Risk of second malignancies in long-term survivors of childhood cancer.

Introduction: Childhood cancer survivors are known to be at increased risk for second malignancies.

Patients And Methods: The risk of second malignancies was assessed in 1368 5-year survivors of childhood cancer treated in the Emma Children's Hospital AMC in Amsterdam. The median follow-up time was 16.

AMORE protocol in pediatric head and neck rhabdomyosarcoma: descriptive analysis of failure patterns.

Background: The AMORE protocol is a local treatment for patients with nonorbital pediatric head and neck rhabdomyosarcoma (HNRMS). The objectives of this study were: (1) to assess the adequacy of the concept, and (2) to identify factors associated with relapse.

Methods: We performed a retrospective multidisciplinary review of 22 children primarily treated according to the AMORE protocol, excluding two children with inadequate imaging data.

Quality of life, self-esteem and worries in young adult survivors of childhood cancer.

This study assessed quality of life, self-esteem and worries in young adult survivors of childhood cancer compared to a group of young adults with no history of cancer. The impact of demographic, medical and treatment factors and self-esteem on survivors' quality of life and worries was studied. Participants were 400 long-term survivors (LTS) of childhood cancer (age range 16-49 years, 45% female) who had completed treatment an average of 16 years previously and 560 persons (age range 16-53 years, 55% female) with no history of cancer.

The AMORE protocol as salvage treatment for non-orbital head and neck rhabdomyosarcoma in children.

Aim: To investigate the feasibility and outcome of the AMORE protocol as salvage treatment in paediatric head and neck rhabdomyosarcoma (HNRMS).

Methods: The AMORE protocol is a local treatment regimen, consisting of Ablative surgery, Moulage technique brachytherapy and surgical Reconstruction, scheduled in 1 week. Patients with recurrent or residual non-orbital HNRMS were eligible for AMORE salvage treatment.

Posttraumatic stress symptoms in adult survivors of childhood cancer.

Background: Previous research suggests that posttraumatic stress disorder (PTSD) is present in survivors of childhood cancer. The aim of the current study was to explore posttraumatic stress symptoms in a sample of young adult survivors of childhood cancer. In addition, the impact of demographic, medical and treatment factors on survivors' posttraumatic stress symptoms was studied.

Long-term cause-specific mortality among five-year survivors of childhood cancer.

Background: The purpose of our study was to assess long-term cause-specific mortality of 5-year childhood cancer survivors.

Procedure: The study population consisted of 1,378 patients who had been treated for childhood cancer in The Netherlands between 1966 and 1996 and survived at least 5 years; follow-up was complete for 99% of survivors. Cause-specific mortality was compared with general population rates to assess relative and absolute excess risks of death (standardized mortality ratio (SMR) and AER).

Survival in nephroblastoma treated according to the trial and study SIOP-9/GPOH with respect to relapse and morbidity.

Background: Recent Wilms' tumor (WT) trials and studies have tried to determine the minimal therapy needed for cure. The goal was survival without morbidity.

Patients And Methods: From January 1989 to March 1994 the German Society of Pediatric Oncology and Hematology registered 440 patients (median age 2.

Clustering of hypermethylated genes in neuroblastoma.

CpG-island hypermethylation of gene promoters is a frequent mechanism for gene inactivation in tumors. Many neuroblastomas have hypermethylation and down-regulation of CASP8, leading to resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We recently found hypermethylation of the four TRAIL receptors in 9 neuroblastoma cell lines.

The N-myc paradox: N-myc overexpression in neuroblastomas is associated with sensitivity as well as resistance to apoptosis.

Neuroblastomas are characterized by defects in tumor necrosis factor-related apoptosis inducing ligand (TRAIL) induced apoptosis, especially down-regulation and methylation of Caspase-8 (CASP8). This defect is associated with amplification of N-myc. However, N-myc has also been implicated in induction of apoptosis, especially activation of CASP9 mediated apoptosis.

A novel local treatment strategy for advanced stage head and neck rhabdomyosarcomas in children: results of the AMORE protocol.

The AMORE protocol is a local treatment regimen for head and neck rhabdomyosarcomas (HNRMS), consisting of Ablative surgery, Moulage technique brachytherapy and surgical Reconstruction. The aim of AMORE is to intensify local treatment for children with HNRMS and to avoid external beam radiation therapy (EBRT) and its long-term sequelae. All children with primary irresectable, non-orbital HNRMS in whom EBRT was indicated, were evaluated for the feasibility of AMORE.

Educational achievement, employment and living situation in long-term young adult survivors of childhood cancer in the Netherlands.

This paper investigated educational achievement, employment status, living situation, marital status and offspring in 500 Dutch long-term young adults survivors of childhood cancer (age range, 16-49 years, 47% female). The results were compared with a reference group of 1092 persons with no history of cancer (age range, 15-33 years, 55% female). The impact of demographic and medical characteristics on psychosocial adjustment was studied.

