Impact of the COVID-19 pandemic on incidence, time of diagnosis and delivery of healthcare among paediatric oncology patients in Germany in 2020: Evidence from the German Childhood Cancer Registry and a qualitative survey.

ABSTRACT Background The indirect impact of the COVID-19 pandemic on cancer care and timely diagnosis is of increasing concern. We investigated the impact of the COVID-19 pandemic on incidence, time of diagnosis and delivery of healthcare among paediatric oncology patients in Germany in 2020. Methods We analysed incident paediatric cancer cases diagnosed in 0- to 17-year olds in Germany in 2020 using data of the German Childhood Cancer Registry. Absolute numbers and age-standardised incidence rates (ASR) in 2020 were compared to the previous five years (2015–2019). Moreover, we conducted a survey with open-ended questions, gathering perceptions of the diagnostic process and healthcare delive…

Early deaths from childhood cancer in Germany 1980-2016

Abstract Background Even though the survival of childhood cancer has improved over the last decades, there are still children dying shortly after diagnosis. The aim of the study is to add to understanding of the reasons for deaths shortly after date of diagnosis. Methods Using data of the population-based German Childhood Cancer Registry (cancer below 15 years of age diagnosed between 1980 and 2016), we compared characteristics of 671 children with cancer who died within 30 days of diagnosis to 53,649 patients with childhood cancer who survived longer. In addition to a descriptive analysis, we used logistic regression with multivariable fractional polynomials to describe the relationship be…

Health status, health-related quality of life, and socioeconomic outcome in childhood brain tumor survivors: a German cohort study

Abstract Background With rising numbers of childhood cancer survivors, somatic and socioeconomic outcome as well as health-related quality of life (QoL) gain increasing relevance. Based on the first nationwide German Survey on Life Situation, State of Health, and Quality of Life of Childhood Cancer Survivors, the VIVE survey, we report the outcome of survivors of childhood brain tumors localized in the posterior fossa. Methods Two hundred seventy participants with a median follow-up period of 21.9 years completed a questionnaire on socioeconomic and somatic late effects as well as a standardized QoL questionnaire (European Organisation for Research and Treatment of Cancer QLQ-C30). Comparis…

Temporal trends in the incidence rate of childhood cancer in Germany 1987-2004.

The German Childhood Cancer Registry regularly presents graphs of childhood cancer incidence rates by period, but no systematic analysis. The Automated Childhood Cancer Information System-project found an increasing trend in Europe. Against this background we present the first detailed trend analysis of childhood (aged under 15) malignancies in Germany. We examined incidence rates separately in western Germany 1987-2004 and eastern Germany 1991-2004. We analyzed all malignancies, all main diagnostic groups and relevant subsets using an age-period-cohort model. Additionally we fitted fractional polynomials to assess the linearity of the drift. All malignancies combined (excluding Central Ner…

Epidemiologie, Ätiologie, Prävention

Welches sind die Ursachen von Krebserkrankungen im Kindes- und Jugendalter? Welche Rolle spielen Umweltfaktoren bei der Entstehung dieser Erkrankungen? Eine Grundlage zur Beantwortung dieser Fragen bilden epidemiologische Krebsregister, wie etwa das 1980 auf Initiative der deutschsprachigen padiatrischen Onkologen gegrundete Deutsche Kinderkrebsregister. Mit einem solchen Register kann z. B. beantwortet werden, wie haufig Krebserkrankungen auftreten, ob Veranderungen in der Auftretenshaufigkeit zu beobachten sind oder ob sich die Prognose generell verbessert hat. Dies ist dank der guten Zusammenarbeit der Krebsregister untereinander moglich und wird intensiv ge nutzt. Aufbauend auf der dami…

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…

Second malignancies after treatment of childhood non-Hodgkin lymphoma: a report of the Berlin-Frankfurt-Muenster study group

Haematologica : journal of the European Hematology Association 106(5), 1390-1400 (2021). doi:10.3324/haematol.2019.244780

Increased Cancer Incidence Following up to 15 Years after Cardiac Catheterization in Infants under One Year between 1980 and 1998—A Single Center Observational Study

