177 results on '"Wesenberg F"'
Search Results
2. The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse
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Schmiegelow, K, Heyman, M, Gustafsson, G, Lausen, B, Wesenberg, F, Kristinsson, J, Vettenranta, K, Schroeder, H, Forestier, E, and Rosthoej, S
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- 2010
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3. Thiopurine methyltransferase activity is related to the risk of relapse of childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study
- Author
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Schmiegelow, K, Forestier, E, Kristinsson, J, Söderhäll, S, Vettenranta, K, Weinshilboum, R, and Wesenberg, F
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- 2009
- Full Text
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4. Deletion of the Ink4-locus (the p16ink4a, p14ARF and p15ink4b genes) predicts relapse in children with ALL treated according to the Nordic protocols NOPHO-86 and NOPHO-92
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Calero Moreno, TM, Gustafsson, G, Garwicz, S, Grandér, D, Jonmundsson, GK, Frost, B-M, Mäkipernaa, A, Rasool, O, Savolainen, E-R, Schmiegelow, K, Söderhäll, S, Vettenranta, K, Wesenberg, F, Einhorn, S, and Heyman, M
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- 2002
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5. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort
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Waszak, SM, Northcott, PA, Buchhalter, I, Robinson, GW, Sutter, C, Groebner, S, Grund, KB, Brugières, L, Jones, DTW, Pajtler, KW, Morrissy, AS, Kool, M, Sturm, D, Chavez, L, Ernst, A, Brabetz, S, Hain, M, Zichner, T, Segura-Wang, M, Weischenfeldt, J, Rausch, T, Mardin, BR, Zhou, X, Baciu, C, Lawerenz, C, Chan, JA, Varlet, P, Guerrini-Rousseau, L, Fults, DW, Grajkowska, W, Hauser, P, Jabado, N, Ra, YS, Zitterbart, K, Shringarpure, SS, De La Vega, FM, Bustamante, CD, Ng, HK, Perry, A, MacDonald, TJ, Hernáiz Driever, P, Bendel, AE, Bowers, DC, McCowage, G, Chintagumpala, MM, Cohn, R, Hassall, T, Fleischhack, G, Eggen, T, Wesenberg, F, Feychting, M, Lannering, B, Schüz, J, Johansen, C, Andersen, TV, Röösli, M, Kuehni, CE, Grotzer, M, Kjaerheim, K, Monoranu, CM, Archer, TC, Duke, E, Pomeroy, SL, Shelagh, R, Frank, S, Sumerauer, D, Scheurlen, W, Ryzhova, MV, Milde, T, Kratz, CP, Samuel, D, Zhang, J, Solomon, DA, Marra, M, Eils, R, Bartram, CR, von Hoff, K, Rutkowski, S, Ramaswamy, V, Gilbertson, RJ, Korshunov, A, Taylor, MD, Lichter, P, Malkin, D, Gajjar, A, Korbel, JO, Pfister, SM, Waszak, SM, Northcott, PA, Buchhalter, I, Robinson, GW, Sutter, C, Groebner, S, Grund, KB, Brugières, L, Jones, DTW, Pajtler, KW, Morrissy, AS, Kool, M, Sturm, D, Chavez, L, Ernst, A, Brabetz, S, Hain, M, Zichner, T, Segura-Wang, M, Weischenfeldt, J, Rausch, T, Mardin, BR, Zhou, X, Baciu, C, Lawerenz, C, Chan, JA, Varlet, P, Guerrini-Rousseau, L, Fults, DW, Grajkowska, W, Hauser, P, Jabado, N, Ra, YS, Zitterbart, K, Shringarpure, SS, De La Vega, FM, Bustamante, CD, Ng, HK, Perry, A, MacDonald, TJ, Hernáiz Driever, P, Bendel, AE, Bowers, DC, McCowage, G, Chintagumpala, MM, Cohn, R, Hassall, T, Fleischhack, G, Eggen, T, Wesenberg, F, Feychting, M, Lannering, B, Schüz, J, Johansen, C, Andersen, TV, Röösli, M, Kuehni, CE, Grotzer, M, Kjaerheim, K, Monoranu, CM, Archer, TC, Duke, E, Pomeroy, SL, Shelagh, R, Frank, S, Sumerauer, D, Scheurlen, W, Ryzhova, MV, Milde, T, Kratz, CP, Samuel, D, Zhang, J, Solomon, DA, Marra, M, Eils, R, Bartram, CR, von Hoff, K, Rutkowski, S, Ramaswamy, V, Gilbertson, RJ, Korshunov, A, Taylor, MD, Lichter, P, Malkin, D, Gajjar, A, Korbel, JO, and Pfister, SM
- Abstract
Background: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MB WNT ), SHH (MB SHH ), group 3 (MB Group3 ), and group 4 (MB Group4 ). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we co
- Published
- 2018
6. Osteoporotic Fractures in Childhood Cancer Survivors - ALICCS Cohort Study
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Oskarsson, T., Duun-Henriksen, A. K., Harila-Saari, A., Montgomery, Scott, Niinimaki, R., Madanat-Harjuoja, L., Tryggvadottir, L., Wesenberg, F., Holmqvist, A. S., Hasle, H., Heyman, M., Winther, J. F., Oskarsson, T., Duun-Henriksen, A. K., Harila-Saari, A., Montgomery, Scott, Niinimaki, R., Madanat-Harjuoja, L., Tryggvadottir, L., Wesenberg, F., Holmqvist, A. S., Hasle, H., Heyman, M., and Winther, J. F.
- Abstract
Background/Objectives: Children and adolescents undergoing treatment for cancer are exposed to multiple factors that impact the development of peak bone mass and bone quality. The aims of this study were to examine the risks and cumulative incidence of osteoporotic fractures in childhood cancer survivors and identify subgroups at higher risk. Design/Methods: In the national cancer registries of Denmark, Finland, Iceland and Sweden we identified patients diagnosed with cancer before 20 years of age from the start of registration in the 1940s and 1950s through 2008. We compared 26.334 one‐year survivors with a cohort of 162.372 age‐ and sex‐matched population comparison subjects selected from the national population registries. With data derived from national hospital registries we estimated the standardized hospitalization rate ratios (SHRR) and the mean cumulative count (MCC) of hospital admissions for osteoporotic fractures. To identify subgroups at risk we used Cox regression models to generate hazard ratios (HR) for osteoporotic fractures. Death and new cancer were treated as competing risks. Results: The estimated SHRR for the first osteoporotic fracture was 1.41 (95% CI; 1.27‐1.58) but the MCC for recurrent osteoporotic fractures did not differ between the survivors and the comparison group. The SHRR for isolated hip fractures was 2.90 (2.32‐3.63). The adjusted HR for osteoporotic fracture as the first event was 1.53 (1.09‐2.16) if cancer was diagnosed 15‐19 years and 2.10 (1.48‐2.98) for long‐term survivors of CNS tumors. Survivors 15‐19 years at cancer diagnosis and long‐term survivors of CNS tumors were also at higher risk of experiencing a second fracture, HR 3.29 (1.65‐6.55) and HR 2.71 (1.45‐5.05), respectively. Conclusions: Childhood cancer survivors are at higher risk of being hospitalized for osteoporotic fractures but the burden of recurrent fractures is not higher. For subgroups at risk, surveillance of bone health and measures to increase bone stren
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- 2018
7. Rational use of blood products
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Solheim, B.G and Wesenberg, F
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- 2001
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8. Mononuclear Cells IgG Associated with Human Malignant Tissue
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Tønder, O., Matre, R., Wesenberg, F., Hanna, M. G., Jr., editor, and Witz, Isaac P., editor
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- 1980
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9. Pathways through relapses and deaths of children with acute lymphoblastic leukemia: Role of allogeneic stem cell transplantation in Nordic data
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Saarinen-Pihkala, UM, Heilmann, C, Winiarski, J, Glomstein, A, Abrahamsson, J, Arvidsson, J, Bekassy, AN, Forestier, E, Jonmundsson, G, Schrøder, Henrik, Vettenranta, K, Wesenberg, F, and Gustafsson, G
- Published
- 2006
10. Expression and Significance of Fc Receptors in Malignancies
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T�nder, O., primary, Matre, R., additional, and Wesenberg, F., additional
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11. Post-induction residual disease in translocation (12;21)-positive childhood ALL
- Author
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Seyfarth, J., Madsen, H.O., Nyvold, C., Ryder, L.P., Clausen, N., Jonmundsson, G., Wesenberg, F., and Schmiegelow, K.
