Expression of neural cell adhesion molecule L1 (CD171) in neuroectodermal and other tumors: An immunohistochemical study of 5155 tumors and critical evaluation of CD171 prognostic value in gastrointestinal stromal tumors.

The neural cell adhesion molecule L1 (CD171) is a multidomain type 1 membrane glycoprotein of the immunoglobulin superfamily important in the nervous system development, kidney morphogenesis, and maintenance of the immune system. Recent studies reported CD171 expression being associated with adverse clinical outcome in different types of cancer and there has been a growing interest in targeting this cell membrane molecule on neoplastic cells by chimeric antigen receptor redirected T lymphocytes or specific antibodies. Nevertheless, conflicting results regarding the prognostic value of CD171 expression in renal cell carcinomas and gastrointestinal stromal tumors were published. In this study, CD171 expression was immunohistochemically analyzed in 5155 epithelial, mesenchymal, melanocytic, and lymphohematopoietic tumors to assess its utility in diagnostic pathology and to pinpoint potential targets for CD171-targeting therapy. A newly developed anti-CD171 rabbit monoclonal antibody, clone 014, was selected from the panel of commercially available CD171 antibodies. Immunohistochemistry was performed using Leica Bond Max automation and multitumor blocks containing up to 60 tumor samples. CD171 was constitutively and strongly expressed in neuroectodermal tumors such as schwannoma, neuroblastoma, and paraganglioma, whereas other mesenchymal tumors including schwannoma mimics showed only rarely CD171 positivity. Frequent CD171-expression was also detected in ovarian serous carcinoma, malignant mesothelioma, and testicular embryonal carcinoma. CD171 immunohistochemistry may have some role in immunophenotypic differential diagnosis of neurogenic tumors and pinpointing potential candidates for anti-CD171 therapy. Though, because of its rare expression and lack of predictive value, CD171 is neither a diagnostic nor prognostic marker for gastrointestinal stromal tumors.

Extraskeletal Ewing sarcomas in late adolescence and adults: a study of 37 patients.

BACKGROUND: Extraskeletal Ewing sarcoma (EES)/primitive neuroectodermal tumours (PNET) are rare soft tissue sarcomas. Prognostic factors and optimal therapy are still unconfirmed. MATERIALS AND METHODS: We performed a retrospective analysis on patients to explore the clinic characteristics and prognostic factors of this rare disease. A total of 37 patients older than 15 years referred to our institute from Jan., 2002 to Jan., 2012 were reviewed. The characteristics, treatment and outcome were collected and analyzed. RESULTS: The median age was 28 years (range 15-65); the median size of primary tumours was 8.2 cm (range 2-19). Sixteen patients (43%) had metastatic disease at the initial presentation. Wide surgical margins were achieved in 14 cases (38%). Anthracycline or platinum-based chemotherapy was performed on 29 patients (74%). Radiotherapy was delivered in 13 (35%). At a median follow-up visit of 24 months (range 2-81), the media event-free survival (EFS) and overall survival (OS) were 15.8 and 30.2 months, respectively. The 3-year EFS and OS rates were 24% and 43%, respectively. Metastases at presentation and wide surgical margins were significantly associated with OS and EFS. Tumour size was significantly associated with OS but not EFS. There were no significant differences between anthracycline and platinum based chemotherapy regarding EFS and OS. CONCLUSIONS: EES/PNET is a malignant tumour with high recurrence and frequent distant metastasis. Multimodality therapy featuring wide surgical margins, aggressive chemotherapy and adjuvant local radiotherapy is necessary for this rare disease. Platinum-based chemotherapy can be used as an adjuvant therapy.

Trilateral retinoblastoma: neuroimaging characteristics and value of routine brain screening on admission.