Objective: To evaluate the incidence of cancer within the first 15 years of life in children who underwent cardiac catheterization under the age of one year. Methods: In this retrospective, single center study, 2770 infants (7.8% with trisomy 21) were studied. All infants underwent cardiac catheterization under one year of age between January 1980 and December 1998. Newly diagnosed cancer in the first 15 years of life was assessed through record linkage to the German Childhood Cancer Registry (GCCR). Cancer risk in study patients was compared to the GCCR population of children less than 15 years. Patients with trisomy 21 were compared to the Danish Cytogenic Register for trisomy 21. Effecti…

Second follow-up of a German cohort on childhood cancer incidence after exposure to postnatal diagnostic x-ray.

Studies on children exposed to ionizing radiation by computed tomography (CT) indicate an increased risk of leukemia and central nervous system (CNS) tumors. Evidence of the risks associated with diagnostic X-ray examinations, the most frequent examination in pediatric radiology, in which the radiation dose is up to 750 times lower compared to CT examinations, is less clear.a#13; This study presents results of the second follow-up for the risk of childhood cancer in a cohort of children (alt;15 years) with diagnostic X-ray exposure at a large German hospital during 1976-2003 followed for additional 10 years until 2016.a#13; With a latency period of six months, 92,998 children contributed 79…

Childhood Cancer Risk From Conventional Radiographic Examinations for Selected Referral Criteria: Results From a Large Cohort Study

OBJECTIVE: Little is known about the long-term effects of exposure to diagnostic ionizing radiation in childhood. Current estimates are made with models derived mainly from studies of atomic bomb survivors, a population that differs from today's patients in many respects. MATERIALS AND METHODS: We analyzed the cancer incidence among children who underwent diagnostic x-ray exposures between 1976 and 2003 in a large German university hospital. We reconstructed individual radiation doses for each examination and sorted results by groups of referral criteria for all cancers combined, solid tumors, and leukemia and lymphoma combined. RESULTS: A total of 68 incidence cancer cases between 1980…

PanCareLIFE

Aims: Survival after cancer diagnosed during childhood or adolescence continues to improve with new treatments and supportive therapies. Optimal long-term care requires that risks to vulnerable organs are clearly defined and translated into guidelines that are implemented into practice. PanCareLIFE is a pan-European consortium that addresses survivorship issues comprising fertility, hearing impairment and quality of life. This article describes the scientific basis of PanCareLIFE's studies.Methods: PanCareLIFE involves 17 partner institutions from eight European countries, with additional 11 data providers from five other countries. Study designs and methods include molecular genetic, cohor…

A Cohort Study of Childhood Cancer Incidence after Postnatal Diagnostic X-Ray Exposure

Ionizing radiation is an established cause of cancer, yet little is known about the health effects of doses from diagnostic examinations in children. The risk of childhood cancer was studied in a cohort of 92.957 children who had been examined with diagnostic X rays in a large German hospital during 1976-2003. Radiation doses were reconstructed using the individual dose area product and other exposure parameters, together with conversion coefficients developed specifically for the medical devices and standards used at the radiology department. Newly diagnosed cancers occurring between 1980 and 2006 were determined through record linkage to the German Childhood Cancer Registry. The median ra…

Pilotstudie zur sonogra- phischen Fr�herkennung des Nierenzellkarzinoms

Die zunehmende Zahl der zufallig mit der Ultraschalluntersuchung entdeckter, kleiner, asymptomatischer Nierenzellkarzinome, wirft die Frage der Praktikabilitat und Effektivitat einer systematisierten Screeninuntersuchung des Nierenzellkarzinoms mittels Sonographie auf. Vor diesem Hintergrund wurde eine Machbarkeitsstudie im Rahmen des Fruherkennungsprogramms des Bundesministeriums fur Gesundheit initiiert. Methodik: In 2 Stadten, Mainz und Wuppertal, wurde ein Fruherkennungsprogramm fur das Nierenzellkarzinom etabliert, bei dem allen Einwohnern (Alter uber 40 Jahre) eine kostenlose Ultraschalluntersuchung der Nieren angeboten wurde. Das Screening unterteilte sich in 2 Phasen (Laufzeit 1 Jah…

