Cranial radiotherapy of childhood brain tumours: Growth hormone deficiency and its relation to the biological effective dose of irradiation in a large population based study

Schmiegelow, Marianne; Lassen, S.; Hs, Poulsen; Feldt‐Rasmussen, Ulla; Schmiegelow, Kjeld; Hertz, H; Müller, Jørn

doi:10.1046/j.1365-2265.2000.01079.x

Cited by 102 publications

(66 citation statements)

References 35 publications

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“…Numerous studies found a lack in GH (GH-deficiency) to be a dose dependent adverse effect of an irradiation of the neurocranium (18,19,45,46). Surprisingly, only 1.1% of participants in our current study received a GH replacement therapy.…”

Section: Clinical Study J Gebauer E-m Fick and Others Endocrine Latecontrasting

confidence: 41%

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Self-reported endocrine late effects in adults treated for brain tumours, Hodgkin and non-Hodgkin lymphoma: a registry based study in Northern Germany

Gebauer

Fick

Waldmann

et al. 2015

European Journal of Endocrinology

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Objective: Due to the increasing success and survival rates in the primary treatment of malignancies derived from the CNS as well as the hematopoietic system, endocrine late effects of cancer and its therapy are of growing importance. Despite evaluation of these late effects in patients treated for cancer in childhood, the impact on adults remains largely unclear. Methods: 1035 adult patients primarily diagnosed with a CNS malignancy, a Hodgkin (HL) or non-Hodgkin lymphoma (NHL) between 1998 and 2008 were recruited via the regional epidemiological cancer registry covering w2.8 million inhabitants in the federal state of Schleswig-Holstein, Northern Germany. The prevalence of endocrine disorders and current psychosocial impairment was assessed employing several questionnaires (SF-36v1, WHO-5). Results: Fully completed questionnaires of 558 patients were available for subsequent analysis showing markedly reduced overall performance and psychological status when compared to German reference data. Thyroid disorders were reported in 16.3% of patients with 10.4% suffering from hypo-and 5.9% from hyperthyroidism. Overall, 17.6% stated to be affected by diabetes mellitus with an increased rate of 21.1% among NHL patients and 11.5% of participants were affected by osteoporosis. Conclusion: Compared to German population based studies on the prevalence of diabetes mellitus, osteoporosis and thyroid disorders the frequency of all these endocrine problems was significantly increased in CNS, HL, and NHL cancer survivors. These data confirm that not only children and adolescents but also adult cancer patients are at risk for therapy associated endocrine late effects.

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Section: Clinical Study J Gebauer E-m Fick and Others Endocrine Latecontrasting

confidence: 41%

“…As data from children and adolescents suggested that the highest frequency of endocrine late effects are observed in patients with Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and CNS tumours (CNS-T) we restricted our analysis to these patients (15,16,17,18,19).…”

Section: Introductionmentioning

confidence: 99%

Self-reported endocrine late effects in adults treated for brain tumours, Hodgkin and non-Hodgkin lymphoma: a registry based study in Northern Germany

Gebauer

Fick

Waldmann

et al. 2015

European Journal of Endocrinology

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“…There is an increase in the frequency and severity of hormonal deficits with a longer time interval after radiotherapy. The progressive nature of the hormonal deficits following radiation damage to the hypothalamic-pituitary axis can be attributed to the delayed effects of radiotherapy on the axis or the development of secondary pituitary atrophy following previous hypothalamic damage (Spoudeas et al 1996, Clayton & Shalet 1991b, Schmiegelow et al 2000. This necessitates prolonged follow-up with yearly testing of pituitary function in patients treated with cranial irradiation for brain tumours.…”

Section: Role Of Radiationmentioning

confidence: 99%

“…The formula used to calculate the BED incorporates total dose, fraction size and tissue response to radiation (Schmiegelow et al 2000). Calculation of the BED provides a useful method of comparing radiation schedules and predicting the effect on hypothalamic-pituitary function (Schmiegelow et al 2000).…”

