Radiation-induced lung injury

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Abstract

Radiation therapy (RT) for thoracic-region tumors often causes lung injury. The incidence of lung toxicity depends on the method of assessment (eg, radiographs, patient’s symptoms, or functional endpoints such as pulmonary function tests). Three-dimensional (3D) treatment planning tools provide dosimetric predictors for the risk of symptomatic RT-induced lung injury and allow for beams to be selected to minimize these risks. A variety of cytokines have been implicated as indicators/mediators of lung injury. Recent work suggests that injury-associated tissue hypoxia perpetuates further injury. Sophisticated planning/delivery methods, such as intensity modulation, plus radioprotectors such as amifostine, hold promise to reduce the incidence of RT-induced lung injury.

Section snippets

Radiographic

Within a few months of RT, increases in tissue density associated with acute inflammation or late fibrosis are typically seen on either chest x-rays (CXR) or computed tomography (CT).37 The latter is more sensitive because it provides better 3-dimensional (3D) visualization of the lung. Pleural, interlobar, and pericardial effusions may also be present. These tend to be small, asymptomatic, and often resolve spontaneously. By 12 to 24 months, the majority of patients receiving moderate-high

Clinical

RT-induced lung injury has classically been divided into acute and late. Acute pneumonitis typically presents 1 to 6 months after RT, with symptoms of shortness of breath, cough, and occasionally mild fever. The radiographic findings are variable and often unrevealing. Pneumonitis usually responds well to steroids. Typically, 40 to 60 mg of prednisone every day for several weeks, followed by a several-week taper, provides relief for most patients. It is important to consider the possibility of

Functional endpoints

The lungs’ primary function is to provide oxygen to, and extract carbon dioxide from, the pulmonary circulation. This requires effective transfer of large volumes of air through the conducting airways and effective transfer of gases at the alveolar surface. These functions are quantified by the 3 components of standard pulmonary function tests. Spirometry assesses the rate of gas movement; the most commonly measured parameter is the forced expiratory volume in 1 second (FEV1). When normalized

Dosimetric predictors of RT-induced lung injury

The complex 3D dose distribution within the lung is often displayed as a 2D dose-volume histogram (DVH). A single value of merit can be extracted from the DVH (Fig 2) , eg, the percent of lung receiving ≥20 or 30 Gy (V20 or V30), the mean lung dose (MLD), or the normal tissue complication probability.70, 71, 72, 73, 74, 75, 76

Dosimetric parameters are related to the incidence of symptomatic lung injury (Table 3) .17, 20, 75, 78, 79, 80 However, pneumonitis occurs in only a minority of

Management/modifiers of lung injury

WR-2721 (amifostine) is a phosphorylated aminothiol showing cytoprotection of normal tissues with chemotherapy and RT.87 Amifostine undergoes dephosphorylation by cellular-bound alkaline phosphatase to an active metabolite, WR-1065. Cytoprotection is believed to result from elimination of free radicals produced by the interaction of ionizing RT and water molecules, as well as radicals produced by certain cytotoxic drugs.87, 88, 89 A separate amifostine metabolite, WR-33278, has also been shown

Biology of RT-induced pulmonary injury

RT-induced lung injuries are traditionally divided into early (acute, 1-6 months post-RT) pneumonitis and late (chronic, >6 mo post-RT) fibrosis. Classically, pneumonitis results from injury to type II pneumocytes, and endothelial cells manifest after an initial latent period reflecting the inherent turnover time of the affected cells.120 Histologically, there is exudation of proteinaceous material into the alveoli, desquamation of epithelial cells from the alveolar walls, alveolar edema, and

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    Supported in part by NCI Grants CA69579 and CA83721 and NIH Grant 21CA83721.

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