Pulmonary Complications of Anticancer Treatment

Summary of Key Points

• Radiation-Induced Lung Injury (Radiation Pneumonitis or Fibrosis)

• Risk factors include radiation dose and volume of lung irradiated, which may be expressed as mean lung dose or as the Vx, that is, the percentage of normal lung tissue irradiated to a dose above a certain threshold dose.

• Older age, comorbidities (including chronic obstructive pulmonary disease), and low performance status are risk factors.

• The location of the tumor is a risk factor; irradiation of lower lobe primary lung tumors may carry a higher risk than irradiation of other tumors, although this may reflect the higher lung volume irradiated with lower lobe tumors.

• Biological factors can carry risk, including levels of circulating cytokines such as transforming growth factor–β and interleukin-6.

• The predominant symptoms are dyspnea and hypoxia, especially upon exertion.

• Fever (usually low grade if present at all), cough, pleuritic chest pain, and other pulmonary symptoms also frequently occur.

• Diffusing capacity of the lung for carbon dioxide is the most sensitive pulmonary function.

• Interstitial or ground-glass infiltrate usually corresponds to the irradiated volume. Consolidation, bronchiectasis, or pleural effusion may also be seen, particularly in later stages.

• Findings at bronchoscopy are unremarkable. (Bronchial lavage may reveal lymphocytosis.)

• Pulmonary embolism, infection, and recurrent or progressive tumor must be ruled out. These conditions can coexist with and mimic radiation pneumonitis.

• Response to corticosteroids is usually relatively rapid, at least for acute pneumonitis.

• Prevention is far more important than treatment. Patients must be selected carefully for thoracic radiation, and irradiated volumes must be limited.

• Corticosteroids are very useful in the management of acute and subacute pneumonitis, although they have no prophylactic or therapeutic value in the management of long-term radiation fibrosis.

• A pulmonologist should be consulted for all grade 3 cases and most grade 2 cases.

• Oxygen should be administered as indicated to prevent hypoxia.

• Corticosteroids should be introduced at a relatively high dose (60 mg/day of prednisone), with slow tapering (over several weeks to months) for severe grade 2 or any grade 3 radiation pneumonitis.

• If prolonged corticosteroid treatment is anticipated, prophylaxis against corticosteroid complications is needed, including gastrointestinal, infectious, and osteoporosis prophylaxis and dietary and pharmacologic management of hyperglycemia.

• Antibiotics, bronchodilators, diuretics, and anticoagulation should be used as indicated for coexisting cardiopulmonary illnesses.

• Drug-Induced Lung Injury

• Among the cytotoxic therapies, bleomycin, nitrosoureas, and mitomycin or combinations of several potentially pneumotoxic agents that on their own may only have modest pneumotoxicity (e.g., gemcitabine and weekly docetaxel) are risk factors.

• Bone marrow transplantation/high-dose chemotherapy with or without total-body irradiation is a risk factor.

• Immunotherapy may induce pulmonary toxicity, particularly combinations of multiple immunotherapeutic agents (e.g., an anti-PD1 agent plus an anti-CTLA4 agent).

• Concurrent or recent thoracic radiation therapy is a risk factor.

• Poor baseline pulmonary function is a risk factor.

• Dyspnea and hypoxemia are predominant, but a wide range of possible symptoms exists.

• Interstitial or ground-glass infiltrate usually is diffuse throughout both lungs and may be worse in the lower lobes.

• Findings at bronchoscopy are unremarkable. (Bronchial lavage may reveal lymphocytosis.)

• Pulmonary embolism, infection, and progressive tumor must be ruled out and may coexist with drug-induced lung injury.

• Injury is usually, but not universally, responsive to corticosteroids; it is less likely to respond well to steroids than radiation pneumonitis but more likely to respond well than late radiation fibrosis.

• When the diagnosis is suspected, the suspected causative agent should be discontinued.

• Consultation with a pulmonologist is necessary.

• Oxygen should be administered as indicated to prevent hypoxia. (High fraction of inspired oxygen levels may be dangerous in bleomycin-related pneumonopathy.)

• High doses of corticosteroids (≥60 mg/day of prednisone) with slow taper may be needed for severe grade 2 or any grade 3 pneumonitis.

• If prolonged corticosteroid treatment is anticipated, prophylaxis against corticosteroid complications entails gastrointestinal, infectious and osteoporosis prophylaxis and dietary or pharmacologic management of hyperglycemia.

• Antibiotics, bronchodilators, diuretics, and anticoagulation should be administered to manage coexisting cardiopulmonary illnesses.