Trilateral retinoblastoma (TRb) is a rare disease associating intraocular retinoblastoma with intracranial primitive neuroectodermal tumor. Treatment is difficult and prognosis is poor. This multicenter study evaluates clinical findings and MR imaging characteristics of associated intracranial tumors in Rb patients. Clinical data of 17 patients (16 TRb and 1 quadrilateral Rb patients) included time intervals between Rb and TRb diagnosis and presence of baseline brain-imaging (BBI). Two reviewers reviewed all images individually and one reviewer per center evaluated their images. Consensus was reached during a joint scoring session. Studies were reviewed for tumor location, size and imaging characteristics (signal intensity (SI) on T1- and T2-weighted images, enhancement pattern and cystic appearance). Of 18 intracranial tumors, 78 % were located in the pineal gland and 22 % suprasellar. All tumors showed well-defined borders with mostly heterogenous enhancement (72 %) and isointense SI on T1- (78 %) and T2-weighted images (72 %) compared to gray matter. The majority of pineal TRbs showed a cystic component (57 %). TRb detected synchronously with the intraocular tumors on BBI (n = 7) were significantly smaller (P = 0.02), and mainly asymptomatic than TRb detected later on (n = 10). Overall, 5-year-survival of TRb patients detected on BBI was 67 % (95 % CI 29-100 %) compared to 11 % (95 % CI 0-32 %) for the group with delayed diagnosis. TRb mainly develops in the pineal gland and frequently presents with a cystic appearance that could be misinterpreted as benign pineal cysts. Routine BBI in all newly diagnosed Rb patients can detect TRb at a subclinical stage.

Is there a role for high dose chemotherapy with hematopoietic stem cell rescue in patients with relapsed supratentorial PNET?

Supratentorial primitive neuroectodermal tumors (sPNET) are rare childhood brain tumors. There is no standard strategy for treating relapsed sPNETs. The role of high dose chemotherapy with hematopoietic stem cell rescue (HDC with HSCR) in treating relapsed sPNET is controversial. A systematic review of the literature regarding outcome of patients with relapsed sPNET treated with HDC and HSCR was performed to examine the potential predictive factors that would justify its use in this subset of patients. Forty-six patients were identified fulfilling the inclusion criteria. Of those, 15 patients were infants and 15 were pineoblastomas. With a median follow-up of 40 months (range 3-123 months) 15 patients were reported alive. Thirteen patients out of the 15 survivors did not receive craniospinal irradiation (CSRT). The 12 month overall survival (OS) of the cohort was 44.2 ± 7.5 months. Twelve-month OS for children less than 36 months was 66.7 ± 12.2 months while for older children it was 27.8 ± 10.6 (P = 0.003). Twelve-month OS was 20.0 ± 10.3 for those patients with pineoblastoma versus 54.6 ± 9.0 for those with non-pineal sPNETs (P < 0.001). Cox regression analysis revealed pineal location as the only independent adverse prognostic factor. In conclusion high dose chemotherapy with HSCR might lead to survival primarily in younger children with relapsed sPNET even in the absence of concomitant use of radiotherapy, whereas the outcome in older children and/or in pineal location is extremely poor with this modality.

Intracranial tumors in infants: a single institution experience of 22 patients.

OBJECTIVES: The prognosis in infants with brain tumors has hitherto been very poor. The purpose of the study was to collect and analyze information regarding the clinical presentation, diagnosis, and management of these patients and to assess the eventual prognosis regarding survival and response to treatment. MATERIALS AND METHODS: This study retrospectively reviewed the records of 22 infants with brain tumors at our institution between November 1995 and October 2009. Their medical records were retrieved for age at diagnosis, presenting features, location, histology, surgical procedures, adjuvant treatment, recurrence, and survival. RESULTS: The patients included 18 boys and four girls. The median age at diagnosis was 3 months with a range of antenatal diagnosis at 36 weeks of gestation up to 11.9 months. The group included four patients with definite congenital tumors presented in the perinatal period. The common presenting signs included increased head circumference, seizure, and vomiting. Over half of the tumors were histologically benign; however, medulloblastoma/primitive neuroectodermal tumor is the most frequent tumor type, accounting for six patients. Surgical resection was attempted in 18 patients, and three of them died in early postoperative period. Cerebrospinal fluid diversion was required in 11 patients, and seven of these patients needed VP shunting. Four patients received adjuvant chemotherapy, but one of them subsequently received salvage radiotherapy. CONCLUSION: Because of the expandability of the skull, brain tumors in infants may have protean manifestations. Although pathology categorization was quite a variable in our study, three quarters have tangibly survived after current therapeutic modalities.

[Supratentorial primitive neuroectodermal tumor: a single center experience and comparison with the literature]. / Supratentorieller primitiver neuroektodermaler Tumor: Erfahrungen in einem Zentrum im Vergleich zur Literatur.