Spontaneous and Radiation-Induced Chromosome Aberrations in Primary Fibroblasts of Patients With Pediatric First and Second Neoplasms

Frontiers in oncology 10, 1338 (2020). doi:10.3389/fonc.2020.01338

Das Langzeit-Follow-up in der deutschen pädiatrischen Onkologie als Basis für die Durchführung von Studien mit Langzeitüberlebenden

BACKGROUND In recent years, the long-term survival of childhood cancer patients has increased considerably. While this is desirable, more patients with late effects are to be expected and studies thereof become increasingly important. We will need to be able to stay in touch with as many former patients as possible in order to make a systematic and comprehensive long-term follow-up possible. PATIENTS Childhood cancer patients under 15 years of age at diagnosis resident in Germany and registered at the German Childhood Cancer Registry (GCCR). METHODS The GCCR has established a 3-phase procedure for follow-up. We developed principles for the long-term follow up of these patients. They are bas…

Nephron-sparing surgery of renal cell carcinoma with a normal opposite kidney: long-term outcome in 180 patients

Abstract Objectives. To investigate the long-term outcome of an organ-saving approach for renal cell carcinoma (RCC) with a normal opposite kidney (elective indication). Methods. Since 1979, 180 patients have undergone nephron-sparing surgery at our institution for RCC in the presence of a normal contralateral kidney. The mean age was 56 years (range 23 to 83), and the mean follow-up was 4.7 years (maximum 14.8). Most of these tumors were found incidentally, with a mean tumor diameter on ultrasound of 3.3 cm (range 1.0 to 8.6). Results. The postoperative course was unremarkable in 173 patients. Postoperative bleeding was encountered in 4 patients and urinary extravasation in an additional 3…

Parental informed consent in pediatric cancer trials: A population-based survey in Germany

In Germany, nearly every child afflicted by a malignant dis-ease or a central nervous system tumor is enrolled in a clinicaltrial during treatment. Many of these children are under the age of5 years when they are first diagnosed [1]. The decision whether ornot to participate in a clinical trial is normally made by theparents on behalf of their child. Therefore, ensuring adequatelyinformed parental consent is essential to ethical practice in pedi-atric oncology.However, many empirical studies have revealed difficultieswith the informed consent process when parents are faced withthe decision to enroll their child in a clinical trial. Previous studyfindings have indicated that recalling signing th…

Effect of genetic variation in CYP450 on Gonadal impairment in a European cohort of female childhood cancer survivors, based on a candidate gene approach

Background: Female childhood cancer survivors (CCSs) carry a risk of therapy-related gonadal dysfunction. Alkylating agents (AA) are well-established risk factors, yet inter-individual variability in ovarian function is observed. Polymorphisms in CYP450 enzymes may explain this variability in AA-induced ovarian damage. We aimed to evaluate associations between previously identified genetic polymorphisms in CYP450 enzymes and AA-related ovarian function among adult CCSs. Methods: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function in a discovery cohort of adult female CCSs, from the pan-European PanCareLIFE cohort (n = 743

Strategy for Long-Term Surveillance at the German Childhood Cancer Registry - an Update

Background The objective of this paper is to provide information about the quality (e.g. completeness, response) of long-term surveillance in German paediatric oncology and haematology based on the structures implemented by the German Childhood Cancer Registry (GCCR). Methods The GCCR contacts parents or patients to collect and update information on a minimal set of follow-up health status data (e.g. late relapses, subsequent neoplasms, current address) and exchanges this information regularly with the appropriate clinical trials. Results Between 2006 and 2010, GCCR approached a total of about 20,000 patients (contact at the age of 16 years, inquiry concerning the health status) in the cont…

Pediatric second primary malignancies after retinoblastoma treatment

Background Children with retinoblastoma carry a high risk to develop second primary malignancies in childhood and adolescence. This study characterizes the type of pediatric second primary malignancies after retinoblastoma treatment and investigates the impact of different treatment strategies and prognostic factors at presentation. Procedure All national patients treated for retinoblastoma at the German referral center with a current age of 6–27 years were invited to participate in a study to characterize late effects. Results Data on pediatric second primary malignancies were recorded from 488 patients. Ten developed a malignancy before the age of 18 years. For children with heterozygous …

Second Malignancies Following Childhood Cancer Treatment in Germany From 1980 to 2014.

