Radionecrosis is a form of tissue damage that can arise as a delayed consequence of radiation therapy. It involves the death of healthy tissue, occurring months or even years after treatment, even though radiation therapy primarily targets cancerous cells. This delayed onset makes it a serious long-term side effect.
Understanding Radionecrosis
Radionecrosis results from damage to healthy cells and tissues by ionizing radiation. Radiation therapy creates ionized oxygen species that react with cellular DNA, causing damage and cell death. While cancer cells have a reduced ability to repair this DNA damage, healthy cells are also affected, leading to their eventual death and inflammation.
Several factors contribute to the development of radionecrosis. The total radiation dose delivered plays a significant role, with higher doses increasing the risk. The volume of tissue treated and the size of individual radiation doses, known as fraction size, also influence its development. Additionally, individual patient sensitivity to radiation can vary, impacting whether radionecrosis occurs.
Unlike immediate radiation side effects, which manifest during or shortly after treatment and are often reversible, radionecrosis is a delayed injury. It can appear from six months to several years, or even decades, after radiation exposure.
The primary mechanism of this delayed injury is often linked to vascular endothelial injury or direct damage to oligodendroglia, specialized brain cells. This damage can lead to impaired blood supply, known as relative tissue hypoxia, causing further tissue breakdown and fibrosis. This chronic inflammation and microcirculatory impairment contribute to the characteristic changes seen in radionecrosis.
Where Radionecrosis Occurs
Radionecrosis can manifest in various parts of the body, with distinct challenges depending on the affected tissue. The brain is a common site, particularly after treatment for brain tumors or head and neck malignancies. Cerebral radionecrosis can cause symptoms that closely resemble tumor recurrence, such as neurological deficits, seizures, headaches, or cognitive impairment, depending on the affected brain region.
Bone radionecrosis, specifically osteoradionecrosis (ORN), often affects the jaw (mandibular osteoradionecrosis). This occurs because radiation therapy to the head and neck can damage the bone’s blood supply, hindering healing from trauma or infection. Symptoms include exposed bone in the mouth, pain, swelling, and difficulty opening the jaw. While the lower jaw is most commonly affected due to its limited blood supply, ORN can also occur in the upper jaw or other bones exposed to significant radiation.
Soft tissue radionecrosis can develop in other areas, including the lung, skin, or gastrointestinal tract. In the lung, radiation can lead to pneumonitis, an inflammation that may progress to chronic pulmonary fibrosis. Skin changes can involve dryness, increased fibrous tissue, and a decrease in small blood vessels. In the gastrointestinal tract, symptoms can include intestinal inflammation, rectal bleeding, or bladder dysfunction.
Identifying and Confirming Radionecrosis
Diagnosing radionecrosis involves assessing symptoms and using specialized imaging techniques. Patients may experience pain, swelling, non-healing wounds, or neurological deficits, depending on the affected tissue. These symptoms often mimic other conditions, such as tumor recurrence or infection.
Magnetic Resonance Imaging (MRI) is a primary tool for diagnosing suspected radionecrosis. However, imaging features of radionecrosis and tumor recurrence can overlap, both showing contrast enhancement and surrounding edema. Advanced MRI techniques, such as MR perfusion imaging and magnetic resonance spectroscopy (MRS), help differentiate by measuring blood volume and metabolic markers. For example, radiation necrosis shows decreased relative cerebral blood volume (rCBV) and reduced levels of metabolites like N-acetyl aspartate (NAA) and creatine (Cr), while tumors often exhibit increased rCBV and high choline (Cho) levels.
Positron Emission Tomography (PET) scans, using amino acid tracers, also distinguish radionecrosis from tumor recurrence, as tumors tend to have higher amino acid uptake. Despite advanced imaging, a definitive diagnosis sometimes requires a biopsy. Biopsies can reveal necrotic tissue, reactive gliosis, and the absence of tumor cells, or sometimes a mixture of both radionecrosis and viable tumor.
Treating Radionecrosis
Managing radionecrosis involves a combination of approaches to alleviate symptoms and prevent progression. Conservative management includes supportive care and watchful waiting, particularly for asymptomatic lesions. Medical therapies are used to reduce inflammation and improve blood flow. Corticosteroids, such as dexamethasone, reduce cerebral edema and modulate inflammation, providing prompt symptomatic relief. However, their use requires careful consideration due to potential side effects like hyperglycemia and weight gain.
Hyperbaric oxygen therapy (HBOT) is another treatment option, involving breathing pure oxygen in a pressurized chamber. This increases blood oxygen levels, enhancing oxygenation of damaged tissues, promoting new blood vessel formation, and reducing swelling. While HBOT can improve symptoms and promote healing, the tissue may not fully recover. A typical HBOT protocol might involve 30 to 60 sessions, each lasting 90 to 120 minutes daily.
Surgical interventions may be necessary to remove necrotic tissue or reconstruct damaged areas, especially when medical therapies are insufficient or diagnosis remains uncertain. Surgical debulking can relieve increased intracranial pressure and improve neurological function. For osteoradionecrosis of the jaw, surgical debridement or reconstructive surgery may be performed. While surgery can provide significant relief, it carries risks of complications and potential neurological deficits, making careful patient selection important.