- Published
- 2003
12. Acremonium strictum fungaemia in a paediatric patient with acute leukemia
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Warris, A., Wesenberg, F., Gaustad, P., Verweij, P.E., and Abrahamsen, T.G.
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Pathogenesis, epidemiology, and treatment of microbial infections ,Immuunstoornissen in relatie tot kinderen met (pre-)maligne aandoeningen ,Immune deficiencies in children (pre-)malignant diseases ,Pathogenese, epidemiologie en behandeling van microbiële infecties - Abstract
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- Published
- 2000
13. Thiopurine methyltransferase activity is related to the risk of relapse of childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study
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Schmiegelow, K, Forestier, E, Kristinsson, J, Söderhäll, S, Vettenranta, K, Weinshilboum, R, Wesenberg, F, Schmiegelow, K, Forestier, E, Kristinsson, J, Söderhäll, S, Vettenranta, K, Weinshilboum, R, and Wesenberg, F
- Abstract
Udgivelsesdato: 2009-Mar, Myelotoxicity during thiopurine therapy is enhanced in patients, who because of single nucleotide polymorphisms have decreased activity of the enzyme thiopurine methyltransferase (TPMT) and thus more thiopurine converted into 6-thioguanine nucleotides. Of 601 children with acute lymphoblastic leukemia (ALL) who were treated by the NOPHO ALL-92 protocol, 117 had TPMT genotype determined, whereas for 484 patients only erythrocyte TPMT activity was available. The latter were classified as heterozygous, if TPMT activity was <14 IU/ml, or deficient (<1.0 IU/ml). 526 patients had TPMT wild type, 73 were presumed heterozygous, and two were TPMT deficient. Risk of relapse was higher for the 526 TPMT wild type patients than for the remaining 75 patients (18 vs 7%, P=0.03). In Cox multivariate regression analysis, sex (male worse; P=0.06), age (higher age worse, P=0.02), and TPMT activity (wild type worse; P=0.02) were related to risk of relapse. Despite a lower probability of relapse, patients in the low TPMT activity group did not have superior survival (P=0.82), possibly because of an excess of secondary cancers among these 75 patients (P=0.07). These data suggest that children with ALL and TPMT wild type might have their cure rate improved, if the pharmacokinetics/-dynamics of TPMT low-activity patients could be mimicked without a concurrent excessive risk of second cancers.
- Published
- 2008
14. Increased uptake of social security benefits among long-term survivors of cancer in childhood, adolescence and young adulthood: a Norwegian population-based cohort study
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Ghaderi, S, primary, Engeland, A, additional, Moster, D, additional, Ruud, E, additional, Syse, A, additional, Wesenberg, F, additional, and Bjørge, T, additional
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- 2013
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15. Deletion of the Ink4-locus (the p16ink4a, p14ARF and p15ink4b genes)predicts relapse in children with ALL treated according to the Nordicprotocols NOPHO-86 and NOPHO-92.
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Calero Moreno, TM, Gustafsson, G, Garwicz, S, Grander, D, Jonmundsson, GK, Frost, BM, Makipernaa, A, Rasool, O, Savolainen, ER, Schmiegelow, K, Soderhall, S, Vettenranta, K, Wesenberg, F, Einhorn, S, Heyman, M, Calero Moreno, TM, Gustafsson, G, Garwicz, S, Grander, D, Jonmundsson, GK, Frost, BM, Makipernaa, A, Rasool, O, Savolainen, ER, Schmiegelow, K, Soderhall, S, Vettenranta, K, Wesenberg, F, Einhorn, S, and Heyman, M
- Published
- 2002
16. Microcephalus, medulloblastoma and excessive toxicity from chemotherapy: an unusual presentation of Fanconi anaemia
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Ruud, E, primary and Wesenberg, F, additional
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- 2007
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17. Prevalence of Norwegian patients diagnosed with childhood cancer, their working ability and need of health insurance benefits
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Johannesen, T. B., primary, Langmark, F., additional, Wesenberg, F., additional, and Lote, K., additional
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- 2007
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18. Adverse drug events in children during hospitalization and after discharge in a Norwegian University Hospital
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Buajordet, I, primary, Wesenberg, F, additional, Brørs, O, additional, and Langslet, A, additional
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- 2002
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19. Microcephalus, medulloblastoma and excessive toxicity from chemotherapy: an unusual presentation of Fanconi anaemia
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Ruud, E, primary and Wesenberg, F, additional
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- 2001
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20. Outcome after first relapse in children with acute lymphoblastic leukemia: A population‐based study of 315 patients from the nordic society of pediatric hematology and oncology (NOPHO)
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Schroeder, H., primary, Garwicz, S., additional, Kristinsson, J., additional, Siimes, M. A., additional, Wesenberg, F., additional, and Gustafsson, G., additional
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- 1995
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21. Central Venous Catheter with Subcutaneous Injection Port (Port-A-Cath): 8 Years Clinical Follow up with Children
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Wesenberg, F., primary, Md, H. Flaatten, additional, and Janssen, C. W., additional
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- 1993
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22. Superior treatment results in females with high‐risk acute lymphoblastic leukemia in childhood
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Lanning, M, primary, Garwicz, S, additional, Hertz, H, additional, Jonmundsson, G, additional, Kreuger, A, additional, Lie, SO, additional, Moe, PJ, additional, Salmi, TT, additional, Schröder, H, additional, Siimes, MA, additional, Wesenberg, F, additional, Yssing, M, additional, Åhström, L, additional, and Gustafsson, G, additional
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- 1992
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23. Central Nervous System Disease in Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Results of Treatment
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Kreuger, A., primary, Garwicz, S., additional, Hertz, H., additional, Jonmundsson, C., additional, Latining, M., additional, Lie, S. O., additional, Moe, P. J., additional, Salmi, T. T., additional, Schröder, H., additional, Siimes, M. A., additional, Wesenberg, F., additional, Yssing, M., additional, Åhström, L., additional, and Gustafsson, G., additional
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- 1991
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24. Children with acute lymphoblastic leukaemia have high plasma levels of total homocysteine at time of diagnosis.
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Ruud, E., Holmstrøm, H., Brosstad, F., and Wesenberg, F.
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LYMPHOBLASTIC leukemia ,CANCER ,HEART diseases ,HEART disease diagnosis ,CARDIAC catheterization ,HOMOCYSTEINE - Abstract
Objective . Cancer can induce venous thromboembolic complications for various reasons. As part of a greater study, acquired and congenital prothrombotic risk factors were investigated in children with leukaemia or non-Hodgkin's lymphoma and compared with similar investigations in children with congenital heart defects. Material and methods . Blood samples were taken from 60 children with newly diagnosed leukaemia or lymphoma and 133 children with congenital heart defects in the course of a scheduled cardiac catheterization. When children with cancer were in remission, analyses of acquired prothrombotic risk factors were repeated. Children with cancer were observed for symptoms of thromboembolism throughout their treatment period. Results . Total homocysteine levels were significantly raised in children with cancer (median value 10.0 µ mol/L) as compared with the levels in children with congenital heart diseases (5.0 µ mol/L) ( p [ABSTRACT FROM AUTHOR]
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- 2006
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25. Lymphocyte Multiplication in Vitro Induced by Mitogens and Antigens.
