Predicting the recurrence of ependymomas from the bromodeoxyuridine labeling index

The usefulness of histopathological grading in predicting the prognosis of patients with ependymomas is controversial. To clarify the discrepancy between the histological malignancy and the prognosis of these tumors, we estimated the proliferative potential of 32 intracranial and intraspinal ependymomas and correlated the findings with the clinical behavior. Each patient received an intraoperative infusion of bromodeoxyuridine (BUdR, 200 mg/m² i.v.) before tumor removal; the BUdR labeling index (LI), or percentage of BUdR-labeled cells, was determined immunohistochemically in excised specimens. The mean BUdR LI (±SD) of intracranial malignant ependymomas was 4.1±2.8%. Nonmalignant intracranial and intraspinal ependymomas and subependymomas had mean LIs of 1.5±0.9%, 1.1±0.3%, and <1%, respectively. Overall, 44% of the tumors recurred. There were no statistically significant differences in the recurrence rates of intracranial and intraspinal ependymomas, including subependymomas (43% and 44%, respectively), or of intracranial ependymomas with LIs greater than 1.0% and less than 1.0% (67% and 44%, respectively). However, the early recurrence rate (within 24 months after treatment) of tumors with LIs greater than 1.0% was higher than that of tumors with LIs of less than 1.0% (100% vs. 25%, P<0.05). The BUdR LI also showed a statistically significant inverse correlation with the time to recurrence. These findings indicate that BUdR LI reflects the proliferative potential of individual ependymomas and can be used to help predict the recurrence and estimate the prognosis of these tumors.     

In situ analysis of cell kinetics in human brain tumors

Summary A newly developed in vitro labeling method with bromodeoxyuridine (BrdU) identifies S phase cells in situ in freshly obtained surgical tissue of human brain tumors which is subsequently fixed and embedded in paraffin for BrdU immunovisualization. For the first time, the BrdU labeling index (LI) is successfully compared here with the LI obtained by immunostaining of frozen sections of the same tumors with monoclonal antibody Ki-67 which identifies all proliferating cells, i.e., the growth fraction. LIs were counted in at least five different areas with high density of labeled cells; at least 1,000 cells were counted. In 13 metastatic tumors, Ki-67 LI was 8.3%–62.6%, and BrdU LI was 5.1%–28.0%. In 18 gliomas, Ki-67 LI was 1.4%–19.3%, and BrdU LI was 0.2%–11.6%. In 7 meningiomas, Ki-67 LI was 0.3%–3.0%, and BrdU LI was 0%–2.0%. Statistical comparison of Ki-67 and BrdU LIs by linear regression analysis revealed a highly significant correlation: BrdU LI=0.99+0.34 Ki-67 LI (r=0.92,P<0.001). A significant heterogeneity of proliferation patterns may occur within one sample from area to area, as well as between different samples of the same tumor, especially in gliomas; thus, some subjective influence on LIs by arbitrary sampling and selection could occur in quantitative evaluation of in situ cell kinetics of human brain tumors. This study indicates that our in vitro BrdU-labeling method allows the in situ identification of S phase cells in excellently preserved fixed tumor tissue which is well suited for further histological examination. This method compares favorably with Ki-67 labeling of frozen sections and might emerge as a powerful new tool for the routine study of cell proliferation in surgical specimens of human brain tumors.Supported by funds from the Commission for Cancer Research of the Medical Faculty of the University of Vienna     

Proliferative potential of vascular components in human glioblastoma multiforme

Summary Sixteen patients with glioblastoma multiforme received a 1-h intravenous infusion of 5-bromodeoxyuridine (BrdU), 150–200 mg/m² at the start of surgery, to label S-phase cells in tumor tissue. Labeled cells of vascular components and of tumor parenchyma were detected in excised tumor specimens by indirect immunoperoxidase staining using anti-BrdU monoclonal antibodies followed by periodic acid-Schiff staining. The BrdU labeling index (LI, defined as the percentage of labeled cells in relation to the total number of cells scored) was calculated separately for vascular components and tumor parenchyma in each specimen. The BrdU LI of vascular components of glioblastoma multiforme was remarkably higher than that of normal brain (1.1%–8.7% vs.<0.05%). The mean BrdU LIs of vascular components and tumor cells in eight primary glioblastomas were 4.5±0.8% (mean±SE) and 9.9±1.1%, respectively, while the corresponding BrdU LIs in eight recurrent tumors were 2.7±0.5% and 9.3±0.7%. The differences in the BrdU LIs of primary and recurrent tumors were not statistically significant, but the BrdU LI of vascular components was consistently much lower than that of tumor cells. BrdU labeling of vascular components was inconsistent and occurred mostly in glomerular-shaped vessels, but only about 20% of them contained labeled cells. These results suggest that unusual vascular proliferation, such as the formation of glomerular-shaped vessels and endothelial or adventitial proliferation, in glioblastoma multiforme may have been programmed to slow down or even to cease at a certain stage, and is not likely to be the result of neoplastic transformation.Supported in part by grant PDT-159 from the American Cancer Society and by grant CA 13525 from the National Cancer Institute     

