Radiation Pneumonitis

Objectives

• Background

• Pathophysiology

• Morbidity and Mortality

• Treatment

Background

• Clinical radiation pneumonitis is an interstitial pulmonary inflammation that can develop in as many as 5-15% of patients receiving thoracic irradiation

•Most often in radiation treatment due to lung cancer, breast cancer, lymphoma, or thymoma.

•Rate of radiological changes in as many as 50%

Background

Risks factors for clinical radiation pneumonitis:• radiation treatment factors

• Prior radiation

• use of chemotherapy (bleomycin)

•steroid therapy withdrawal

• comorbid lung disease

• smoking history

Background

radiation treatment factors

• The rad is defined as the energy absorption by one gram of body tissue. This has been replaced by the Gy defined as the energy absorption of 1 joule per kilogram of body tissue.

• Pulmonary damage is rare using total doses of radiation of 25-30Gy, and in essentially universal with doses >40 Gy. Or least 4000 rads, given in 5-6 weeks

• Factors that influence the extent of lung damage from radiation are total dose, fractionation, volume of radiated lung, and portal arrangement. Symptoms are unlikely to develop when <25% of lung is irradiated.

Received by the bone marrow during a chest x ray approx. 0.01 rads

If you were curious?.. The amount of radiation....

Received by the bone marrow during a barium enema

approx. .875 rads

Background

•Clinical radiation pneumonitis occurs within 1-6 months following treatment.

•Symptoms can include dyspnea, low-grade fever, cough (usually nonproductive), and fullness in the chest.

•Severe reactions can result in dyspnea, pleuritic chest pain, hemoptysis, acute respiratory distress, and death.

Background

•Fibrosis can occur without previous pneumonitis but once pneumonitis occurs, fibrosis is almost certain to take place.

•The radiographic hallmark of radiation pneumonitis is a diffuse infiltrate corresponding with a previous radiation treatment field.

Background

On physical exam:

• rales, possible friction rub, rhonchi

• skin changes do not correlate well with extent of pulmonary radiation damage

• In general the early onset of symptoms implies a more serious and protracted clinical course

Picture 1. Radiation pneumonitis. Patient had received radiation treatment to left upper lobe. There is a focal linear area of soft tissue density in the left upper lobe with volume loss.

Picture 2. Radiation pneumonitis. CT demonstrating localized area of peripheral fibrosis in the left upper lobe with a sharp edge corresponding to prior anteroposterior/posteroanterior treatment fields.

Pathophysiology

Two separate and distinct mechanisms are involved in the pathogenesis of acute radiation pneumonitis.

• The first, classical radiation pneumonitis, involves direct toxic injury to endothelial and epithelial cells from the radiation.

• The accumulation of leukocytes distorts the normal alveolar structures resulting initially in an acute aveolitis at the site of radiation.

• The alveolar macrophage is thought to play a central role in the subsequent development of fibrosis.

Pathophysiology

• The second mechanism, sporadic radiation pneumonitis, results in an "out-of-field" response. This is thought to be an immunologically mediated process resulting in bilateral lymphocytic aveolitis.

• In contrast to acute radiation pneumonitis, permanent changes of radiation fibrosis can take months to years to evolve but normally stabilize within 1-2 years.

• Pulmonary fibrosis is characterized by progressive fibrosis of the alveolar septa thickened by bundles of elastic fibers.

Pathophysiology

• Classic radiation pneumonitis has 3 main phases.

• Early phase (first month): This represents a latent period of pneumonitis. During this phase, loss of both type I and type II pneumonocytes occurs. Type II pneumonocytes produce surfactant, and decreased amounts result in transudation of serum proteins into the alveoli. This leads to edema of the interstitial spaces.

Pathophysiology

• Intermediate phase (1-6 months): This is characterized by dose-dependent leakage of proteins into the alveolar space, thickening of the alveolar septa, and development of clinical symptoms. Common clinical symptoms include nonproductive cough, low-grade fever, tachycardia, and dyspnea.

Pathophysiology

• Late phase (6 months and later): This is characterized by a loss of capillaries and increased collagen deposition. This results in restrictive changes within the lung characterized by reductions in vital capacity, lung volumes, diffusing capacity of lung for carbon monoxide (DLCO), and total lung capacity.

Evolution of radiation-induced lung disease in a 65-year-old man with non-small cell lung cancer. Pretreatment chest radiograph shows a nodule in the left upper lobe (arrow).

Radiograph obtained 3 months after completion of radiation therapy shows ill-defined, patchy haziness in the irradiated regions of both upper lungs

Same patient 6 months after radiation

1 year after completion of therapy demonstrate evolution of the disease with increasing volume loss, homogenicity of opacity, and sharpness of lateral margins.

Roberts, C. M. et. al. Ann Intern Med 1993;118:696-700

Important Variables in Patients with and without Clinical Radiation Pneumonitis

Mortality/Morbidity

• Morbidity and mortality vary greatly based on the volume of lung irradiated, dose per fraction of radiation delivered, use of concomitant chemotherapy, total dose of radiation delivered, and performance status of the patient.

• Patients treated for lung cancer with combination chemotherapy and irradiation represents the high-risk group. In this high-risk group, mortality is estimated to be 1-2%

radiation pneumonitis in right lung

Treatment

• When clinical radiation pneumonitis is suspected, initial therapy may include NSAIDS and inhaled corticosteroids

• In more symptomatic patients, systemic steroids are indicated. The recommended treatment is to begin prednisone at 1 mg/kg as soon as the diagnosis is reasonably certain.

•The initial dose is maintained for several weeks and then reduced slowly. If steroids are tapered too soon or too quickly, exacerbation of symptoms has been reported, requiring higher doses and longer treatment with steroids.

Treatment

•Prophylactically administered corticosteroids have been shown to decrease the physiologic effects of radiation in mice. However, in human studies, this approach has failed to prevent the development of clinical pneumonitis.

•Antibiotics and anticoagulants have been evaluated as treatment options but neither has been found to be clinically beneficial.

Treatment

•Current research focuses on chemotactic factors for fibroblasts, including transforming growth factor-beta (TGF-B, a cytokine known to promote connective tissue formation), fibronectin, and platelet-derived growth factor (PDGF). The most important stimulator of collagen synthesis is believed to be TGF-B, for which the alveolar macrophage is the main source

The End

References

1. Morgan GW, Breit SN: Radiation and the lung: a reevaluation of the mechanisms mediating pulmonary injury. Int J Radiat Oncol Biol Phys 1995 Jan 15; 31(2): 361-9

2. Movas B, Raffin TA, et al: Pulmonary Radiation Lung injury. Chest 1997; 111:1061-76

3. Roberts CM, Foulcher E, et al: Radiation pneumonitis:a possible lymphocyte mediated hypersensitivity reaction. Annals of Internal Medicine vol 118(9), May 1993, pp.696-700

4. Monson JM, Stark P, et al: Clinical Radiation Pneumonitis and Radiographic Changes after Thoracic Radiation Therapy for Lung Carcinoma. Cancer, March 1998 vol82 pp.842-849

5. Nieder C, Jeremic B, et al. Radiotherapy-induced lung toxicity: risk factors and prevention strategies. Anticancer Research. Nov-Dec 2003, pp4991-4998

6. Park KJ, Chung JY, et al. Radiation-induced Lung Disease and the Impact of Radiation Methods on Imaging Features. Radiographics. 2000;20:83-98