Long-term neuro-endocrine sequelae after treatment for childhood medulloblastoma

Heikens, Janneke; Michiels, Erna; Behrendt, H.; Endert, E.; Bakker, Piet; Fliers, Eric

doi:10.1016/s0959-8049(98)00212-3

Cited by 91 publications

(65 citation statements)

References 24 publications

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“…In adults who have been disease-free for many years, these sequelae involve radiation-induced alterations in the hypothalamo -pituitary axis, and the hypothalamus is generally recognized as the more radiation-sensitive structure (1 -4). These neuroendocrine alterations cannot be attributed to the location of the tumour or the surgical procedures, and they do not appear to be related to the presence or absence of chemotherapy (5,6).…”

Section: Introductionmentioning

confidence: 91%

“…The intra-assay coefficient of variation (CV) was 4 -6% (5 -24 mg/l) and the interassay CV was 5.5 -7.2% (4 -50 mg/l), with reference values for plasma PRL of 4.0 -25 mg/l in women and 0.5 -19.0 mg/l in men (18). An insulin tolerance test in the postabsorptive state had been performed as part of a previous study (6). Briefly, blood samples were drawn to determine GH and cortisol 30 and 15 min before and 15, 30, 45, 60, 90 and 120 min after an intravenous injection of 0.15 U insulin/kg body weight (Actrapid, Novo Nordisk, Bagsvaerd, Denmark).…”

Section: Participantsmentioning

confidence: 99%

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

Someren

Swart-Heikens

Endert

et al. 2004

European Journal of Endocrinology

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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 ¼ 17) or other intracranial tumours (n ¼ 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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Section: Introductionmentioning

confidence: 91%

Section: Participantsmentioning

confidence: 99%

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

Someren

Swart-Heikens

Endert

et al. 2004

European Journal of Endocrinology

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“…For CSI patients treated with a multi-discipline approach of chemotherapy and radiation therapy in particular, long-term sequelae include: endocrine effects, hearing and/or vision loss, gonadal dysfunction, neurocognitive deficits, cardiopulmonary impairment, and secondary malignancies (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Pediatric cases have been given special attention regarding the risk for secondary malignancies following radiation therapy after the publication of data indicating an increase in the development of these malignancies in persons irradiated at younger ages (21,22).…”

Section: Introductionmentioning

confidence: 99%

Pediatric Cranio-spinal Axis Irradiation

Myers

Mavroidis

Komisopoulos

et al. 2015

Technol Cancer Res Treat

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Pediatric cranio-spinal axis irradiation (CSI) is a valuable treatment for many central nervous system (CNS) diseases, but due to the life expectancies and quality of life expectations for children, the minimization of the risk for radiation-induced secondary malignancies must be a high priority. This study compared the estimated CSI-induced secondary malignancy risks of three radiation therapy modalities using three different models. Twenty-four (n 5 24) pediatric patients previously treated with CSI for tumors of the CNS were planned using three different treatment modalities: three-dimensional conformal radiation therapy (3D-CRT), volume modulated arc therapy (VMAT), and Tomotherapy. Each plan was designed to deliver 23.4 Gy (1.8 Gy/fraction) to the target which was defined as the entire brain and spinal column with a 0.7 cm expansion. The mean doses as well as the dose volume histograms (DVH) of specific organs were analyzed for secondary malignancy risk according to three different methods: the effective dose equivalent (EDE), the excess relative risk (ERR), and the linear quadratic (LQ) models. Using the EDE model, the average secondary risk was highest for the 3D-CRT plans (37.60%), compared to VMAT (28.05%) and Tomotherapy (27.90%). The ERR model showed similarly that the 3D-CRT plans had considerably higher risk (10.84%) than VMAT and Tomotherapy, which showed almost equal risks (7.05 and 7.07%, respectively). The LQ model requires organ-specific cell survival parameters, which for the lungs, heart, and breast relevant values were found and applied. The lung risk for secondary malignancy was found to be 1.00, 1.96, and 2.07% for 3D-CRT, VMAT, and Tomotherapy, respectively. The secondary cancer risk for breast was estimated to be 0.09, 0.21, and 0.27% and for heart it was 9.75, 6.02 and 6.29% for 3D-CRT, VMAT, and Tomotherapy, respectively. Based on three methods of secondary malignancy estimation, the 3D-CRT plans produced highest radiationinduced secondary malignancy risk, and the VMAT and Tomotherapy plans had nearly equal risk. Pediatric patients must be treated with reducing long term sequelae as a priority.

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“…[4][5][6] Long-term survivors experience a spectrum of radiation-related treatment effects including hearing loss, 7 endocrine deficiencies, 8 somatic effects, 9 cognitive decline, 10 cerebrovascular damage 11,12 and secondary malignancies. 13 Measures have been taken to lessen the effects of radiation therapy for patients who have favorable outcomes including those with average-risk MB 14 defined as no evidence of neuraxis dissemination, a minimal amount of residual tumor and no evidence of brainstem invasion or transtentorial extension from the primary site.…”

Section: Introductionmentioning

confidence: 99%

Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma

Merchant¹,

Kun²,

Krasin³

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

153

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Purpose/Objective-Limiting neurocognitive sequelae of radiation therapy (RT) has been an objective in the treatment of medulloblastoma (MB). Conformal RT to less than the entire posterior fossa (PF) after craniospinal irradiation (CSI) may reduce neurocognitive sequelae and requires evaluation. October 1996 and August 2003, 86 patients, 3-21 years of age, with newly diagnosed, average-risk MB were treated on a prospective, IRB-approved, multi-institution trial of risk-adapted RT and dose-intensive chemotherapy. RT began within 28 days of definitive surgery and consisted of CSI (23.4 Gy), conformal PF RT (36.0 Gy) and primary site RT (55.8 Gy). The planning target volume for the primary site included the post-operative tumor bed surrounded by an anatomically confined margin of 2 cm which was then expanded with a geometric margin of Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Materials/Methods-Between CONFLICT OF INTEREST NOTIFICATION:There are no conflicts of interest with the authors or materials in this manuscript. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 0.3-0.5 cm. Chemotherapy was initiated 6 weeks after RT and included 4 cycles of high-dose cyclophosphamide, cisplatin and vincristine.Results-With a median follow-up of 61.2 months (5.2-115.0 months), the estimated 5-year eventfree survival and cumulative incidence of PF failure were 83.0% ± 5.3% and 4.9% ± 2.4% (±SE), respectively. Targeting guidelines used in this study resulted in a mean reduction of 13% in the volume of the PF receiving doses above 55Gy compared to conventionally planned RT. Reductions in dose to the temporal lobes, cochleae and hypothalamus were statistically significant.Conclusions-This prospective trial demonstrates that irradiation of less than the entire PF after 23.4 Gy CSI for average-risk MB results in disease control comparable to treatment of the entire PF.

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Long-term neuro-endocrine sequelae after treatment for childhood medulloblastoma

Cited by 91 publications

References 24 publications

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

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

Pediatric Cranio-spinal Axis Irradiation

Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma

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