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Haneberg, B., Wesenberg, F., and Aarskog, D.
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LYMPHOCYTES ,B cells ,MITOSIS ,CELL division ,CELL cycle ,ANTIGENS ,ANTIGEN-antibody reactions - Abstract
A simple technique requiring only 0.2 ml whole blood for measuring the response of lymphocytes in cultures lo each of various mitogens and antigens has been elaborated. The response is quantified by comparing the number of lymphocytes with and without a stimulating agent. The increment of cell numbers is given by a cell multiplication index. In healthy subjects PHA induced almost a doubling of the cell numbers in 3 days, i.e. an index of 1.90±0.38. After 7 days the indexes for PHA, PWM and Con A were 7.25±4.12, 2.72±0.65 and 1.81±0.31, respectively. PPD and Candida-extract induced cell multiplication in skin positive individuals, with indexes ranging from 1.12 to 3.05. In contrast, patients with various severe immune deficiencies showed decreased responses to at least one mitogen, depending on the type of the deficiency. Likewise, skin test negative individuals had no or faint in vitro response to the antigens. The method, which correlated well with the response by a conventional method for incorporation of tritiated thymidine, has a high degree of precision and sensitivity, and should be applicable for routine use. [ABSTRACT FROM AUTHOR]
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- 1978
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26. Central Venous Catheter with Subcutaneous Injection Port (Port-A-Cath): Clinical Experience with Children.
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Wesenberg, F., Anker, C., Sommerschild, H., and Flaatten, H.
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- 1987
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27. Competitive PCR for quantification of minimal residual disease in acute lymphoblastic leukaemia
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Nyvold, C., Madsen, H.O., Ryder, L.P., Seyfarth, J., Engel, C.A., Svejgaard, A., Wesenberg, F., and Schmiegelow, K.
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- 2000
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28. Antibodies to staphylococcal peptidoglycan and its peptide epitopes, teichoic acid, and lipoteichoic acid in sera from blood donors and patients with staphylococcal infections
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Wergeland, H I, Haaheim, L R, Natås, O B, Wesenberg, F, and Oeding, P
- Abstract
Antibodies to the staphylococcal antigens peptidoglycan, beta-ribitol teichoic acid, and lipoteichoic acid, as well as to the peptidoglycan epitopes L-Lys-D-Ala-D-Ala, L-Lys-D-Ala, and pentaglycine, were found over a wide range of concentrations in sera from both blood donors and patients with verified or suspected staphylococcal infections. The patient group was heterogeneous with regard to both age and type of staphylococcal infections, being representative for sera sent to our laboratory. In single-antigen assays antibodies to pentaglycine had the highest predictive positive value (67%), although only 32% of the patients had elevated levels of such antibodies. Combinations of test antigens could yield positive predictive values as high as 100%, but then the fraction of positive sera was low. Indeed, the fraction of patient sera which was positive in multiple-antigen tests never exceeded 61%. The clinical usefulness of these seroassays for identifying Staphylococcus aureus as a causative agent was limited, owing to the considerable overlap in the range of antibody concentrations between patient and blood donor sera.
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- 1989
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29. Modified erythrocytes in indirect haemagglutination with Neisseria gonorrhoeae antigen.
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Maeland, J A, Wesenberg, F, and Tönder, O
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- 1973
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30. Human renal glomeruli possess no Fcγ receptors
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Matre, R., primary, Tönder, O., additional, and Wesenberg, F., additional
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- 1980
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31. Modified erythrocytes in indirect haemagglutination with Neisseria gonorrhoeae antigen.
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Maeland, J A, primary, Wesenberg, F, additional, and Tonder, O, additional
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- 1973
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32. Phenotypic Markers in Chronic Lymphocytic Leukemia
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Per Magne Ueland, Wesenberg F, S. Kvinnsland, and Helga Refsum
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chemistry.chemical_compound ,chemistry ,business.industry ,Anesthesia ,Medicine ,Methotrexate ,General Medicine ,Nitrous oxide ,business ,medicine.drug - Published
- 1986
33. Evaluation of dendritic cells loaded with apoptotic cancer cells or expressing tumour mRNA as potential cancer vaccines against leukemia
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Sæbøe-Larssen Stein, Pettersen Rolf D, Jarnjak-Jankovic Silvija, Wesenberg Finn, and Gaudernack Gustav
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Leukemia is a clonal disorder characterized by uncontrolled proliferation of haematopoietic cells, and represents the most common form of cancer in children. Advances in therapy for childhood leukemia have relied increasingly on the use of high-dose chemotherapy often combined with stem-cell transplantation. Despite a high success rate and intensification of therapy, children still suffer from relapse and progressive disease resistant to further therapy. Thus, novel forms of therapy are required. Methods This study focuses on dendritic cell (DC) vaccination of childhood leukemia and evaluates the in vitro efficacy of different strategies for antigen loading of professional antigen-presenting cells. We have compared DCs either loaded with apoptotic leukemia cells or transfected with mRNA from the same leukemia cell line, Jurkat E6, for their capacity to induce specific CD4+ and CD8+ T-cell responses. Monocyte-derived DCs from healthy donors were loaded with tumor antigen, matured and co-cultured with autologous T cells. After one week, T-cell responses against antigen-loaded DCs were measured by enzyme-linked immunosorbent spot (ELISPOT) assay. Results DCs loaded with apoptotic Jurkat E6 cells or transfected with Jurkat E6-cell mRNA were both able to elicit specific T-cell responses in vitro. IFNγ-secreting T cells were observed in both the CD4+ and CD8+ subsets. Conclusion The results indicate that loading of DCs with apoptotic leukemia cells or transfection with tumour mRNA represent promising strategies for development of cancer vaccines for treatment of childhood leukemia.
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- 2005
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34. Male breast cancer after childhood cancer: Systematic review and analyses in the PanCareSurFup cohort.
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Wang Y, Reulen RC, Kremer LCM, de Vathaire F, Haupt R, Zadravec Zaletel L, Bagnasco F, Demoor-Goldschmidt C, van Dorp WJ, Haddy N, Hjorth L, Jakab Z, Kuehni CE, Lähteenmäki PM, van der Pal HJH, Sacerdote C, Skinner R, Terenziani M, Wesenberg F, Winther JF, van Leeuwen FE, Hawkins MM, Teepen JC, van Dalen EC, and Ronckers CM
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- Adult, Child, Cohort Studies, Female, Humans, Incidence, Male, Registries, Risk Factors, Breast Neoplasms, Male epidemiology, Cancer Survivors, Neoplasms complications, Neoplasms therapy
- Abstract
Background: Breast cancer is a well-recognised late adverse effect in female childhood cancer survivors (CCSs), especially after chest radiotherapy; information on subsequent male breast cancer (SMBC) is limited. We summarised the existing evidence on SMBC after childhood cancer in a systematic review and investigated the risk of SMBC among males in a Pan-European cohort., Methods: We searched Medline/PubMed for cohort studies and case reports/series that assessed SMBC after childhood cancer (≤21 years). Furthermore, we analysed data on SMBC in the PanCareSurFup cohort, reporting standardised incidence ratios (SIRs), absolute excess risks (AERs), and 5- and 10-year survival rates., Results: The systematic review included 38 of 7080 potentially eligible articles. Cohort-specific SMBC frequencies were 0-0.40% (31 studies). SMBC occurred after a follow-up ranging from 24.0 to 42.0 years. Nine case reports/series described 11 SMBC cases, occurring 11.0-42.5 years after primary childhood cancer. In the PanCareSurFup cohort (16 SMBC/37,738 males; 0.04%), we observed a 22.3-fold increased risk of SMBC relative to the general male population (95% CI 12.7-36.2; absolute excess risk/100,000 person-years: 2.3, 95% CI 1.3-3.7). The five- and ten-year survival rates after SMBC diagnosis were 60.3% (95% CI 35.6%-85.0%) and 43.0% (95% CI 16.1%-69.9%), respectively. Clear evidence of risk factors did not emerge from these comprehensive efforts., Conclusions: Compared to the general population, male CCSs have an elevated risk of developing subsequent breast cancer, although the absolute risk is low. Health care providers should be aware of this rare yet serious late effect; male CCSs with symptoms potentially related to SMBC warrant careful examination., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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35. Temporal changes in the probability of live birth among female survivors of childhood cancer: A population-based Adult Life After Childhood Cancer in Scandinavia (ALiCCS) study in five nordic countries.
