Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease.

Purpose: Pediatric Oncology Group (POG) studies 9426 and 9425 evaluated dexrazoxane (DRZ) as a cardiopulmonary protectant during treatment for Hodgkin's disease (HD). We evaluated incidence and risk factors of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and second malignant neoplasms (SMNs).

Patients And Methods: Treatment for low- and high-risk HD with doxorubicin, bleomycin, vincristine, and etoposide (ABVE) or dose-intensified ABVE with prednisone and cyclophosphamide (ABVE-PC), respectively, was followed by low-dose radiation.

Does MYCN amplification manifested as homogeneously staining regions at diagnosis predict a worse outcome in children with neuroblastoma? A Children's Oncology Group study.

Purpose: MYCN amplification in neuroblastoma tumor cells is manifested primarily as double minutes (dmins), whereas in cell lines it often appears in the form of homogeneously staining regions (HSR), suggesting that HSRs are associated with a more aggressive tumor phenotype and worse clinical outcome. The aim of this study was to determine whether children with neuroblastoma in which MYCN oncogene amplification is manifested as HSRs at diagnosis have a worse prognosis than those whose tumors exhibit dmins.

Experimental Design: A retrospective analysis of primary neuroblastomas analyzed for MYCN amplification by the Children's Oncology Group between 1993 and 2004 was done.

Acculturation and breast density in foreign-born, U.S. Chinese women.

The role of acculturation in the breast cancer risk increase among U.S. Chinese women is unclear.

Survivin mRNA levels are associated with biology of disease and patient survival in neuroblastoma: a report from the children's oncology group.

Alterations in apoptotic mechanisms favoring cell survival may be vital for modifying tumor behavior. Survivin, an inhibitor of apoptosis, and caspase 8, a proapoptotic enzyme, are key players in cellular apoptotic mechanisms. We investigated whether the levels of survivin and caspase 8 and the ratio between these 2 apoptotic factors correlate with tumor biology and predicts outcome in patients with neuroblastoma.

Past HBV viral load as predictor of mortality and morbidity from HCC and chronic liver disease in a prospective study.

Background And Aims: In a prospective cohort study with 11 yr of follow-up, we assessed the relationship between past hepatitis B virus (HBV) viral load and mortality. Surviving cohort members were evaluated for current liver disease.

Methods: We measured HBV viral load by real-time polymerase chain reaction on stored samples from cohort entry (1992-1993) in 2,763 hepatitis B surface antigen (HBsAg)-positive adults.

POG 8625: a randomized trial comparing chemotherapy with chemoradiotherapy for children and adolescents with Stages I, IIA, IIIA1 Hodgkin Disease: a report from the Children's Oncology Group.

To determine if 6 courses of chemotherapy alone could achieve the same or better outcome than 4 courses of chemotherapy followed by radiation therapy (chemoradiotherapy) in pediatric and adolescent patients with Hodgkin disease. Children < or =21 years old with biopsy-proven, pathologically staged I, IIA, or IIIA1 Hodgkin disease were randomly assigned 6 courses of alternating nitrogen mustard, oncovin, prednisone, and procarbazine/doxorubicin, bleomycin, vinblastine, and dacarbazine (treatment 1) or 4 courses of alternating nitrogen mustard, oncovin, prednisone, and procarbazine/doxorubicin, bleomycin, vinblastine, and dacarbazine +2550 cGy involved-field radiotherapy (treatment 2). The complete response rate was 89%, with a complete response and partial response rate of 99.

Intensified platinum therapy is an ineffective strategy for improving outcome in pediatric patients with advanced hepatoblastoma.

Purpose: The INT-0098 Intergroup Liver Tumor Study demonstrated no statistically significant differences in event-free and overall survival between patients randomized to treatment with either cisplatin + fluorouracil + vincristine (C5V) or cisplatin + doxorubicin. Results from this and other therapeutic trials suggested that cisplatin was the most active agent against hepatoblastoma. To increase the platinum dose-intensity, a novel regimen was developed alternating carboplatin and cisplatin (CC) every 2 weeks.

Integrative genomics identifies distinct molecular classes of neuroblastoma and shows that multiple genes are targeted by regional alterations in DNA copy number.

