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Case History

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Image not available. A 45-year-old man has recently completed chemoradiation for a glioblastoma multiforme and is taking adjuvant temozolomide. The patient presents following a seizure at home and has residual right-sided lower limb weakness. He is complaining of a frontal headache and nausea.

What causes CNS toxicity after radiotherapy?

What is the differential diagnosis?

What are the common side effects encountered following CNS radiotherapy?

How should post-radiotherapy complications be managed?

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Background

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What causes CNS toxicity after radiotherapy?

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Image not available. Central nervous system (CNS) toxicity of radiotherapy is divided into three phases of damage: acute, consequential and late. The majority of problems likely to be encountered in the acute oncology setting are acute and consequential (continuing after completion of radiation); late is classed as over 90 days after completion of treatment.

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Acute toxicity is thought to be secondary to blood-brain barrier disruption, glial cell damage and swelling. Radiation damages DNA and hence cellular structure, both directly and also indirectly via the production of free radicals. Glial cells, such as oligodendrocytes, experience higher rates of cell turnover and are therefore subject to damage by fractionated courses of treatment. Radiation does not significantly damage the neurons themselves. Subsequent demyelination, altered cytokine production and apoptosis can lead to loss of function. Chemotherapy prior to radiotherapy can increase neurotoxicity.

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Longer-term complications are a combination of the above effects along with radiotherapy damage to the vascular structures of the CNS that manifest as dysregulated cell division.1 This results primarily in a reduction in cognitive ability and the onset of dementia-type symptoms.

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What is the differential diagnosis?

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Prognosis for CNS malignancy is highly variable and may range from 6 to15 months in high-grade glioblastoma, whereas median survival in metastatic CNS disease is only four months.2,3 A significant proportion of patients may also undergo CNS radiotherapy in a setting with a more favourable prognosis, including low-grade primary CNS tumours and prophylactic therapy in small-cell lung cancer.

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Neurological deterioration can result from radiotherapy toxicity or disease progression. The differential diagnosis, investigation and management of individual patients is directed by the underlying diagnosis, treatment timing and intent. Direct contact with the acute oncology team and treating neuro-oncologist will often represent the most important aspect of patient care.

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In the setting of primary brain tumours there is a cohort of patients who present during or shortly after treatment with side effects directly attributable to radiotherapy. However, caution must be observed because this group have often recently undergone surgery. Therefore, they are prone to complications secondary to structural disturbance, such as bleeding, infarcts, and raised intracranial pressure due to cerebrospinal fluid (CSF) obstruction. In addition, the cancer itself predisposes to these complications. Particular care must be taken with those patients on long-term steroids, as these will mask signs of infection by suppressing fever and ...

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