BACKGROUND Because of improvements in cancer treatment, more than 80% of all children with cancer now survive at least five years from the time of diagnosis. As a result, late sequelae of cancer and its treatment have become more common, particularly second malignancies. We studied the current incidence of second malignancies among childhood cancer survivors in Germany. METHODS This study is based on the cohort of the German Childhood Cancer Registry (Deutsches Kinderkrebsregister, DKKR). Persons given the diagnosis of a first malignancy at any time in the years 1980-2014 who were no more than 14 years old at the time of diagnosis and survived at least six months thereafter were included in…

Cancer patterns among children of Turkish descent in Germany: A study at the German Childhood Cancer Registry

Abstract Background Cancer risks of migrants might differ from risks of the indigenous population due to differences in socioeconomic status, life style, or genetic factors. The aim of this study was to investigate cancer patterns among children of Turkish descent in Germany. Methods We identified cases with Turkish names (as a proxy of Turkish descent) among the 37,259 cases of childhood cancer registered in the German Childhood Cancer Registry (GCCR) during 1980–2005. As it is not possible to obtain reference population data for children of Turkish descent, the distribution of cancer diagnoses was compared between cases of Turkish descent and all remaining (mainly German) cases in the reg…

Screening

Background The early detection of cancer and other diseases is generally considered beneficial, yet there is evidence that in some diseases screening may be of limited benefit. To clarify this issue, we present the statistical principles that underlie screening. Methods We define screening and discuss the conditions for its successful use. We give illustrative examples from among the currently recommended types of screening in Germany and from the recent medical literature, particularly with regard to mammography.

Childhood cancer predisposition syndromes-A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology.

Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient. This review su…

Prevalence of cardiovascular late sequelae in long-term survivors of childhood cancer: A systematic review and meta-analysis

Background Cardiovascular diseases are well-known late effects of childhood cancer and research on these late effects is a highly important emerging field. We conducted a systematic review with a meta-analysis to give an overview of the current evidence and the prevalence of late cardiovascular events. Procedure We included publications in which the study populations were children and adolescents who survived cancer. Outcome was defined as all cardiovascular clinical and subclinical endpoints or diagnoses appearing at least one year after cancer diagnosis. A systematic overview is presented for all included studies. A quantitative meta-analysis was conducted for hypertension and stroke. Res…

Childhood Leukemia in the Vicinity of Nuclear Power Plants in Germany

SUMMARY The causes of leukemia are largely unclear. The question whether leukemia rates are increased near nuclear power plants is controversial. The German Childhood Cancer Registry has published an epidemiological case-control study on childhood cancer and nuclear power plants. Method: The study was based on the distance of children's residences from nuclear power plants and addressed the question whether children under age 5 with cancer live closer, on average, to nuclear power plants than randomly selected controls. Odds Ratios (OR) for distance categories and standardized incidence ratios (SIR) were calculated. Results: An association was found between the nearness of residence to nucl…

Screening for renal cell carcinoma using ultrasonography: a feasibility study

OBJECTIVE To assess the practicability and efficacy of systematic screening for renal cell carcinoma (RCC) by ultrasonography (US), as more small RCCs are being detected incidentally by US. SUBJECTS AND METHODS A 2-year screening programme for RCC was established for the general population (aged ≥ 40 years) in two German cities, Mainz and Wuppertal. In cooperation with different health insurers, the organisers recruited general practitioners, internists and urologists in private practice who were experienced in and equipped to conduct renal US. The screening was offered in the form of cost-free renal US in the first year and a re-examination in the second. For any equivocal or positive rena…

Return and Disclosure of Research Results: Parental Attitudes and Needs Over Time in Pediatric Oncology.

