Cerebral radiation necrosis

Cerebral radiation necrosis or radionecrosis refers to necrotic degradation of brain tissue following intracranial or regional radiation either delivered for the treatment of intracranial pathology (e.g. astrocytoma, cerebral arteriovenous malformation) or as a result of irradiation of head and neck tumors (e.g. nasopharyngeal carcinoma). 

Terminology

Although post-radiation treatment effects include pseudoprogression, which by definition is considered to be radiation treatment-related necrosis, particularly in the setting of concurrent chemotherapy for glioblastoma (Stupp protocol), this article focuses on the delayed onset effects of radiation necrosis, which appears months to several years after radiation therapy and involves a space-occupying necrotic lesion with mass effect and neurological dysfunction. 

Clinical presentation

The clinical features of radiation necrosis vary depending on severity and location. Thus, patients may be asymptomatic or may be symptomatic with focal neurological deficits, seizures, features of raised intracranial pressure, or cognitive impairment. 

Pathology

There are numerous potential pathways to radiation necrosis which include:

• vascular injury

  • acutely endothelial damage can lead to vasogenic edema

  • chronically fibrosis, hyalinisation and stenosis can occur with eventual thrombosis and infarction

  • vascular ectasia and telangiectasia are also seen frequently, with capillary telangiectasias and cavernous malformations common findings post whole-brain irradiation.

• oligodendrocytes and white matter damage

  • oligodendrocytes are sensitive to radiation

  • loss of white matter accounts for the majority of volume loss

• effects on the fibrinolytic enzyme system

  • increase in urokinase plasminogen activator and a simultaneous decrease in tissue plasminogen activator may contribute to cytotoxic edema and tissue necrosis

• immune mechanisms

Radiographic features

MRI

• T2/FLAIR: white matter high signal

  • edema and mass effect early

  • loss of volume later

• T1 C+ (Gd)

  • white (more common) or grey matter

  • single or multiple

  • nodular or curvilinear

  • "soap-bubble", “cut green pepper” or "Swiss-cheese" enhancement

  • occasionally can be ring-enhancing (see MAGIC DR mnemonic)

• MR spectroscopy: typically low choline, creatine, and NAA

• MR perfusion: areas of enhancement and high T2/FLAIR don't show increased rCBV in radiation necrosis or pseudoprogression and could be helpful in distinguishing them from residual lesion or recurrence 

PET

FDG-PET

• radiation necrosis is usually hypometabolic whereas tumor is hypermetabolic

¹⁸F-FET-PET

• Radiation necrosis has both lower mean and max uptake compared to normal brain parenchyma ⁷

• tumor recurrence has an earlier peak uptake compared to radiation necrosis ⁷

Treatment and prognosis

For symptomatic patients, corticosteroids such as dexamethasone are considered first-line ⁵. In patients refractory to corticosteroids, other therapies may be trialed including bevacizumab, laser interstitial thermal therapy, and investigational therapies such as hyperbaric oxygen therapy ^5,6.

Practical points

Radiation necrosis occurs within areas of irradiated brain, and therefore, examining the isodose curves of prior radiation treatment can be helpful in confirming whether or not the area that appears abnormal received a high dose. 

It has been suggested that involvement of the corpus callosum with the crossing of the midline and multiple lesions or subependymal spread would favor a recurrent tumor over radiation necrosis ², however, conventional imaging can be misleading, and no individual feature is reliable.