Prognostic factors in the treatment of Ewing's sarcoma

From 1981 up to February 1985, a total of 93 protocol patients entered the study CESS 81. The protocol recommended an initial 18-week period of polychemotherapy (VACA) followed by local therapy and two additional cycles of chemotherapy. Local therapy consisted either of radical surgery or of incomplete resection plus postoperative irradiation with 36 Gy or of radiotherapy alone (46 and 60 Gy). Centrally located lesions were always irradiated with 60 Gy. This article summarizes the data after 5 years. Data of 93 patients were analysed in October 1986 after a median follow-up of 37 months. The projected 5-year survival is 50%. The relapse rate was 42%, distant relapses occurred in 19%, local …

Zweitmalignome nach malignen Erkrankungen im Kindesalter

Since 1980 the German Registry of Childhood Malignancies has been established. In the framework of the long-term follow-up secondary malignancies are reported continually to the registry. An additional retrospective inquiry to all treating clinicians and principal investigators of clinical trials as well as a link to a previously existing pool of secondary malignancies (1) lead to a completion of the data. At the registry now 329 patients with second malignant neoplasms have been observed. 41.3% of them had been developed the first malignancy before the registry started its work in 1980. The most common primary malignancies are acute lymphoblastic leukaemia (ALL, 28.6%), brain tumours (12.2…

Lead-time and overdiagnosis estimation in neuroblastoma screening.

In Germany, neuroblastoma is the most frequent extracranial solid childhood tumour. Its properties made it seem an ideal candidate for screening. A German trial assessed the effect of screening at one year of age from 1995-2001 in a nationwide project. We present here the methods developed for the estimation of lead-time and overdiagnosis in this project. Follow up on 1.5 million screened children and 2.1 million control children is currently available until June 2002. Ascertainment of control cohort cases and false negative cases is complete up to this date. A method for determining an empirical lead-time distribution and overdiagnosis estimate from comparing the age specific incidences in…

Quantitative ECG analysis for individual risk assessment of future myocardial infarct-results from the MARISK study

From 1980 to 1990 the authors performed an epidemiological cohort study in order to explore the predictive power of computer electrocardiogram (ECG) measurements for individual risk assessment of future myocardial infarct in combination with commonly known risk factors. Out of 7542 participants, 83 experienced a myocardial infarct during the course of the study. Multivariate logistic regression analysis revealed that vector cardiogram (VCG) measurements provide significant additional information to risk estimation which is equivalent to that of other risk factors. Measurement changes are stronger risk indicators than single measurements. The results confirm previous findings from H.V. Pipbe…

Untersuchung der Häufigkeit von Krebserkrankungen im Kindesalter in der Umgebung von Kernkraftwerken

Seit 1983 das Britische Fernsehen in der vielbeachteten Dokumentation „Windscale — The Nuclear Laundry“ uber eine Haufung kindlicher Leukamien in der Umgebung von Windscale berichtete, ist die Diskussion uber einen Zusammenhang zwischen Leukamieclustern und ionisierender Strahlung aus kerntechnischen Anlagen nicht abgebrochen. Grose Studien in England und Wales (2,3,6), in den USA (9) und in Frankreich (8), in denen die Krebsinzidenz bzw. Krebsmortalitat in der Umgebung kerntechnischer Anlagen ausgewahlten Vergleichsregionen gegenubergestellt wurde, sind zu unterschiedlichen Ergebnissen gekommen. Wahrend in den Vereinigten Staaten keine Erhohung der Krebsmortalitat in der Umgebung kerntechn…

Case Control Study on Childhood Leukemia in Lower Saxony, Germany

In two municipalities in Lower Saxony statistically valid clusters were observed, which attracted great public interest. Committees were set up to initiate a large variety of on-the-spot-investigations. Finally, it was decided to conduct a case control study throughout Lower Saxony to explore potential risk factors which might explain the observed clusters. A limited number of already established and currently discussed hypotheses was chosen for investigation. The study was based on patients registrated at the German Children's Cancer Registry (GCCR). For each child with leukemia diseased between 1988 and 1993 two population-based controls (local and state controls) and one tumour control w…

Trends in infant leukaemia in West Germany in relation to in utero exposure due to Chernobyl accident.

