Tumors In Young Children Research Articles

Incidence of atypical teratoid/rhabdoid tumors in children

Atypical teratoid/rhabdoid tumors are highly malignant embryonal central nervous system (CNS) tumors that were defined as an entity in 1996. As compared with other malignant CNS tumors, their biological behavior is particularly aggressive, but patients may benefit from an intensified treatment. Atypical teratoid/rhabdoid tumors display a complex histomorphology, which renders them prone to misdiagnosis. They occur predominantly in young children, with an estimated prevalence of 1% to 2% among all pediatric CNS tumors. However, population-based data on the incidence of these tumors are not yet available. A nation-wide survey of malignant high-grade CNS tumors (World Health Organization grade III/IV), diagnosed in children (aged birth to 14 years) from 1996 to 2006 was conducted by the Austrian Brain Tumor Registry. A central histopathology review was performed including the assessment of SMARCB1 (INI1) protein status. A total of 311 newly diagnosed, malignant CNS tumors were included. Atypical teratoid/rhabdoid tumors constituted the sixth most common entity (6.1%), referring to an age-standardized incidence rate of 1.38 per 1,000,000 person-years in children. Peak incidence was found in the birth to 2 years age group, where they were as common as CNS primitive neuroectodermal tumors and medulloblastomas. A total of 47.4% of atypical teratoid/rhabdoid tumors were initially diagnosed, whereas 52.6% were retrospectively detected by the central review. The 5-year survival of atypical teratoid/rhabdoid tumor patients was 39.5%, with 66.7% in the correctly diagnosed group versus 15.0% in the not recognized group (P = .0469). Clinicians and pathologists should be aware of the high incidence of atypical teratoid/rhabdoid tumors in young children to optimize diagnostic and therapeutic management of patients with these tumors.

Abstract 5832: Overexpression of ODC1 is associated with poor outcome in childhood neuroblastoma and represents an important therapeutic target

Abstract MYCN gene amplification is a powerful predictor of poor clinical outcome in neuroblastoma, the most common solid tumor of young children. The mechanism by which MYCN amplification influences the prognosis of this disease has not been well defined. MYCN is a known transcription factor and available evidence indicates that ornithine decarboxylase (ODC1) is a critical downstream target for this oncoprotein. ODC1 is the rate-limiting enzyme in the synthesis of polyamines and overexpression of this gene has been observed in a range of tumor cells, including neuroblastoma. In particular, a number of studies have provided evidence for the oncogenic and transforming abilities of ODC1. To investigate the role of ODC1 in neuroblastoma, we used Real-Time PCR to analyze ODC1 expression in a large cohort (n=209) of primary untreated neuroblastomas from patients enrolled on POG biology protocol 9047. Older age, advanced stage, and MYCN amplification were all predictive of poor outcome in this cohort. ODC1 expression was significantly higher in MYCN-amplified tumors by comparison with non-amplified tumors (p<0.0001). Kaplan-Meier survival analysis indicated that high levels of ODC1 expression were strongly predictive of both event-free-survival (p<0.001) and overall survival (p<0.001) in this cohort as well as in patients whose tumors lacked MYCN amplification (p=0.01). Furthermore, a functionally important single nucleotide polymorphism within the ODC1 promoter (G316A) that has been shown previously to influence gene transcription rates, was found to be significantly associated with outcome in patients whose tumors lacked MYCN amplification (p<0.05). These data suggest that inhibiting ODC1 activity would have therapeutic advantage in treating neuroblastoma. To test this hypothesis, MYCN transgenic mice that spontaneously develop neuroblastoma closely mimicking the human disease, were treated either with cisplatin alone or in combination with the ODC1 inhibitor, α-difluoromethylornithine (DFMO). Importantly, DFMO therapy, either concomitant with or following cisplatin treatment, resulted in prolonged tumor-free survival (p<0.01) in these mice, by comparison with cisplatin administered alone. Similar results were obtained with cyclophosphamide treatment in combination with DFMO. No overt toxicity attributable to DFMO therapy was noted in treated mice. Collectively, these findings provide strong evidence that ODC1 contributes to the malignant phenotype of neuroblastoma and suggest that targeting this oncogene for suppression of polyamine synthesis is potentially a valuable therapeutic approach for inhibiting neuroblastoma growth.

