Therapeutic radiation used to destroy cancerous tumors can result in a late complication known as radionecrosis. This condition involves the death of tissue within the area that received the radiation treatment. Radionecrosis often manifests long after the initial therapy is complete. The resulting tissue death can lead to significant functional impairment depending on the affected organ.
Defining Radionecrosis and Common Locations
Radionecrosis is a form of coagulative necrosis, meaning it is characterized by the death of cells in a localized area due to insufficient blood flow. It is a complication of therapeutic radiation, distinct from acute side effects that occur during or immediately following treatment. This delayed onset means the condition can appear anywhere from a few months to several years after the final dose of radiation has been delivered.
The severity of radionecrosis depends on the total radiation dose, the size of the treatment area, and the sensitivity of the tissue involved. The central nervous system, particularly the brain and spinal cord, is the most frequently affected site and where the condition is often most severe. When bone tissue dies due to radiation exposure, it is specifically termed osteoradionecrosis, commonly affecting the jawbone following treatment for head and neck cancers. Soft tissues, such as the skin, can also develop radionecrosis, leading to non-healing wounds or ulceration.
The Biological Mechanism of Tissue Damage
The underlying pathology of radionecrosis involves damage at both the cellular and vascular levels. One primary theory focuses on direct cellular death, particularly affecting specialized cells like oligodendroglia, which are sensitive to radiation. Oligodendroglia maintain the myelin sheath around nerve fibers, and their loss can lead to demyelination and subsequent white matter injury.
A second mechanism centers on progressive damage to the tiny blood vessels supplying the irradiated tissue. Radiation injures the endothelial cells lining the small arteries, causing the vessel walls to thicken due to the abnormal accumulation of material like fibrinoid deposits and collagen, a process called hyalinization. This thickening leads to a narrowing of the vessel lumen, causing progressive occlusion and thrombosis. The reduction of blood flow results in chronic ischemia, or oxygen and nutrient deprivation, in the area supplied by the damaged vessels, causing the irreversible cell death characteristic of radionecrosis.
Recognizing the Signs and Confirmation
The signs of radionecrosis are non-specific and vary widely based on the location of the tissue damage. If the brain is affected, symptoms can include headache, cognitive impairment, focal neurological deficits, and seizures. In cases of osteoradionecrosis, patients may experience pain, swelling, and the presence of exposed bone or non-healing sores in the mouth.
The symptoms and conventional imaging findings of radionecrosis often look identical to those of a recurrent tumor. Both conditions can appear as contrast-enhancing lesions with surrounding swelling on a standard magnetic resonance imaging (MRI) scan. Distinguishing between the two is crucial because the required treatments are vastly different.
To overcome this diagnostic dilemma, clinicians rely on advanced functional imaging techniques that assess the biological behavior of the lesion. Perfusion MRI, which measures blood flow, often shows lower relative cerebral blood volume (rCBV) in radionecrosis than in highly vascularized, actively growing tumors. Magnetic resonance spectroscopy (MRS) can analyze the metabolic profile, often showing reduced levels of cell membrane components in radionecrosis compared to tumor recurrence. Positron Emission Tomography (PET) scans using specific radiotracers, such as 18F-fluciclovine, differentiate the two conditions. While a tissue biopsy remains the only definitive test, these advanced imaging modalities provide non-invasive confirmation to guide treatment decisions.
Managing and Treating Radionecrosis
The management of radionecrosis focuses on controlling symptoms, reducing inflammation, and promoting tissue healing. Initial treatment for symptomatic radionecrosis often involves the use of corticosteroids, such as dexamethasone. These medications reduce the inflammation and swelling surrounding the necrotic tissue, which relieves pressure and improves neurological symptoms.
For cases that do not respond sufficiently to steroids, other medical therapies are considered. The drug bevacizumab targets vascular endothelial growth factor (VEGF). Since VEGF is often overexpressed in radionecrosis, causing blood vessels to be leaky and fragile, bevacizumab helps to normalize the damaged vasculature.
Hyperbaric oxygen therapy (HBOT) involves breathing 100% oxygen in a pressurized chamber. This increases the oxygen concentration in the affected tissues, stimulating the growth of new blood vessels and promoting tissue repair in the ischemic area. HBOT is typically administered in multiple sessions over several weeks.
Surgical intervention is reserved for severe cases where medical management has failed or when the necrotic lesion is causing a significant mass effect. Surgeons may remove the necrotic tissue in a procedure called debridement or resection to relieve pressure and improve neurological function. Newer, minimally invasive techniques like laser interstitial thermal therapy (LITT) are also used in some cases to ablate the necrotic tissue.