Growth hormone treatment and risk of recurrence or progression of brain tumors in children: a review

Introduction  Brain tumors are one of the most common types of solid neoplasm in children. As life expectancy of these patients has increased with new and improved therapies, the morbidities associated with the treatments and the tumor itself have become more important. Discussion  One of the most common morbidities is growth hormone deficiency, and since recombinant growth hormone (GH) became available, its use has increased exponentially. There is concern that in the population of children with brain tumors, GH treatment might increase the risk of tumor recurrence or progression or the appearance of a second neoplasm. In the light of this ongoing concern, the current literature has been reviewed to provide an update on the risk of tumor recurrence, tumor progression, or new intracranial tumor formation when GH is used to treat GH deficiency in children, who have had or have intracranial tumors. Conclusion  On the basis of this review, the authors conclude that the use of GH in patients with brain tumor is safe. GH therapy is not associated with an increased risk of central nervous system tumor progression or recurrence, leukemia (de novo or relapse), or extracranial non-leukemic neoplasms.     

脑肿瘤中P53蛋白的表达及Ki－67LI的相关性研究

利用突变型Ｐ５３蛋白的单抗及Ｋｉ－６７单抗对５０例冰冻标本进行检测，结果发现，脑肿瘤中突变型Ｐ５３蛋白的表达阳性率为４６％。低恶度胶质瘤、高恶度胶质瘤及转移癌中Ｐ５３蛋白表达的阳性率不同，分别为１８．２％、５３．８％及１００％。Ｐ５３蛋白表达阳性的肿瘤中高Ｋｉ－６７ＬＩ比例为７０％，其中位数及均数为１４．３％、２０．７６±１８．３（％），而无Ｐ５３蛋白表达的脑瘤中，ｋｉ－６７ＬＩ中位数及均数分别为１．３９及５．１９±９．０（％）。结果表明，突变型Ｐ５３蛋白的表达与脑肿瘤的组织类型，分化程度及细胞的增殖有关，而它的高表达又可能是肿瘤恶性表型或转移的标志之一。     

Immunocytochemical demonstration of S-phase cells by anti-bromodeoxyuridine monoclonal antibody in human brain tumor tissues

Summary Five patients with various brain tumors received bromodeoxyuridine (BrdU), 150–200 mg/m² i.v.; at the time of craniotomy. Biopsied materials were fixed in 70% ethanol, sectioned, denatured with hydrochloric acid, and reacted with monoclonal antibodies against BrdU. Immunofluorescence and immunocytochemical methods were used to visualize BrdU-labeled nuclei. Our results showed that both methods demonstrated BrdU-labeled nuclei satisfactorily in tissue sections. Thus, BrdU can be used to measure the proliferative potential of human tumors in situ.Supported by grant PDT-159 from the American Cancer Society and by grant CA 13525 from the National Cancer Institute     

Immunostaining for proliferating cell nuclear antigen: its role in determination of proliferation in routinely processed human brain tumor specimens

