Long‐term follow‐up of endocrine function among young children with newly diagnosed malignant central nervous system tumors treated with irradiation‐avoiding regimens

Cochrane, A. M. G.; Cheung, Clement C.; Rangan, Kasey; Freyer, David R.; Nahata, Leena; Dhall, Girish; Finlay, Jonathan L.

doi:10.1002/pbc.26616

Cited by 8 publications

(7 citation statements)

References 36 publications

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“…This may be attributed to brain-related side effects of radiation therapy (23). In addition, the risk of endocrine disorders was higher in relatively younger patients; this was probably related to brain development (24). The findings suggest that the treatment of endocrine (26).…”

Section: Discussionmentioning

confidence: 88%

Prevalence of Endocrine Disorders in Childhood Brain Tumor Survivors in South Korea

Heo

Lee

Hwang

et al. 2019

In Vivo

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Background/Aim: This longitudinal study aimed to analyze the prevalence of endocrine disorders in childhood brain tumor survivors in South Korea using claims data. Patients and Methods: We identified in 1,058 patients from a nationwide cohort of patients diagnosed with brain tumors between January 1st 2009 to March 29th 2016. Multivariable logistic regression was used to evaluate associations between clinical factors and endocrine disorders. Results: After a median follow-up of 60.0 months, 393 (37.1%) patients had at least 1 endocrine disorder. The commonest endocrine disorders were hypopituitarism (17.4%) and hypothyroidism (6.1%). Female gender (odds ratio(OR)=1.45, p=0.005) and age <10 years (OR=1.65, p=0.001) conferred a higher risk. Patients who received radiotherapy were more likely to have endocrine disorders compared to those who did not (OR=1.79, p<0.001). Conclusion: Regular assessment of endocrine function and timely interventions are necessary for childhood brain tumor survivors with a risk of endocrine disorders. Brain tumors are the second commonest cause of cancer in children and account for 21% of all pediatric cancers (1). Advancements in treatment have allowed 74% of children diagnosed with brain tumors to become long-term survivors (2). Despite improvements in prognosis, cancer survivors continue to suffer from treatment-related side-effects that impair their quality of life (3). These adverse effects may be related to the tumor burden, surgical interventions, chemotherapy, or radiotherapy (4). Many of the late effects are attributable to direct damage of brain development (5), and include disorders of the endocrine system (6). Among them, childhood brain tumors located near the hypothalamic-pituitary area are particularly associated with an increased risk of hypothalamic pituitary axis (HPA) dysfunction (7). Common endocrine complications include the growth hormone (GH) deficiency and insufficient levels of thyrotropic and adrenocorticotropic hormones (8). In addition, the prevalence of endocrine disease among patients with childhood brain tumors is 49%, and that of more than one endocrine deficiency is estimated to be 40% (9). Reports suggest that the lack of an appropriate and timely follow-up escaping diagnosis of developing endocrine disorders could result in late referrals, adversely affecting the hormone balance of these patients (10). Reports on the number of childhood brain tumor survivors being currently treated for endocrine disorders in South Korea are scarce. In addition, recommendations for screening endocrinopathy are based on limited variables and as a result of studies in small patient populations (11). For all these reasons, we aimed to analyze large-scale nationwide data for identifying the prevalence of endocrine disorders among childhood brain tumor survivors. We also evaluated the risk factors associated with these disorders. Patients and Methods Patients under 18 years of age who were diagnosed with pediatric brain tumors between January 2007 and December 2016 were ident...

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Section: Discussionmentioning

confidence: 88%

Prevalence of Endocrine Disorders in Childhood Brain Tumor Survivors in South Korea

Heo

Lee

Hwang

et al. 2019

In Vivo

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“…[28][29][30][31] The risk for pituitary dysfunction increases with the radiation dose delivered to the pituitary axis and the exposure duration, ranging from 25% to 50% after 8 to 14.4 Gy, 32 0% to 66% after 18 to 24 Gy 33 and 80% to 90% after ≥30 Gy CRT. 30,34 The endocrine complications usually take years to develop, and the clinical symptoms are usually hidden and imperceptible, 35 but the signalling pathways and the molecular mechanisms, es- However, excessive activation of the p53 signalling pathway induces either viable cell growth arrest or apoptosis. 38 In this study, Neuroinflammation is a significant problem after irradiation, and our previous studies using the rodent irradiation model to measure inflammation in the cerebellum, hippocampus and hypothalamus showed that irradiation can increase the inflammatory response and the release of inflammatory factors.…”