Solid tumors in young children in Moscow Region of Russian Federation

Background. The aim of the study was to assess the main epidemiologic characteristics of solid tumours in young children. Methods. The data were retrieved from the Childhood Cancer Registry of Moscow Region, Russian Federation. Children aged 0-4 years with solid tumours diagnosed in 2000-2006 were included in the analysis. Results. The data on total 142 children with solid tumours were analyzed. The average number of annually registered cases was 5.9 ± 1.1 in infants and 14 ± 1.8 in older children with male-to-female ratio 1.1:1 and 0.92:1, respectively. The average incidence rate (IR) of all solid tumours was 10.6 per 100.000 children/ year in infants and 7.35 per 100.000 children/year in children 1-4 years old. The prevalent types of solid tumours in infants were hepatic (IR 2.46) and renal (IR 2.26) tumours. In children aged 1-4 years the following IRs for certain malignancies were found: CNS tumours 1.70, renal tumours 1.76, sympathetic nervous system tumours 1.73, retinoblastoma 0.87, soft tissue sarcomas 0.70, germ-cell tumours 0.19, hepatic tumours 0.14, and bone tumours 0.13. Conclusions. The lower IR of CNS tumours can be explained by under-reporting of this cancer type in Moscow region as a result of patient scattering through non-oncological hospitals. As compared to the data from cancer registries of the most European countries and US, lower IR of sympathetic nervous system tumours and retinoblastoma and higher IR of liver tumours and soft tissue sarcomas in infants were revealed in this study.

A Phase 2 Feasibility Study of Sequential, Dose Intensive Chemotherapy to Treat Progressive Low-grade Gliomas in Children

Low-grade gliomas (LGGs) comprise nearly 35% of pediatric brain tumors and often occur in young children. Many cannot be resected and radiation therapy can be associated with excessive toxicity in children. Centrally located tumors in young children, and those that progress after radiation remain therapeutic challenges. This phase 2 feasibility trial investigated dose intense, sequential chemotherapy in children with LGG. Ten patients less than 21 years of age with progressive LGGs were enrolled. Courses 1 and 4 consisted of carboplatin and etoposide; courses 2 and 5 consisted of cyclophosphamide and vincristine; courses 3 and 6 consisted of lomustine, procarbazine, and vincristine. Dose adjustments were made to maximize dose intensity but minimize toxicity. Fifty-five of 60 planned chemotherapy courses were administered in 10 patients. One patient with stable disease after 3 courses had complete surgical resection. Two patients taking anticonvulsants experienced prolonged myelosuppression, necessitating removal from study after 5 chemotherapy courses. During 5 of 6 chemotherapy courses, more than 80% of the planned chemotherapy dose intensity was delivered. Two patients had complete responses, 2 patients had partial responses, 3 patients had minor responses, and 3 patients had disease stabilization. No children had life threatening infection or hemorrhage. No patient experienced progressive disease during therapy. Administration of sequential, dose intense chemotherapy was feasible and clinically tolerated. Concurrent anticonvulsant therapy limited dose intensity in 2 patients. Although efficacy appeared consistent with published larger series, small patient number in this study precludes definitive conclusions.

