Summary of the International Symposium on Childhood Non-Rhabdomyosarcoma Soft-Tissue Sarcomas, Padua, Italy, February 10-12, 1994.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
M C Stevens
Publications and source records attributed to M C Stevens.
Ifosfamide nephrotoxicity in children: histopathological features in two cases.
We report on two children with rhabdomyosarcoma who received ifosfamide as part of their chemotherapy schedule. Both children subsequently developed severe ifosfamide-induced nephrotoxicity, necessitating electrolyte supplementation. We describe the histopathological findings of renal biopsies performed in these children after the onset of renal dysfunction and comment on the possible mechanisms involved in ifosfamide nephrotoxicity.
Adult↗
Paediatric meningeal tumours.
We review our experience of meningeal tumours in patients under 16 years who were treated between 1957 and 1993. These were 16 with meningiomas (median age 12 years) and 5 with poorly differentiated malignant meningeal tumours (median age 3 years). The incidence of meningeal tumours in this period was 1.62% of all CNS tumours. There were 19 supratentorial tumours (5 intraventricular), 1 tentorial and 1 cervical. Surgical excision was complete in 12 patients and incomplete in 6; in 2 patients a biopsy only was undertaken. The remaining patient had radiological diagnosis only. All 5 patients in the group with malignant poorly differentiated tumours died (median survival 5 months), confirming the aggressive nature of these lesions. Of the 16 patients with meningiomas, 4 died during followup but 11 of the 12 meningioma patients remaining alive had complete resections. There is a strong tendency for paediatric meningeal tumours to have a supratentorial origin and intraventricular location. The female preponderance found in adults is not evident in children. Incomplete surgical excision or focal neurological deficit at presentation was associated with poor outcome.
Adolescent↗
The long-term survivors.
Recent research indicates that approximately 60% of children diagnosed with cancer in Britain are cured and as a result, about 1 in a 1000 of the general population will soon be survivors of childhood cancer. Unfortunately some elements of the therapies which are responsible for this remarkable success are associated with serious complications, sometimes decades after their administration. Therefore, a comprehensive knowledge of the risks and benefits of different therapies will only be obtained by monitoring the health of survivors indefinitely. With such therapeutic success, increasingly the composition of future treatment protocols will be influenced by knowledge of the risks of long term morbidity and mortality associated with past therapies. An awareness of the long term risks of complications of treatment is also important for estimating the future demand on the health services of this increasing proportion of the general population who together represent many life years of care. This chapter reviews what is known concerning the long term risks of complications of different treatments. Appropriate strategies for future clinical and epidemiological follow-up of the survivor population are discussed and the need for indefinite follow-up of the survivor population is emphasised.
Adolescent↗
Treatment for children with brain tumours.
The overall survival for children with malignant brain tumours has not greatly improved in recent years, so that apparently innovative treatments may seem attractive, especially in cases with a poor prognosis. Problems associated with treating such children include balancing the need to provide optimum treatment for individual patients with the need to properly evaluate advances in treatment in clinical trials and determining who should be responsible for decisions about funding such treatments. Treatment abroad is rarely justified when judged on the basis of whether the treatment is available in Britain (or European Community) and whether there is accepted evidence for its clinical benefit. However, referral to specialist paediatric centres is essential. The range of daily experience in such centres allows an educated choice between established and new treatments. Close collaboration between these centres is essential for clinical trials.
Brain Neoplasms↗
Clustering of childhood peritoneal mesothelioma in the Midlands, UK.
Explore the source record for details and available documents.
Adolescent↗
Clinical examination compared with anthropometry in evaluating nutritional status.
Clinical assessments of nutritional status in a group of 44 inpatients, made by a panel of experienced childcare specialists, were compared with anthropometric assessments. Assessors were uniformly poor at detecting severe malnutrition and at assessing the nutritional status of infants. Nutritional status cannot be accurately assessed clinically and anthropometry is crucial.
Anthropometry↗
Hyperaemia in rat neocortex produced by acute exposure to methylenedioxymethamphetamine.
Cerebral blood flow and glucose utilization were measured in rat neocortex, hippocampus and striatum following methylenedioxymethamphetamine injection (5 mg/kg, i.v.), using the tracers [14C]iodoantipyrine and [14C]2-deoxyglucose, respectively. In control rats, blood flow was coupled to glucose metabolism, but in methylenedioxymethamphetamine-treated rats, marked hyperperfusion was measured in frontal and parietal cortex with no change in glucose use. This suggests that methylenedioxymethamphetamine has the potential to disrupt cerebrovascular control.
Animals↗
Neonatal tumours: a thirty-year population-based study.