Supratentorial primitive neuroectodermal tumors (stPNETs) are malignant tumors. We saw within three years six children with stPNETs. In four of the six children radical resection could be achieved. All had craniospinal irradiation and chemotherapy according to the HIT-91 protocol. The two children with incomplete resection died due to tumor progression after 7 and 10 months. Two of the 4 children with complete tumor resection had local relapses 8 months after diagnosis and died after 14 and 18 months. One child had a diffuse meningeal relapse 12 months after diagnosis. Despite (high-dose) systemic chemotherapy and intraventricular mafosfamide, he died 21 months after diagnosis due to tumor although remission could be achieved. Only one child is still in remission 86 months after diagnosis.

Does sophisticated diagnostic workup on neuroectodermal tumors have an impact on the treatment of esthesioneuroblastoma?

BACKGROUND: The diagnostic workup on esthesioneuroblastoma is more extensive than ever before. We have investigated whether improvements in diagnosis of sinonasal neuroectodermal tumors, including esthesioneuroblastomas (ENB), sinonasal neuroendocrine carcinomas (SNEC) and sinonasal undifferentiated carcinomas (SNUC), have had an impact on treatment and outcome. PATIENTS AND METHODS: 11 ENB, 7 SNEC and 1 SNUC in 13 men and 6 women (average age 52.9 years (range 26-82)), diagnosed between 1986 and 2001, were analyzed with regard to histopathologic and clinical diagnosis as well as outcome. Our results were compared with the available literature. RESULTS: According to the Morita classification considering endoscopy, CT and MRI scans, 2 tumors were staged D, 14 were found to be stage C, 2 were stage B and 1 was stage A. Lightmicroscopically only 4 of 19 showed higher differentiation and rosette-like structures, the others were poorly differentiated. 18 of 19 tumors were examined immunohistochemically. Neuronal markers (NSE, synaptophysin, chromogranin, S-100 and neurofilaments) were heterogeneously expressed in both ENB and NEC, only NSE stained all but 2 tumors. Coexpression of neuronal markers and cytokeratins was proven in all NEC and 5 of 11 ENB. Some tumors expressed atypical markers. Despite extensive diagnostic steps it was not possible to exclude a different histopathological diagnosis in 10 of 19 cases. CONCLUSION: For sinonasal neuroectodermal tumors no pathognomonic antigenic profiles are known. Immunohistochemical markers lack specificity and sensitivity. Nevertheless, in many sinonasal neuroectodermal tumors a panel of differentiation markers allows to specify the light-microscopic diagnosis. Until now no therapeutic consequence arises from a more extensive diagnostic workup. However, the histopathologic identification of subtypes (SNUC) and proliferation markers may help to identify patients with poor prognosis.

Intensive chemotherapy for children and young adults with metastatic primitive neuroectodermal tumors of the soft tissue.

The MMT4 study was designed to explore an intensive chemotherapy regimen (MMT4-89) and the role of high-dose melphalan (MMT4-91) in children with metastatic soft tissue sarcoma, including extraosseous peripheral neuroectodermal tumor (PNET). Thirty-one patients with PNET were treated between 1989 and 1995 (11 according to MMT4-89 and 20 according to MMT4-91). Chemotherapy consisted of four CEVAIE cycles, each including three 3-week courses: CEV (carboplatin 500 mg/m(2), epirubicin 150 mg/m(2), vincristine 1.5 mg/m(2)), IVA ifosfamide 9 g/m(2), actinomycin 1.5 mg/m(2), vincristine 1.5 mg/m(2)), IVE (ifosfamide 9 g/m(2), etoposide 600 mg/m(2), vincristine 1.5 mg/m(2)). In MMT4-91 the fourth CEVAIE was replaced with melphalan 200 mg/m(2) with stem cell rescue. The CEV combination was evaluated as a window study. Surgery followed the second cycle. Radiotherapy was administered to post-surgical residual disease. The response rate was 55% after CEV, rising to 80% after the first CEVAIE. Twenty-five patients achieved complete remission (CR). Overall, the 5-year EFS was 22.6%: 36.4% and 15% for patients treated according to MMT4-89 and MMT4-91, respectively (P = 0.3). Local control was achieved in 77% of irradiated patients vs 45% of non-irradiated. Age >10 years was associated with significantly poorer outcome (P = 0.04). In conclusion, despite the high CR rate, intensive chemotherapy with or without high-dose melphalan appeared to have little impact on the survival of patients with metastatic extraosseus PNET.

Primitive neuroectodermal tumors of the pancreas: a report of seven cases of a rare neoplasm.