Role of Radiotherapy in Supratentorial Primitive Neuroectodermal Tumor in Young Children: Results of the German HIT-SKK87 and HIT-SKK92 Trials

Role of Radiotherapy in Supratentorial Primitive Neuroectodermal Tumor in Young Children: Results of the German HIT-SKK87 and HIT-SKK92 Trials

Bronchial granular cell tumor in a child: impact of diagnostic delay on the type of surgical resection

Bronchial granular cell tumor is an uncommon tumor in young children. Recurrent pneumonia in the same site should raise suspicion of an obstructing granular cell tumor of the bronchus. We present a 10-year-old girl with an 18-month history of recurrent pneumonia caused by obstruction of the main lingular bronchus by this type of tumor. In our patient, an upper left lobectomy was only technically feasible instead of a lingulectomy alone because of the spread pulmonary inflammation and the depth of bronchial wall invasion by the tumor. Delayed diagnosis resulted in a more extensive pulmonary resection.

Role of Radiotherapy in Supratentorial Primitive Neuroectodermal Tumor in Young Children: Results of the German HIT-SKK87 and HIT-SKK92 Trials

To assess the outcome of young children with supratentorial primitive neuroectodermal tumor (stPNET) treated by intensive postoperative chemotherapy alone compared with treatment with chemotherapy and delayed radiotherapy (RT). From 1987 to 1992, children younger than 3 years of age with stPNET were enrolled in the HIT-SKK87 trial in Germany and Austria. After surgery, low-risk patients received maintenance chemotherapy before RT. In high-risk patients, intensive induction chemotherapy was followed by maintenance chemotherapy until delayed RT was initiated. In the following trial, HIT-SKK92 methotrexate-based chemotherapy was applied. In children with complete remission after three cycles, therapy was finished without irradiation. Otherwise, radiotherapy or salvage chemotherapy was administered. Twenty-nine children were eligible (age, 3.0 to 37.0 months). All children received chemotherapy. In 15 children, no RT was administered. Four children had tumor progression during chemotherapy and underwent irradiation. In 10 patients, RT was given after chemotherapy. Overall survival (OS) and progression-free survival (PFS) rates after 3 years were 17.2% and 14.9%, respectively. Twenty-four children relapsed (13 at the tumor site only, three at distant site, and eight at both local and distant sites). Positive impact on survival was observed in children with complete resection but without statistical significance. Administration of RT was the only significant predictive factor for OS and PFS. Only one child not having RT survived. Outcome of infants and babies with stPNET is unsatisfactory. Omission of RT jeopardizes survival, even if intensive chemotherapy is applied. We suggest to limit any delay of RT to a maximum of 6 months even in young children.

Neuroradiological findings in atypical teratoid/rhabdoid tumor of the central nervous system

To evaluate the computed tomography (CT) and magnetic resonance imaging (MRI) findings of atypical teratoid tumor/rhabdoid tumor (AT/RT) of the central nervous system (CNS). Twenty cases of CNS AT/RT have been found over the past 23 years in our hospital; these involving 11 boys and 9 girls whose mean age at diagnosis was 5.5 years. Their clinical data, the CT, and MRI findings were reviewed retrospectively. AT/RT was located in the cerebellum in 15 cases. Four cases arose from the supratentorial region, while only one occurred primarily in the lumbar spinal cord. Almost all cases revealed heterogeneous intensity and heterogeneous enhancement. Peripheral cystic components were common. Survival time ranged from 2 months to 3 years, with a mean survival of 11.6 months. Most cases of AT/RT are located in the cerebellum. The radiologic manifestations are non-specific. The diagnosis mainly depends on the pathologic findings. However, AT/RT should still remain in the differential diagnosis of brain tumors in young children, especially those located in the cerebellar hemisphere and with eccentric cysts.