Objectives To explore parental attitudes regarding the return and disclosure of research findings in pediatric cancer trials over time. Study design Two surveys were set up to evaluate the stability of parental attitudes. One survey was carried out among 581 parents whose child was diagnosed recently (response rate, 53.5%). A second, population-based survey was set up with a time interval of 4 years between first cancer diagnosis and survey in which 1465 parents were included (response rate, 55.1%). Results Almost all surveyed parents stated a parental right to receive aggregate research results. Fifty-five percent of the parents who recently participated in trials and 62% of those asked af…

Inzidenz von Kinderkrebs nach Röntgendiagnostik im Patientenkollektiv der Jahre 1976 – 2003 einer Universitäts-Kinderklinik

Purpose: Although the carcinogenic effect of ionizing radiation is well known, knowledge gaps persist on the health effects of low-dose radiation, especially in children. The cancer incidence rate in a cohort of 92,957 children diagnosed using X-rays in the years 1976-2003 in the radiology department of a large university clinic was studied. Materials and Methods: Individual radiation doses per examination were reconstructed using an algorithm taking into account the dose area product and other exposure parameters together with conversion factors computed specifically for the equipment and protocols used in the radiology department. Incident cancer cases in the period 1980-2006 were identif…

Extremely low-frequency magnetic fields and survival from childhood acute lymphoblastic leukemia: an international follow-up study

A previous US study reported poorer survival in children with acute lymphoblastic leukemia (ALL) exposed to extremely low-frequency magnetic fields (ELF–MF) above 0.3 μT, but based on small numbers. Data from 3073 cases of childhood ALL were pooled from prospective studies conducted in Canada, Denmark, Germany, Japan, UK and US to determine death or relapse up to 10 years from diagnosis. Adjusting for known prognostic factors, we calculated hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival and event-free survival for ELF–MF exposure categories and by 0.1 μT increases. The HRs by 0.1 μT increases were 1.00 (CI, 0.93–1.07) for event-free survival analysis and 1.04 (CI…

Cancer in Children With Fanconi Anemia and Ataxia-Telangiectasia—A Nationwide Register-Based Cohort Study in Germany

PURPOSE Fanconi anemia (FA) and ataxia-telangiectasia (AT) are rare inherited syndromes characterized by abnormal DNA damage response and caused by pathogenic variants in key DNA repair proteins that are also relevant in the pathogenesis of breast cancer and other cancer types. The risk of cancer in children with these diseases is poorly understood and has never been assessed in a population-based cohort before. METHODS We identified 421 patients with FA and 160 patients with AT diagnosed between 1973 and 2020 through German DNA repair disorder reference laboratories. We linked patients' laboratory data with childhood cancer data from the German Childhood Cancer Registry. RESULTS Among 421 …

Burden of cardiovascular risk factors and cardiovascular disease in childhood cancer survivors: Data from the German CVSS-study.

Aims: The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS)-study aimed to quantify the prevalence of cardiovascular risk factors (CVRF) and cardiovascular disease (CVD) in German childhood cancer survivors (CCS). Methods and results: In the CVSS-study (NCT02181049), 1002 CCS (age range 23-48 years) diagnosed with neoplasia prior to 15 years of age between 1980 and 1990 prospectively underwent a systematic, standardized clinical and laboratory cardiovascular screening, identical to the population-based Gutenberg Health Study (GHS) cohort. For 951 individuals, prevalences of CVRF and CVD were primarily compared to the GHS sample and to two further German po…

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…

Mental health and health-related quality of life in preschool-aged childhood cancer survivors. Results of the prospective cohort study ikidS-OEVA.

Objectives Long-term survivors of childhood cancer are at increased risk for sequelae such as poor mental health (MH) or impaired health-related quality of life (HrQoL). We aimed to evaluate early adverse effects on MH and HrQoL in young childhood cancer survivors (YCCS) before school entry. Methods In a nationwide prospective cohort study, children with cancer other than brain tumors diagnosed at preschool age and completed cancer treatments were identified from the German Childhood Cancer Registry. The comparison group was children of the same age without a cancer diagnosis who participated in the prospective population-based health survey ikidS. MH problems and HrQoL were assessed by par…

Complementary and alternative treatment methods in children with cancer. A population based retrospective survey on the prevalence of use in Germany

