Sofie de Fine Licht1, Jeanette Falck Winther2, Thorgerdur Gudmundsdottir2, Anna Sällfors Holmqvist3, Trine Gade Bonnesen4, Peter Haubjerg Asdahl4, Laufey Tryggvadottir5, Harald Anderson6, Finn Wesenberg7, Nea Malila8, Kirsten Holm9, Henrik Hasle4, Jørgen Helge Olsen2. 1. Danish Cancer Society Research Centre, Copenhagen, Denmark. Electronic address: sofielie@cancer.dk. 2. Danish Cancer Society Research Centre, Copenhagen, Denmark. 3. Division of Paediatric Oncology and Haematology, Skane University Hospital, Lund, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden. 4. Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark. 5. The Icelandic Cancer Registry, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 6. Department of Cancer Epidemiology, Lund University, Lund, Sweden. 7. Department of Paediatrics, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Norwegian Cancer Registry, Oslo, Norway. 8. Finnish Cancer Registry, Helsinki, Finland. 9. Department of Paediatrics, Hilleroed Hospital, Hilleroed, Denmark.
Abstract
BACKGROUND: The pattern of endocrine disorders in long-term survivors of childhood cancer has not been investigated comprehensively. Here, we aimed to assess the lifetime risk of these disorders in Nordic survivors of childhood cancer. METHODS: From the national cancer registries of Denmark, Finland, Iceland, Norway, and Sweden, we identified 31,723 1-year survivors of childhood cancer, notified since the start of registration in the 1940s and 1950s. From the national population registries, we randomly selected a comparison cohort of people matched by age, sex, and country. Study participants were linked to the national hospital registries, and observed numbers of first-time hospital contacts for endocrine disorders in survivors of childhood cancer were compared with the expected numbers derived from the population comparison cohort. We calculated the absolute excess risks attributable to status as a childhood cancer survivor and standardised hospitalisation rate ratios (SHRRs). FINDINGS: Of the childhood cancer survivors, 3292 had contact with a hospital for an endocrine disorder, yielding a SHRR of 4·8 (95% CI 4·6-5·0); the highest risks were in survivors of leukaemia (SHRR 7·3 [95% CI 6·7-7·9]), CNS tumours (6·6 [6·2-7·0]), and Hodgkin's lymphoma (6·2 [5·6-7·0]). The absolute excess risk for endocrine disorders was roughly 1000 per 100,000 person-years before 20 years of age, and 400 per 100,000 person-years during the remaining lifetime. For children with cancer diagnosed at 5-9 years of age, the cumulative risk for endocrine disorders was highest, and reached 43% at the age of 60 years. Diagnoses of pituitary hypofunction (SHRR 88·0), hypothyroidism (9·9), and testicular and ovarian dysfunction (42·5 and 4·7, respectively) together constituted 61% (655 of 1078) of all excess disease-induced and treatment-induced endocrine disorders in survivors of childhood cancer. INTERPRETATION: A cumulative risk for endocrine disorders at 60 years of age of above 40% in survivors of childhood cancer emphasises the importance of minimisation of damaging treatment, intensification of secondary prevention, and targeting of survivor follow-up throughout life. Since most long-term childhood cancer survivors are not followed in a specialised late-effect clinic, they are a growing challenge for the primary care physician and medical specialists working outside the late-effect area. FUNDING: The Danish Council for Strategic Research.