Evaluation of Cardiac Tumors in Children by Electron-Beam Computed Tomography Rhabdomyoma and Fibroma

The most common cardiac tumors in young children are rhabdomyoma and fibroma, and prognosis depends on the tumor's characteristics. In the present study electron-beam computed tomography (EBT) was used to evaluate tumor characteristics and myocardial perfusion in 6 children with cardiac tumors. Five children had rhabdomyomas and 1 had a fibroma. In the precontrast study, the computed tomography numbers of rhabdomyomas were higher and those of the fibroma were slightly lower than those of the normal myocardium. In the early postcontrast study, the size, location, shape and number of the tumor were clearly detected, and in the late postcontrast study, the fibrous characteristics of the tumor were seen. The fibroma contained calcification and 2 rhabdomyomas contained a fat density spot. In the cine-mode study, both the tumor and ventricular wall motion could be simultaneously evaluated. There was a filling defect of the left ventricular myocardium on the early postcontrast scan of 1 child with a rhabdomyoma and dyskinetic wall motion at the same region in the cine-mode study. EBT was useful for evaluating tumor characteristics in children.

Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas

Hepatoblastoma is one of the most common malignant liver tumors in young children. Recent evidences have suggested that the abnormalities in Wnt signaling pathway, as seen in frequent mutation of the beta-catenin gene, may play a role in the genesis of hepatoblastoma. However, the precise mechanism to cause the tumor has been elusive. To identify novel hepatoblastoma-related genes for unveiling the molecular mechanism of the tumorigenesis, a large-scale cloning of cDNAs and differential screening of their expression between hepatoblastomas and the corresponding normal livers were performed. We constructed four full-length-enriched cDNA libraries using an oligo-capping method from the primary tissues which included two hepatoblastomas with high levels of alpha-fetoprotein (AFP), a hepatoblastoma without production of AFP, and a normal liver tissue corresponded to the tumor. Among the 10,431 cDNAs randomly picked up and successfully sequenced, 847 (8.1%) were the genes with unknown function. Of interest, the expression profile among the two subsets of hepatoblastoma and a normal liver was extremely different. A semiquantitative RT-PCR analysis showed that 86 out of 1188 genes tested were differentially expressed between hepatoblastomas and the corresponding normal livers, but that only 11 of those were expressed at high levels in the tumors. Notably, PLK1 oncogene was expressed at very high levels in hepatoblastomas as compared to the normal infant's livers. Quantitative real-time RT-PCR analysis for the PLK1 mRNA levels in 74 primary hepatoblastomas and 29 corresponding nontumorous livers indicated that the patients with hepatoblastoma with high expression of PLK1 represented significantly poorer outcome than those with its low expression (5-year survival rate: 55.9 vs 87.0%, respectively, p=0.042), suggesting that the level of PLK1 expression is a novel marker to predict the prognosis of hepatoblastoma. Thus, the differentially expressed genes we have identified may become a useful tool to develop new diagnostic as well as therapeutic strategies of hepatoblastoma.

Supratentorial embryonal tumors in children under 5 years of age: an SFOP study of treatment with postoperative chemotherapy alone.

To determine the effectiveness of multiagent chemotherapy as sole post-operative treatment of supratentorial central nervous system (CNS) embryonal tumors in young children. The data of 25 children under 5 years of age diagnosed with supratentorial embryonal tumors (17 primitive neuroectodermal tumors, four pinealoblastomas, and four medulloepitheliomas) treated exclusively by postoperative chemotherapy (CT) between 1990 and 1997 were reviewed. Fifteen tumors were hemispheric and 10 were deeply seated. Four children presented with disseminated leptomeningeal disease. Total resection was performed in nine patients, subtotal in 9, partial in 3, and a diagnostic biopsy only in 2. Two children did not undergo surgery. Twenty-four children relapsed with a median time of 5.5 months. The median overall survival was 12 months, and the 2-, and 5- year survivals were 30 and 14%, respectively. The 2- year disease-free survival was 4%. There was a significantly worse prognosis in patients undergoing incomplete resection and in the group with deeply situated tumors. Four relapses were treated by second surgery followed by high-dose chemotherapy and radiotherapy. Two of them remain in CR2, and all these children are free of late sequelae. CT alone failed to maintain disease-free survival in most of the children, although, disease progression was delayed to some extent. Children under 5 years with supratentorial embryonal tumors should undergo total surgical resection if possible.