Introduction Few studies have been conducted to date on the prevalence of use of complementary and alternative treatment methods (CAM) in paediatric oncology and those that have been conducted are often not representative. We therefore decided to study a representative sample of children with cancer in the German population. Patients and methods The study took the form of a retrospective survey amongst all parents whose children were first diagnosed with a disease covered by the German Childhood Cancer Registry in 2001. The primary objectives of the survey were to establish the prevalence of use of CAM and the factors related to its use. Results Of the 1595 questionnaires sent out, 1063 (67…

28-year incidence and time trends of childhood leukaemia in former East Germany compared to West Germany after German reunification: A study from the German Childhood Cancer Registry

Abstract Background The aetiology of childhood leukaemia is largely unknown. Analyses of geographical differences may enhance aetiologic insights. The reunification of Germany in 1990 provides a unique opportunity to evaluate incidence patterns and time trends in two merging countries with substantial lifestyle, social and socioeconomic differences. With this study we provide an extensive assessment of 28-year incidence patterns and temporal trends after the German reunification. Methods We identified all children diagnosed with a lymphoid leukaemia (LL) or acute myeloid leukaemia (AML) before the age of 15 years between 1991 and 2018 using the German Childhood Cancer Registry (N = 14,922),…

Incidence, Trends, and Survival of Children With Embryonal Tumors.

BACKGROUND: Central nervous system (CNS) and non-CNS embryonal tumors occur principally in children and are rarely seen in adults. The incidence rates for rare entities such as atypical teratoid/rhabdoid tumors (AT/RT) or primitive neuroectodermal tumors in the CNS are rarely published. Incidence rates for certain subgroups, such as hepatoblastomas, have been increasing in some countries. METHODS: Data of 8337 embryonal tumors, registered in children (0–14 years) between 1991 and 2012 (for AT/RT 2000–2012) in the population-based German Childhood Cancer Registry with complete national coverage were analyzed for incidence rates, time trends, and survival. RESULTS: For most entities, the inc…

CAF-like state in primary skin fibroblasts with constitutional BRCA1 epimutation sheds new light on tumor suppressor deficiency-related changes in healthy tissue

Constitutive epimutations of tumor suppressor genes are increasingly considered as cancer predisposing factors equally to sequence mutations. In light of the emerging role of the microenvironment for cancer predisposition, initiation, and progression, we aimed to characterize the consequences of a BRCA1 epimutation in cells of mesenchymal origin. We performed a comprehensive molecular and cellular comparison of primary dermal fibroblasts taken from a monozygous twin pair discordant for recurrent cancers and BRCA1 epimutation, whose exceptional clinical case we previously reported in this journal. Comparative transcriptome analysis identified differential expression of extracellular matrix-r…

Methods of spatial cluster detection in rare childhood cancers: Benchmarking data and results from a simulation study on nephroblastoma

Abstract The potential existence of spatial clusters in childhood cancer incidence is a debated topic. Identification of rare disease clusters in general may help to better understand disease etiology and develop preventive strategies against such entities. The incidence of newly diagnosed childhood malignancies under 15 years of age is 140/1,000,000. In this context, the subgroup of nephroblastoma represents an extremely rare entity with an annual incidence of 7/1,000,000. We evaluated widely used statistical approaches for spatial cluster detection in childhood cancer (Ref. [22] Schundeln et al., 2021, Cancer Epidemiology). For the simulation study, random high risk clusters of 1 to 50 ad…

Treatment of embryonal tumors with multilayered rosettes with carboplatin/etoposide induction and high-dose chemotherapy within the prospective P-HIT trial

Abstract Background Embryonal tumors with multilayered rosettes (ETMR) are highly aggressive tumors occurring in early childhood. Published clinical data refer to retrospective, heterogeneously treated cohorts. Here, we describe the outcome of patients treated according to the prospective P-HIT trial and subsequent HIT2000-interim-registry. Patients and methods Age-stratified treatment included carboplatin/etoposide induction, tandem high-dose chemotherapy (“CARBO/ETO + HDCT”), and response-stratified radiotherapy. Patients with centrally reviewed neuropathological and molecularly confirmed diagnosis of ETMR recruited within the P-HIT trial (2001-2011; n = 19), the HIT2000-interim-registry …

Health-related quality of life in European childhood cancer survivors: Protocol for a study within PanCareLIFE

Background Survival after childhood cancer has improved to more than 80% during the last few years, leading to an increased number of childhood cancer survivors. Cancer itself, or its treatment, may cause chronic health conditions, including somatic and mental sequelae, which may affect survivors’ health-related quality of life (HRQoL). Objective The project PanCareLIFE aims to establish a large database with comprehensive data on childhood cancer survivors from different European countries, including data on HRQoL. Within PanCareLIFE, this study aims to describe HRQoL in survivors, investigate predictors of HRQoL, and describe the association of HRQoL with hearing and female fertility imp…

Incidence of childhood cancer of the head and neck in Germany.

