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Aims: Paediatric brain tumours are rare, and establishing a precise diagnosis can be challenging. Analysis of DNA methylation profiles has been shown to be a reliable method to classify central nervous system (CNS) tumours with high accuracy. We aimed to prospectively analyse CNS tumours diagnosed in Sweden, to assess the clinical impact of adding DNA methylation-based classification to standard paediatric brain tumour diagnostics in an unselected cohort. Methods: All CNS tumours diagnosed in children (0-18 years) during 2017-2020 were eligible for inclusion provided sufficient tumour material was available. Tumours were analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier. The initial histopathological diagnosis was compared with the DNA methylation-based classification. For incongruent results, a blinded re-evaluation was performed by an experienced neuropathologist. Results: Two hundred forty tumours with a histopathology-based diagnosis were profiled. A high-confidence methylation score of 0.84 or more was reached in 78% of the cases. In 69%, the histopathological diagnosis was confirmed, and for some of these also refined, 6% were incongruent, and the re-evaluation favoured the methylation-based classification. In the remaining 3% of cases, the methylation class was non-contributory. The change in diagnosis would have had a direct impact on the clinical management in 5% of all patients. Conclusions: Integrating DNA methylation-based tumour classification into routine clinical analysis improves diagnostics and provides molecular information that is important for treatment decisions. The results from methylation profiling should be interpreted in the context of clinical and histopathological information., Funding Agencies|Swedish government; ALF-agreement; Lions Cancer Research Fund of Western Sweden; Swedish Research Council; Swedish Cancer Society; Swedish Childhood Cancer Fund

Complex social outcomes, including those related to education and employment, depend on compound combinations of background factors that are significantly different for childhood and adult cancers. Medical and psychosocial prerequisites related to the age at cancer diagnosis and treatment require surveillance for complex social outcomes that meets the particularized needs of corresponding patient subgroups.

Background The aim was to investigate whether children born after assisted reproduction technology (ART), particularly after frozen-thawed embryo transfer (FET), are at higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception. Methods and findings We performed a registry-based cohort study using data from the 4 Nordic countries: Denmark, Finland, Norway, and Sweden. The study included 7,944,248 children, out of whom 171,774 children were born after use of ART (2.2%) and 7,772,474 children were born after spontaneous conception, representing all children born between the years 1994 to 2014 in Denmark, 1990 to 2014 in Finland, 1984 to 2015 in Norway, and 1985 to 2015 in Sweden. Rates for any cancer and specific cancer groups in children born after each conception method were determined by cross-linking national ART registry data with national cancer and health data registries and population registries. We used Cox proportional hazards models to estimate the risk of any cancer, with age as the time scale. After a mean follow-up of 9.9 and 12.5 years, the incidence rate (IR) of cancer before age 18 years was 19.3/100,000 person-years for children born after ART (329 cases) and 16.7/ 100,000 person-years for children born after spontaneous conception (16,184 cases). Adjusted hazard ratio (aHR) was 1.08, 95% confidence interval (CI) 0.96 to 1.21, p = 0.18. Adjustment was performed for sex, plurality, year of birth, country of birth, maternal age at birth, and parity. Children born after FET had a higher risk of cancer (48 cases; IR 30.1/ 100,000 person-years) compared to both fresh embryo transfer (IR 18.8/100,000 personyears), aHR 1.59, 95% CI 1.15 to 2.20, p = 0.005, and spontaneous conception, aHR 1.65, 95% CI 1.24 to 2.19, p = 0.001. Adjustment either for macrosomia, birth weight, or major birth defects attenuated the association marginally. Higher risks of epithelial tumors and melanoma after any assisted reproducti

Giorgio Tettamanti,1 Rickard Ljung,1 Anders Ahlbom,1 Mats Talbäck,1 Birgitta Lannering,2 Tiit Mathiesen,3,4 Jenny Pettersson Segerlind,3 Maria Feychting1 1Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Pediatric Oncology, Department of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden; 3Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 4Department of Clinical Medicine, University of Copenhagen and Rigshospitalet, Copenhagen, Denmark Background: The Swedish Cancer Register (SCR) is characterized by excellent quality and completeness overall, but the quality of the reporting may vary according to tumor site and age, and may change over time. The aim of the current study was to investigate the completeness of the reporting of central nervous system (CNS) tumor cases to the SCR. Materials and methods: Individuals hospitalized for a CNS tumor between 1990 and 2014 were identified using the Inpatient Register; the proportion of identified cases that did not have any cancer diagnosis reported to the SCR was subsequently assessed. Results: Between 1990 and 2014, 58,698 individuals were hospitalized for a CNS tumor, and a large proportion of them did not have any cancer diagnosis reported to the SCR (26%). This discrepancy was particularly pronounced for benign tumors and among elderly patients (over 30%). It was substantially lower for malignant brain tumors among adults (10%); moreover, no increase in the discrepancy between the two registers was observed in this group during the study period. Similar findings were found when assessing the concordance between the Cause of Death Register and the SCR. Among CNS tumor patients who were not reported to the SCR, a large proportion had only one hospital discharge diagnosis containing a CNS tumor (35%) and were less likely to be found in the Outpatient Register, which indicates that a large proportion of patients may have re