Primitive neuroectodermal tumors (PNETs) have rarely been described in solid organs. We report a series of seven PNETs of the pancreas. The clinical, gross, microscopic, and immunohistochemical features of these seven PNETs of the pancreas are described, as are the genetic analyses in five cases. The patients ranged in age from 6 to 25 years (mean 18 years). Four of the patients were male. All of the patients presented with jaundice and/or abdominal pain. All of the tumors were located in the head of the pancreas, and they ranged in size from 3.5 to 9.0 cm. Light microscopy revealed the typical morphologic features of PNETs. By immunohistochemistry the neoplastic cells in all seven cases expressed O13 (CD99, p30/32MIC2). In five of six tested cases, the neoplastic cells also expressed cytokeratin. All of the tumors expressed neural-neuroendocrine markers. Two of the three cases examined ultrastructurally showed prominent epithelial features. There was cytogenetic or molecular genetic evidence of the t(11;22)(q24;q12) in four of five cases examined. Clinical follow-up was available in five cases. Two of the patients were alive with no evidence of disease at 33 and 43 months. One patient was alive with disease at 27 months. One patient died of postoperative complications. Another patient died of disease 4 years after diagnosis. PNET can sometimes arise as a primary neoplasm of the pancreas. Like PNETs arising in more conventional sites, pancreatic PNETs occur in the pediatric and adolescent population, show the characteristic staining with O13, and typically harbor the t(11;22)(q24;q12) chromosomal translocation. PNETs should be included in the differential diagnosis of poorly differentiated small round cell tumors of the pancreas. Moreover, they should not be confused with pancreatic endocrine tumors, which also demonstrate dual epithelial and neuroendocrine differentiation by immunohistochemistry and express O13 in 30% of cases.

Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91.

PURPOSE: To evaluate the outcome of children with supratentorial primitive neuroectodermal tumors after surgery, irradiation, and chemotherapy and to identify factors predictive for survival. PATIENTS AND METHODS: Sixty-three children in the prospective trials HIT 88/89 and HIT 91 were eligible. Complete resection was performed in 21 patients. Patients were randomized for preirradiation chemotherapy, consisting of two cycles of ifosfamide, etoposide, methotrexate, cisplatin, and cytarabine (n = 40), or chemotherapy after irradiation, consisting of eight cycles with cisplatin, vincristine, and lomustine (n = 23). Irradiation volume was recommended to encompass the neuraxis with 35.2-Gy total dose followed by a boost (20.0 Gy) to the primary tumor site (n = 54). Seven patients were irradiated to the tumor region only with a total dose of 54.0 Gy. RESULTS: Overall survival at 3 years was 48.4%. Progression occurred in 38 children, with local recurrences in 27 patients. The only significant prognostic factor was dose and volume of radiotherapy (progression-free survival after 3 years was 49.3% with correct treatment compared with 6.7% for 15 children with major violations of radiotherapy). Ten early progressions occurred during adjuvant therapy (eight before and two during radiotherapy), nine of them treated with preirradiation chemotherapy. There was a positive trend in outcome for nonmetastatic and pineal tumors. CONCLUSION: Significant predictive factors were dose and volume of radiotherapy. Volume of irradiation should encompass the whole CNS with additional boost to the tumor region. Local doses of at least 54 Gy and a craniospinal dose of 35 Gy are necessary. Preirradiation chemotherapy seems to increase risk of early progression.

Metastatic Ewing sarcoma/PNET of bone at diagnosis: prognostic factors--a report from Saudi Arabia.

BACKGROUND: To evaluate outcome and prognostic factors in Saudi Arabian patients with metastatic Ewing sarcoma and PNET of bone (PMES) at diagnosis. PROCEDURE: Ninety-nine of 304 (33%) consecutive patients with Ewing sarcoma and PNET of bone registered at our centre from 1975 to 1998, had metastatic disease at registration and 93 were available for analysis. The maximum x-axis diameter of the primary tumor was used as the measure of primary tumor size. Usually a trial of systemic treatment was undertaken before a decision was made on local treatment. Standard chemotherapy regimens were used in all treated patients. Forty-one (44%) patients did not receive radical local treatment due to an inadequate response to chemotherapy, or a decision not to undertake more than palliative treatment. Radical treatment of the primary site was radiation alone 41 (79%), resection alone 7 (13%), and resection and radiation 4 (8%). RESULTS: The 5-year survival rates were 9% for all 93 evaluable patients, 16% for 52 patients who received chemotherapy and radical local treatment, 0% for 41 patients who received lesser treatment, 19% for 43 patients with lung metastases alone, and 0% (P = 0.002) for 50 patients with other sites involved. For 60 patients with imaging data, 5-year survivals were 34 and 0% when the maximum transverse diameter of the primary tumor was < 10 cm (N = 20) and > or = 10 cm (N = 40), respectively. CONCLUSIONS: Small primary tumor size and the presence of lung metastases alone were the only significant favorable prognostic factors. Earlier diagnosis will be the basis for better results.