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Licht SF, Rugbjerg K, Andersen EW, Nielsen TT, Norsker FN, Kenborg L, Holmqvist AS, Madanat-Harjuoja LM, Tryggvadottir L, Stovall M, Wesenberg F, Hjorth L, Hasle H, and Winther JF
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- Adult, Child, Female, Humans, Live Birth epidemiology, Pregnancy, Probability, Scandinavian and Nordic Countries epidemiology, Survivors, Cancer Survivors, Neoplasms epidemiology, Neoplasms therapy
- Abstract
Background: During the past 4 decades, there has been a growing focus on preserving the fertility of patients with childhood cancer; however, no large studies have been conducted of live births across treatment decades during this period. Therefore, the authors estimated the potential birth deficit in female childhood cancer survivors and the probability of live births., Methods: In total, 8886 women were identified in the 5 Nordic cancer registries in whom a childhood cancer had been diagnosed during 1954 through 2006. A population comparison cohort of 62,903 women was randomly selected from the central population registries matched by age and country. All women were followed for live births recorded in medical birth registries. The cumulative probability and the risk ratio (RR) with 95% confidence intervals (CIs) of a live birth were calculated by maternal age across treatment decades., Results: The probability of a live birth increased with treatment decade, and, at age 30 years, the rate for survivors most recently diagnosed was close to the rate among the general population (1954-1969: RR, 0.65 [95% CI, 0.54-0.78]; 1970s: RR, 0.67 [95% CI, 0.60-0.74]; 1980s: RR, 0.69 [95% CI, 0.64-0.74]; 1990s: RR, 0.91 [95% CI, 0.87-0.95]; 2000s: RR, 0.94 [95% CI, 0.91-0.97])., Conclusions: Female childhood cancer survivors had a lower probability of a live birth than women in the general population, although, in survivors diagnosed after 1989, the probability was close to that of the general population. Because the pattern of live births differs by cancer type, continuous efforts must be made to preserve fertility, counsel survivors, and refer them rapidly to fertility treatment if necessary., Lay Summary: The purpose of this study was to compare the probability of giving birth to a liveborn child in female survivors of childhood cancer with that of women in the general population. Survivors of childhood cancer had a lower probability of live births than women in the general population, although survivors diagnosed after 1989 had a probability close to that of the general population. Continuing focus on how to preserve the potential for fertility among female patients with childhood cancer during treatment is important to increase their chances of having a child., (© 2021 American Cancer Society.)
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- 2021
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36. Risk of digestive cancers in a cohort of 69 460 five-year survivors of childhood cancer in Europe: the PanCareSurFup study.
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Reulen RC, Wong KF, Bright CJ, Winter DL, Alessi D, Allodji RM, Bagnasco F, Bárdi E, Bautz A, Byrne J, Feijen EA, Fidler-Benaoudia MM, Diallo I, Garwicz S, Grabow D, Gudmundsdottir T, Guha J, Haddy N, Høgsholt S, Jankovic M, Kaatsch P, Kaiser M, Kuonen R, Linge H, Øfstaas H, Ronckers CM, Hau EM, Skinner R, van Leeuwen FE, Teepen JC, Veres C, Zrafi W, Debiche G, Llanas D, Terenziani M, Vu-Bezin G, Wesenberg F, Wiebe T, Sacerdote C, Jakab Z, Haupt R, Lähteenmäki PM, Zadravec Zaletel L, Kuehni CE, Winther JF, de Vathaire F, Kremer LC, Hjorth L, and Hawkins MM
- Abstract
Background: Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide., Methods: The PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe. Risks of digestive SPNs were quantified using standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence., Results: 427 digestive SPNs (214 colorectal, 62 liver, 48 stomach, 44 pancreas, 59 other) were diagnosed in 413 survivors. Wilms tumour (WT) and Hodgkin lymphoma (HL) survivors were at greatest risk (SIR 12.1; 95% CI 9.6 to 15.1; SIR 7.3; 95% CI 5.9 to 9.0, respectively). The cumulative incidence increased the most steeply with increasing age for WT survivors, reaching 7.4% by age 55% and 9.6% by age 60 years (1.0% expected based on general population rates). Regarding colorectal SPNs, WT and HL survivors were at greatest risk; both seven times that expected. By age 55 years, 2.3% of both WT (95% CI 1.4 to 3.9) and HL (95% CI 1.6 to 3.2) survivors had developed a colorectal SPN-comparable to the risk among members of the general population with at least two first-degree relatives affected., Conclusions: Colonoscopy surveillance before age 55 is recommended in many European countries for individuals with a family history of colorectal cancer, but not for WT and HL survivors despite a comparable risk profile. Clinically, serious consideration should be given to the implementation of colonoscopy surveillance while further evaluation of its benefits, harms and cost-effectiveness in WT and HL survivors is undertaken., Competing Interests: Competing interests: HL and TW are shareholders in, and have signed an intellectual property agreement with the company Concidera Health. The company develops clinical decision support tools for childhood cancer survivorship., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2020
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37. Unmet rehabilitation needs in 86% of Norwegian paediatric embryonal brain tumour survivors.
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Stensvold E, Stadskleiv K, Myklebust TÅ, Wesenberg F, Helseth E, Bechensteen AG, and Brandal P
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- Child, Humans, Norway epidemiology, Survivors, Brain Neoplasms, Cerebellar Neoplasms radiotherapy, Medulloblastoma therapy
- Abstract
Aim: To study incidence, types and degrees of late effects in a geographical cohort of paediatric medulloblastoma and central nervous system primitive neuroectodermal tumour (CNS-PNET) survivors, and identify the need for rehabilitation., Methods: Between 1974 and 2013, 63 patients survived treatment for paediatric medulloblastoma and CNS-PNET at Oslo University Hospital, Norway. Of these, 50 accepted invitation and were included in this study., Results: Median follow-up was 20 years (range 3.2-41), and 96% of participants had developed late effects. Cognitive impairment was found in 72%, reduced hearing in 68%, endocrine deficits in 66%, epilepsy in 32% and another 30% had been diagnosed with one or more second primary neoplasms. Radiotherapy significantly increased risk of secondary primary neoplasms and endocrinological deficits, chemotherapy risk of ototoxicity and endocrinological deficits, and epilepsy was found significantly more often in CNS-PNET than medulloblastoma patients. Epilepsy was the main cause of cognitive impairments (full-scale IQ) in our study. 86% of participants had an unmet rehabilitation need., Conclusion: Significant late effects and unmet rehabilitation needs were documented in the large majority of survivors after treatment for paediatric medulloblastoma and CNS-PNET., (© 2020 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)
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- 2020
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38. Germline Elongator mutations in Sonic Hedgehog medulloblastoma.
