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Biomedical subjects

G Bunin

Publications and source records attributed to G Bunin.

11 recordsLinked to original sources

What causes childhood brain tumors? Limited knowledge, many clues.

Little is known about the causes of brain tumors in children. Children with one of several genetic disorders including tuberous sclerosis and Li-Fraumeni syndrome are at increased risk, as are children who have received therapeutic irradiation to their head. The multifactorial causation of brain tumors, the inaccuracies of recall of past exposures, and the study of all pediatric brain tumors as a single etiologic entity may be contributing to the difficulty in identifying additional risk factors. The evidence that frequent cured meat consumption by the mother during pregnancy increases the risk is suggestive but not conclusive. For other potential risk factors, the evidence is limited and/or conflicting. These exposures and characteristics include pesticides, carcinogen metabolizing genes, and polyomaviruses.

Age of Onset↗

Screening for neuroblastoma is ineffective in reducing the incidence of unfavourable advanced stage disease in older children.

Neuroblastoma exhibits many characteristics which would suggest that preclinical detection may improve outcome. The Quebec Neuroblastoma Screening Project was initiated to determine whether mass screening could reduce mortality in a large cohort of infants. All 476,603 children born in the province of Quebec during a 5-year period of time (1 May 1989 to 30 April 1994) were eligible for determinations of urinary catecholamine metabolites at 3 weeks and 6 months of age. Children with positive screening were referred to one of four paediatric cancer centres in Quebec for uniform evaluation and treatment. Standardised incidence ratios (SIRs) were calculated for neuroblastoma in Quebec and two comparable population-based controls during the same period of time using similar ascertainment procedures. Compliance with screening in Quebec was 91% at 3 weeks (n = 425,816) and 74% at 6 months (n = 349,706). Up to 31 July 1995 with a follow-up of the birth cohort of 15-75 months, 118 cases of neuroblastoma were diagnosed, 43 detected preclinically by screening, 20 detected clinically prior to screening at 3 weeks of age and 55 detected clinically after 3 weeks of age having normal screens (n = 52) or never screened (n = 3). Based on data from concurrent control populations, 54.5 cases of neuroblastoma would have been expected in Quebec during the study period for an SIR of 2.17 (95% CI 1.79-2.57, P < 0.0001). For the two control groups, the overall SIR was 1.00 (NS). SIRs for Quebec by age at diagnosis in yearly intervals show a marked increased incidence under 1 year of age (SIR = 2.85, 95% CI 2.26-3.50), with no reduction in incidence in subsequent years. We conclude that screening for neuroblastoma markedly increases the incidence in infants without decreasing the incidence of unfavourable advanced stage disease in older children. It is unlikely that screening for neuroblastoma in infants will reduce the mortality of this disease.

Canada↗

Breast cancer and other second neoplasms after childhood Hodgkin's disease.

BACKGROUND: Patients who survive Hodgkin's disease are at increased risk for second neoplasms. As survival times increase, solid tumors are emerging as a serious long-term complication. METHODS: The Late Effects Study Group followed a cohort of 1380 children with Hodgkin's disease to determine the incidence of second neoplasms and the risk factors associated with them. RESULTS: In this cohort, there were 88 second neoplasms as compared with 4.4 expected in the general population (standardized incidence ratio, 18.1; 95 percent confidence interval, 14.3 to 22.3). The estimated actuarial incidence of any second neoplasm 15 years after the diagnosis of Hodgkin's disease was 7.0 percent (95 percent confidence interval, 5.2 to 8.8 percent); the incidence of solid tumors was 3.9 percent (95 percent confidence interval, 2.3 to 5.5 percent). Breast cancer was the most common solid tumor (standardized incidence ratio 75.3; 95 percent confidence interval, 44.9 to 118.4), with an estimated actuarial incidence in women that approached 35 percent (95 percent confidence interval, 17.4 to 52.6 percent) by 40 years of age. Older age (10 to 16 vs. <10 years) at the time of radiation treatment (relative risk, 1.9) and a higher dose (2000 to 4000 vs. <2000 cGy) of radiation (relative risk, 5.9) were associated with significantly increased risk of breast cancer. The estimated actuarial incidence of leukemia reached a plateau of 2.8 percent (95 percent confidence interval, 0.8 to 4.8 percent) 14 years after diagnosis. Treatment with alkylating agents, older age at the diagnosis of Hodgkin's disease, recurrence of Hodgkin's disease, and a late stage of disease at diagnosis were risk factors for leukemia. CONCLUSIONS: The risk of solid tumors, especially breast cancer, is high among women who were treated with radiation for childhood Hodgkin's disease. Systematic screening for breast cancer could be important in the health care of such women.