Background: Only very limited data are available in the literature on the incidence of childhood cancer of the head and neck worldwide. Methods: Based on data obtained from the national German Childhood Cancer Registry, a total of 370 malignancies of the head and neck in children under the age of 15 (199 boys and 171 girls), which were reported to this institution between 1994 and 2003, were analysed in this study. Results: The overall incidence of malignancies of specific sites of the head and neck in Germany is 4.48 per 100000 children. The most frequently observed entities, representing primary tumours, are soft tissue sarcomas (0.39/100000), lymphomas (0.09/100000) and thyroid carcinoma…

Searching for Gene Expression Differences in Primary Fibroblasts Between Patients with One and Two Neoplasms in Childhood

Genetic factors are important for developing primary and subsequent malignancies in children. This study investigated the role of genetic factors involved in DNA-repair. Designed as a feasibility study, it addressed the possibility of obtaining samples for genetic analyses from former patients through the German Childhood Cancer Registry. Testing feasibility was as important as the biological question itself. We analyzed the expression of DNA-repair genes in untreated primary fibroblasts of 20 individuals with a second neoplasm compared to 20 matched single neoplasm cases using customized cDNA microarrays (1344 gene sequences, about 800 genes). Matching was by first neoplasm, age, and year …

Screening for renal cell carcinoma using ultrasonography: a feasibility study

Association of candidate pharmacogenetic markers with platinum-induced ototoxicity

Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patien…

Incidence and time trends of soft tissue sarcomas in German children 1985-2004 - a report from the population-based German Childhood Cancer Registry.

Abstract The incidence of soft tissue sarcoma (STS) in Europe is increasing, but it is unclear whether this increase can also be seen in Germany. We analysed the heterogeneous group of STS recorded to the German Childhood Cancer Registry (GCCR) between 1985 and 2004 with respect to incidence data. Age-specific, age-standardised and cumulative incidence rates were calculated. Additionally, the average annual percent change (AAPC), derived from a Poisson regression model, was estimated, using time in years as the explanatory, continuous variable. Two thousand sixty-one children were diagnosed at a median age of 72 months. Most common are rhabdomyosarcomas (RMS) (n = 1202) and fibrosarcomas (n…

Sonographisches Screening von Nierenzellkarzinomen

Die zunehmende Zahl kleiner und zufallig meist beim Ultraschall entdeckter Nierenzellkarzinome, wirft die Frage auf der Praktikabilitat und Effektivitat einer systematischen Fruherkennungsuntersuchung des Nierenzellkarzinoms mittels Sonographie. Ein 2-Jahres Fruherkennungsprogramm fur das Nierenzellkarzinom (NZK) wurde in den Stadten Mainz und Wuppertal errichtet und der Bevolkerung (Alter > 40 Jahre) kostenlos angeboten. Das Screening wurde in Kooperation mit niedergelassenen Internisten, Allgemeinmediziner und Urologen organisiert und durchgefuhrt. Das Screening beinhaltete eine kostenlose Ultraschalluntersuchung der Nieren, sowie eine Nachuntersuchung nach einem Jahr. Eine Referenzsonogr…

Statistical methods for spatial cluster detection in childhood cancer incidence : A simulation study

BACKGROUND AND OBJECTIVE: The potential existence of spatial clusters in childhood cancer incidence is a debated topic. Identification of such clusters may help to better understand etiology and develop preventive strategies. We evaluated widely used statistical approaches to cluster detection in this context.; METHODS: Incidence of newly diagnosed childhood cancer (140/1,000,000 children under 15 years) and nephroblastoma (7/1,000,000) was simulated. Clusters of defined size (1-50) were randomly assembled on the district level in Germany. Each cluster was simulated with different relative risk levels (1-100). For each combination 2000 iterations were done. Simulated data was then analyzed …

