9-34: Radiation Lung Injury

The lung is an exquisitely radiosensitive organ that can be damaged by external beam radiation therapy. The degree of pulmonary injury is determined by the volume of lung irradiated, the dose and rate of exposure, and potentiating factors (eg, concurrent chemotherapy, previous radiation therapy in the same area, and simultaneous withdrawal of corticosteroid therapy). Symptomatic radiation lung injury occurs in about 10% of patients treated for carcinoma of the breast, 5–15% of patients treated for carcinoma of the lung, and 5–35% of patients treated for lymphoma. Two phases of the pulmonary response to radiation are apparent: an acute phase (radiation pneumonitis) and a chronic phase (radiation fibrosis).

1. RADIATION PNEUMONITIS

Acute radiation pneumonitis usually occurs 2–3 months (range 1–6 months) after completion of radiotherapy and is characterized by insidious onset of dyspnea, intractable dry cough, chest fullness or pain, weakness, and fever. Late radiation pneumonitis may develop 6–12 months after completion of radiation. Occasionally, patients who are months to years removed from radiation therapy will experience “radiation recall” with an inflammatory reaction in the radiated region after treatment with a new round of chemotherapy; this phenomenon has also been reported with immune checkpoint inhibitors. The pathogenesis of acute radiation pneumonitis is unknown, but there is speculation that hypersensitivity mechanisms are involved. The dominant histopathologic findings are a lymphocytic interstitial pneumonitis progressing to an exudative alveolitis. Inspiratory crackles may be heard in the involved area. In severe disease, respiratory distress and cyanosis occur that are characteristic of ARDS. An increased WBC count and elevated ESR are common. PFTs reveal reduced lung volumes, reduced lung compliance, hypoxemia, reduced diffusing capacity, and reduced maximum voluntary ventilation. Chest radiography, which correlates poorly with the presence of symptoms, usually demonstrates alveolar or nodular opacities limited to the irradiated area. Air bronchograms are often observed. Sharp borders of an opacity may help distinguish radiation pneumonitis from other conditions, such as infectious pneumonia, lymphangitic spread of carcinoma, and recurrent tumor; however, the opacity may extend beyond the radiation field.

No specific therapy is proved to be effective in radiation pneumonitis, but prednisone (1 mg/kg/day orally) is commonly given immediately for about 1 week; higher doses may be given in patients who are critically ill. The dose is reduced and maintained at 20–40 mg/day for several weeks, then slowly tapered. Radiation pneumonitis may improve in 2–3 weeks following onset of symptoms as the exudative phase resolves. Acute respiratory failure, if present, is treated supportively. Death from ARDS is unusual in radiation pneumonitis.