Publications by authors named "Spix C"

Objective: To discover new variants associated with low ovarian reserve after gonadotoxic treatment among adult female childhood cancer survivors using a genome-wide association study approach.

Design: Genome-wide association study.

Setting: Not applicable.

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Background: Tumors of the central nervous system (CNS) are the second most common type of pediatric cancer in Germany. We aimed to describe registration practice, incidence, and survival patterns for childhood CNS tumors in Germany for the past 40 years.

Procedure: Including all CNS tumor cases in children diagnosed at ages 0-14 years registered at the German Childhood Cancer Registry (GCCR) in 1980-2019 (for survival analysis 1980-2016), we calculated age-specific and age-standardized incidence rates (ASIR) over time, average annual percentage changes (AAPC), and 1- and 5-year overall survival.

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Background: This article describes the study design of the quantitative part of the VersKiK study, The primary objectives of this study are to examine the occurrence of late effects in survivors of childhood or adolescent cancer (module 1), investigate health-related vulnerabilities and medical service utilization within this survivor group (modules 1 and 3), and assess the alignment between documented follow-up care for cardiological and audiological late effects with guideline recommendations, along with evaluating the extent of adherence among paediatric cancer survivors (module 3).

Methods: This is a non-interventional retrospective observational cohort study. It is based on stochastically linked insurance claims data from approximately 150,000 statutory insured persons with information concerning around 25,000-30,000 cancer survivors recorded in the German Childhood Cancer Register (GCCR).

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Background The CVSS (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer) study aimed to investigate the prevalence of different stages of heart failure (HF) in childhood cancer survivors (CCSs) compared with the general population. Methods and Results A total of 1002 CCSs (age range, 23-48 years) diagnosed with neoplasia before an age of 15 years underwent a comprehensive cardiovascular screening. An age- and sex-matched sample from the population-based GHS (Gutenberg Health Study) served as a comparison group.

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The impact of the temporal sequence by which cranial radiotherapy (CRT) and platin-based chemotherapy (PCth) are administered on sensorineural hearing loss (SNHL) in pediatric and adolescent central nervous system (CNS) and head-and-neck (HN) cancer patients has not yet been studied in detail. We examined the ototoxic effects of sequentially applied CRT and PCth. This study included children and adolescents with CNS and HN tumors who participated in the multicountry PanCareLIFE (PCL) consortium.

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Introduction: In 2013, a new federal law obligated all German federal states to collect additional clinical data in population-based cancer registries as an active tool for monitoring and improving the quality of cancer care, increasing transparency and promoting health research. Now, 10 years later, the current status of the expanded cancer registration is presented, including current figures on cancer in Germany.

Methods: Reporting of cancer is mandatory for physicians, and about 5 to 10 reports from different healthcare providers are expected for each case.

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Background: Subsequent primary neoplasms (SPN) are among the most severe late effects and the second most frequent cause of death in childhood cancer patients. In this paper we introduce method and properties of the STATT-SCAR study (Second Tumor After Tumor Therapy, Second Cancer After Radiotherapy), which is a joint nested matched case-control study to evaluate the impact of chemotherapy (STATT) as well as radiotherapy (SCAR) on the risk of developing a SPN.

Methods: Based on the cohort of the German childhood cancer registry (GCCR), we selected patients diagnosed with a first neoplasm before age 15 or younger between 1980 and 2014.

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Background: Childhood and adolescent cancer constitutes only a very small fraction of the cancer cases in Germany and throughout the world, but it is the most frequent cause of disease-related death in children. The diagnostic spectrum differs markedly from that of adults. More than 90% of all cases of childhood and adolescent cancer in Germany are treated according to centralised protocols or in therapy studies.

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Introduction: Long non-coding ribonucleic acids (lncRNAs) are involved in the cellular damage response following exposure to ionizing radiation as applied in radiotherapy. However, the role of lncRNAs in radiation response concerning intrinsic susceptibility to late effects of radiation exposure has not been examined in general or in long-term survivors of childhood cancer with and without potentially radiotherapy-related second primary cancers, in particular.

Methods: Primary skin fibroblasts (n=52 each) of long-term childhood cancer survivors with a first primary cancer only (N1), at least one second primary neoplasm (N2+), as well as tumor-free controls (N0) from the KiKme case-control study were matched by sex, age, and additionally by year of diagnosis and entity of the first primary cancer.

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Childhood cancer is the leading disease-related cause of death among under 15 year olds in Europe. Since primary preventive measures are lacking, improving survival probabilities and long-term well-being remain primary goals. With this report, we provide the first long-term assessment and interpretation of patterns in childhood cancer survival in Germany, covering a period of 30 years.