A temporary increase in the incidence of infant leukaemia in Greece was reported by Petridou et al., which was attributed to in utero exposure to ionising radiation resulting from the Chernobyl accident. We performed a similar analysis based on the data of the German Childhood Cancer Registry in order to check whether the observation could be confirmed by means of independent data. Applying the same definitions as Petridou et al., we also observed an increased incidence of infant leukaemia in a cohort of children born after the Chernobyl accident. More detailed analyses, regarding areas with different contamination levels and dose rate gradients over time after the accident, showed, however…

Fever in pregnancy and congenital anomalies.

erman case control study on childhood leukaemia - Basic considerations, methodology and summary of the results

In order to explore potential risk factors of childhood leukaemia, a case control study was performed including all incident cases from 1992 to 1994. The study was based on the German Childhood Cancer Registry. It was restricted to cases from West Germany and extended retrospectively until 1980 for children who were living in regions covered by a previous incidence study on nuclear installations (21). The study was conducted in close correspondence with a preceding case control study in Lower Saxony (13). Results of this study and of others published in the literature were used to define explicit hypotheses for the present study. This paper presents the methodology of the study and gives an…

Cancer consequences of the Chernobyl accident in Europe outside the former USSR: A review

The accident which occurred during the night of April 25-26, 1986 in reactor 4 of the Chernobyl nuclear power plant in the Ukraine released considerable amounts of radioactive substances into the environment. Outside the former USSR, the highest levels of contamination were recorded in Bulgaria, Austria, Greece and Romania, followed by other countries of Central, Southeast and Northern Europe. Studies of the health consequences of the accident have been carried out in these countries, as well as in other countries in Europe. This report presents the results of a critical review of cancer studies of the exposed population in Europe, carried out on the occasion of the 10th anniversary of the …

Untersuchungen zur Entdeckung räumlicher Cluster im Kinderkrebsregister Mainz

Im Rahmen des Mainzer Kinderkrebsregisters beschaftigen wir uns mit der Frage, ob die Inzidenzen kindlicher Krebserkrankungen regional besonders hoch oder besonders niedrig sind. Nicht nur regionale Haufungen sind fur das Register von Interesse, sondern, als Hinweis auf systematische Erfassungslucken, auch regional besonders niedrige Inzidenzen. Dies fuhrt auf die Frage, ob die Inzidenzen von Krebserkrankungen bei Kindern raumliche Autokorrelation aufweisen. Ob man auf einer Landkarte Cluster visuell wahrnimmt und ob Tests auf raumliche Autokorrelation Cluster entdecken, hangt auch von der Klasseneinteilung der beobachteten Werte und von den verwendeten Verfahren ab. Wir haben daher mehrere…

Population density and childhood leukaemia: results of the EUROCLUS study

The EUROCLUS study assembled incidence data for 13,551 cases of childhood leukaemia (CL) diagnosed between 1980 and 1989 in 17 countries (or regions of countries). These were referenced by location at diagnosis to small census areas of which there were 25,723 in the study area. Population counts, surface area and, hence, population density were available for all these small areas. Previous analyses have shown limited extra-Poisson variation (EPV) of case counts within small areas; this is most pronounced in areas of intermediate population density (150-499 persons/km2). In this study, the data set was examined in more detail for evidence that variations in incidence and EPV of CL are associ…

High-birth weight and other risk factors for Wilms tumour: results of a population-based case-control study.