Alcohol- and formalin-fixed, paraffin-embedded samples of 71 brain tumors (35 gliomas, 22 metastatic carcinomas, 8 meningiomas and 6 other tumors) were investigated by immunocytochemistry with three different monoclonal antibodies against proliferating cell nuclear antigen (PCNA)/cyclin (19A2; 19F4; PC10). PC10 was found to work best; it is applicable to both alcohol- and formalin-fixed tumor samples. PCNA labeling indices (LIs) were compared in the same tumors with LIs obtained by Ki-67 immunostaining of frozen sections and by in vitro incubation with bromodeoxyuridine (BrdUrd); in the latter preparations, BrdUrd LIs could be compared with PCNA LIs in the very same areas of serial sections. In gliomas, PCNA LIs were 0.7–80.2% (mean 31.7%), in metastases 0–76.0% (mean 47.8%), and in meningiomas 0–53.0% (mean 19.3%). In general, PCNA LIs were highly significantly correlated with Ki-67 LIs (P=0.0002) and BrdUrd LIs (P=0.0001). However, when tumor subgroups are considered, only gliomas show a significant correlation with Ki-67 and BrdUrd LIs. Despite this statistical correlation, PCNA expression was out of proportion to proliferation indices as determined by both other methods in almost one third of all brain tumors. Immunocytochemistry for PCNA produces a broad spectrum of staining intensity of labeled nuclei, whose number is dependent upon the sensitivity of the immunocytochemical technique used. Thus, inter-oberserver and inter-laboratory variabilities in PCNA LI determination may occur. Overlapping of PCNA LIs between tumor subgroups of varying malignancy further limits the informational value for the individual case. In some classic meningiomas, high PCNA scores do not reflect the proliferative activity of the tumor, as Ki-67 and BrdUrd LIs are very low in these cases. We conclude that PCNA immunolabeling is of limited value in the individual tumor, mainly due to overexpression in many tumors, and at present cannot be recommended to replace Ki-67 and/or BrdUrd labeling methods for routine determination of proliferative activity in human tumor specimens.Supported in part by a grant from the Oncology Commission, Medical Faculty, University of Vienna     

Cyclic nucleotides in cerebrospinal fluid of patients with intracranial and spinal tumors

Since the cyclic nucleotides (CN) adenosine 3',5'-monophosphate (cAMP) and guanoside 3',5'-monophosphate (cGMP) are involved in the regulation of cell proliferation and tumor growth in vitro, a study was made of the levels of these compounds in the lumbar cerebrospinal fluid (CSF) of 20 patients with intracranial and spinal tumors. In the presence of benign or malignant intracranial tumors there was a slight and not significant decrease of cAMP as well as cGMP levels in the CSF, as compared to control patients. While there was no significant correlation between the levels of the two CN in controls, there was a positive correlation in tumor patients. Total protein content and cAMP were negatively correlated in malignant intracranial tumors. Possible influences of tumor growth and intracranial pressure increases on CN levels are discussed. In spinal tumor patients normal CN levels were observed. However, in a patient with meningeal sarcoma an extremely marked elevation of cAMP occurred in parallel with the extension of the tumor to the spinal meningeal space, suggesting massive secretion of cAMP from the tumor cells.     

A clinicopathological, immunohistochemical and neuroradiological study of eight patients with central neurocytoma

Central neurocytomas are low-grade tumors of neuronal origin located in the lateral ventricle that present predominantly with raised intracranial pressure. In this retrospective study, we investigated the clinical, radiological, histopathological and immunohistochemical features of eight patients (seven males and one female; age range 16-61 years; mean = 35.1 years) with neurocytoma. Raised intracranial pressure was the most common presenting feature. In addition, one patient presented with marked visual deterioration and one presented with a visual field defect. All lesions were located in the lateral ventricle (right lateral ventricle: four patients, left lateral ventricle: three patients, both ventricles: one patients). Radiology showed marked intratumoral calcification in two patients. Total microsurgical excision was achieved in seven patients. Histopathology showed sheets of monotonously small-to-medium-sized neoplastic cells with uniform round-to-oval nuclei and inconspicuous nucleoli. Immunohistochemistry was positive for synaptophysin and neuron-specific enolase (NSE) in all tumors, and glial fibrillary acidic protein was focally positive in two patients. One patient had lipomatous differentiation within the tumor. No recurrence was noted in any of our patients until the last follow-up; however, there were two deaths in our series.     

