Endocrine Disorders

Since the start of cancer registration in the Nordic countries in the 1940s and 1950s around 55,000 children, aged 0-19 years, have been diagnosed with cancer (1). Therapeutic advances for the management of childhood cancer have resulted in remarkably improved long-term survival with around 81% surviving today (2;3). As a result of the continuous success of treatment, there is now a fast growing population, who have been cured of childhood cancer and have survived for decades. As the vast majority of these survivors received intensive exposure to radiation and chemotherapy as part of their treatment and during a period of life distinguished by organ growth and maturation, they now face significant, often uncharacterized sequelae, most of which become clinically apparent many years after the cancer has been cured (4). These complications are of a broad spectrum, from insignificant and treatable ones to severe permanent damage or even life threatening and fatal. 

Late effects of childhood cancer treatment occur in all organ systems including the endocrine system (5). Approximately 18% of childhood cancer survivors develop an endocrine  disorder which is a 6 times higher risk compared with their siblings (5). Furthermore, survivors continue to face new-onset endocrine disorders as they age and even up to 30 years after diagnosis (4;5). Endocrine late effects lead to a wide variety of different disorders, in example radiation induced pituitary hormone deficiencies are among the most common late effects after childhood cancer treatment. They are irreversible and have a negative impact on growth, skeletal health, disrupted puberty, sexual function and fertility, and ultimately on quality of life (6).

Aims of this PhD study

A two-step approach will be used in this PhD-project. The aim of the first phase is, to examine whether the survivors of childhood cancer are at greater risk of a wide variety of endocrine disorders compared with the general population. In the second phase, we will investigate the effect of different treatment regiments on the development of a number of selected serious outcomes identified in the first phase of the project.

Methods

Cohort study

In a cohort of approximately 55,000 childhood cancer survivors from Denmark, Finland, Iceland, Norway and Sweden, we will investigate whether childhood cancer survivors have an increased risk of endocrine late effects. We will conduct a wide screening in the national patient registries which include all discharge diagnoses from hospitals. A population comparison cohort of approximately 270,000 individuals, reflecting the morbidity in the background population, will be randomly selected from the central population registries and matched by country, sex and age.

In the screening for endocrine late effects in the national patient registries all main classifications of endocrine-, nutritional- and metabolic diseases will be included such as; thyroid diseases, parathyroid disease, diabetes, pituitary diseases, adrenal cortical diseases, ovarian dysfunction, testicular dysfunction, avitaminosis, nutritional deficiencies, amyloid degeneration and obesity.

Case-cohort study

The second part of the study is a case-cohort study, investigating the effects of specific treatment regimens for childhood cancer on selected outcomes. Cancer treatment of cases with selected serious outcomes, identified for further investigation in the first part of the study, will be compared with that in a sub-cohort of survivors. Dose-response analyses will be based on treatment information abstracted from medical records.

References
(1) Olsen JH, Moller T, Anderson H, Langmark F, Sankila R, Tryggvadottir L et al. Lifelong cancer incidence in 47,697 patients treated for childhood cancer in the Nordic countries. J Natl Cancer Inst 2009; 101(11):806-813.

(2) de Nully BP, Olsen JH, Hertz H, Carstensen B, Bautz A. Trends in survival after childhood cancer in Denmark, 1943-87: a population-based study. Acta Paediatr 1995; 84(3):316-324.

(3) Gatta G, Zigon G, Capocaccia R, Coebergh JW, Desandes E, Kaatsch P et al. Survival of European children and young adults with cancer diagnosed 1995-2002. Eur J Cancer 2009; 45(6):992-1005.

(4) Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 2006; 355(15):1572-1582

(5) Diller L, Chow EJ, Gurney JG, Hudson MM, Kadin-Lottick NS, Kawashima TI et al. Chronic disease in the Childhood Cancer Survivor Study cohort: a review of published findings. J Clin Oncol 2009; 27(14):2339-2355.

(6) Wallace WHB, Kelnar CJH. Endocrinopathy after childhood cancer treatment. Basel: Karger; 2009.