Actuarial Analysis↗

Recombinant human erythropoietin reduces the need for erythrocyte and platelet transfusions in pediatric patients with sarcoma: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the effect of recombinant human erythropoietin (EPO) and iron supplementation on transfusion requirements in pediatric patients with sarcoma who were receiving chemotherapy, we performed a double-blind, placebo-controlled, randomized trial. METHODS: Twenty-four pediatric patients with malignant solid tumors were randomly assigned to receive either placebo (saline solution) or EPO for a 16-week study period. The starting dose was 150 IU/kg per dose three times a week and was escalated by 50 IU/kg per dose increments monthly until packed red blood cell (PRBC) transfusion independence was achieved or a dosage of 300 IU/kg per dose was reached. Iron supplementation was prescribed at a dose of 6 mg of elemental iron per kilogram daily. The primary study end point was the comparison of PRBC transfusion requirements in the two groups. RESULTS: Of 24 patients, 20 were evaluable for response. The median PRBC transfusion requirement during the 16-week period was 23 ml/kg in EPO-treated patients versus 80 ml/kg in placebo patients (p = 0.02). The median number of single-donor platelet units transfused was zero in the EPO-treated patients compared with four in the placebo group (p = 0.005). No statistical difference in the intensity of bone marrow suppression was seen, as measured by the median number of complete blood cell counts with an absolute neutrophil count of < 1000 cells/microliter. CONCLUSIONS: Treatment with EPO and iron significantly reduces PRBC transfusions in pediatric patients receiving concomitant chemotherapy for malignant sarcomas. A decrease in the number of platelet transfusions was also seen and deserves further study.

Adolescent↗

Assessment of environmental and genetic factors in the etiology of childhood cancers: the Childrens Cancer Group epidemiology program.

The occurrence of cancer during childhood represents one of the leading causes of death within the pediatric and adolescent age group. It is estimated that approximately 8000 children will be diagnosed annually with cancer in the United States. Epidemiologic research addressing the etiology of childhood cancer has been limited because of the difficulties in identifying a sufficiently large study population. Moreover, the use of retrospectively ascertained childhood cancer cases in epidemiologic investigations has restricted the incorporation of biological and clinical parameters. The Childrens Cancer Group has developed an active program in epidemiologic research, with over a decade of experience demonstrating the feasibility and strengths of conducting analytic epidemiologic studies within a cooperative clinical trials network. The availability of detailed clinical and biologic data on cases diagnosed within the cooperative group facilitates the transfer of state-of-the-art technology to epidemiologic research.

Acute Disease↗

A population-based study of neuroblastoma incidence, survival, and mortality in North America.