Neuroblastoma is remarkable for its clinical heterogeneity and is characterized by genomic alterations that are strongly correlated with tumor behavior. The specific genes that influence neuroblastoma biology and are targeted by genomic alterations remain largely unknown. We quantified mRNA expression in a highly annotated series of 101 prospectively collected diagnostic neuroblastoma primary tumors using an oligonucleotide-based microarray.

Prognostic factors in children with extragonadal malignant germ cell tumors: a pediatric intergroup study.

Purpose: To investigate prognostic factors for pediatric extragonadal malignant germ cell tumors (PEMGCT).

Materials And Methods: Between 1990 and 1996, patients with stage I through IV PEMGCT were eligible for a trial of cisplatin dose intensity. We retrospectively investigated prognostic factors for PEMGCT, including age, stage, primary site, treatment, and elevated alfa fetoprotein by univariate and multivariate analysis.

International neuroblastoma pathology classification adds independent prognostic information beyond the prognostic contribution of age.

Age has been used as a prognostic factor for patients with peripheral neuroblastic tumours (pNTs). The latest analysis disclosed a cut-off around 18 months for the optimal prognostic distinction. The International Neuroblastoma Pathology Classification (INPC) distinguishes favourable and unfavourable histology based on the age-appropriate evaluation of histologic indicators (grade of neuroblastic differentiation, mitosis-karyorrhexis index) in the categories of neuroblastoma and ganglioneuroblastoma, nodular.

Association of high-level MRP1 expression with poor clinical outcome in a large prospective study of primary neuroblastoma.

Purpose: We have previously shown in a retrospective study that expression of the multidrug transporter gene MRP1 (ABCC1) is associated with outcome in neuroblastoma. We have now undertaken a prospective analysis to examine the independent prognostic significance of MRP1 expression in a large cohort of primary untreated neuroblastomas.

Patients And Methods: Two hundred nine diagnostic neuroblastoma samples from patients prospectively enrolled onto the Pediatric Oncology Group biology protocol 9047 were analyzed for expression of the MRP1, MDR1, MYCN, and TRKA genes using real-time polymerase chain reaction.

Outcomes of children with intermediate-risk neuroblastoma after treatment stratified by MYCN status and tumor cell ploidy.

Purpose: The goal of Pediatric Oncology Group 9243 was to improve outcomes for children with intermediate-risk neuroblastoma (NB).

Patients And Methods: Patients were assigned to treatments on the basis of age, tumor MYCN status, and tumor cell ploidy. Children in the less intensive arm A received cyclophosphamide/doxorubicin and surgery.

Chromosome 1p and 11q deletions and outcome in neuroblastoma.

Background: Neuroblastoma is a childhood cancer with considerable morbidity and mortality. Tumor-derived biomarkers may improve risk stratification.

Methods: We screened 915 samples of neuroblastoma for loss of heterozygosity (LOH) at chromosome bands 1p36 and 11q23.

APE chemotherapy for children with relapsed Hodgkin disease: a Pediatric Oncology Group trial.

Background: MOPP (mechlorethamine, vincristine, procarbazine, prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) are effective therapies for Hodgkin disease (HD) that may cause long-term toxicities in children. APE (cytosine arabinoside, cisplatin, etoposide) is a non-cross-resistant regimen with limited toxicities. We evaluated this regimen for patients with recurrent or refractory disease.

Treatment of stage I, IIA, IIIA1 pediatric Hodgkin disease with doxorubicin, bleomycin, vincristine and etoposide (DBVE) and radiation: a Pediatric Oncology Group (POG) study.

Purpose: The objectives of this study were to evaluate the feasibility of reducing therapy, while maintaining treatment efficacy, in the context of a cooperative group clinical trial that allowed for clinical staging in early stage Hodgkin disease (HD).

Patients And Methods: Between August 1992 and December 1993, 51 eligible children < or =21 years of age, 31 male and 20 female, were enrolled in this study which was designed for low stage (IA, IIA, IIIA1) HD. Laparotomy and surgical staging was optional.

One- and two-stage designs for stratified phase II clinical trials.

A global one-sample test for response rates for stratified phase II clinical trials is proposed. Such a test is analogous to that of a stratified log-rank test for time-to-event data. Both one- and two-stage tests are developed, and conditional and unconditional approaches are introduced in each case, where the conditional approach involves conditioning on the observed samples sizes within the strata.

Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group.