Advances in biology and treatment of childhood brain tumors.

Childhood brain tumors are collectively the most common solid neoplasm and the leading cause of cancer-related death in children. They are a diverse group of diseases and outcome is extremely variable. Current treatment is dependent on histology, location, and in some instances, patient age. Advances in treatment have led to improved survival for some patients, but for many the outcome remains dismal despite aggressive treatment. A growing body of work is aimed at improving the outcome for children with brain tumors not only through clinical trials, but also by focusing on the biologic underpinning of these diseases that have been poorly understood.

Neurogenic tumours of the mediastinum: a report of 60 cases.

OBJECTIVES: To analyze retrospectively 60 patients (13 infants and children, 47 adults--21 men and 39 women) with mediastinal neurogenic tumours admitted to Atatürk Centre for Chest Disease and Chest Surgery, Ankara, Turkey between 1988 and 1999. This comprised 21.2% of 283 patients who had surgical operations for all mediastinal masses during the same period. PATIENTS AND METHODS: The patients ranged from four to 67 years of age. Thirteen patients were younger than 15 years and 47 were 15 years of age or older. Medical records were reviewed for demographic data, clinical presentation, diagnostic investigations, operative procedures, and tumour location and invasion. Postoperative morbidity and mortality were noted as well as long term follow-up. The clinical investigations included chest x-ray and computed tomography of the thorax in all patients, and spinal magnetic resonance imaging and bronchoscopical examination in some. Clinical variables were compared. RESULTS: The tumours had the following characteristics: 42 (70%) were nerve sheath tumours; 15 (25%) were autonomic ganglion tumours; two (3.6%) were paragangliomas; and one (1.4%) was a malignant peripheral neuroectodermal tumour (Askin's tumour). Nerve cell tumours comprised the majority of tumours in infants and children (nine of 13, 69%), whereas the nerve sheath tumours were most frequent in adults (39 of 47, 83%). There were 48 benign and 12 (20%) malignant tumours when all age groups were considered; the malignancy rate was 61.5% (eight of 13) in children and 8.5% (four of 47, P<0.05) in adults. All patients were operated via a posterolateral thoracotomy. Surgical resection of the tumour was complete in 56 of 60 patients (93.3%). Resection of malignant tumours was grossly incomplete in four cases (four of 12, 33.3%). All benign tumours were totally excised. There were two major complications (respiratory failure and pulmonary emboli) and 14 minor complications in the perioperative period. The mean follow-up period was five years and seven months. Tumours recurred in 5.3% (three of 56) of patients who had a complete resection initially. There were no late deaths related to benign tumours. CONCLUSIONS: Complete resection of tumours can be performed safely by a thoracotomy approach and is important for achieving satisfactory long term survival in most mediastinal neurogenic tumours.

Epidemiology of childhood brain tumors in Japan.

Using the vital statistics issued annually by the Japanese Government from 1960 to 1994, the mortality of brain tumors during childhood (0-14 years of age) in Japan was estimated. Since there are few nationwide registries of childhood cancers with a sufficiently high registration rate, the incidence of brain tumors was calculated using the Registry of Childhood Malignancies in Hokkaido Prefecture from 1969 to 1996. Though the mortality due to malignant diseases as a whole during childhood has been decreasing, and though there should be progress in therapeutic methods, the mortality due to brain tumors in children has been increasing. The incidence of brain tumors in Hokkaido Prefecture has been increasing as well. There was no tendency for the incidence of medulloblastoma to decrease. The incidence of childhood brain tumors has been increasing in Japan, though the cause is unknown. The period of the present study corresponded to a period of high economic growth. Thus, a study on environmental factors would be interesting.

Adults with Ewing's sarcoma/primitive neuroectodermal tumor: adverse effect of older age and primary extraosseous disease on outcome.