PURPOSE: The purpose of this study was twofold: (1) to provide a population-based estimate of neuroblastoma incidence, disease stage and age distribution, and survival and mortality rates in North America; and (2) to compare these figures in the province of Quebec at a time shortly before the institution of province-wide screening with those in a population-based control group, the Greater Delaware Valley (GDV) Pediatric Tumor Registry. MATERIALS AND METHODS: In Quebec, the four major pediatric teaching hospital records were searched for children with a diagnosis of neuroblastoma. Tumor board registry data and information supplied to the Division of Vital Statistics were also reviewed. Birth statistics were obtained from the population registry. The GDV Pediatric Tumor Registry is a population-based registry of pediatric cancer covering all of Delaware and parts of New Jersey, Pennsylvania, and Maryland. Age, stage of disease, and follow-up data were obtained through December 31, 1989, with Evans neuroblastoma staging data used for all comparisons. RESULTS: One hundred thirty children with neuroblastoma were identified in Quebec and 165 in the GDV, in a combined population of 3,178,736 children. The annual incidence of neuroblastoma was 10.95/10(6) under the age of 15 years and 27.75/10(6) between the ages of 0 and 4 years. The annual mortality rate due to neuroblastoma was 4.89/10(6) and 9.10/10(6) for the age groups 0 to 14 and 0 to 4, respectively. The overall 10-year survival rate for the 295 cases of neuroblastoma was 55%. The 10-year survival rates for patients with Evans stage I-IV and IVS disease were 88%, 90%, 63%, 21%, and 81%. There was no significant difference observed in the incidence, mortality, or survival in the two populations. CONCLUSION: These data represent the first large, population-based description of the clinical presentation and outcome of patients with neuroblastoma in North America, with no significant differences noted between Quebec patients and the GDV patients.

Adolescent↗

Regression methods for estimating attributable risk in population-based case-control studies: a comparison of additive and multiplicative models.

A regression method that utilizes an additive model is proposed for the estimation of attributable risk in case-control studies carried out in defined populations. In contrast to previous multivariate procedures for the estimation of attributable risk, which have utilized logistic regression techniques to adjust for confounding factors, the model assumes an additive relation between the covariates included in the regression equation. As an empirical example, additive and logistic models were fitted to matched case-control data from a population-based study of childhood astrocytoma brain tumors. Although both models fitted the data well, the additive model provided a more satisfactory estimate of the risk attributable to multiple exposures, in the absence of significant additive interaction. In contrast to the results from the logistic model, the adjusted estimates of the risk attributable to each factor included in the additive model summed to the overall estimate for all of the factors considered jointly. Thus, the additive approach provides a useful alternative to existing procedures for the multivariate estimation of attributable risk when the additive model is determined to be appropriate on the basis of goodness-of-fit.

Astrocytoma↗

Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma.

Between 1975 and 1989, 108 children with newly diagnosed medulloblastoma/primitive neuroectodermal tumor (MB/PNET) of the posterior fossa were treated at the authors' institution. The patients were managed uniformly, and treatment included aggressive surgical resections, postoperative staging evaluations for extent of disease, and craniospinal radiation therapy with a local boost. Beginning in 1983, children with MB/PNET were prospectively assigned to risk groups; those with "standard-risk" MB/PNET were treated with radiation therapy alone, while those in the "poor-risk" group received similar radiation therapy plus adjuvant chemotherapy with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), vincristine, and cisplatin. The 5-year actuarial disease-free survival rate for all patients treated between 1975 and 1982 was 68%, and 73% when patients who died within 2 weeks after operation were excluded. This survival rate was statistically better for patients treated after 1982 (82%) compared to those treated between 1975 and 1982 (49%) (p less than 0.004). There was no difference in disease-free survival rates over time for children with standard-risk factors; however, there was a significant difference in the 5-year survival rate for poor-risk patients treated prior to 1982 (35%) compared to those treated later (87%) (p less than 0.001). For the group as a whole, a younger age at diagnosis correlated with a poorer survival rate; however, this relationship between age and outcome was significant only for children treated before 1983 (p less than 0.001). These results demonstrated an encouraging survival rate for children with MB/PNET, especially those treated with aggressive surgical resection followed by both radiation therapy and chemotherapy. The results strongly suggest that chemotherapy has a role for some, and possibly all, children with MB/PNET.

Adolescent↗

Racial patterns of childhood brain cancer by histologic type.