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Waszak SM, Robinson GW, Gudenas BL, Smith KS, Forget A, Kojic M, Garcia-Lopez J, Hadley J, Hamilton KV, Indersie E, Buchhalter I, Kerssemakers J, Jäger N, Sharma T, Rausch T, Kool M, Sturm D, Jones DTW, Vasilyeva A, Tatevossian RG, Neale G, Lombard B, Loew D, Nakitandwe J, Rusch M, Bowers DC, Bendel A, Partap S, Chintagumpala M, Crawford J, Gottardo NG, Smith A, Dufour C, Rutkowski S, Eggen T, Wesenberg F, Kjaerheim K, Feychting M, Lannering B, Schüz J, Johansen C, Andersen TV, Röösli M, Kuehni CE, Grotzer M, Remke M, Puget S, Pajtler KW, Milde T, Witt O, Ryzhova M, Korshunov A, Orr BA, Ellison DW, Brugieres L, Lichter P, Nichols KE, Gajjar A, Wainwright BJ, Ayrault O, Korbel JO, Northcott PA, and Pfister SM
- Subjects
- Cerebellar Neoplasms genetics, Cerebellar Neoplasms pathology, Child, Female, Humans, Male, Medulloblastoma genetics, Pedigree, RNA, Transfer metabolism, Transcriptional Elongation Factors genetics, Cerebellar Neoplasms metabolism, Germ-Line Mutation, Medulloblastoma metabolism, Transcriptional Elongation Factors metabolism
- Abstract
Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children
1,2 , and genetic events that cooperate with known somatic driver events are poorly understood. Pathogenic germline variants in established cancer predisposition genes have been recently identified in 5% of patients with the malignant brain tumour medulloblastoma3 . Here, by analysing all protein-coding genes, we identify and replicate rare germline loss-of-function variants across ELP1 in 14% of paediatric patients with the medulloblastoma subgroup Sonic Hedgehog (MBSHH ). ELP1 was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among paediatric patients with MBSHH . Parent-offspring and pedigree analyses identified two families with a history of paediatric medulloblastoma. ELP1-associated medulloblastomas were restricted to the molecular SHHα subtype4 and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1, which suggests that germline ELP1 loss-of-function variants predispose individuals to tumour development in combination with constitutive activation of SHH signalling. ELP1 is the largest subunit of the evolutionarily conserved Elongator complex, which catalyses translational elongation through tRNA modifications at the wobble (U34 ) position5,6 . Tumours from patients with ELP1-associated MBSHH were characterized by a destabilized Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to Elongator deficiency in model systems7-9 . Thus, genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers. These results support investigation of the role of protein homeostasis in other cancer types and potential for therapeutic interference.- Published
- 2020
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39. Children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor in Norway from 1974 through 2013: Unexplainable regional differences in survival.
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Stensvold E, Myklebust TÅ, Cappelen J, Due-Tønnessen BJ, Due-Tønnessen P, Kepka A, Johannesen TB, Krossnes B, Lundar T, Maric S, Miletic H, Moholdt V, Myrmel KS, Nordberg T, Rydland J, Stokland T, Solem K, Solheim O, Torsvik I, Wikran GC, Zeller B, Wesenberg F, Bechensteen AG, and Brandal P
- Subjects
- Adolescent, Cerebellar Neoplasms therapy, Child, Child, Preschool, Combined Modality Therapy methods, Disease-Free Survival, Female, Humans, Infant, Infant, Newborn, Male, Medulloblastoma therapy, Neuroectodermal Tumors, Primitive therapy, Norway epidemiology, Retrospective Studies, Supratentorial Neoplasms therapy, Survival Analysis, Treatment Outcome, Young Adult, Cerebellar Neoplasms mortality, Medulloblastoma mortality, Neuroectodermal Tumors, Primitive mortality, Supratentorial Neoplasms mortality
- Abstract
Background: A previous study based on Norwegian Cancer Registry data suggested regional differences in overall survival (OS) after treatment for medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. The purpose of the present study was to confirm in an extended cohort whether there were regional differences in outcome or not, and if so try to identify possible explanations., Material and Methods: Data from patients aged 0-20 years diagnosed with and treated for MB/CNS-PNET at all four university hospitals in Norway from 1974 to 2013 were collected and compared., Results: Of 266 identified patients, 251 fulfilled inclusion criteria. MB was diagnosed in 200 and CNS-PNET in 51 patients. Five-year OS and event-free survival (EFS) were 59% and 52%, respectively. There was a significant difference in five-year OS and EFS between MB and CNS-PNET patients; 62% versus 47% (P = 0.007) and 57% versus 35% (P < 0.001). In multivariable analysis, two factors were found to significantly contribute to improved five-year OS and EFS, whereas one factor contributed to improved five-year OS only. Gross total resection (GTR) versus non-GTR (hazard ratio [HR] 0.53, P = 0.003; HR 0.46, P < 0.001) and cerebrospinal irradiation (CSI) versus non-CSI (HR 0.24, P < 0.001; HR 0.28, P < 0.001) for both, and treatment outside Oslo University Hospital for OS only (HR 0.64, P = 0.048)., Conclusion: Survival was comparable with data from other population-based studies, and the importance of GTR and CSI was confirmed. The cause for regional survival differences could not be identified., (© 2019 The Authors Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.)
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- 2019
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40. Risk of subsequent primary leukaemias among 69,460 five-year survivors of childhood cancer diagnosed from 1940 to 2008 in Europe: A cohort study within PanCareSurFup.
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Allodji RS, Hawkins MM, Bright CJ, Fidler-Benaoudia MM, Winter DL, Alessi D, Fresneau B, Journy N, Morsellino V, Bárdi E, Bautz A, Byrne J, Feijen ELA, Teepen JC, Vu-Bezin G, Rubino C, Garwicz S, Grabow D, Gudmundsdottir T, Guha J, Hau EM, Jankovic M, Kaatsch P, Kaiser M, Linge H, Muraca M, Llanas D, Veres C, Øfstaas H, Diallo I, Mansouri I, Ronckers CM, Skinner R, Terenziani M, Wesenberg F, Wiebe T, Sacerdote C, Jakab Z, Haupt R, Lähteenmäki P, Zaletel LZ, Kuehni CE, Winther JF, Michel G, Kremer LCM, Hjorth L, Haddy N, de Vathaire F, and Reulen RC
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Europe epidemiology, Female, Follow-Up Studies, Humans, Incidence, Infant, Infant, Newborn, Leukemia diagnosis, Male, Neoplasms, Second Primary epidemiology, Neoplasms, Second Primary pathology, Prognosis, Registries, Risk Factors, Young Adult, Cancer Survivors statistics & numerical data, Leukemia epidemiology, Neoplasms, Second Primary etiology, Risk Assessment methods
- Abstract
Background: Survivors of childhood cancers are at risk of developing subsequent primary leukaemias (SPLs), but the long-term risks beyond 20 years of treatment are still unclear. We investigated the risk of SPLs in five-year childhood cancer survivors using a large-scale pan-European (PanCareSurFup) cohort and evaluated variations in the risk by cancer and demographic factors., Methods: This largest-ever assembled cohort comprises 69,460 five-year childhood cancer survivors from 12 European countries. Standardised incidence ratios (SIRs) and absolute excess risks (AERs) were calculated., Results: One hundred fifteen survivors developed an SPL including 86 myeloid leukaemias (subsequent primary myeloid leukaemias [SPMLs]), 17 lymphoid leukaemias and 12 other types of leukaemias; of these SPLs, 31 (27%) occurred beyond 20 years from the first childhood cancer diagnosis. Compared with the general population, childhood cancer survivors had a fourfold increased risk (SIR = 3.7, 95% confidence interval [CI]: 3.1 to 4.5) of developing leukaemia, and eight leukaemias per 100,000 person-years (AER = 7.5, 95% CI: 6.0 to 9.2) occurred in excess of that expected. The risks remained significantly elevated beyond 20 years from the first primary malignancy (SIR = 2.4, 95% CI: 1.6 to 3.4). Overall, the risk ratio for SPML (SIR = 5.8, 95% CI: 4.6 to 7.1) was higher than that for other SPLs., Conclusions: We demonstrate that beyond 20 years after childhood cancer diagnosis, survivors experience an increased risk for SPLs compared with that expected from the general population. Our findings highlight the need for awareness by survivors and their healthcare providers for potential risk related to SPL., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
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- 2019
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41. Hyperthyroidism as a late effect in childhood cancer survivors - an Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study.