Section: Role Of Radiationmentioning

confidence: 99%

The impact of cancer therapy on the endocrine system in survivors of childhood brain tumours

Gleeson¹,

Shalet²

2004

Endocr Relat Cancer

147

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Survival rates are improving following cancer therapy for childhood brain tumours. There is therefore a growing cohort of survivors at risk of late effects of cancer therapy. Endocrine problems are very common in these patients. The recognition and prompt management of these are essential to prevent further morbidity and impairment of quality of life.Cranial radiation can damage hypothalamic-pituitary function, most frequently affecting GH status; however, higher radiation doses may cause more widespread hypothalamic-pituitary damage. Early puberty secondary to cranial irradiation is now being managed with gonadotrophin-releasing hormone analogues to improve final height. Prompt diagnosis and management of GH deficiency may improve final height outcome; continued GH therapy beyond final height aids the achievement of adult body composition (lean body mass and bone mass) and GH therapy in adulthood improves quality of life. Both cranial irradiation alone and with spinal irradiation can result in radiation damage to the thyroid resulting in hypothyroidism and thyroid nodules, a high proportion of which are malignant. Gonadal damage secondary to spinal irradiation and adjuvant chemotherapy may have long-term consequences including infertility.

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“…GH deficiency (GHD) is an endocrinopathy found in childhood cancer survivors, resulting from tumors affecting the hypothalamic-pituitary axis or from cancer therapy, especially cranial irradiation (1,2,3). For example, GHD has been found in 58% of long-term survivors of childhood acute lymphoblastic leukemia treated with R24 Gy whole brain radiation (4).…”

Section: Introductionmentioning

confidence: 99%

Incidence of second neoplasm in childhood cancer survivors treated with GH: an analysis of GeNeSIS and HypoCCS

Woodmansee

Zimmermann

Child³

et al. 2013

European Journal of Endocrinology

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Objective: Childhood cancer survivors are commonly treated with GH for GH deficiency that develops either as a result of primary malignancy or its treatment. One study -the Childhood Cancer Survivor Study (CCSS) -demonstrated increased risk of second neoplasm (SN) in GH-treated childhood cancer survivors compared with non-GH treated, after adjusting for key risk factors. We assessed the incidence of SN in GH-treated childhood cancer survivors in outpatient observational studies of GH replacement. Design: Retrospective analysis of two prospective cohort studies that collected data on safety of GH replacement as prescribed in clinical practice. Methods: Childhood cancer survivors enrolled in Eli Lilly and Company's pediatric (Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS)) and adult (Hypopituitary Control and Complications Study (HypoCCS)) observational studies of GH treatment were assessed for incidence of SN. Results: The percentage of childhood cancer survivors treated with GH who developed a SN was 3.8% in pediatric GeNeSIS participants and 6.0% in adult HypoCCS participants. The estimated cumulative incidence of SN at 5 years of follow-up in these studies was 6.2 and 4.8% respectively. Conclusions: The incidence of SN in GeNeSIS and HypoCCS GH-treated participants is similar to the published literature and is thus consistent with increased risk of SN in childhood cancer survivors treated with GH. As follow-up times were relatively short (!3 years), longer observation is recommended. Nevertheless, clinicians should be alerted to the possibility of increased risk of SN in childhood cancer survivors treated with GH and continue chronic surveillance.

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Cranial radiotherapy of childhood brain tumours: Growth hormone deficiency and its relation to the biological effective dose of irradiation in a large population based study

Cited by 102 publications

References 35 publications

Self-reported endocrine late effects in adults treated for brain tumours, Hodgkin and non-Hodgkin lymphoma: a registry based study in Northern Germany

Self-reported endocrine late effects in adults treated for brain tumours, Hodgkin and non-Hodgkin lymphoma: a registry based study in Northern Germany

The impact of cancer therapy on the endocrine system in survivors of childhood brain tumours

Incidence of second neoplasm in childhood cancer survivors treated with GH: an analysis of GeNeSIS and HypoCCS

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