Estimates of the incidence and outcome of tumours in neonates are uncertain and most reports relate to selected experience in single centres. The definition of neonatal tumour is also unclear and histology is not always an accurate predictor of outcome. This report documents the incidence, clinical features, and outcome of neonatal tumours (birth-3 months) in a population-based paediatric register over a 30-year period from 1960-89. Case note and pathology review identified 170 cases for analysis, of which 21 were leukaemias, 14 CNS tumours, and 135 solid tumours of differing types. Fifty-eight percent were diagnosed in the first month and mature teratoma was the most common diagnosis (29%). Overall incidence increased over the period of the study. Important family medical history was identified in 16% of cases and 15% of patients had associated congenital abnormalities. Overall survival at 1 year was 55%, with leukaemia having the poorest prognosis. Treatment strategies must be individualised but many patients may have a better prognosis than expected and would benefit from assessment at a designated paediatric oncology centre.
Age Distribution↗
DNA ploidy and proliferative activity (S-phase) in childhood soft-tissue sarcomas: their value as prognostic indicators.
The value of DNA ploidy as a prognostic indicator is well established in many cancers, but recent studies in childhood rhabdomyosarcoma (RMS) have been contradictory. In a retrospective study of 128 cases of soft-tissue sarcoma (STS) diagnosed since 1980, the prognostic value of clinical, histological and flow cytometric parameters was compared, using univariate and multivariate methods. Eighty-one RMSs, 18 extraosseous Ewing's (EOE)/peripheral neuroectodermal tumours (PNETs) and 29 other non-RMS STSs were histologically and clinically reviewed. Five year actuarial survival was 63.4% for all STSs and 69.4% for RMSs. Paraffin-embedded tissue blocks were available for flow cytometry in 90 cases. Of the RMSs, 65.5% were aneuploid [DNA index (DI) > 1.1] compared with 23% of the EOE/PNETs and 31% of non-RMS STSs. Median S-phase was also significantly higher in RMSs (17.0%) than in other STSs (10.8%) (P = 0.0023). Univariate analysis in RMSs showed that stage, ploidy status, S-phase, site and tumour size all had a significant impact on survival. In multivariate analysis of 59 cases of RMS, one clinical and two flow cytometric parameters were independently associated with poor prognosis. These were stage (IV), nonhyperdiploidy (DI < 1.10 and > 1.8) and a high rate of proliferative activity (S-phase > 14.0%). These results confirm that ploidy and S-phase are important new prognostic indicators in rhabdomyosarcoma.
Adolescent↗
The mechanism of low testosterone levels in homozygous sickle-cell disease.
Significantly lower testosterone levels are common in male patients with homozygous sickle-cell (SS) disease and have been attributed to either abnormalities of the hypothalamo-pituitary axis or primary testicular failure. The mechanism has now been investigated by observing the response to gonadotropin-thyrotropin releasing hormones (GnRH-TRH) in 10 male patients with SS disease and in 10 matched male sibling controls without sickle-cell disease. Mean basal levels of luteinizing hormone (LH), follicular stimulating hormone (FSH) and thyrotropin (TSH) were significantly elevated but prolactin (PRL) levels were within the normal range in the SS group. All hormones increased following GnRH-TRH, and proportionate increases over baseline were similar for FSH and TSH in SS and AA subjects, but SS patients showed a lesser percentage increase in LH at 30 minutes, and a higher percentage increase in PRL at 60 minutes. These observations are more consistent with primary testicular failure than with abnormalities of the hypothalamic-pituitary-testicular axis.
Adult↗
Treatment of childhood acute myeloid leukaemia using the BFM-83 protocol.
Thirty children presenting with acute nonlymphoblastic leukaemia from June 1984 to December 1989 were treated at one UK centre using a West German protocol, AML-BFM-83. This consisted of Induction, an intensive outpatient-based Consolidation regimen with seven different drugs and cranial irradiation, and Continuation therapy with thioguanine and cytosine arabinoside for 2 years with additional Adriamycin in the first year. Twenty-five children achieved complete remission (83%). There were two early deaths from haemorrhage and infection and three from Induction failure. After a median follow-up time of 60 months, nine relapses have occurred, all in the bone marrow. Life table analysis revealed a probability for survival at 5 years of 47%, event-free survival 43%, and event-free interval 50%. Median bed occupancy for chemotherapy and toxicity was 41 days, with median hospital stays of 29 days for Induction, 11 days for Consolidation and less than 1 day for Continuation. This data suggests that long-term remissions can be achieved in just under half of children with acute nonlymphoblastic leukaemia while creating only modest demands on inpatient resources.
Acute Disease↗
Neuroblastoma: a 32-year population-based study--implications for screening.
This paper describes a retrospective population-based study of neuroblastoma in the West Midlands Health Authority Region--childhood population 1.12 million (OPCS, census 1981)--in which 239 cases were diagnosed between 1st January 1957 and 31st December 1988. The age standardised rate of tumour incidence has remained constant at 7.2 cases per million children per year. The median age at diagnosis was 2 years with 18% of children presenting before the age of 6 months. Fifty children (21%) presented before the age of one year, and for this group of children, the prognosis has improved significantly over the 32-year period (10 year survival increasing from 63% in 1957-67 to 87% in 1978-88), whereas for the 189 (79%) children who presented after one year of age, the prognosis has remained very poor during the study period (10 year survival 1957-67 = 9.5%, 1978-88 = 8.5%). This study supports the need for a prospective study of mass screening at several intervals rather than only at 6 months of age.