Usefulness of current candidate genetic markers to identify childhood cancer patients at risk for platinum-induced ototoxicity: Results of the European PanCareLIFE cohort study

Background Irreversible sensorineural hearing loss is a common side effect of platinum treatment with the potential to significantly impair the neurocognitive, social and educational development of childhood cancer survivors. Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in the FDA drug label and a pharmacogenetic guideline. The aim of this cross-sectional cohort study was to confirm the genetic associations in a large pan-European population and to evaluate the diagnostic accuracy of the genetic…

Abstract 5504: Second neoplasms after childhood cancer and gene expression differences in primary fibroblasts

Abstract Treatment of the primary neoplasm with radiotherapy or chemotherapy is an established risk factor for second neoplasms (SNs) after childhood cancer. As only a small percentage of the treated children suffer from SN, other shared risk factors must be involved. A predisposition for the occurrence of a SN might be a pre-existing somatic genetic defect associated with DNA repair. We investigated the association between gene expression involved in DNA-repair and the development of SNs after childhood cancer. Designed as a feasibility study this project addressed the possibility of obtaining samples for genetic analyses from former patients through the German Childhood Cancer Registry. W…

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 …

Complementary and alternative treatment methods in children with cancer: A population-based retrospective survey on the prevalence of use in Germany.

Abstract Introduction Few studies have been conducted to date on the prevalence of use of complementary and alternative treatment methods (CAMs) in paediatric oncology, and those that have been conducted are often not representative. We therefore decided to study a representative sample of children with cancer in the German population. Patients and methods The study took the form of a retrospective survey amongst all parents whose children were first diagnosed with a disease covered by the German Childhood Cancer Registry in 2001. The primary objectives of the survey were to establish the prevalence of use of CAM and the factors related to its use. Results Of the 1595 questionnaires sent ou…

Doubling Recruitment of Pediatric Low-grade Glioma within Two Decades does not change Outcome – Report from the German LGG Studies

Successive multicenter studies for pediatric low-grade glioma (LGG) in Germany were accompanied by a doubling of annual recruitment over 2 decades. We investigated whether this increase conveyed a change of epidemiologic characteristics or survival.Participating centers reported 4634 patients with the radiologic/histologic diagnosis of LGG (1996-2018), rising from 109 to 278/year. Relating these numbers to all pediatric CNS tumors registered at the German Childhood Cancer Registry, the LGG fraction and annual crude incidence rates increased (32% to 51%; 0.94 to 2.12/100,000 children/adolescents15 years). The consecutive LGG studies recruited 899 (HIT-LGG 1996), 1592 (SIOP-LGG 2004), and 183…

Children may not benefit from neuroblastoma screening at 1 year of age. Updated results of the population based controlled trial in Germany

Neuroblastoma is the second most frequent malignancy in childhood. We investigated whether screening for neuroblastoma at 1 year of age reduces the incidence of metastatic disease or mortality. Screening was offered in 6 of the 16 German states from 1995 to 2000 with the remaining states serving as controls. We studied 2,581,188 children in the screening area born between 1994 and 1999 and 2,117,600 in the control area. We compared mortality from neuroblastoma and the incidence of disseminated disease in the two groups. The screened group and the control group had similar rates of stage 4 neuroblastoma and mortality due to neuroblastoma. Comparison of the screened group and the control area…

Mortality risk among 5‐year survivors of childhood cancer in Germany—Results from the CVSS study (Cardiac and Vascular late Sequelae in long‐term Survivors of childhood cancer study)

The growing population of long-term childhood cancer survivors is at increased risk for severe, therapy-related late effects and premature mortality. The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS) study is a cohort of patients from Germany diagnosed with a neoplasia prior to 15 years of age in the time period 1980 to 1990. Late mortality was evaluated in a total of 4505 individuals who survived 5 years or more after the initial diagnosis (5-year survivors). Survivors with a second primary tumor were excluded. Standardized mortality ratios (SMRs) were calculated. By December 2014, 400 patients had died. Available cause of death information from 188 i…