Ischemic stroke after radiation therapy for pituitary adenomas: a systematic review

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Abstract

Radiation therapy is widely used for the treatment of residual and recurrent pituitary adenomas and proved to effectively control tumor growth. However, it is suggested that this treatment might result in an increased risk of ischemic stroke. This review aims to evaluate the radiotherapy-related risk of stroke in pituitary adenoma patients. PubMed and Embase databases were systematically searched for current literature on ischemic stroke risk after radiotherapy in pituitary adenoma, in accordance with the PRISMA statement. Two authors independently selected eligible studies and extracted data. The New Castle Ottawa-scale was used for quality assessment. Out of 264 publications, 11 studies were selected, including 4394 irradiated patients. Incidence of ischemic stroke ranged from 0 to 11.6% (mean 6.7%). While one large, long term follow-up study showed a threefold increased risk of stroke after radiation therapy, another nationwide study of high quality found no significant difference in stroke risk after irradiation. Four studies, which applied stereotactic radiosurgery (SRS) or Gamma-knife surgery (GKS), found no ischemic strokes. Included studies described different radiation techniques and regimens and different lengths of follow-up. In conclusion, complications of cerebral ischemia after radiotherapy for pituitary adenoma are infrequently reported. Moreover, after correction for several confounders, no significant difference in ischemic stroke rate between irradiated and non-irradiated patients could be identified.

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Determination of cell survival after irradiation via clonogenic assay versus multiple MTT Assay - A comparative study

Karl Buch, Tanja Peters, Thomas Nawroth … (2012)

For studying proliferation and determination of survival of cancer cells after irradiation, the multiple MTT assay, based on the reduction of a yellow water soluble tetrazolium salt to a purple water insoluble formazan dye by living cells was modified from a single-point towards a proliferation assay. This assay can be performed with a large number of samples in short time using multi-well-plates, assays can be performed semi-automatically with a microplate reader. Survival, the calculated parameter in this assay, is determined mathematically. Exponential growth in both control and irradiated groups was proven as the underlying basis of the applicability of the multiple MTT assay. The equivalence to a clonogenic survival assay with its disadvantages such as time consumption was proven in two setups including plating of cells before and after irradiation. Three cell lines (A 549, LN 229 and F 98) were included in the experiment to study its principal and general applicability.

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Mortality in patients with pituitary disease.

Mark Sherlock, John Ayuk, Jeremy W. Tomlinson … (2010)

Pituitary disease is associated with increased mortality predominantly due to vascular disease. Control of cortisol secretion and GH hypersecretion (and cardiovascular risk factor reduction) is key in the reduction of mortality in patients with Cushing's disease and acromegaly, retrospectively. For patients with acromegaly, the role of IGF-I is less clear-cut. Confounding pituitary hormone deficiencies such as gonadotropins and particularly ACTH deficiency (with higher doses of hydrocortisone replacement) may have a detrimental effect on outcome in patients with pituitary disease. Pituitary radiotherapy is a further factor that has been associated with increased mortality (particularly cerebrovascular). Although standardized mortality ratios in pituitary disease are falling due to improved treatment, mortality for many conditions are still elevated above that of the general population, and therefore further measures are needed. Craniopharyngioma patients have a particularly increased risk of mortality as a result of the tumor itself and treatment to control tumor growth; this is a key area for future research in order to optimize the outcome for these patients.

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Hypopituitarism following radiotherapy.

