Radiation-Induced Lung Injury

Allen P. Burke, M.D.

Joseph J. Maleszewksi, M.D.

General

Radiation-induced lung injury is clinically classified into acute radiation pneumonitis, chronic radiation pneumonitis (radiation fibrosis), and sporadic radiation pneumonitis, characterized by migratory pulmonary infiltrates. This process is usually confined to the field of radiation but can spread outside of the irradiated field via a presumed immunologic reaction.¹ The frequency of lung injury is dependent on a number of complex factors.

Factors influencing the incidence and severity include total dose of radiation, rate of delivery of radiation, volume of irradiated lung tissue, history of prior radiation, previous or concomitant chemotherapy, withdrawal of steroid therapy, and pre-existing lung disease.

Patients with a variety of malignancies are at risk for radiation pneumonitis (Table 60.1). In patients with lung cancer, pneumonitis risk is lessened by more localized treatments such as intensity-modulated radiation therapy. Stereotactic radiation therapy is sometimes a primary treatment for peripheral lesions and carries a small risk for radiation pneumonitis. Patients with Hodgkin lymphoma frequently present with mediastinal disease and are especially prone to radiation pneumonitis.¹⁰ The incidence of clinical effects is relatively lower in patients treated for breast cancer.

Treatment with bleomycin, cyclosporine, gemcitabine, cisplatin, and melphalan may enhance the risk, which is dependent on total lung dose. Patients with relapsed Hodgkin lymphoma who undergo stem cell transplant are particularly susceptible to radiation pneumonitis, because of combined effects of radiation for local disease control and high-dose chemotherapy given during the transplant. Other pulmonary complications, such as obliterative bronchiolitis, are frequent in patients with stem cell transplants, especially those with allogeneic transplants, resulting in a total risk of 11% to 50% for any severe lung complications.¹⁰^,¹²

Clinical Findings

Acute radiation pneumonitis usually occurs between 2 weeks and 6 months following completion of radiation therapy. Dyspnea, nonproductive cough, and fever are common symptoms. If there is extensive acute alveolar injury, patients develop acute respiratory distress syndrome, which may even progress to death from respiratory failure¹³ (Table 60.2). The most common laboratory findings include polymorphonuclear leukocytosis and elevated erythrocyte sedimentation rate.¹⁴

Chronic radiation pneumonitis is the resultant scarring that develops from organizing diffuse alveolar damage and becomes apparent typically at about 1 year. Patients exhibit signs and symptoms of interstitial lung disease, and pulmonary function tests show restrictive abnormalities.

TABLE 60.1 Selected Conditions with Increased Risk for Radiation Pneumonitis

Condition Treated	Treatment	Approximate Rate of Radiation Pneumonitis, %^a	Risk Factors	References
Lung cancer	Stereotactic body radiation	10%	Female, smoking history, tumor size, dose^b
Baker et al.² Barriger et al.³
Lung cancer	Intensity modulated RT + chemotherapy	10%	Dose, COPD	Shi et al.⁴
Lung cancer	Conventional (3DRT) + chemotherapy	20%	Dose	Hernando et al.⁵
Esophageal cancer	Conventional (3DRT) with or without prior chemotherapy	20%	Dose	Nomura et al.⁶ Kumar et al.⁷
Breast cancer	Conventional	<3%	Taxanes (up to 15%)	Taghian et al.⁸
Multiple myeloma	Autologous SCT with TBI^c	Up to 30%		Chen et al.⁹
Mediastinal HL	Conventional 3DRT	2%-3% up to 30% (older series)	Chemotherapy, dose, older age, dose	Fox et al.¹⁰ Koh et al.¹¹
Relapsed or refractory HL	Autologous SCT with TBI (no prior radiation) or without TBI (prior radiation)	21%-23%	Pretransplant radiation, dose	Fox et al.¹⁰ Moskowitz et al.¹²
SBRT, stereotactic body radiation; IMRT, intensity-modulated radiation therapy.
^aAt least grade 2, in most series.^bUsually defined as mean lung dose, Gy (MLD), or as volume % of lung volume (excluding tumor) receiving a certain level of radiation in Gy, for example, V20, V30.^cIncludes high-dose chemotherapy.