Wilms tumour, or nephroblastoma, is one of the childhood cancers included in two recent population-based case-control studies in West Germany. Altogether, 177 children under the age of 10 years with Wilms tumour diagnosed between 1988 and 1994 and 2006 control children sampled from population registration files participated. Information on potential risk factors was obtained from the parents using a questionnaire and by subsequent telephone interview. We found an association with a high birth weight >4000 g (odds ratio 1.58; 95% confidence interval 1.01–2.48), which was somewhat stronger for children aged 2 years or older. Findings for young maternal age at birth and certain parental occupa…

Extremely low frequency magnetic fields in residences in Germany. Distribution of measurements, comparison of two methods for assessing exposure, and predictors for the occurrence of magnetic fields above background level.

We examined the results of 1,835 magnetic field measurements in German residences conducted between November 1997 and September 1999. The measurements were part of an epidemiological study on the relationship between magnetic fields and childhood leukemia. We performed a fixed-location measurement of the magnetic field at 50 Hz and 16 2/3 Hz (frequency of the German railway system) over 24 h in the child's bedroom in the residence of each study participant. In addition, we conducted a second 24 h-measurement in the living room at 50 Hz, and spot measurements while walking through all rooms of the respective dwelling. Median 50 Hz magnetic fields above 0.2 muT were found to be infrequent in …

Regionale Analysen der Krebsinzidenz bei kleinen Fallzahlen

Seit 1980 dokumentiert das Mainzer Kinderkrebsregister bundesweit die malignen Erkrankungen bei Kindern unter 15 Jahren. Zu den registrierten Daten gehort neben Angaben wie Name, Alter, Diagnose und Erkrankungsdatum die Gemeinde, in der das erkrankte Kind bei Diagnosestellung wohnte. Diese Angabe dient als Grundlage zur kartographischen Aufbereitung der regionalen Inzidenzen, die eine wichtige Aufgabe von Krebsregistern darstellt (1).

Meta-analyses of studies on the association between electromagnetic fields and childhood cancer.

During the last 15 years several studies have investigated a possible relationship between exposure to electromagnetic fields (EMF) and childhood cancer. There is considerable variation between these studies with respect to methods of exposure assessment and reported results. Methods of exposure assessment range from simple visual criteria to costly and time consuming measurements or estimations of electric flux density. Additional individual refinements further hinder the comparability of results. We carried out several meta-analyses of data published so far taking into account the heterogeneity between studies as far as possible. Our particular interest was to investigate a potential dose…

Residential magnetic fields as a risk factor for childhood acute leukaemia: Results from a German population-based case-control study

Our objective was to investigate whether exposure to residential power-frequency (50 Hz) magnetic fields above 0.2 μT increases a child's risk of leukaemia and to confirm or reject a finding from a previous German study on this topic, which reported increased leukaemia risk with exposure to stronger magnetic fields during the night. A population-based case-control study was used, covering the whole of the former West Germany. Residential magnetic fields were measured over 24 hr for 514 children with acute leukaemia identified by the German Childhood Cancer Registry and 1,301 control children taken from population registration files. Magnetic fields above 0.2 μT were relatively rare in Germa…

Atopic disease and childhood acute lymphoblastic leukemia

Our objective was to test the hypothesis that the risk of childhood leukemia is associated with allergies or a family history of allergy. We used a German population-based case-control study with self-reported information on allergies of the children and their first-degree relatives. Our study included a total of 1,130 cases of acute lymphoblastic leukemia (ALL), 164 cases of acute myeloid leukemia (AML) and 2,957 controls. A major finding of our study is that hay fever, neurodermatitis and contact eczema are underrepresented within the group of children with ALL, with respective odds ratios (OR) of 0.45 (95% confidence interval [CI] 0.31-0.66) for hay fever, of 0.49 (CI 0.34-0.71) for neur…

Applicability of the Poisson distribution to model the data of the German Children's Cancer Registry.