Abdominal Neoplasms↗
Incidence and etiology of ifosfamide nephrotoxicity: report of a meeting held in Rhodes, Greece, October 3, 1991, sponsored by Asta Medica, Frankfurt, Germany.
The nephrotoxic potential of ifosfamide is now clearly recognized but the true incidence is unknown and risk factors are uncertain. There are, as yet, few studies which systemically explore these issues although many centers have collected data from patients receiving ifosfamide. These support the need for collaborative studies to look at the influence of probable risk factors such as age, cumulative/dose, schedule, and exposure to other nephrotoxic drugs. The ability to detect acute subclinical changes in renal function may provide the opportunity to predict subsequent clinical toxicity. The consensus of opinion recorded so far provides the basis of recommendations for future studies.
Child↗
Nebulised pentamidine prophylaxis for Pneumocystis pneumonia in acute lymphoblastic leukaemia.
Explore the source record for details and available documents.
Administration, Inhalation↗
21-day schedule oral etoposide in children--a feasibility study.
To determine the feasibility and toxicity of prolonged oral etoposide in children, 22 patients with relapsed or refractory disease were commenced on etoposide 50-100 mgs/m2 per day for 21 days. A second course was administered after full blood count recovery, followed by disease reassessment. In total, 72 courses were evaluable for toxicity, with 10% of completed courses complicated by febrile neutropenia. 15 patients were evaluable for response, with 1 partial response, 10 stable disease and 4 progressive disease. This schedule was well tolerated with acceptable toxicity when doses of less than 80 mg/m2/day were administered and warrants further evaluation.
Administration, Oral↗
Retrospective study of prognostic value of DNA ploidy and proliferative activity in neuroblastoma.
AIM: To assess the prognostic value of age and stage at diagnosis, site of primary tumour, cell ploidy and N-myc copy number in children with neuroblastoma. METHODS: Flow cytometry was used to determine the cellular DNA content of paraffin wax embedded archival material from 69 cases of neuroblastoma and was successful in 52. RESULTS: The age, stage, and survival distribution of the sampled cases was not significantly different from that in a larger population based series. There were seven diploid ("non-aneuploid") and 45 aneuploid (including two tetraploid and four triploid) tumours. The 10 year survival was significantly better for cases of aneuploid rather than diploid tumours (p < 0.05). An important new finding was that 10 year survival was also significantly better for tumours with a low percentage of cells in S phase (p < 0.03). CONCLUSION: The percentage of cells in S phase, a measure of the proliferative activity of the tumour, correlated with prognosis in neuroblastoma. This should be measured with other biological features of the disease, such as N-myc copy number, when prognostic indicators are being assessed.
Adolescent↗
Carboplatin pharmacokinetics in children: the development of a pediatric dosing formula. The United Kingdom Children's Cancer Study Group.
PURPOSE: The aim of this study was to define the pharmacokinetics of carboplatin in children and use the data to develop a pediatric dose formula. It was anticipated that renal function would be a major determinant of carboplatin disposition and the relationship between carboplatin clearance and glomerular filtration rate (GFR) was examined in detail. PATIENTS AND METHODS: Plasma carboplatin pharmacokinetics were measured as ultrafiltrable platinum in 22 patients (5 to 63 kg) following 200 to 1,000 mg/m2 of carboplatin. GFR was measured by the plasma clearance of chromium 51-edathamil (51Cr-EDTA). RESULTS: Carboplatin pharmacokinetics in children were best described in most patients (16 of 22) by a two-compartment model. The dose-normalized area under the plasma carboplatin concentration versus time curve (AUC) ranged from 3.1 to 9.6 mg/mL.min/400 mg/m2 and there was only a weak linear relationship between carboplatin dose and AUC (R2 = .31). There was a significant relationship between absolute carboplatin and 51Cr-EDTA clearances (R2 = .56), but the relationship was weaker (R2 = .28) when both clearances were normalized for body surface area. Carboplatin plasma clearance was predicted by the equation: clearance = GFR (mL/min) + 0.36 x body weight (BW; kg), and a modified form of the adult carboplatin dose formula is proposed: dose (mg) = target AUC x (GFR [mL/min] + [0.36 x BW(kg)]). Two further equations were developed that use the 51Cr-EDTA half-life (t1/2) to calculate the GFR and these may reduce errors resulting from inaccurate measurement of the volume of distribution for 51Cr-EDTA. In patients treated with single-agent carboplatin or carboplatin plus vincristine, there was a significant sigmoidal relationship between AUC and thrombocytopenia (R2 = .56). CONCLUSION: GFR-based carboplatin dosing in children should be feasible and will be evaluated prospectively.
Adolescent↗