Purpose: In the Children's Oncology Group, risk group assignment for neuroblastoma is critical for therapeutic decisions, and patients are stratified by International Neuroblastoma Staging System stage, MYCN status, ploidy, Shimada histopathology, and diagnosis age. Age less than 365 days has been associated with favorable outcome, but recent studies suggest that older age cutoff may improve prognostic precision.

Methods: To identify the optimal age cutoff, we retrospectively analyzed data from the Pediatric Oncology Group biology study 9047 and Children's Cancer Group studies 321p1-p4, 3881, 3891, and B973 on 3,666 patients (1986 to 2001) with documented ages and follow-up data.

Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: a Pediatric Oncology Group study.

Purpose: To determine predictive strength of tumor cell ploidy and MYCN gene amplification on survival of children older than 12 months with disseminated neuroblastoma (NB).

Patients And Methods: Of 648 children with stage D NB enrolled onto the Pediatric Oncology Group NB Biology Study 9047 (1990-2000), 560 children were assessable for ploidy and MYCN amplification. Treatment of patients older than 12 months varied; most receiving high-dose chemotherapy with stem-cell rescue.

The role of age in neuroblastoma risk stratification: the German, Italian, and children's oncology group perspectives.

Recent evidence suggests that the cut-off for age utilized in neuroblastoma risk groups should be increased from the 365-day cut-off currently in use. Separate cooperative group analyses were performed by German and Italian groups and two analyses by the Children's Oncology Group (North America, Australia, New Zealand, Switzerland, Netherlands). In general, the results are in agreement regarding the prognostic contribution of age.

Amifostine does not protect against the ototoxicity of high-dose cisplatin combined with etoposide and bleomycin in pediatric germ-cell tumors: a Children's Oncology Group study.

Background: High-dose cisplatin combined with etoposide and bleomycin (HDPEB) improves event-free survival (EFS) in advanced pediatric germ-cell tumors (PGCT), but has significant ototoxicity. Amifostine appears to protect against toxicity. The authors combined amifostine with HDPEB and evaluated the efficacy and toxicity, specifically whether ototoxicity decreased.

Epidural compression in neuroblastoma: Diagnostic and therapeutic aspects.

The involvement by tumour of intervertebral foramina and the consequent invasion of the spinal space, accompanied or not by neurological symptoms, represent a well-recognised pattern of presentation of neuroblastoma. The main peculiarity of this condition stands in the fact that, in case of its late detection or inadequate treatment, severe, permanent neurological compromise may ensue. Surprisingly enough, remarkable disagreements still exist regarding its optimal treatment and the related literature provide contrasting indications at this respect.

Expression of multidrug transporter MRP4/ABCC4 is a marker of poor prognosis in neuroblastoma and confers resistance to irinotecan in vitro.

Members of the multidrug resistance-associated protein (MRP) family of transporters are believed to contribute to cytotoxic drug resistance and chemotherapy failure. We observed frequent MRP4 overexpression in aggressive primary neuroblastoma, a disease for which we have previously shown MRP1 to be a prognostic indicator. High MRP4 expression correlated with MYCN oncogene amplification and was significantly associated with poor clinical outcome.

Epidemiology and natural history of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major contributor to cancer incidence and mortality. There is a wide variation, however, in the global distribution of HCC. Eighty percent of the burden is borne by countries in Asia and sub-Saharan Africa.

Toenail selenium and risk of hepatocellular carcinoma mortality in Haimen City, China.

Selenium (Se) is an essential trace mineral with known anticarcinogenic properties in humans. However, few studies have examined the association between Se nutrient status and risk of liver cancer. We conducted a nested case-control study comparing the Se content in toenail clippings of 166 individuals (154 men, 12 women) with hepatocellular carcinoma (HCC) to 394 healthy controls (360 men, 34 women) in Haimen City, China, where HCC is a leading cause of mortality.

Chronic hepatitis B virus infection and mortality from non-liver causes: results from the Haimen City cohort study.

Background: Studies of chronic hepatitis B virus (HBV) infection in endemic populations have rarely documented causes of mortality other than liver disease and hepatocellular carcinoma (HCC).

Methods: We analysed all-cause mortality related to HBV infection, focusing on the deaths not related to liver disease in a prospective cohort of adults living in Haimen City, China, who were followed from 1992 to 2002. Death certificate data from 4590 deaths among 83 794 individuals were analysed.