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Clausen CT, Hasle H, Holmqvist AS, Madanat-Harjuoja L, Tryggvadottir L, Wesenberg F, Bautz A, Winther JF, and de Fine Licht S
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- Adolescent, Adult, Age of Onset, Aged, Aged, 80 and over, Child, Child, Preschool, Cohort Studies, Female, Follow-Up Studies, Hospitalization statistics & numerical data, Humans, Hyperthyroidism etiology, Infant, Infant, Newborn, Male, Middle Aged, Morbidity, Neoplasms complications, Registries, Risk Factors, Scandinavian and Nordic Countries epidemiology, Young Adult, Cancer Survivors statistics & numerical data, Hyperthyroidism epidemiology, Neoplasms epidemiology
- Abstract
Background: Hyperthyroidism is a rare disorder which may negatively affect health and quality of life. Its occurrence in childhood cancer survivors has not previously been investigated in detail., Material and Methods: In the hospital registers of the five Nordic countries, 32,944 childhood cancer survivors and 212,675 population comparisons were followed for the diagnosis of hyperthyroidism. Hospitalisation rates, standardised hospitalisation rate ratios and absolute excess risks were calculated with 95% confidence intervals (CI)., Results: Hyperthyroidism was diagnosed in 131 childhood cancer survivors, yielding an overall relative risk of 1.6 (95% CI: 1.3-1.9) compared with population comparisons. The risk was greatest 1-5 years after the diagnosis of cancer and in survivors of thyroid cancers, neuroblastomas, acute lymphoblastic leukaemia and Hodgkin lymphoma. Sixty-seven percent of survivors with hyperthyroidism had tumours located in the head, neck or upper body and half of survivors with hyperthyroidism were irradiated with 77% of them in the head and neck area., Conclusion: Childhood cancer survivors are at an increased risk of hyperthyroidism, potentially resulting in non-endocrine morbidity.
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- 2019
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42. Risk of cardiovascular disease among Nordic childhood cancer survivors with diabetes mellitus: A report from adult life after childhood cancer in Scandinavia.
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Winther JF, Bhatia S, Cederkvist L, Gudmundsdottir T, Madanat-Harjuoja L, Tryggvadottir L, Wesenberg F, Hasle H, and Sällfors Holmqvist A
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- Adolescent, Adult, Cancer Survivors, Cardiovascular Diseases etiology, Child, Child, Preschool, Diabetes Mellitus etiology, Female, Humans, Infant, Longitudinal Studies, Male, Registries, Risk Assessment, Scandinavian and Nordic Countries epidemiology, Adult Survivors of Child Adverse Events, Cardiovascular Diseases epidemiology, Diabetes Mellitus epidemiology, Neoplasms complications
- Abstract
Background: Childhood cancer survivors have an increased risk of cardiovascular disease (CVD) and diabetes mellitus. Because diabetes is a potentially modifiable risk factor for CVD in the general population, it is important to understand how diabetes affects the risk of CVD among childhood cancer survivors., Methods: This study examined the risk of CVD among survivors with diabetes and 142,742 population comparison subjects. From the national cancer registries of the 5 Nordic countries, 29,324 one-year survivors of cancer diagnosed before the age of 20 years between 1968 and 2008 were identified. Study subjects were linked to the national hospital registers. The cumulative incidence of CVD was determined with competing risk methods. A Cox proportional hazards model was used to estimate the effects of diabetes and cancer on the hazard of CVD. The interaction between diabetes and cancer was analyzed., Results: Diabetes was diagnosed in 324 of the 29,324 one-year survivors, and CVD was diagnosed in 2108. The hazard of diabetes was 1.7 times higher among survivors than comparison subjects (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.5-1.9), whereas the HR of CVD was 3.6 (95% CI, 3.3-3.8) 1 to 15 years after the cancer diagnosis and 1.9 (95% CI, 1.8-2.0) after more than 15 years. Individuals with diabetes had a 2.4 times higher hazard of CVD (95% CI, 2.1-2.8) among both survivors and comparison subjects in comparison with individuals without diabetes., Conclusions: Childhood cancer survivors with diabetes have a markedly increased risk of CVD in comparison with survivors without diabetes. However, diabetes does not increase the risk of CVD more in survivors than the general population., (© 2018 American Cancer Society.)
- Published
- 2018
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43. The PanCareSurFup consortium: research and guidelines to improve lives for survivors of childhood cancer.
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Byrne J, Alessi D, Allodji RS, Bagnasco F, Bárdi E, Bautz A, Bright CJ, Brown M, Diallo I, Feijen EAML, Fidler MM, Frey E, Garwicz S, Grabow D, Gudmundsdottir T, Hagberg O, Harila-Saari A, Hau EM, Haupt R, Hawkins MM, Jakab Z, Jankovic M, Kaatsch P, Kaiser M, Kremer LCM, Kuehni CE, Kuonen R, Ladenstein R, Lähteenmäki PM, Levitt G, Linge H, LLanas D, Michel G, Morsellino V, Mulder RL, Reulen RC, Ronckers CM, Sacerdote C, Skinner R, Steliarova-Foucher E, van der Pal HJ, de Vathaire F, Vũ Bezin G, Wesenberg F, Wiebe T, Winter DL, Winther JF, Witthoff E, Zadravec Zaletel L, and Hjorth L
- Subjects
- Biomedical Research, Child, Feasibility Studies, Female, Guidelines as Topic, Humans, Male, Neoplasms mortality, Pilot Projects, Survivors, Neoplasms therapy
- Abstract
Background: Second malignant neoplasms and cardiotoxicity are among the most serious and frequent adverse health outcomes experienced by childhood and adolescent cancer survivors (CCSs) and contribute significantly to their increased risk of premature mortality. Owing to differences in health-care systems, language and culture across the continent, Europe has had limited success in establishing multi-country collaborations needed to assemble the numbers of survivors required to clarify the health issues arising after successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European project to evaluate some of the serious long-term health risks faced by survivors. This article sets out the overall rationale, methods and preliminary results of PCSF., Methods: The PCSF consortium pooled data from 13 cancer registries and hospitals in 12 European countries to evaluate subsequent primary malignancies, cardiac disease and late mortality in survivors diagnosed between ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of second malignancies and to the heart, developed evidence-based guidelines for long-term care and for transition services, and disseminated results to survivors and the public., Results: We identified 115,596 individuals diagnosed with cancer, of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single data set forms the basis for cohort analyses of subsequent malignancies, cardiac disease and late mortality and case-control studies of subsequent malignancies and cardiac disease in 5-year survivors., Conclusions: PCSF delivered specific estimates of risk and comprehensive guidelines to help survivors and care-givers. The expected benefit is to provide every European CCS with improved access to care and better long-term health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
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- 2018
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44. Risk of Soft-Tissue Sarcoma Among 69 460 Five-Year Survivors of Childhood Cancer in Europe.