Quoi de neuf en oncologie pédiatrique

The significant progress made in pediatric oncology during recent years has been due to a major breakthrough in the field of molecular biology and the introduction of new therapeutic strategies that take into account both the quality and the duration of life. Molecular biology has already been instrumental in more fully categorizing the 'small round-cell tumor' group, and in reclassifying the 'Ewing family' tumors. It also provides a valuable tool for the prognostic evaluation of neuroblastomas through the analysis of the N-myc oncogene. In addition, it has permitted the identification of the Li-Fraumeni syndrome of predisposition to cancer in the child, thereby raising the problematical ethical issue of communicating relevant information to subjects at risk. Two examples illustrate innovative strategic concepts: 1) Burkitt's lymphoma, or an example of the successful de-intensification of treatment; and 2) brain tumors in young children, regarding which the desire to improve the quality of life has led to innovative attempts to replace radiotherapy by chemotherapy. Considerable progress has been made in the field of neuropsychology, thereby permitting an improved assessment of disorders and a better management of rehabilitation programs. New anti-cancer agents and also chemo- and radiotherapy that spare healthy tissue are also being developed. Gene therapy and molecular biology will play a major role in future therapeutic strategies; and are now at the preclinical trial stage. This significant overall progress leads to a reconsideration of the organizational approach toward treatment of the pediatric patient population suffering from cancer, and a critical assessment of disease management, which should take into account not only the technical aspects of the disease but also familial and social considerations.

Radiotherapy of central nervous system tumors in young children: benefits and pitfalls.

The prognosis for young children suffering from brain tumors is, as many authors report, generally poor. The probability of late complications in young children is also high, and their quality of life is significantly worse than that of older children. This study presents the experience of one center in management of central nervous system tumors in children in aged 1-3 years with radiation therapy. From 1981 to 1990, 52 children (aged 1-3 years) with CNS tumors were treated at the First Radiotherapy Department in the Center of Oncology in Warsaw, Poland. These patients represented 18% of the total number of 293 children with brain and spine tumors treated in this period. The radiation treatment policy for young children was similar to that applied to older children, but total doses and doses per fraction were lower and did not exceed 50 Gy to the tumor site and 30 Gy to the CNS axis. Overall 5-year survival was 52%, and disease-free survival was 50%. These results were similar to those obtained in older children (53% and 50%, respectively). Serious mental retardation (IQ < 70) was observed in 30% of young children in comparison to 7% of older patients, but in 62% these symptoms were noted even before the start of radiotherapy. The results obtained in this series did not confirm the hypothesis of more aggressive biology of CNS tumors in younger children. The proportion of children with serious psychological disturbances in this group is apparently high, although in most cases these symptoms were observed before the start of radiotherapy and were a result of tumor mass effects.

Disomy 1 with terminal 1p deletion is frequent in mass-screening-negative/late-presenting neuroblastomas in young children, but not in mass-screening-positive neuroblastomas in infants.