Since 1980 the German Children's Cancer Registry has documented all childhood malignancies in the Federal Republic of Germany. Various statistical procedures have been proposed to identify municipalities or other geographic units with increased numbers of malignancies. Usually the Poisson distribution, which requires the malignancies to be distributed homogeneously and uncorrelated, is applied. Other discrete statistical distributions (so-called cluster distributions) like the generalized or compound Poisson distributions are applicable more generally. In this paper we present a first explorative approach to the question of whether it is necessary to use one of these cluster distributions t…

The Cohort of Long-term Survivors at the German Childhood Cancer Registry

Background With the increasing number of long-term survivors among patients diagnosed with cancer during childhood, questions concerning late effects have become a major research topic. To ascertain late effects, it is necessary to contact former patients. An essential requirement for such studies is a long-term surveillance (LTS) of former childhood cancer patients in their adolescence and their adulthood. The paper describes the role of the German Childhood Cancer Registry (GCCR) in LTS. A cohort of long-term survivors has been built up over the years. The characteristics of this LTS cohort and strategies for further improvement of LTS will be presented. Patients and methods Since 1980 th…

Sero-epidemiological analysis of the risk of virus infections for childhood leukaemia.

Virus infections have been thought to be involved in the development of childhood leukaemia. In order to address this issue we determined, in a case-control study, the prevalence of antibodies to viruses infecting blood or bone-marrow cells [Epstein-Barr virsus (EBV), human herpes virus type 6 (HHV-6), parvovirus B19] as well as to the human virus known for its tumour-suppressive properties, the adeno-associated virus type 2 (AAV-2), in the sera of 121 children with leukaemia in Germany, and in 197 control individuals, hospitalized for other reasons, and matched for age and gender to the cases. In addition, we developed a questionnaire to be answered by the children's parents, in order to g…

Electromagnetic Fields and Childhood Leukemia: Pooled Analyses of Two German Population-Based Case-Control Studies

From 1992 to 1995 we conducted a population-based case-control study on residential magnetic fields and childhood leukemia in Lower Saxony, a region in northwestern Germany with 7.4 million inhabitants.1,2 Because of the rural character of this area, we detected elevated magnetic fields in only 1.5% of all dwellings. We therefore expanded the EMF-measurements to an ongoing case-control study on childhood leukemia in the capital of Germany, Berlin. We applied the same methods of exposure assessment, intending to pool the data of the two studies and to calculate combined risk estimates.3

Risk factors for pediatric tumors of the central nervous system: Results from a German population-based case-control study

From 1993 to 1997 we conducted two population-based case-control studies on childhood cancer and a variety of potential risk factors in Germany. One case group involved children under the age of 15 years having a tumor of the central nervous system (CNS).For both studies, one conducted in the northwestern area of Germany, the other covering the whole of West Germany, incident cases were identified from the nationwide German Childhood Cancer Registry, and controls were randomly selected from complete population registration files.In total 466 pediatric CNS tumor cases and 2,458 controls were available for analyses. We observed only few positive associations, namely, between CNS tumors and lo…

OPS — Operation Planning System for Neurosurgery

The departments for neuroradiology and neurosurgery intend to use computer aided methods for individual planning of operations in the sella region. Essential structures like the optic nerve, arteries, aneurysms, the pituitary stalk, ventricles, and tumors should be segmented, reconstructed and visualized. The computed 3D view shall simulate the neurosurgeon’s view through the operation microscope into the scene. This approach shall remedy the lack of available medical image analysis systems for neurosurgical intervention. The emphasis in this article will be on the segmentation algorithms and the impact of the system on daily neuroradiological work.

Use of quantitative ECG analysis for early detection and prediction of coronary heart disease

(1985). Use of quantitative ECG analysis for early detection and prediction of coronary heart disease. Medical Informatics: Vol. 10, No. 3, pp. 207-214.