Endothelial cell-based cytokine gene delivery inhibits 9L glioma growth in vivo

Malignant brain neoplasms present great therapeutic challenges due to their extremely aggressive behavior and relative isolation by the blood-brain and blood-tumor barriers. Endothelial cells may be versatile platforms for delivering genes to solid tumors by virtue of their location at blood-tissue interfaces and their proliferation in response to endothelial mitogens produced by tumors. Immortalized rat brain endothelial cells that express the E. coli lacZ reporter gene and the gene for murine interleukin-2 (RBEZ-IL2) were co-inoculated with 9L glioma cells to Fisher rats to examine the effects of endothelial cell-based cytokine delivery on glioma growth in vivo. 9L glioma growth was not affected by the implantation of control RBEZ cells. The growth of subcutaneous and intracranial 9L gliomas was significantly inhibited by RBEZ-IL2 cells (P < 0.005 and P < 0.001, respectively) when compared to control transfected RBEZ cells. Rats receiving intracranial 9L glioma cells with RBEZ-IL2 cells showed increased survival (P < 0.001). Histologic and immunohistologic analysis showed enhanced activation of microglia/macrophages and CD8-positive T lymphocytes and/or natural killer cells within brain at sites of 9L inoculation with RBEZ-IL2 cells. This report establishes that immortalized endothelial cells can be used for cytokine gene delivery and to activate anti-tumor host responses to experimental gliomas within the central nervous system.     

Intraoperative utilization of Microvascular Doppler for the detection of intracranial venous structures during tumor resection – A technical note

BackgroundMicrovascular Doppler (MVD) has been widely used for the detection of arterial blood flow in the brain, especially during aneurysm clipping, vascular malformation resection, or bypass surgeries. However, the benefits obtained from early identification of intracranial sinuses and deep draining veins during tumor resection has not been reported.MethodsWe reviewed the clinical data and imaging from our cases and conducted a systemic review of the medical literature using PubMed and keywords. Bibliographies of each result were evaluated to determine if additional reports describing the use of MVD during tumor resection could be found.ResultsNo reports were found in the literature where MVD was specifically used for venous identification during the resection of deep-seated brain tumors. In our patient cohort, MVD was used successfully to detect and ultimately allow immediate protection of large dural venous sinuses as well as smaller deep cerebral veins during tumor resection. Each patient developed no new venous infarcts and made a satisfactory recovery with no new postoperative neurological deficits.ConclusionMVD is a reliable tool for the intraoperative detection of intracranial venous blood flow to allow for quick identification and protection of venous structures. MVD is an additional safety measure for the patient as its accuracy in detecting venous structures is less susceptible to many of the inherent weaknesses of stereotactic neuro-navigation including the accompanying brain shift or anatomical distortion produced by long duration deep seated brain tumor resection.     

Proliferating cell nuclear antigen immunoreactivity in human central nervous system neoplasms

Summary Formalin-fixed, paraffin-embedded surgical specimens from 140 primary human central nervous system tumors, including 51 meningiomas, 26 astrocytomas, 26 anaplastic astrocytomas, 9 glioblastomas, 1 gliosarcoma, 8 oligodendrogliomas, 5 ependymomas, 2 subependymomas, 9 medulloblastomas, and 3 paragangliomas, were immunostained using a streptavidin/peroxidase method and the PC10 monoclonal antibody, which recognizes an epitope on the proliferating cell nuclear antigen (PCNA). The following PCNA labeling index (LI) mean values were found for the above neoplasms: meningiomas, 3.80±7.35%; astrocytomas, 0.65±1.03%; anaplastic astrocytomas, 8.46±7.95%; glioblastomas, 10.26±11.21; gliosarcoma, 46.34%; oligodendrogliomas, 2.31±3.59%; ependymomas, 1.12±2.10%; medulloblastomas, 23.91±11.95%; and paragangliomas, 2.07±1.86%. Collectively, our findings indicate that while benign central nervous system tumors generally have low PCNA LI values, consistent over-expression of PCNA epitopes was noted in some examples, especially in a number of meningiomas. Among the malignant neuroectodermal tumors, medulloblastomas were found to have the highest PCNA LI values, corresponding to their histological grade of malignancy, and malignant glial tumors generally displayed significantly higher PCNA LI values, than their benign counterparts. Although in our study mean PCNA LI values seemed to reflect histological grading, large discrepancies were noted in all tumor groups. Our data, therefore, suggest than PCNA immunoreactivity can not be considered reliable for predicting the prognosis of the disease in individual cases.Presented in part at the 14th Meeting of Swiss Neuropathologists with International Participation, Saint-Moritz, Switzerland, March 1992     

Primary peripheral PNET/Ewing's sarcoma arising in the meninges,confirmed by the presence of the rare translocation t(21;22) (q22;q12)

Peripheral primitive neuroectodermal tumor/Ewing's sarcoma (ES) (pPNET/ES) of intracranial origin are very rare. These tumors are characterized by specific translocations involving a gene on chromosome 22q12, the most common being t(11;22) (q24;q12). We report a case of 37‐year‐old man with pPNET/ES arising in the meninges and bearing the rare translocation t(21;22) (q22;q12). The tumor was composed of sheets and nests of monotonous small cells with round to oval nuclei, finely dispersed chromatin, small nucleolus and scant cytoplasm. We discuss the importance of the differential diagnosis with central primitive neuroectodermal tumors (cPNET).     