The mass screening (MS) of neuroblastoma has been undertaken in Japan by measuring urinary catecholamine metabolites in infants at the age of 6 months. To clarify the biological characteristics of MS-positive (MS+) tumors in infants and MS-negative (MS-)/late-presenting tumors in young children, metaphase cytogenetic and/or interphase 2-color FISH analyses using terminal 1p and pericentromeric 1q probes were performed on 246 (186 MS+ and 60 MS-) patients with neuroblastomas. The 246 tumors were classified into 4 groups on the basis of the constitution of chromosome 1; 22 tumors had disomy 1 with no 1p deletion (Dis1Norm1p); 41 tumors had disomy 1 or tetrasomy 1, all with the 1p deletion (Dis1Del1p); 164 tumors had trisomy 1, pentasomy 1, or a mixed population of cells with trisomy 1 and cells with tetrasomy 1, none with 1p deletion (Tris1Norm1p); 19 tumors with the same copy numbers of chromosome 1 as the Tris1Norm1p group, had 1p deletion (Tris1Del1p). mycn amplification was absent in the Dis1Norm1p and Tris1Del1p groups, frequent in the Dis1Del1p group (24/41), and rare in the Tris1Norm1p group (3/164) (p < 0.0001). Event-free survival at 5 years was lowest [19.5%; 95% confidence interval (CI), 5.1-33.9] in the Dis1Del1p group, highest in the Tris1Norm1p (96.3%; 95% CI, 93.5-99.2) and Tris1Del1p (94.7%; 95% CI, 84.7-104.8) groups, and intermediate but varied (54.5%; 95% CI, 33.7-75.4) in the Dis1Norm1p group (p < 0.0001). Of the MS+ tumors, 90% were Tris1Norm1p or Tris1Del1p, and 55% of the MS- tumors were Dis1Del1p. The finding that the Dis1Del1p tumors were frequent in MS- but not in MS+ tumors suggests the limited efficacy of the MS program into reducing mortality from neuroblastoma.

Differential Expression of p53, c-kit, and CD34 in Prepubertal and Postpubertal Testicular Germ Cell Tumors

BACKGROUND The origin of testicular germ cell tumors (TGCTs) in children is poorly understood. There are clear differences between tumors in young children and those in adolescents and adults, which may suggest that they follow different pathways of tumorigenesis. METHODS Tissue sections from 25 TGCTs (15 from patients age 4 years or younger and 10 from adolescents or adults) were stained immunohistochemically with anti-p53 (DO-1), CD34, and c-kit proto-oncogene protein product. RESULTS CD34 expression was noted only in 5 prepubertal tumors. Expression of c-kit was observed in 9 of the 15 prepubertal tumors versus 2 of the 10 postpubertal cases. The intensity of expression was equal to that of the adjacent normal tubules in the prepubertal tumors, whereas the intensity was less in the postpubertal tumors. Expression of p53 was strong in 8 of the 10 tumors in adolescents or adults, with a 40-70% positivity, whereas only 6 of 15 prepubertal tumors expressed p53, with <10% positivity. CONCLUSIONS CD34 expression in tumors in the group of young children suggests a possible link to teratomas and further provides insight into the fundamental differences between this group and the adolescent/adult group. The expression of c-kit and p53 provides further evidence that c-kit/SCF signaling and p53 play potentially different roles in the initiation and progression of these tumors. Future studies will be required to clarify this issue. Cancer 1997; 79:2430-4. © 1997 American Cancer Society.

Differential expression of p53, c-kit, and CD34 in prepubertal and postpubertal testicular germ cell tumors.

The origin of testicular germ cell tumors (TGCTs) in children is poorly understood. There are clear differences between tumors in young children and those in adolescents and adults, which may suggest that they follow different pathways of tumorigenesis. Tissue sections from 25 TGCTs (15 from patients age 4 years or younger and 10 from adolescents or adults) were stained immunohistochemically with anti-p53 (DO-1), CD34, and c-kit proto-oncogene protein product. CD34 expression was noted only in 5 prepubertal tumors. Expression of c-kit was observed in 9 of the 15 prepubertal tumors versus 2 of the 10 postpubertal cases. The intensity of expression was equal to that of the adjacent normal tubules in the prepubertal tumors, whereas the intensity was less in the postpubertal tumors. Expression of p53 was strong in 8 of the 10 tumors in adolescents or adults, with a 40-70% positivity, whereas only 6 of 15 prepubertal tumors expressed p53, with < 10% positivity. CD34 expression in tumors in the group of young children suggests a possible link to teratomas and further provides insight into the fundamental differences between this group and the adolescent/adult group. The expression of c-kit and p53 provides further evidence that c-kit/SCF signaling and p53 play potentially different roles in the initiation and progression of these tumors. Future studies will be required to clarify this issue.