Section: Discussionmentioning

confidence: 99%

“…The risk for pituitary dysfunction increases with the radiation dose delivered to the pituitary axis and the exposure duration, ranging from 25% to 50% after 8 to 14.4 Gy, 32 0% to 66% after 18 to 24 Gy 33 and 80% to 90% after ≥30 Gy CRT 30,34 . The endocrine complications usually take years to develop, and the clinical symptoms are usually hidden and imperceptible, 35 but the signalling pathways and the molecular mechanisms, especially in the pituitary after irradiation, remain unknown. Due to the difficulty in using human samples, animal models, especially rat models, have been widely used in pituitary studies.…”

Section: Discussionmentioning

confidence: 99%

Cranial irradiation alters neuroinflammation and neural proliferation in the pituitary gland and induces late‐onset hormone deficiency

Sun

Zhou

et al. 2020

J Cellular Molecular Medi

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“…Schmiegelow et al compared HPAA function via ITT and ACTH test in 73 childhood brain tumours with 17 controls and concluded no additional effect from chemotherapy to the impact of cranial irradiation (Schmiegelow et al 2003). Cochrane et al reported no cases of cortisol deficiency among 30 childhood cancer survivors with CNS tumours treated with radiation avoiding therapies after a mean of 8 years (Cochrane et al 2017).…”

Section: Chemotherapymentioning

confidence: 99%

The hypothalamic–pituitary–adrenal axis in childhood cancer survivors

Wei¹,

Crowne²

2018

Endocrine-Related Cancer

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Endocrine abnormalities are common among childhood cancer survivors. Abnormalities of the hypothalamic-pituitary-adrenal axis (HPAA) are relatively less common, but the consequences are severe if missed. Patients with tumours located and/or had surgery performed near the hypothalamic-pituitary region and those treated with an accumulative cranial radiotherapy dose of over 30 Gy are most at risk of adrenocorticotrophic hormone (ACTH) deficiency. Primary adrenal insufficiency may occur in patients with tumours located in or involving one or both adrenals. The effects of adjunct therapies also need to be considered, particularly, new immunotherapies. High-dose and/or prolonged courses of glucocorticoid treatment can result in secondary adrenal insufficiency, which may take months to resolve and hence reassessment is important to ensure patients are not left on long-term replacement steroids inappropriately. The prevalence and cumulative incidences of HPAA dysfunction are difficult to quantify because of its non-specific presentation and lack of consensus regarding its investigations. The insulin tolerance test remains the gold standard for the diagnosis of central cortisol deficiency, but due to its risks, alternative methods with reduced diagnostic sensitivities are often used and must be interpreted with caution. ACTH deficiency may develop many years after the completion of oncological treatment alongside other pituitary hormone deficiencies. It is essential that health professionals involved in the long-term follow-up of childhood cancer survivors are aware of individuals at risk of developing HPAA dysfunction and implement appropriate monitoring and treatment.

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Long‐term follow‐up of endocrine function among young children with newly diagnosed malignant central nervous system tumors treated with irradiation‐avoiding regimens

Abstract: These findings demonstrate that the use of relatively brief, intensive chemotherapy regimens including marrow-ablative chemotherapy with AuHCR results in fewer endocrine sequelae than treatment schemes utilizing CNS irradiation.

Cited by 8 publications

References 36 publications

Prevalence of Endocrine Disorders in Childhood Brain Tumor Survivors in South Korea

Prevalence of Endocrine Disorders in Childhood Brain Tumor Survivors in South Korea

Cranial irradiation alters neuroinflammation and neural proliferation in the pituitary gland and induces late‐onset hormone deficiency

The hypothalamic–pituitary–adrenal axis in childhood cancer survivors

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