The relationship between Ki-67 labeling and mitotic index in gliomas and meningiomas: demonstration of the variability of the intermitotic cycle time

Summary The monoclonal antibody (mAb) Ki-67 is a marker for the growth fraction (GF) of tumor cells. The exact relationship between the Ki-67 labeling index (LI) and the conventional diagnostic criterion of the proliferative activity of brain tumors, the mitotic index (MI), is unknown except for some general references. On serial frozen sections Ki-67 LI and MI were determined in nearly identical areas of 32 glioblastomas, 20 grade III astrocytomas, 21 grade II astrocytomas and 20 selected cases of meningioma. The data not only clearly showed different median values of LI and MI for the various malignancy grades, but also similar regression coefficients for each glioma type. A non-linear relationship between the two indices was found for all glioma cases with high significance and high correlation coefficient; (LI)=5.6 (MI)^0.59. This results from differing intermitotic cycle times, the variability of which can be estimated from the data given.Dedicated to Prof. Dr. Dr. W. MüllerSupported by the Verein der Freunde und Förderer der Universität Köln     

Multiple intracranial mixed germ cell tumors

A case of sequential occurrence of multiple intracranial mixed germ cell tumors is presented. An 8-year-old boy with a cystic calcified tumor in the basal ganglia and an increased serum α-fetoprotein concentration was initially treated with radiotherapy. Six years later, a tumor composed of embryonal carcinoma and immature teratoma arose from the right temporo-parietal lobe. This tumor was treated successfully with surgery and radiochemotherapy. The possibility of multicentricity or intra-axial metastasis distant from the original site during the long-term course should be considered in treatment for intracranial germ cell tumors. Received: 6 November 1995 Revised: 17 July 1996     

Ki-67 immunoreactivity in human central nervous system tumors: a study with MIB 1 monoclonal antibody on archival material

Paraffin-embedded surgical specimens from 136 primary human central nervous system (CNS) tumors, including 50 meningiomas, 24 astrocytomas, 26 anaplastic astrocytomas, 9 glioblastomas, 8 oligoden-drogliomas, 4 ependymomas, 1 anaplastic ependymoma, 2 subependymomas, 9 medulloblastomas, and 3 paragangliomas, were immunostained, following microwave processing, using a streptavidin/peroxidase method and the MIB 1 monoclonal antibody (mAb) against the Ki-67 antigen. The following mean Ki-67 labeling index (LI) values ± SD were found: meningiomas, 2.47 ± 1.83; astrocytomas, 2.03 ± 2.03; anaplastic astrocytomas, 12.80 ± 6.29; glioblastomas, 14.57 ± 6.77; oligodendrogliomas, 5.06 ± 4.78; ependymomas, 2.63 ± 2.58; anaplastic ependymoma, 6.89; subependymomas, 1.79 ± 1.54; medulloblastomas, 18.77 ± 9.65; and paragangliomas, 2.19 ± 2.51. Our findings indicate that while malignant CNS tumors always exhibited high Ki-67 LI values, and benign CNS tumors generally displayed lower values, increased immunoreactivity for Ki-67 epitopes (Ki-67 LI higher than 4) was noted in a number of meningiomas, astrocytomas, ependymomas, oligodendrogliomas and paragangliomas, contrasting with their benign histological features. Further investigations of the Ki-67 immunoreactivity in CNS tumors and systematic correlation with the postoperative follow-up of patients are necessary to determine the value of Ki-67 LI in predicting the biological behavior of CNS neoplasms.Presented at the 69th Annual Meeting of the American Association of Neuropathologists, June 10–13, 1993, Salt Lake City, Utah, USA     