BACKGROUND: The pattern of endocrine disorders in long-term survivors of childhood cancer has not been investigated comprehensively. Here, we aimed to assess the lifetime risk of these disorders in Nordic survivors of childhood cancer. METHODS: From the national cancer registries of Denmark, Finland, Iceland, Norway, and Sweden, we identified 31,723 1-year survivors of childhood cancer, notified since the start of registration in the 1940s and 1950s. From the national population registries, we randomly selected a comparison cohort of people matched by age, sex, and country. Study participants were linked to the national hospital registries, and observed numbers of first-time hospital contacts for endocrine disorders in survivors of childhood cancer were compared with the expected numbers derived from the population comparison cohort. We calculated the absolute excess risks attributable to status as a childhood cancer survivor and standardised hospitalisation rate ratios (SHRRs). FINDINGS: Of the childhood cancer survivors, 3292 had contact with a hospital for an endocrine disorder, yielding a SHRR of 4·8 (95% CI 4·6-5·0); the highest risks were in survivors of leukaemia (SHRR 7·3 [95% CI 6·7-7·9]), CNS tumours (6·6 [6·2-7·0]), and Hodgkin's lymphoma (6·2 [5·6-7·0]). The absolute excess risk for endocrine disorders was roughly 1000 per 100,000 person-years before 20 years of age, and 400 per 100,000 person-years during the remaining lifetime. For children with cancer diagnosed at 5-9 years of age, the cumulative risk for endocrine disorders was highest, and reached 43% at the age of 60 years. Diagnoses of pituitary hypofunction (SHRR 88·0), hypothyroidism (9·9), and testicular and ovarian dysfunction (42·5 and 4·7, respectively) together constituted 61% (655 of 1078) of all excess disease-induced and treatment-induced endocrine disorders in survivors of childhood cancer. INTERPRETATION: A cumulative risk for endocrine disorders at 60 years of age of above 40% in survivors of childhood cancer emphasises the importance of minimisation of damaging treatment, intensification of secondary prevention, and targeting of survivor follow-up throughout life. Since most long-term childhood cancer survivors are not followed in a specialised late-effect clinic, they are a growing challenge for the primary care physician and medical specialists working outside the late-effect area. FUNDING: The Danish Council for Strategic Research.
Authors: Smita Bhatia; Saro H Armenian; Gregory T Armstrong; Eline van Dulmen-den Broeder; Michael M Hawkins; Leontien C M Kremer; Claudia E Kuehni; Jørgen H Olsen; Leslie L Robison; Melissa M Hudson Journal: J Clin Oncol Date: 2015-08-24 Impact factor: 44.544
Authors: Emily S Tonorezos; Melissa M Hudson; Angela B Edgar; Leontien C Kremer; Charles A Sklar; W Hamish B Wallace; Kevin C Oeffinger Journal: Lancet Diabetes Endocrinol Date: 2015-04-12 Impact factor: 32.069
Authors: Wassim Chemaitilly; Qi Liu; Laura van Iersel; Kirsten K Ness; Zhenghong Li; Carmen L Wilson; Tara M Brinkman; James L Klosky; Nicole Barnes; Karen L Clark; Rebecca M Howell; Susan A Smith; Matthew J Krasin; Monika L Metzger; Gregory T Armstrong; Michael W Bishop; Hanneke M van Santen; Ching-Hon Pui; Deo Kumar Srivastava; Yutaka Yasui; Melissa M Hudson; Leslie L Robison; Daniel M Green; Charles A Sklar Journal: J Clin Oncol Date: 2019-09-26 Impact factor: 44.544
Authors: Stacy Tessler Lindau; Emily M Abramsohn; Shirley R Baron; Judith Florendo; Hope K Haefner; Anuja Jhingran; Vanessa Kennedy; Mukta K Krane; David M Kushner; Jennifer McComb; Diane F Merritt; Julie E Park; Amy Siston; Margaret Straub; Lauren Streicher Journal: CA Cancer J Clin Date: 2016-01-19 Impact factor: 508.702
Authors: Gitte Vrelits Sørensen; Jeanette Falck Winther; Sofie de Fine Licht; Klaus Kaa Andersen; Anna Sällfors Holmqvist; Laura Madanat-Harjuoja; Laufey Tryggvadottir; Andrea Bautz; Timothy L Lash; Henrik Hasle Journal: J Natl Cancer Inst Date: 2019-09-01 Impact factor: 13.506
Authors: Wassim Chemaitilly; Zhenghong Li; Sujuan Huang; Kirsten K Ness; Karen L Clark; Daniel M Green; Nicole Barnes; Gregory T Armstrong; Matthew J Krasin; Deo Kumar Srivastava; Ching-Hon Pui; Thomas E Merchant; Larry E Kun; Amar Gajjar; Melissa M Hudson; Leslie L Robison; Charles A Sklar Journal: J Clin Oncol Date: 2015-01-05 Impact factor: 44.544