Stephen Shalet, Ken Darzy (2008)

Deficiencies in anterior pituitary hormones secretion ranging from subtle to complete occur following radiation damage to the hypothalamic-pituitary (h-p) axis, the severity and frequency of which correlate with the total radiation dose delivered to the h-p axis and the length of follow up. Selective radiosensitivity of the neuroendocrine axes, with the GH axis being the most vulnerable, accounts for the high frequency of GH deficiency, which usually occurs in isolation following irradiation of the h-p axis with doses less than 30 Gy. With higher radiation doses (30-50 Gy), however, the frequency of GH insufficiency substantially increases and can be as high as 50-100%. Compensatory hyperstimulation of a partially damaged h-p axis may restore normality of spontaneous GH secretion in the context of reduced but normal stimulated responses; at its extreme, endogenous hyperstimulation may limit further stimulation by insulin-induced hypoglycaemia resulting in subnormal GH responses despite normality of spontaneous GH secretion in adults. In children, failure of the hyperstimulated partially damaged h-p axis to meet the increased demands for GH during growth and puberty may explain what has previously been described as radiation-induced GH neurosecretory dysfunction and, unlike in adults, the ITT remains the gold standard for assessing h-p functional reserve. Thyroid-stimulating hormone (TSH) and ACTH deficiency occur after intensive irradiation only (>50 Gy) with a long-term cumulative frequency of 3-6%. Abnormalities in gonadotrophin secretion are dose-dependent; precocious puberty can occur after radiation dose less than 30 Gy in girls only, and in both sexes equally with a radiation dose of 30-50 Gy. Gonadotrophin deficiency occurs infrequently and is usually a long-term complication following a minimum radiation dose of 30 Gy. Hyperprolactinemia, due to hypothalamic damage leading to reduced dopamine release, has been described in both sexes and all ages but is mostly seen in young women after intensive irradiation and is usually subclinical. A much higher incidence of gonadotrophin, ACTH and TSH deficiencies (30-60% after 10 years) occur after more intensive irradiation (>60 Gy) used for nasopharyngeal carcinomas and tumors of the skull base, and following conventional irradiation (30-50 Gy) for pituitary tumors. The frequency of hypopituitarism following stereotactic radiotherapy for pituitary tumors is mostly seen after long-term follow up and is similar to that following conventional irradiation. Radiation-induced anterior pituitary hormone deficiencies are irreversible and progressive. Regular testing is mandatory to ensure timely diagnosis and early hormone replacement therapy.

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Contributors

M. L. D. Broekman: +31-887557059 , M.L.D.Broekman-4@umcutrecht.nl

Journal

Journal ID (nlm-ta): J Neurooncol

Journal ID (iso-abbrev): J. Neurooncol

Title: Journal of Neuro-Oncology

Publisher: Springer US (New York )

ISSN (Print): 0167-594X

ISSN (Electronic): 1573-7373

Publication date (Electronic): 28 June 2017

Publication date PMC-release: 28 June 2017

Publication date (Print): 2017

Volume: 135

Issue: 1

Pages: 1-11

Affiliations

[1 ]ISNI 0000000090126352, GRID grid.7692.a, Utrecht, , University Medical Center Utrecht, ; P.O. Box 85500, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands

[2 ]ISNI 000000041936754X, GRID grid.38142.3c, Cushing Neurosurgery Outcomes Center, Department of Neurosurgery, Brigham and Women’s Hospital, , Harvard Medical School, ; 15 Francis Street, Boston, MA 02115 USA

[3 ]ISNI 0000000090126352, GRID grid.7692.a, Department of Radiation Oncology, , University Medical Center Utrecht, ; Heidelberglaan 100, 3584 CX Utrecht, The Netherlands

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A. van Westrhenen http://orcid.org/0000-0002-1987-5793

Article

Publisher ID: 2530

DOI: 10.1007/s11060-017-2530-9

PMC ID: 5658475

PubMed ID: 28660317

SO-VID: f20c8c00-8cdf-401e-8bb9-21f3a56053cc

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Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 3 May 2017

Date accepted : 10 June 2017

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: pituitary adenoma,radiotherapy,radiation,ischemic stroke

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: pituitary adenoma, radiotherapy, radiation, ischemic stroke

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Ischemic stroke after radiation therapy for pituitary adenomas: a systematic review

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Most cited references 29

Determination of cell survival after irradiation via clonogenic assay versus multiple MTT Assay - A comparative study

Mortality in patients with pituitary disease.

Hypopituitarism following radiotherapy.

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