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Bright CJ, Hawkins MM, Winter DL, Alessi D, Allodji RS, Bagnasco F, Bárdi E, Bautz A, Byrne J, Feijen EAM, Fidler MM, Garwicz S, Grabow D, Gudmundsdottir T, Guha J, Haddy N, Jankovic M, Kaatsch P, Kaiser M, Kuehni CE, Linge H, Øfstaas H, Ronckers CM, Skinner R, Teepen JC, Terenziani M, Vu-Bezin G, Wesenberg F, Wiebe T, Sacerdote C, Jakab Z, Haupt R, Lähteenmäki P, Zaletel LZ, Kuonen R, Winther JF, de Vathaire F, Kremer LC, Hjorth L, and Reulen RC
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Europe epidemiology, Female, Follow-Up Studies, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, Registries, Risk Factors, Time Factors, Young Adult, Cancer Survivors statistics & numerical data, Neoplasms, Second Primary epidemiology, Sarcoma epidemiology, Soft Tissue Neoplasms epidemiology
- Abstract
Background: Childhood cancer survivors are at risk of subsequent primary soft-tissue sarcomas (STS), but the risks of specific STS histological subtypes are unknown. We quantified the risk of STS histological subtypes after specific types of childhood cancer., Methods: We pooled data from 13 European cohorts, yielding a cohort of 69 460 five-year survivors of childhood cancer. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated., Results: Overall, 301 STS developed compared with 19 expected (SIR = 15.7, 95% confidence interval [CI] = 14.0 to 17.6). The highest standardized incidence ratios were for malignant peripheral nerve sheath tumors (MPNST; SIR = 40.6, 95% CI = 29.6 to 54.3), leiomyosarcomas (SIR = 29.9, 95% CI = 23.7 to 37.2), and fibromatous neoplasms (SIR = 12.3, 95% CI = 9.3 to 16.0). SIRs for MPNST were highest following central nervous system tumors (SIR = 80.5, 95% CI = 48.4 to 125.7), Hodgkin lymphoma (SIR = 81.3, 95% CI = 35.1 to 160.1), and Wilms tumor (SIR = 76.0, 95% CI = 27.9 to 165.4). Standardized incidence ratios for leiomyosarcoma were highest following retinoblastoma (SIR = 342.9, 95% CI = 245.0 to 466.9) and Wilms tumor (SIR = 74.2, 95% CI = 37.1 to 132.8). AERs for all STS subtypes were generally low at all years from diagnosis (AER < 1 per 10 000 person-years), except for leiomyosarcoma following retinoblastoma, for which the AER reached 52.7 (95% CI = 20.0 to 85.5) per 10 000 person-years among patients who had survived at least 45 years from diagnosis of retinoblastoma., Conclusions: For the first time, we provide risk estimates of specific STS subtypes following childhood cancers and give evidence that risks of MPNSTs, leiomyosarcomas, and fibromatous neoplasms are particularly increased. While the multiplicative excess risks relative to the general population are substantial, the absolute excess risk of developing any STS subtype is low, except for leiomyosarcoma after retinoblastoma. These results are likely to be informative for both survivors and health care providers.
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- 2018
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45. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.
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Waszak SM, Northcott PA, Buchhalter I, Robinson GW, Sutter C, Groebner S, Grund KB, Brugières L, Jones DTW, Pajtler KW, Morrissy AS, Kool M, Sturm D, Chavez L, Ernst A, Brabetz S, Hain M, Zichner T, Segura-Wang M, Weischenfeldt J, Rausch T, Mardin BR, Zhou X, Baciu C, Lawerenz C, Chan JA, Varlet P, Guerrini-Rousseau L, Fults DW, Grajkowska W, Hauser P, Jabado N, Ra YS, Zitterbart K, Shringarpure SS, De La Vega FM, Bustamante CD, Ng HK, Perry A, MacDonald TJ, Hernáiz Driever P, Bendel AE, Bowers DC, McCowage G, Chintagumpala MM, Cohn R, Hassall T, Fleischhack G, Eggen T, Wesenberg F, Feychting M, Lannering B, Schüz J, Johansen C, Andersen TV, Röösli M, Kuehni CE, Grotzer M, Kjaerheim K, Monoranu CM, Archer TC, Duke E, Pomeroy SL, Shelagh R, Frank S, Sumerauer D, Scheurlen W, Ryzhova MV, Milde T, Kratz CP, Samuel D, Zhang J, Solomon DA, Marra M, Eils R, Bartram CR, von Hoff K, Rutkowski S, Ramaswamy V, Gilbertson RJ, Korshunov A, Taylor MD, Lichter P, Malkin D, Gajjar A, Korbel JO, and Pfister SM
- Subjects
- Adolescent, Adult, Cerebellar Neoplasms mortality, Cerebellar Neoplasms pathology, Cerebellar Neoplasms therapy, Child, Child, Preschool, DNA Mutational Analysis, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Heredity, Humans, Infant, Male, Medulloblastoma mortality, Medulloblastoma pathology, Medulloblastoma therapy, Pedigree, Phenotype, Predictive Value of Tests, Progression-Free Survival, Prospective Studies, Reproducibility of Results, Retrospective Studies, Risk Factors, Transcriptome, Exome Sequencing, Young Adult, Biomarkers, Tumor genetics, Cerebellar Neoplasms genetics, DNA Methylation, Genetic Testing methods, Germ-Line Mutation, Medulloblastoma genetics, Models, Genetic
- Abstract
Background: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines., Methods: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MB
WNT ), SHH (MBSHH ), group 3 (MBGroup3 ), and group 4 (MBGroup4 ). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma., Findings: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH . Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH , MBGroup3 , and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes., Interpretation: Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics., Funding: German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2018
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46. Family history of cancer and the risk of childhood solid tumours: a Norwegian nationwide register-based cohort study.
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Del Risco Kollerud R, Blaasaas KG, Claussen B, Nafstad P, Cannon-Albright LA, Ruud E, Wesenberg F, and Næss Ø
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- Adolescent, Child, Child, Preschool, Cohort Studies, Female, Humans, Infant, Infant, Newborn, Male, Neoplasms genetics, Norway epidemiology, Proportional Hazards Models, Registries, Risk, Family Health statistics & numerical data, Neoplasms epidemiology
- Abstract
This corrects the article DOI: 10.1038/bjc.2017.85.
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- 2018
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47. The PanCareSurFup cohort of 83,333 five-year survivors of childhood cancer: a cohort from 12 European countries.
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Grabow D, Kaiser M, Hjorth L, Byrne J, Alessi D, Allodji RS, Bagnasco F, Bárdi E, Bautz A, Bright CJ, de Vathaire F, Feijen EAM, Garwicz S, Hagberg O, Haupt R, Hawkins MM, Jakab Z, Kremer LCM, Kuehni CE, Kuonen R, Lähteenmäki PM, Reulen RC, Ronckers CM, Sacerdote C, Vu-Bezin G, Wesenberg F, Wiebe T, Winter DL, Winther JF, Zaletel LZ, and Kaatsch P
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- Adolescent, Child, Child, Preschool, Cohort Effect, Europe epidemiology, Female, Humans, Male, Survival Rate, Cancer Survivors statistics & numerical data, Neoplasms mortality, Neoplasms therapy, Registries statistics & numerical data
- Abstract
Childhood cancer survivors face risks from a variety of late effects, including cardiac events, second cancers, and late mortality. The aim of the pan-European PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies (PanCareSurFup) Consortium was to collect data on incidence and risk factors for these late effects among childhood cancer survivors in Europe. This paper describes the methodology of the data collection for the overall PanCareSurFup cohort and the outcome-related cohorts. In PanCareSurFup 13 data providers from 12 countries delivered data to the data centre in Mainz. Data providers used a single variable list that covered all three outcomes. After validity and plausibility checks data was provided to the outcome-specific working groups. In total, we collected data on 115,596 patients diagnosed with cancer from 1940 to 2011, of whom 83,333 had survived 5 years or more. Due to the eligibility criteria and other requirements different numbers of survivors were eligible for the analysis of each of the outcomes. Thus, 1014 patients with at least one cardiac event were identified from a cohort of 39,152 5-year survivors; for second cancers 3995 survivors developed at least one second cancer from a cohort of 71,494 individuals, and from the late mortality cohort of 79,441 who had survived at least 5 years, 9247 died subsequently. Through the close cooperation of many European countries and the establishment of one central data collection and harmonising centre, the project succeeded in generating the largest cohort of children with cancer to date.
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- 2018
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48. Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): A population-based cohort study of 32,839 one-year survivors.
