Radiation-induced lung injury

Radiation-induced lung injury (RILI) refers to a spectrum of lung disorders caused by exposure to ionizing radiation, primarily as a result of radiation therapy used in the treatment of thoracic malignancies. RILI is a significant complication that can limit the therapeutic ratio of radiation therapy by causing damage to the lung tissues, leading to pneumonitis and, in severe cases, pulmonary fibrosis. The pathogenesis of RILI involves complex mechanisms including DNA damage, inflammation, cytokine release, and fibroblast activation.

Etiology and Risk Factors

RILI is most commonly associated with the treatment of cancers within the chest area, such as lung cancer, breast cancer, and lymphoma. The risk of developing RILI is influenced by several factors including the total dose of radiation, the volume of lung irradiated, the fractionation schedule, and the use of concurrent chemotherapy. Individual patient factors such as pre-existing lung disease, age, and smoking status also play a significant role.

Pathophysiology

The pathophysiology of RILI can be divided into two phases: an early inflammatory phase known as radiation pneumonitis and a later fibrotic phase leading to pulmonary fibrosis.

Radiation Pneumonitis

This acute phase occurs typically 1 to 6 months post-radiation therapy and is characterized by the infiltration of inflammatory cells into the lung parenchyma. Radiation induces DNA damage in lung cells, leading to cell death and the release of pro-inflammatory cytokines, which in turn recruit inflammatory cells to the lung.

Pulmonary Fibrosis

The chronic phase of RILI, pulmonary fibrosis, can develop months to years after radiation therapy. It is characterized by the excessive deposition of extracellular matrix components by fibroblasts, leading to the thickening and stiffening of the lung tissue. This phase is considered irreversible and can significantly impair lung function.

Clinical Presentation

The symptoms of RILI vary depending on the phase of the disease. In the early phase, patients may present with cough, low-grade fever, dyspnea, and chest discomfort. In the later fibrotic phase, symptoms include progressive dyspnea, chronic cough, and in severe cases, respiratory failure.

Diagnosis

The diagnosis of RILI is primarily based on the clinical history, including recent exposure to chest radiation, and the exclusion of other causes of lung injury. Imaging studies, particularly high-resolution computed tomography (HRCT), play a crucial role in the diagnosis and assessment of the extent of lung injury. Pulmonary function tests may also be used to assess the impact of RILI on lung function.

Treatment and Management

The management of RILI focuses on symptomatic relief and prevention of progression. In the acute phase, corticosteroids are commonly used to reduce inflammation. There is no established treatment for the fibrotic phase, although pirfenidone and nintedanib, antifibrotic agents, are being investigated. Supportive care, including oxygen therapy and pulmonary rehabilitation, may be beneficial for patients with significant lung function impairment.

Prevention

Strategies to prevent RILI include the use of advanced radiation techniques such as intensity-modulated radiation therapy (IMRT) and proton therapy, which allow for more precise targeting of tumors while sparing surrounding healthy lung tissue. Dose-volume constraints are also important to minimize the volume of lung receiving high doses of radiation.

‎