Racial patterns of childhood brain cancer by histologic type were studied using data from the Third National Cancer Survey and the Surveillance, Epidemiology, and End Results Program. Incidence rates for whites of all types combined and of astrocytic glioma and medulloblastoma were slightly higher than those for blacks. Proportionately more black than white cases of astrocytic glioma were diagnosed between the ages of 5-9 years; this difference corresponded to twofold-higher rates at ages of 0-4 and 10-14 years and similar rates at ages of 5-9 years among whites compared to rates among nonwhites. A real difference in age-incidence curves rather than diagnostic delay among blacks appeared to explain the differences. For medulloblastoma, the male-female rate ratio differed between whites (1.7) and blacks (1.0). Time trend analyses revealed statistically significant increases in medulloblastoma and glioma not otherwise specified (NOS) for incidences among blacks. The rate of microscopic confirmation was significantly higher among whites than among blacks, a difference apparently not explained by differences in the accessibility of tumors for biopsy. For avoidance of biased comparisons, differences in rates of microscopic confirmation and time trends for glioma NOS should be considered in studies of racial patterns of childhood brain cancer incidence by histologic type.

Age Factors↗

A population-based study of the usefulness of screening for neuroblastoma.

BACKGROUND: Neuroblastoma has many characteristics which suggest that preclinical detection might improve outcome. The Quebec Neuroblastoma Screening Project was initiated to determine whether mass screening could reduce mortality in a large cohort of infants. As an early endpoint, we report whether screening could reduce the incidence of poor-prognosis neuroblastoma in children with advanced-stage disease over 1 year of age. METHODS: All 476,603 children born in the province of Quebec during the 5-year period of May 1, 1989, to April 30, 1994, were eligible for urinary assay of homovanillic acid and vanillylmandelic acid at 3 weeks and 6 months of age. Children with a positive screen were referred to one of four paediatric cancer centres in the province for uniform evaluation and treatment if necessary. Standardised incidence ratios (SIRs) were calculated for neuroblastoma in the province and two similar population-based controls, the state of Minnesota and the province of Ontario, during the same period of time and with similar ascertainment procedures. FINDINGS: Compliance with screening in Quebec province was 91% at 3 weeks (n = 425,816) and 74% at 6 months (n = 349,706). Through July 31, 1995, with a follow-up of the birth cohort of 15-75 months, 118 cases of neuroblastoma were diagnosed, 43 detected preclinically by screening, 20 detected clinically before screening at 3 weeks of age, and 55 detected clinically after 3 weeks of age having normal screens (52) or never screened (3). Retrospective analysis of stored samples confirmed that 49 of 52 patients missed by screening had levels of catecholamine metabolites that were too low to be detected at 6 months or earlier. Based on US Surveillance, Epidemiology and End Results data, 54.5 cases of neuroblastoma would have been expected in Quebec province during the study period, for an SIR of 2.17 (95% CI 1.79-2.57, p < 0.0001). For the two control groups, 43 and 80 cases of neuroblastoma were detected, respectively, compared with 37.9 and 85.4 expected, overall SIR 1.00 (not significant). SIRs for Quebec province by age at diagnosis in yearly intervals show a marked increased incidence under 1 year of age (SIR 2.85, 2.26-3.50), with no reduction in incidence in subsequent years. Limiting analysis to only patients diagnosed over 1 year of age with advanced-stage disease, 22 cases were detected in Quebec province versus 14.4 expected (SIR 1.52, 0.95-2.23). Data in the two control groups show no significant increase or decrease in any-stage disease in children under or over the age of 1 year, except for an increase in early-stage disease in Minnesota children over 1 year: 10 versus 3.8 expected (SIR 2.67, 1.27-4.58). INTERPRETATION: Screening for neuroblastoma increases the incidence in infants without decreasing the incidence of unfavourable advanced-stage disease in older children. It is unlikely that screening for neuroblastoma in infants will reduce mortality for this disease.

Chromatography, Thin Layer↗