Genetic risk score (GRS) is used to demonstrate the genetic variants contributing to the polygenic architecture of complex diseases. By using a GRS, we have investigated the additive impact of the known adult glioma susceptibility loci on the pediatric brain tumor (PBT) risk and assessed the proportion of PBT heritability attributable to these susceptibility loci. A GRS was generated for PBTs based on the alleles and associated effect sizes derived from a previously published genome-wide association study on adult glioma. The GRS was calculated in CEFALO, a population-based case-control study of brain tumors in children and adolescents including saliva DNA of 245 cases and 489 controls. The unconditional logistic regression model was used to investigate the association between standardized GRS and risk of PBTs. To measure the variance explained by the effect of GRS, Nagelkerke pseudo-R$^{2}$ was calculated. The GRS for adult brain tumors was associated with an increased risk of PBTs (OR 1.25 [95% CI 1.06-1.49], p = 0.009) and 0.3% of the variance in PBTs could be explained by the effect of GRS on the liability scale. This study provides evidence that heritable risks of PBTs are in-part attributable to some common genetic variants associated with adult glioma.

Background: The Swedish Cancer Register (SCR) is characterized by excellent quality and completeness overall, but the quality of the reporting may vary according to tumor site and age, and may change over time. The aim of the current study was to investigate the completeness of the reporting of central nervous system (CNS) tumor cases to the SCR. Materials and methods: Individuals hospitalized for a CNS tumor between 1990 and 2014 were identified using the Inpatient Register; the proportion of identified cases that did not have any cancer diagnosis reported to the SCR was subsequently assessed. Results: Between 1990 and 2014, 58,698 individuals were hospitalized for a CNS tumor, and a large proportion of them did not have any cancer diagnosis reported to the SCR (26%). This discrepancy was particularly pronounced for benign tumors and among elderly patients (over 30%). It was substantially lower for malignant brain tumors among adults (10%); moreover, no increase in the discrepancy between the two registers was observed in this group during the study period. Similar findings were found when assessing the concordance between the Cause of Death Register and the SCR. Among CNS tumor patients who were not reported to the SCR, a large proportion had only one hospital discharge diagnosis containing a CNS tumor (35%) and were less likely to be found in the Outpatient Register, which indicates that a large proportion of patients may have received an erroneous diagnosis. Conclusion: While a large proportion of CNS tumor patients were not reported to the SCR, the discrepancy between the SCR and the Inpatient Register was relatively small for malignant brain tumors among adults and has remained stable throughout the study period. We do not recommend that data from the Inpatient Register are combined with the SCR to estimate CNS tumor incidence, without proper confirmation of the diagnoses, as a considerable proportion of CNS tumor diagnoses registered in the Inpatient Regis

Background: This study examines information needs and satisfaction with provided informationamong childhood central nervous system (CNS) tumor survivors and their parents.Material and methods: In a population-based sample of 697 adult survivors in Sweden, 518 survivorsand 551 parents provided data. Information needs and satisfaction with information were studied usinga multi-dimensional standardized questionnaire addressing information-related issues.Results: Overall, 52% of the survivors and 48% of the parents reported no, or only minor, satisfactionwith the extent of provided information, and 51% of the survivors expressed a need for more informationthan provided. The information received was found useful (to some extent/very much) by 53%,while 47% did not find it useful, or to a minor degree only. Obtaining written material was associatedwith greater satisfaction and usefulness of information. Dissatisfaction with information was associatedwith longer time since diagnosis, poorer current health status and female sex. The survivors experiencedunmet information needs vis-a-vis late effects, illness education, rehabilitation and psychologicalservices. Overall, parents were more dissatisfied than the survivors.Conclusion: These findings have implications for improvements in information delivery. Information inchildhood CNS tumor care and follow-up should specifically address issues where insufficiency wasidentified, and recognize persistent and with time changing needs at the successive stages of longtermsurvivorship., The study was funded also by: Jane and Dan Olsson Foundation for Science, Sweden., The Swedish childhood CNS tumor LIFE study

Maral Adel Fahmideh,1 Giorgio Tettamanti,1 Catharina Lavebratt,2 Mats Talbäck,1 Tiit Mathiesen,3,4 Birgitta Lannering,5 Kimberly J Johnson,6,7 Maria Feychting1 1Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; 3Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 4University of Copenhagen, Copenhagen, Denmark; 5Department of Pediatrics, University of Gothenburg, Gothenburg, Sweden; 6Brown School, Washington University in St Louis, St Louis, MO, USA; 7Department of Pediatrics, School of Medicine, Washington University in St Louis, St Louis, MO, USA Purpose: Phacomatoses are genetic syndromes that are associated with increased risk of developing nervous system tumors. Phacomatoses are usually inherited, but many develop de novo, with unknown etiology. In this population-based study, we investigated the effect of parental age on the risk of phacomatoses in offspring. Patients and methods: The study was a population-based nested case–control study. All individuals born and residing in Sweden between January 1960 and December 2010 were eligible for inclusion. Using the Patient Register, 4625 phacomatosis cases were identified and further classified as familial or nonfamilial. Ten matched controls per case were randomly selected from the eligible population. Data were analyzed using conditional logistic regression. Analyses were conducted for neurofibromatosis alone (n=2089) and other phacomatoses combined (n=2536). Results: Compared with offspring of fathers aged 25–29 years, increased risk estimates of nonfamilial neurofibromatosis were found for offspring of fathers aged 35–39 years (odds ratio [OR]=1.43 [95% CI 1.16–1.74]) and ≥40&a