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Bonnesen TG, Winther JF, Andersen KK, Asdahl PH, de Fine Licht S, Gudmundsdottir T, Sällfors Holmqvist A, Madanat-Harjuoja LM, Tryggvadottir L, Wesenberg F, Heilmann C, Olsen JH, and Hasle H
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- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Female, Humans, Infant, Leukemia epidemiology, Liver Neoplasms epidemiology, Male, Middle Aged, Proportional Hazards Models, Scandinavian and Nordic Countries epidemiology, Young Adult, Cancer Survivors statistics & numerical data, Liver Diseases epidemiology, Neoplasms epidemiology
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Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow-up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all 1-year survivors of childhood cancer treated in the five Nordic countries. A Cox proportional hazards model was used to estimate hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to type of cancer. We used the risk among survivors of central nervous system tumour as internal reference. With a median follow-up time of 10 years, 659 (2%) survivors had been hospitalised at least once for a liver disease. The risk for hospitalisation for any liver disease was high after hepatic tumour (HR = 6.9) and leukaemia (HR = 1.7). The Danish sub-cohort of leukaemia treated with haematopoietic stem cell transplantation had a substantially higher risk for hospitalisation for all liver diseases combined (HR = 3.8). Viral hepatitis accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors hospitalised for liver disease. The 20-year cumulative risk of viral hepatitis was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those diagnosed after 1990. The risk of liver disease was low but significantly increased among survivors of hepatic tumours and leukaemia. Further studies with focus on the different treatment modalities are needed to further strengthen the prevention of treatment-induced late liver complications., (© 2017 UICC.)
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- 2018
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49. Risk of Subsequent Bone Cancers Among 69 460 Five-Year Survivors of Childhood and Adolescent Cancer in Europe.
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Fidler MM, Reulen RC, Winter DL, Allodji RS, Bagnasco F, Bárdi E, Bautz A, Bright CJ, Byrne J, Feijen EAM, Garwicz S, Grabow D, Gudmundsdottir T, Guha J, Haddy N, Jankovic M, Kaatsch P, Kaiser M, Kuonen R, Linge H, Maule M, Merletti F, Øfstaas H, Ronckers CM, Skinner R, Teepen J, Terenziani M, Vu-Bezin G, Wesenberg F, Wiebe T, Jakab Z, Haupt R, Lähteenmäki P, Zaletel LZ, Kuehni CE, Winther JF, de Vathaire F, Kremer LC, Hjorth L, and Hawkins MM
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- Adolescent, Adult, Child, Cohort Studies, Europe epidemiology, Female, Follow-Up Studies, Humans, Male, Osteosarcoma epidemiology, Retinoblastoma epidemiology, Sarcoma epidemiology, Young Adult, Bone Neoplasms epidemiology, Neoplasms, Second Primary epidemiology, Survivors statistics & numerical data
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Introduction: We investigate the risks of subsequent primary bone cancers after childhood and adolescent cancer in 12 European countries. For the first time, we satisfactorily address the risks beyond 40 years from diagnosis and beyond 40 years of age among all survivors., Methods: This largest-ever assembled cohort comprises 69 460 five-year survivors of cancer diagnosed before age 20 years. Standardized incidence ratios, absolute excess risks, and multivariable-adjusted relative risks and relative excess risks were calculated. All statistical tests were two-sided., Results: Overall, survivors were 21.65 times (95% confidence interval = 18.97 to 24.60 times) more likely to be diagnosed with a subsequent primary bone cancer than expected from the general population. The greatest excess numbers of bone cancers were observed after retinoblastoma, bone sarcoma, and soft tissue sarcoma. The excess number of bone cancers declined linearly with both years since diagnosis and attained age (all P < .05). Beyond 40 years from diagnosis and age 40 years, there were at most 0.45 excess bone cancers among all survivors per 10 000 person-years at risk; beyond 30 years from diagnosis and age 30 years, there were at most 5.02 excess bone cancers after each of retinoblastoma, bone sarcoma, and soft tissue sarcoma, per 10 000 person-years at risk., Conclusions: For all survivors combined and the cancer groups with the greatest excess number of bone cancers, the excess numbers observed declined with both age and years from diagnosis. These results provide novel, reliable, and unbiased information about risks and risk factors among long-term survivors of childhood and adolescent cancer., (© The Author 2017. Published by Oxford University Press.)
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- 2018
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50. Long-term inpatient disease burden in the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study: A cohort study of 21,297 childhood cancer survivors.
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de Fine Licht S, Rugbjerg K, Gudmundsdottir T, Bonnesen TG, Asdahl PH, Holmqvist AS, Madanat-Harjuoja L, Tryggvadottir L, Wesenberg F, Hasle H, Winther JF, and Olsen JH
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- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Cohort Studies, Female, Hospitalization statistics & numerical data, Humans, Male, Middle Aged, Morbidity, Neoplasms etiology, Neoplasms mortality, Registries, Retrospective Studies, Risk Assessment, Scandinavian and Nordic Countries epidemiology, Survival Rate, Young Adult, Inpatients statistics & numerical data, Neoplasms epidemiology, Survivors statistics & numerical data
- Abstract
Background: Survivors of childhood cancer are at increased risk for a wide range of late effects. However, no large population-based studies have included the whole range of somatic diagnoses including subgroup diagnoses and all main types of childhood cancers. Therefore, we aimed to provide the most detailed overview of the long-term risk of hospitalisation in survivors of childhood cancer., Methods and Findings: From the national cancer registers of Denmark, Finland, Iceland, and Sweden, we identified 21,297 5-year survivors of childhood cancer diagnosed with cancer before the age of 20 years in the periods 1943-2008 in Denmark, 1971-2008 in Finland, 1955-2008 in Iceland, and 1958-2008 in Sweden. We randomly selected 152,231 population comparison individuals matched by age, sex, year, and country (or municipality in Sweden) from the national population registers. Using a cohort design, study participants were followed in the national hospital registers in Denmark, 1977-2010; Finland, 1975-2012; Iceland, 1999-2008; and Sweden, 1968-2009. Disease-specific hospitalisation rates in survivors and comparison individuals were used to calculate survivors' standardised hospitalisation rate ratios (RRs), absolute excess risks (AERs), and standardised bed day ratios (SBDRs) based on length of stay in hospital. We adjusted for sex, age, and year by indirect standardisation. During 336,554 person-years of follow-up (mean: 16 years; range: 0-42 years), childhood cancer survivors experienced 21,325 first hospitalisations for diseases in one or more of 120 disease categories (cancer recurrence not included), when 10,999 were expected, yielding an overall RR of 1.94 (95% confidence interval [95% CI] 1.91-1.97). The AER was 3,068 (2,980-3,156) per 100,000 person-years, meaning that for each additional year of follow-up, an average of 3 of 100 survivors were hospitalised for a new excess disease beyond the background rates. Approximately 50% of the excess hospitalisations were for diseases of the nervous system (19.1% of all excess hospitalisations), endocrine system (11.1%), digestive organs (10.5%), and respiratory system (10.0%). Survivors of all types of childhood cancer were at increased, persistent risk for subsequent hospitalisation, the highest risks being those of survivors of neuroblastoma (RR: 2.6 [2.4-2.8]; n = 876), hepatic tumours (RR: 2.5 [2.0-3.1]; n = 92), central nervous system tumours (RR: 2.4 [2.3-2.5]; n = 6,175), and Hodgkin lymphoma (RR: 2.4 [2.3-2.5]; n = 2,027). Survivors spent on average five times as many days in hospital as comparison individuals (SBDR: 4.96 [4.94-4.98]; n = 422,218). The analyses of bed days in hospital included new primary cancers and recurrences. Of the total 422,218 days survivors spent in hospital, 47% (197,596 bed days) were for new primary cancers and recurrences. Our study is likely to underestimate the absolute overall disease burden experienced by survivors, as less severe late effects are missed if they are treated sufficiently in the outpatient setting or in the primary health care system., Conclusions: Childhood cancer survivors were at increased long-term risk for diseases requiring inpatient treatment even decades after their initial cancer. Health care providers who do not work in the area of late effects, especially those in primary health care, should be aware of this highly challenged group of patients in order to avoid or postpone hospitalisations by prevention, early detection, and appropriate treatments.
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- 2017
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