Medical assessment of adverse health outcomes in Dutch childhood cancer survivors; a nationwide project; SKION LATER Q2008 onderzoek:
Thyroid function, in children and adults, after treatment for childhood cancer

One of the most common sequelae of childhood cancer treatment is damage to the
endocrine system. Thyroid hormone is essential for a normal growth and
development into adulthood.
In survivors of childhood cancer, primary (thyroidal) hypothyroidism,
subclinical hypothyroidism, benign nodules, radiation thyroiditis and Graves*
hyperthyroidism followed by hypothyroidism as well as secondary thyroid
malignancies have been described following exposure to external cervical and
cranial irradiation in. These thyroid pathologies have been described to occur
in children and in adults; the incidence is highest in young patients.
Patients who undergo bone marrow transplantation (BMT) are also at high risk of
subsequent thyroid dysfunction, with age at BMT and total body irradiation
(TBI) as significant risk factors. In a recent study of the Late Effects
Surveillance System (Germany) thyroid disorders were found in a number of
sarcoma patients treated with chemotherapy without head and neck irradiation.
Changes in thyroid function have also been described after treatment with
chemotherapy.The exact long term effects of chemotherapy on the thyroid
function are, however, still unclear.

To assess the prevalence of hypothyroidism and hyperthyroidism in the entire
cohort of childhood cancer survivors and the therapy related risk factors.
Specifically:
Part I:
1. To systematically review existing studies on the association between
chemotherapeutic agents and thyroid dysfunction among childhood cancer survivors
2. To assess the prevalence of hypothyroidism and hyperthyroidism in the entire
cohort of childhood cancer survivors, including a risk factor analysis (for
therapy related and other risk factors, such as sex, age at diagnosis, family
history etc)
3. To address the role of thyroid dysfunction in relation to other possible
late effects (e.g., growth, fatigue, quality of life) among childhood cancer
survivors
4. To address the role of genetic factors on thyroid dysfunction among
childhood cancer survivors

Part II:
1. To systematically review existing studies on the role of radiation dose from
external beam irradiation at the thyroid gland and/or the
hypothalamic/pituitary axis and thyroid dysfunction/abnormalities.
2. To review existing laboratory-, animal- and human studies on the impact of
TSH - levels on the development of radiation-related thyroid cancer
3. To assess thyroid dysfunction, clinically overt thyroid nodules, and thyroid
cancer in the entire cohort of childhood cancer survivors in relation to
estimated absorbed radiation dose to the thyroid gland, pituitary gland, and/or
hypothalamus
4. To assess the relationship between 131-IMIBG treatments and the risk of
thyroid dysfunction/abnormalities

All patients who were treated for childhood cancer (before age 18) in one of
the Pediatric Oncology Centers between 1960 and 2001 and who survived for at
least 5 years after diagnosis will be included in the SKION LATER study.
Participating centres are located in Amsterdam (VU University Medical Center
(VUMC) ), Groningen (Children's Cancer Center/ University Medical Center
Groningen (UMCG)), Rotterdam (Rotterdam Erasmus MC-Sophia (REMC-S), Nijmegen
(University Medical Center Nijmegen (UMCN)), Leiden (Leiden University Medical
Center (LUMC) and Utrecht (Princess Máxima Center for Pediatric Oncology
(PMC)). From this cohort, 1481 childhood cancer survivors are at risk of
thyroid dysfunction because of radiotherapy including the neck (i.e., thyroid
gland, or pituitary-hypothalamix axis). In view of patient care guidelines,
thyroid funcion will be assessed for clinical purposes. In addition, 400
control subjects treated with chemotherapy and 400 controls treated with
surgery from the same cohort who are not at risk for thyroid dysfunction will
be will be asked to participate in this study. For them, the measurements of
thyroid function are research-based.

The extent of burden will be minimized for all participants of the study.
For survivors at risk for thyroid disorders the vena puncture is part of
patient care.
For the controls, the vena puncture is research based.
If abnormalities of the thyroid function are found, the survivor will be sent
to the (pediatric) endocrinologist for further follow-up and, if necessary,
treatment.