No excess fatigue in young adult survivors of childhood cancer.

Clinical reports suggest that many survivors of childhood cancer experience fatigue as a long-term effect of their treatment. To investigate this issue further, we assessed the level of fatigue in young adult survivors of childhood cancer. We compared the results with a group of young adults with no history of cancer.

Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review.

Background: The aim of this systematic review was to summarise and appraise the published evidence with regard to the frequency and risk factors of subclinical cardiotoxicity in apparently healthy survivors of childhood cancer after anthracycline therapy.

Patients And Methods: A search was made in Medline for studies published between 1966 and May 2001 that included >50 children and reported on the frequency of measures of subclinical cardiotoxicity. Information about the studies was abstracted by two reviewers and a validity score was calculated for each study.

Lack of interstitial chromosome 1p deletions in clinically-detected neuroblastoma.

Loss of heterozygosity (LOH) of the distal part of the short arm of chromosome 1 in neuroblastoma is a well characterised phenomenon. In addition, previous reports have described interstitial deletions outside the common region of loss on chromosome 1p36, suggesting additional tumour suppressor loci. In this study, we have searched extensively for interstitial 1p deletions in a panel of 67 neuroblastoma samples from clinically-detected cases.

Human megakaryocytes cultured in vitro accumulate serotonin but not meta-iodobenzylguanidine whereas platelets concentrate both.

Objective: Thrombocytopenia is the major toxicity of radio-iodinated meta-iodobenzylguanidine (MIBG) therapy in patients with recurrent neuroblastoma. MIBG is taken up in platelets via the serotonin transporter. Given the delayed appearance and long duration of the thrombocytopenia, it seems likely that the precursor megakaryocytes are the primary targets of [131I]MIBG radiotoxicity.

Frequency and risk factors of anthracycline-induced clinical heart failure in children: a systematic review.

Background: Anthracyclines are essential for the treatment of the children with cancer. We performed a systematic review to evaluate the existing evidence of the frequency and risk factors of anthracycline-induced clinical heart failure (A-CHF) in children.

Design: Medline was searched for articles reporting the frequency of A-CHF, published from 1966 to December 2000.

Genetic alterations in childhood medulloblastoma analyzed by comparative genomic hybridization.

Despite intensive therapy, the survival of children with medulloblastoma remains disappointing. Moreover, children who survive are affected by serious long-term sequelae of treatment that impair their quality of life. In search of chromosomal aberrations indicative of sites involved in oncogenic transformation and in an attempt to find reliable prognostic markers, the authors analyzed 15 medulloblastomas by comparative genomic hybridization.

Tumor-specific down-regulation of the tumor necrosis factor-related apoptosis-inducing ligand decoy receptors DcR1 and DcR2 is associated with dense promoter hypermethylation.

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) induces apoptosis in a large variety of cancer cells but not in most normal human cells. This feature makes TRAIL, a potential antitumor agent. TRAIL can bind to four different receptors, two pro-apoptotic death receptors (DRs), DR4 and DR5, and two antiapoptotic decoy receptors (DcRs), DcR1 and DcR2.

Cyclopentenyl cytosine increases the phosphorylation and incorporation into DNA of 1-beta-D-arabinofuranosyl cytosine in a human T-lymphoblastic cell line.

The cytotoxic effect of 1-beta-D-arabinofuranosyl cytosine (araC) depends on the intracellular phosphorylation into its active compound araCTP, on the degree of degradation of araCTP and on the incorporation of araCTP into DNA. Deoxycytidine triphosphate (dCTP) inhibits the phosphorylation of araC (by feedback inhibition of the enzyme deoxycytidine kinase) and the incorporation of araCTP into DNA (by competition for DNA polymerase). In a T-lymphoblastic cell line, we studied whether the cytotoxicity of araC (2 nM-50 microM) could be enhanced by decreasing the concentration of dCTP, using the nucleoside-analogue cyclopentenyl cytosine (CPEC), an inhibitor of the enzyme CTP synthetase.

Troponin T in the first 24 hours after the administration of chemotherapy and the detection of myocardial damage in children.

Early detection of damage to cardiac myocytes after cardiotoxic chemotherapy in paediatric patients may allow timely preventive measures to be taken. We investigated the diagnostic value of cardiac troponin T (cTnT) after the administration of cardiotoxic chemotherapy. In 38 children, cTnT levels were measured at three time points during the first 24 h after 58 cardiotoxic chemotherapy cycles (163 samples).

Second malignancies after ewing tumor treatment in 690 patients from a cooperative German/Austrian/Dutch study.

Background: Ewing tumor treatment involves high cumulative doses of alkylating agents and topoisomerase inhibitors, drugs capable of inducing second cancers. We analyzed the second cancer risk in a large cohort of consistently treated patients.

Patients And Methods: Six hundred ninety Ewing tumor patients were treated between 1992 and 1999 with local therapy and vincristine.