Radiation Necrosis

Updated: Jul 20, 2021
  • Author: Gaurav Gupta, MD, FAANS, FACS; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA  more...
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Overview

Background

Radiation necrosis, a focal structural lesion that usually occurs at the original tumor site, is a potential long-term central nervous system (CNS) complication of radiotherapy or radiosurgery. Edema and the presence of tumor render the CNS parenchyma in the tumor bed more susceptible to radiation necrosis. Radiation necrosis can occur when radiotherapy is used to treat primary CNS tumors, metastatic disease, or head and neck malignancies. It can occur secondary to any form of radiotherapy modality or regimen.

In the clinical situation of a recurrent astrocytoma (postradiation therapy), radiation necrosis presents a diagnostic dilemma. Astrocytic tumors can mutate to the more malignant glioblastoma multiforme. Glioblastoma multiforme's hallmark histology of pseudopalisading necrosis makes it difficult to differentiate radiation necrosis from recurrent astrocytoma using MRI. See Medscape Reference articles Neurologic Manifestations of Glioblastoma Multiforme and Low-Grade Astrocytoma.

Therapeutic effects of radiotherapy

Radiation creates ionized oxygen species that react with cellular DNA. Tumor cells have less ability than healthy cells for DNA repair. Thus, between fractionation doses, healthy cells have a greater probability than tumor cells of repairing themselves. With each subsequent mitosis, the cumulative effects of unrepaired DNA result in apoptosis (cell death) of these tumor cells.

Central nervous system syndromes secondary to radiotherapy

Pathophysiology

Radiation necrosis is coagulative and predominantly affects white matter. This coagulative necrosis is due to small artery injury and thrombotic occlusion. These small arteries demonstrate endothelial thickening, lymphocytic and macrophagic infiltrates, presence of cytokines, hyalinization, fibrinoid deposition, thrombosis, and finally occlusion.

The primary mechanism of the delayed injury in radiation associated with necrosis is secondary to vascular endothelial injury or direct damage to oligodendroglia. As a result, white matter tissue is often more affected than gray matter tissue. Radiation may have effects on fibrinolytic enzyme systems, with an absence of tissue plasminogen activator and an excess in urokinase plasminogen activator impacting tissue fibrinogen and extracellular proteolysis with subsequent cytotoxic edema and tissue necrosis. Whether immune-mediated mechanisms may also contribute to radiation-induced neurotoxicity is unclear, but an autoimmune vasculitis has been postulated as a secondary host response to tissue damage.

Animals exposed to radiation and given antibodies to cytokines (tumor necrosis factor, interleukin-1, tissue growth factor) have decreased survival compared to animals that do not receive these antibodies. These cytokines may be involved in initially protecting healthy tissue from the effects of radiation. With prolonged radiation exposure, these particular cytokines are overexpressed and result in a cascade of inflammatory events and vascular injury [6] .

In addition to vessel occlusion with resultant tissue necrosis, telangiectatic vessels, which may hemorrhage, occasionally form. Demyelination, oligodendrocyte dropout, axonal swelling, reactive gliosis, and disruption of the blood-brain barrier also can be observed.

Epidemiology

Frequency

Natural history of the tumor in terms of prognosis and survival may affect the occurrence of radiation necrosis in a particular tumor population. In glioblastoma multiforme or metastatic disease with a poor long-term prognosis, the patient may not live long enough to develop radiation necrosis. Radiation necrosis can occur as soon as a few months or as long as decades after treatment. It generally occurs 6 months to 2 years after radiation therapy. Radiation injury may occur in 5-37% of patients treated for intracranial neoplasms [7] .

Mortality/Morbidity

Radiation necrosis can be fatal. It also can cause problems associated with a mass lesion, such as seizures, focal deficits, increased intracranial pressure, and herniation syndromes.

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