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Article Synopsis
  • Childhood cancer survivors (CCS) face high risks for long-term health issues, particularly secondary primary neoplasms (SPN), prompting the development and validation of a self-administered questionnaire for assessing past cancer treatments and late effects.
  • The study involved comparing self-reported cancer treatments from CCS with their medical records, revealing perfect agreement for chemotherapy among SPN survivors and varying levels of agreement for other treatments across different groups.
  • Results indicated that CCS who received chemotherapy were less likely to be overweight, but had a higher likelihood of thyroid diseases and hypercholesterolemia, highlighting complex health outcomes linked to their treatment history.
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  • This study investigates expression variability (EV) in primary fibroblasts from childhood cancer survivors and cancer-free controls after exposure to ionizing radiation, focusing on distinguishing the effects across different donor groups.
  • Researchers analyzed skin fibroblasts from 156 donors: 52 with first primary neoplasms (N1), 52 with multiple primary neoplasms (N2+), and 52 cancer-free controls (N0), exposing them to varying doses of X-rays and identifying gene responses to radiation.
  • Key findings include the identification of 22 genes with significant EV variation linked to ionizing radiation, particularly noting unique gene responses in cancer-free individuals (N0) and higher variability in cancer survivors (N2+) related to cell
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Background: Epidemiological research on late effects of therapy shows the necessity to aggregate chemotherapy agents to substance classes. This requires using conversion factors by substance classes.

Aims: The aim of this study was to identify previously used conversion factors from the literature, to present a novel approach for additional factors, and to compare these approaches.

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Article Synopsis
  • * The study assessed the impact of mild replication stress on genomic instability in fibroblasts from long-term survivors of pediatric cancers, comparing those with SPNs, first primary neoplasms (FPNs), and healthy controls.
  • * Results indicated that survival fibroblasts from patients with SPNs showed greater sensitivity to replication stress, suggesting a potential mechanism for increased genomic instability and SPN development following DNA-damaging treatments.
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Background: The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years of diagnosis and provide new analytical perspectives on estimates of long-term survival and the cured fraction of patients with childhood cancer.

Methods: In this population-based study, we analysed 135 847 children (aged 0-14 years) diagnosed during 2000-13 and followed up to the end of 2014, recruited from 80 population-based cancer registries in 31 European countries.

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Background: It has been shown previously that a relevant proportion of childhood cancer survivors suffers from late effects, which are often directly related to the cancer itself or its therapy, resulting in particular follow-up needs, additionally burdening healthcare systems. Being diagnosed with cancer at a vulnerable stage of development, this group of cancer survivors is at comparatively higher risk of relapse or subsequent cancer. Although national and international follow-up guidelines based on treatment modalities have been developed, their implementation seems to leave room for improvement.

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Background: Primary lung malignancies are a heterogeneous group of cancers that occur very rarely in childhood. Due to limited knowledge of their epidemiologic and clinical features, these tumors present a challenge to the treating physicians. This study aimed to increase the knowledge about the occurrence of primary lung malignancies in childhood in Germany.

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Unlabelled: Very rare pediatric tumors (VRTs) pose a challenge for treating physicians as little is known about the best diagnostic assessment and therapeutic decision-making in these malignancies. A large proportion of these cancers occur in adolescence. Therefore, the established structures of pediatric oncology including cancer registration may partly be circumvented.

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Background And Objectives: One-third of childhood cancer long-term survivors suffer from severe late effects (e.g., secondary cancer and cardiovascular diseases).

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Article Synopsis
  • Most childhood cancers arise randomly without clear inherited causes or lifestyle factors, but certain risk factors may initiate cancer cell transformation.
  • The study examined the methylation of intron 2 in 20 childhood cancer patients (both those with a second cancer later and those without) and compared them with cancer-free controls, revealing some elevated methylation levels linked to oncogenic processes.
  • Findings suggest that hypermethylation of intron 2 may correlate with genomic changes and cancer progression, indicating its potential role as a biomarker for leukemia and other tumors in children.
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Background: In childhood cancer survivors (survival of 5 years or more after diagnosis), cardiac toxicity is the most common nonmalignant cause of death attributed to treatment-related consequences. Identifying patients at risk of developing late cardiac toxicity is therefore crucial to improving treatment outcomes. The use of genetic markers has been proposed, together with clinical risk factors, to predict individual risk of cardiac toxicity from cancer therapies, such as doxorubicin.

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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.

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