MR imaging of parosteal osteosarcoma in two skeletally immature patients

Parosteal osteogenic sarcoma is an unusual tumor in young children. It usually has a tendency to affect people with mature skeletons. The biological behavior of this tumor in children appears to be identical to that in adults, resulting in excellent prognosis after curative operative procedures, even if there is minimal extension to the bone marrow. Magnetic resonance imaging has a significant role in staging the tumor, as other imaging modalities are inferior in demonstrating early bone marrow involvement.

What is the etiology of human brain tumors?. A report on the first lebow conference

Although the conference could not provide a definitive etiologic explanation for the observed increase in incidence of human brain tumors, particularly among the elderly, nevertheless, this interdisciplinary gathering of prominent scientists and clinicians proved invaluable in identifying new avenues of research. Clearly, the puzzle of what causes brain tumors is highly complex, involving links to ionizing/electromagnetic radiation, familial, and dietary factors. The Lebow Conference provided an important scientific framework upon which to build further research studies, and its influence will be felt for years to come.

Limb salvage for malignant bone tumors in young children.

From March 1984 to April 1991, the Orthopaedics Department of the Clínica Universitaria de Navarra treated 47 cases of malignant bone tumors in young children by limb-salvage surgery. Mean follow-up time was 4.4 years. The histologic diagnoses were osteosarcoma (33 cases) and Ewing's sarcoma (14 cases). All patients were treated following the Cancer Protocol of the Clínica Universitaria de Navarra. We used allograft reconstruction in 26 patients, autograft reconstruction in seven, and nonbiologic material in seven other patients. Thirty-six of these patients are alive currently; 11 have died. The overall survival rate was 76.6%. Three patients suffered local recurrences, and seven developed metastatic disease. The most significant complications were infection in four cases, and osteosynthesis anchorage detachment in eight cases. We believe that with recent medical, surgical, and rehabilitative advances, limb-salvage surgery has surpassed amputation as the primary treatment for malignant bone tumors in young children.

Relation between maternal diet and subsequent primitive neuroectodermal brain tumors in young children.

It has been hypothesized that a high dietary intake of nitrosamines and their precursors, nitrites and nitrates, is a risk factor for brain tumors. Vitamins C and E inhibit the formation of nitrosamines and thus may be protective. We conducted a case-control study of maternal diet and the risk of primitive neuroectodermal tumors of the brain in children. The case patients were under the age of six years at diagnosis in 1986 to 1989. The controls were selected by random-digit telephone dialing and were matched for age and race to 166 case patients. Telephone interviews with the mothers included questions on the frequency of consumption of alcohol, vitamin and mineral supplements, and 53 foods during pregnancy. Significant protective trends were observed for vegetables (odds ratio for the highest quartile group for intake relative to the lowest, 0.37; P for trend = 0.005), fruits and fruit juices (odds ratio, 0.28; P = 0.003), vitamin A (odds ratio, 0.59; P = 0.03), vitamin C (odds ratio, 0.42; P = 0.009), nitrate (odds ratio, 0.44; P = 0.002), and folate (odds ratio, 0.38; P = 0.005). A nonsignificant trend of increasing risk was observed for nitrosamine (odds ratio, 1.65; P = 0.15). The use of iron (odds ratio, 0.43; P = 0.004), calcium (odds ratio, 0.42; P = 0.05), and vitamin C (odds ratio, 0.35; P = 0.04) supplements at any time during the pregnancy and the use of multivitamins during the first six weeks (odds ratio, 0.56; P = 0.02) were associated with decreased risk. In multivariate analyses, folate, early multivitamin use, and iron supplements generally remained protective. These results do not support the hypothesis that nitrosamines have a role in the development of primitive neuroectodermal tumors in young children, but they do suggest that certain other aspects of maternal diet can influence the risk.