OBJECTIVE: To assess outcome and prognostic factors for survival of adults with Ewing's sarcoma/primitive neuroectodermal tumor (PNET). BACKGROUND: Ewing's sarcoma/PNET is a disease of childhood rarely seen in adults. Accordingly, there is a relative paucity of published literature pertaining to outcome for adults with this disease. METHODS: Between 1979 and 1996, 37 patients with newly diagnosed Ewing's sarcoma/PNET were evaluated and treated at the Adult Sarcoma Program at Dana-Farber Cancer Institute and Brigham & Women's Hospital. Twenty-six patients had localized disease at presentation and 11 had metastatic disease. All but two patients received multiagent chemotherapy. Local treatment consisted of surgery (7 patients), surgery and radiation therapy (19), radiation therapy (6), or no local treatment (5). Median follow-up for living patients was 100 months (range 8 to 199). RESULTS: The 5-year survival rate for the group overall was 37%+/-9%. The 5-year local control rate was 85%+/-7%. Significant favorable predictors for survival on univariate analysis included localized disease at presentation, primary origin in bone, primary size <8 cm, and a favorable objective response to chemotherapy. Patients with localized disease had a 5-year survival rate of 49%+/-11% compared with 0% for those with metastatic disease at presentation. Multivariate analysis showed three significant independent predictors for death: metastatic disease at presentation, primary origin in extraosseous tissue versus bone, and age 26 years or older. CONCLUSION: Adult patients with Ewing's sarcoma/PNET at highest risk for death are those who are older than 26 years and have metastatic disease or an extraosseous primary tumor. The development of novel therapies should target these high-risk groups.

Clusters of histologic characteristics in children with infratentorial neuroglial tumors. The Childhood Brain Tumor Consortium.

Five quantitative histologic factors, differing linear combinations of 26 reliably recognized histologic features, account for much of the histologic variance in 1068 children with infratentorial neuroglial tumors in the Childhood Brain Tumor Consortium (CBTC) database. In this study, we used the scores on the Spongy, Proliferative, Ring, Fibrillary, and Nuclear factors in cluster analyses and identified 11 clusters of children's tumors. Each had statistically significant differences in histology and relative histologic homogeneity. Three clusters had ependymoma-like histologic features; 4 had astrocytoma-like features; and 4 had primitive neuroectodermal-like (PNET or medulloblastoma) features. Each cluster had a unique high/low mean factor score pattern. Multiple operative and other clinical features characterized the three groups of clusters. We used Kaplan-Meier survival models to test for differences in survival among clusters and proportional hazards survival models to adjust for associated covariates. Among the 'ependymoma' clusters the 5 year survival probability ranged from 0.25 to 0.54. Among the 4 'astrocytoma' clusters, 5 year survival probability ranged from 0.59 to 0.94. The 5 year survival probability for the 'medulloblastoma' clusters ranged from 0.20 to 0.44. Within the three groups, clusters had differing covariates associated with survival. The tumor clusters identified in this study ensure relatively homogeneous histologic subsets. The five factor scores of a child's tumor provide the basis for finding the cluster nearest to that tumor. We propose that this tumor clustering strategy be employed for selection of children and for analyses of therapeutic clinical trials.

Effect of dietary vitamin A or N-acetylcysteine on ethylnitrosourea-induced rat gliomas.

It is our hypothesis that low grade gliomas are the glial counterparts of other precancerous lesions such as colon polyps and, therefore, suitable targets for chemoprevention. Steps in the molecular progression of gliomas have been described, indicating that an accumulation of abnormalities is required for progression to a high grade and interruption of this progression might be possible. An animal model of chemical glial carcinogenesis was used to test this hypothesis. Pregnant rats were injected intravenously with ENU (ethylnitrosourea) on the 18th day of gestation to induce gliomas in the offspring, which were randomized to receive control diet, diet supplemented with vitamin A palmitate, or diet supplemented with N-acetylcysteine. Animals exposed to ENU and receiving a control diet developed brain tumors and had a shortened life expectancy compared with rats unexposed to ENU. The animals treated with NAC showed no statistically significant delay in the time to tumor and no change in the histologic grade of the tumors when compared with animals receiving control diet, but the time to death from any cause of NAC treated animals differed significantly from untreated animals. Animals receiving high dose VA had statistically significantly prolonged time to tumor, survived significantly longer than untreated animals, but had no reduction in the total number of tumors or change in the histologic grade of their tumors. The theoretical basis of these results is likely due to the putative mechanism of action of these agents. These data indicate that glioma chemoprevention is possible and deserves further exploration.