Congenital immature teratoma of the fetal brain

Congenital intracranial tumors are very rare and only account for 0.5–1.5% of all childhood brain tumors. Even rarer are those with prenatal manifestation. The most common of these present at birth are teratomas, which show divergent differentiation with 90% of them containing tissues from all three germ layers. We report a rare case of an intrauterine congenital immature teratoma in a female fetus at 23 weeks of gestation, which was sonographically diagnosed in vivo by detection of the tumor and associated craniomegaly. Because of the poor prognosis, termination of the pregnancy was induced by Rivanol instillation. The cerebral tumor was confirmed at autopsy and was not associated with any other malformations. Histological and immunohistochemical features of this tumor are presented. Received: 22 November 1996     

Expression of vascular endothelial growth factor in human brain tumors

Compared to normal brain an increased expression of vascular endothelial growth factor (VEGF) has been reported in many types of brain tumors. However, the numbers of samples analyzed and information about the cellular distribution of VEGF have been limited. Here we used novel monochlonal antibodies against VEGF to analyze, using immunohistochemistry, Western blotting and enzyme-linked immunosorbent assay, its expression in 108 human brain tumors that included astrocytic tumors, meningiomas, pituitary adenomas, primary intracranial germ cell tumors and neuronal tumors. The results showed that 37 of 48 astrocytic tumors (77%) and 15 of 19 meningiomas (79%) were immunoreactive for VEGF, consistent with previous reports. However, in contrast to a previous report that analyzed only VEGF mRNA; all of our 15 pituitary adenomas showed specific immunoreactivity for VEGF. We also extended the studies to previously unanalyzed neoplasms: 13 of 15 primary intracranial germ cell tumors (82%), and 7 of 10 neuronal tumors (70%) were immunoreactive for VEGF. Direct protein analysis by Western blotting confirmed the expression of VEGF in those tumors, and showed differential expression of the isoforms of VEGF protein; a pituitary adenoma expressed both VEGF₁₆₅ and VEGF₁₈₉ proteins, a central neurocytoma expressed only VEGF₁₆₅, while an immature teratoma expressed only VEGF₁₈₉. The data herein show that VEGF is expressed in a wide spectrum of brain tumors and suggest differences among tumor entities in the mechanisms of VEGF up-regulation as well as their employment of distinct VEGF isoforms for neovascularization. Received: 26 January 1998 / Revised, accepted: 15 April 1998     

Effect of dexamethasone on glial fibrillary acidic protein in peritumorous edema of cats: A morphometric study

Summary In 54 cats experimental brain tumors were produced by xenotransplantation of the blastomatous glial cell clone RG2 into the internal capsule of the left hemisphere. Fifteen of these animals were treated with dexamethasone for 1 week and four animals for 2 h. The occurrence of glial fibrillary acidic (GFA) protein in tumor and peritumoral edema was studied by immunocytochemistry at intervals ranging between 3 and 35 days after implantation. High concentrations of GFA protein were present in giant and many of the larger tumor cells but not in small tumor cells. In peritumorous white matter it appeared in reactive astrocytes, where it reached its maximum 2 weeks after implantation. At this time, morphometric evaluation of GFA protein-positive areas revealed an increase from 0.095±0.035% to 5.17±1.42%. Application of dexamethasone for 1 week reduced this area to 1.67±0.57% (P<0.001). The results obtained demonstrate that the development of peritumorous edema is associated with considerable stimulation of GFA protein production which is inhibited by dexamethasone. Production of GFA protein by reactive astrocytes, in consequence, does not seem to be involved in the resolution process of peritumoral edema under dexamethasone therapy.     

Preirradiation chemotherapy for very young children with brain tumors

Standard management of malignant brain tumors includes either surgical resection alone or surgery followed by irradiation. However, neuroaxis irradiation administered to very young children for primary intracranial tumors is often associated with major late side effects. To delay irradiation and evaluate the efficacy of preirradiation chemotherapy, we treated 9 young children (aged less than 3 years), who had newly diagnosed brain tumors and underwent total or subtotal resection, with a combination of chemotherapy including vinblastine, cisplatin, and etoposide every 3–4 weeks for 6–14 courses between 1988 and 1992. There were malignat gliomas in four patients, medulloblastomas in three, and ependymomas in two. A response to preirradiation chemotherapy (complete remission or partial remission) occurred in seven out of nine cases. Only one patient had progressive disease during the chemotherapy period. Preirradiation chemotherapy with vinblastine, cisplatin, and etoposide might be a highly effective combination allowing delay of radiation therapy in very young children with brain tumors. Acute and subacute toxicity of chemotherapy in this study was mild.