Infant leukaemia after the Chernobyl accident

Neuroblastoma in Europe: differences in the pattern of disease in the UK

Summary Background Neuroblastoma is a major contributor to childhood cancer mortality, but its prognosis varies with age and stage of disease, and some tumours regress spontaneously. Urinary screening programmes or clinical examination may detect the disease before symptoms appear, but the benefit of early diagnosis is uncertain. We examined the incidence, pattern, and presentation of neuroblastoma in four European countries. Methods Population-based incidence rates were derived for France, Austria, Germany, and the UK. Age, sex, and stage distribution were analysed by Mantel-Haenszel techniques and Poisson regression. The proportion of incidental diagnoses (cases without symptoms found at …

Association of childhood cancer with factors related to pregnancy and birth

It has been hypothesized that risk factors of childhood cancers may already operate during the prenatal and neonatal period. Results of previous epidemiological studies have been inconsistent.During 1992-1997 a large case-control study on childhood cancers and a variety of potential risk factors was conducted in Germany. Cases were ascertained by the German Childhood Cancer Registry. Each case was matched to a population-based control of the same age and gender, sampled from the district where the case lived at the date of diagnosis. For the analyses, 2358 cases and 2588 controls were available.Risk of childhood acute leukaemia increased with maternal ageor =20 years at time of delivery (od…

Multidisciplinary treatment of primary Ewing's sarcoma of bone.A 6-year experience of a European cooperative trial

The German Society of Pediatric Oncology in 1981 initiated the Cooperative Ewing's Sarcoma Study (CESS 81) using a four-drug combination of chemotherapy prior to definitive local control with surgery and/or radiation. From January 1, 1981 until February 28, 1985, 93 patients were registered at the trial office from 54 participating institutions in West Germany, Austria, Switzerland, and the Netherlands. On February 1, 1987, 54 of 93 patients were disease-free. Using the Kaplan-Meier life table analysis, the estimated disease-free survival (DFS) rate was 60% at 36 months and 55% at 69 months. The median period of observation was 29 months, ranging from 22 months to 69 months. Twenty-one of 9…

Risk factors for neuroblastoma at different stages of disease. Results from a population-based case-control study in Germany

Neuroblastoma is one of the childhood cancers included in two recent population-based case-control studies in West Germany. Altogether, 183 children under the age of 8 with neuroblastoma diagnosed in 1988-1994 and 1785 control children sampled from population registration files participated. Information on potential risk factors was obtained from the children's parents by a self-administered questionnaire and subsequent telephone interview. We observed positive associations with the use of oral contraceptives or other sex hormones during pregnancy (particularly with male offspring), a shorter gestational duration, lower birth weight, and maternal alcohol consumption during pregnancy. While …

Population-based epidemiologic data on brain tumors in German children.

BACKGROUND Brain tumors are the most common disease group of solid tumors in childhood, and children with brain tumors have a relatively poor survival rate. Epidemiologic data from a population-based cancer registry provide the necessary information to obtain a full picture of the frequency of this disease, which is a great challenge in pediatric oncology. METHODS The German Childhood Cancer Registry (GCCR) is a population-based registry. The level of completeness of patient registration is 95%, but it is somewhat lower for patients with brain tumors. More than 300 children with newly diagnosed brain tumors are reported every year. Analyses of GCCR data are performed according to the Intern…

Case Control Study of Neuroblastoma in West-Germany after the Chernobyl Accident

Background To explore possible causes of a 1988 incidence peak of infant neuroblastoma in west German regions which were contaminated with more than 6000 Bq/m2 Cs137 from the Chernobyl accident. The primary working hypothesis was that parents of the diseased children had been contaminated by an excessive intake of locally produced food, especially mushrooms or deer. Design Case control study with 1:2 (cases:controls) matching. Data were collected from the children's parents by questionnaires and telephone interviews. Setting Nation-wide study (former FRG) based on the German Childhood Cancer Registry. Subjects Cases born in 1988 and reported with a neuroblastoma to the registry until March …