Long-term effects of cranial irradiation for childhood malignancy on sleep in adulthood

BACKGROUND: Cranial radiation therapy (CRT) is required for successful treatment of a variety of brain tumours in childhood. OBJECTIVE: To investigate whether childhood CRT leads to altered sleep-wakefulness organization in adulthood, and to identify the determinants of such alterations. SUBJECTS AND METHODS: Subjective (questionnaires) and objective (actigraphy) measures of circadian rhythmicity and sleep were assessed in 25 individuals, 8-29 years after CRT for medulloblastoma (n=17) or other intracranial tumours (n=8), and in a group of 34 age-matched healthy individuals. Serum GH peak during insulin-induced hypoglycaemia and serum concentrations of prolactin and leptin (expressed per fat mass) were determined in the CRT group. RESULTS: The CRT group showed a markedly increased sleep duration (8.66 h, compared with 7.66 h in controls). In addition, the sleep-wake rhythm showed greater amplitude and less fragmentation, and less tolerance for alterations in the timing of sleep. Regression analysis showed both radiation dosage and neuroendocrine status to be determinants of sleep changes, suggesting that some of the alterations may be normalized with hormone supplementation. CONCLUSION: The present study shows that high-dose cranial radiation therapy in childhood is associated with objective and subjective changes in the sleep-wake rhythm in adulthood.

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Long-term effects of cranial radiation therapy on attention functioning in survivors of childhood leukemia

Journal of Pediatric Psychology ◽

10.1093/jpepsy/24.1.55 ◽

1999 ◽

Vol 24 (1) ◽

pp. 55-56 ◽

Cited By ~ 45

Author(s):

K. Lockwood

Keyword(s):

Radiation Therapy ◽

Childhood Leukemia ◽

Long Term Effects ◽

Cranial Radiation

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Neuroinflammatory changes of the normal brain tissue in cured mice following combined radiation and anti-PD-1 blockade therapy for glioma

Scientific Reports ◽

10.1038/s41598-021-84600-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mariano Guardia Clausi ◽

Alexander M. Stessin ◽

Zirun Zhao ◽

Stella E. Tsirka ◽

Samuel Ryu

Keyword(s):

Brain Tissue ◽

Cranial Irradiation ◽

Subcortical White Matter ◽

Glioma Cell Line ◽

Hippocampal Neurogenesis ◽

Normal Brain ◽

Long Term Effects ◽

Normal Brain Tissue ◽

Molecule Inhibitor

AbstractThe efficacy of combining radiation therapy with immune checkpoint inhibitor blockade to treat brain tumors is currently the subject of multiple investigations and holds significant therapeutic promise. However, the long-term effects of this combination therapy on the normal brain tissue are unknown. Here, we examined mice that were intracranially implanted with murine glioma cell line and became long-term survivors after treatment with a combination of 10 Gy cranial irradiation (RT) and anti-PD-1 checkpoint blockade (aPD-1). Post-mortem analysis of the cerebral hemisphere contralateral to tumor implantation showed complete abolishment of hippocampal neurogenesis, but neural stem cells were well preserved in subventricular zone. In addition, we observed a drastic reduction in the number of mature oligodendrocytes in the subcortical white matter. Importantly, this observation was evident specifically in the combined (RT + aPD-1) treatment group but not in the single treatment arm of either RT alone or aPD-1 alone. Elimination of microglia with a small molecule inhibitor of colony stimulated factor-1 receptor (PLX5622) prevented the loss of mature oligodendrocytes. These results identify for the first time a unique pattern of normal tissue changes in the brain secondary to combination treatment with radiotherapy and immunotherapy. The results also suggest a role for microglia as key mediators of the adverse treatment effect.

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Long-Term Effects of Treatment for Acute Lymphoblastic Leukemia with and without Cranial Irradiation on Growth and Puberty: A Comparative Study

Pediatric Research ◽

10.1203/00006450-199306000-00008 ◽

1993 ◽

Vol 33 (6) ◽

pp. 577-582 ◽

Cited By ~ 54

Author(s):

A C S Hokken-Koelega ◽

J W D Van Doorn ◽

K Hählen ◽

T Stijnen ◽

S M P F De Muinck Keizer-Schrama ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Comparative Study ◽

Lymphoblastic Leukemia ◽

Cranial Irradiation ◽

Long Term Effects

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Radiation therapy for pediatric craniopharyngioma

Neurosurgical FOCUS ◽

10.3171/2010.1.focus09297 ◽

2010 ◽

Vol 28 (4) ◽

pp. E10 ◽

Cited By ~ 70

Author(s):

Erin N. Kiehna ◽

Thomas E. Merchant

Keyword(s):

Radiation Therapy ◽

Disease Control ◽

Conservative Surgery ◽

Tumor Control ◽

Extensive Literature ◽

Long Term Effects ◽

Secondary Tumors ◽

Limited Surgery

Object The treatment of craniopharyngioma is highly controversial. Continued advances in limited surgery and radiation therapy have maintained excellent local disease control while minimizing treatment-related sequelae. Further analyses of outcomes are necessary to characterize the long-term effects of radiation therapy. Methods An extensive literature review was performed for all studies including radiation therapy, with or without surgery, for pediatric craniopharyngioma. Results The authors identified 32 papers describing radiation therapy for treatment of pediatric craniopharyngioma, with disease control ranging from 44 to 100%. Modern studies report at least 90% disease control with 5-year follow-up. Fifteen studies reported outcomes, demonstrating that more than two-thirds of patients treated with surgery and radiation therapy have favorable outcomes, and this rate is more than 85% in the modern era. Conclusions Conservative surgery and radiation therapy results in long-term disease control in pediatric patients with craniopharyngioma that is comparable to results obtained with radical surgery alone. However, children with craniopharyngioma remain vulnerable to late treatment failures and side effects from radiation therapy, including endocrinopathies, vasculopathies, and secondary tumors, which may be detrimental to the quality of life. Long-term follow-up beyond 5–10 years is necessary to assess tumor control relative to functional outcomes.

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