 patients who underwent gross total or radical subtotal removal and 74% for the 35 who had subtotal tumor removal or biopsy. No association was found between pathologic features such as histologic grade or flow cytometric characteristics and patient survival. CONCLUSIONS: Supratentorial pilocytic astrocytomas behave differently from low-grade astrocytomas of the diffuse or fibrillary type in that they have a favorable prognosis. Radiation therapy appears not to be needed for patients undergoing gross total removal. In patients undergoing subtotal resection, close follow-up with additional surgery or radiation therapy at the time of tumor progression is recommended. Patients who have biopsy only should receive radiation therapy. Histologic grading and flow cytometric analysis add little to clinical decision making with regard to patients with pilocytic astrocytoma.

[Association of 5-FU, CDDP and hypofractionated radiotherapy in recurrences of subtentorial astrocytomas and malignant gliomas in adults]. / L'association 5-FU/CDDP/radiothérapie hypofractionnée dans les récidives des astrocytomes et des gliomes malins sustentoriels de l'adulte.

Twenty-seven patients who had a relapse of astrocytomas or supra-tentorial malignant gliomas, previously treated by radio-surgical combination or exclusive irradiation, underwent a combination of 3 courses of 5-FU, cis-platyl and hypofractionated irradiation. No objective response was observed, but there was a progression of the tumor in 33% of the cases, and no change in 67%. Overall median survival was 7 +/- 1.5 months. The 20 patients with grade III or IV astrocytomas had a lower median rate than the 7 patients with grade II astrocytomas or oligodendrogliomas: 6 +/- 1.8 months versus 18 +/- 3.2 (P = 0.16). Median survival was 14 +/- 2.7 months for neurological responders and 6 +/- 2.1 months for non-responders (P = 0.017).

Selenium in the treatment of patients with brain gliomas. A pilot study.

The authors have added selenium tablets to the diet of 15 patients with malignant brain tumors. In twelve patients with glioblastoma multiforme this treatment didn't prolong the postoperative survival. Further clinical observations are necessary to precise the usefulness of selenium in cases of low-grade gliomas.

Astrocytoma in children. A review of 79 cases--1960-1976.

Seventy-nine children with histologically proven astrocytomas, 32 cerebral, 30 cerebellar, 9 thalamic, 6 optic nerve, and 2 in the 4th ventricular floor were reviewed retrospectively. Seventy-one per cent of the astrocytomas were well differentiated. Unlike adult astrocytomas, there was slight female predominance in our group. Cerebral astrocytomas were more frequent beyond nine years of age. The overall five-year survival rate of cerebral astrocytomas was 95% (19/20) for well-differentiated, and 19% (2/12) for poorly-differentiated tumors. In cerebellar astrocytomas the survival rates were 75% (18/24) and 33% (2/6) respectively.

Radiation therapy of tumors of the central nervous system in childhood.

The results of radiation therapy for CNS tumors of childhood are presented and discussed according to histologic type. In this material the 5-year recurrence-free survival rates were about 35% for medulloblastomas, 48% for the hypothalamic and brain stem tumors, 86% for lowgrade ependymomas, and 57% for germinomas. Complications or CNS injury from irradiation were rare and the quality of life in survivors was generally good. Current methods of radiation therapy may possibly improve these results. Tumors of the CNS in children do not necessarily carry a hopeless prognosis; aggressive therapy is indicated.