A STUDY ON PULMONARY CHANGES INDUCED BY COMBINED RADIATION AND ANTITUMOR AGENTS

Abstract

Combined radiotherapy and chemotherapy have been recently carried out effectively to have a good prognosis in malignant lymphoma and small cell carcinoma of the lung. This treatment has been often said to be complicated by bilateral diffuse interstitial pneumonitis, which is sometimes fatal.In this study, bilateral diffuse interstitial pneumonitis was recognized in 10 cases with malignant lymphoma (7 cases) and primary lung cancer (3 cases), treated by combined radiotherapy and chemotherapy. No bilateral diffuse interstitial pneumonitis could be discovered in cases without combined chemotherapy. Mediastinum was irradiated in 8 cases and bilateral supraclavicular region in 6 cases. Radiation doses were ranged from 25 to 60 Gy.Cyclophosphamide (CPM) was given to 9 cases ranging from 1050 mg to 9900 mg. Vincristine (VCR) was given to 9 cases from 1 mg to 9 mg. ACNU was given to one case 100 mg. Antitumor agents were given before or after radiotherapy, or concurrently.This pneumonitis was observed in the period 30 to 130 days after onset of radiotherapy and 25 to 100 days after onset of chemotherapy.These patients had a low grade fever (<38°C), dyspnea and shortness of breath frequently, and rarely had rales or leucocytosis.Chest radiographs were characterized by bilateral diffuse interstitial changes or hazy, homogeneous shadows. Ga-67 scannings were positive in 5 cases performed at the time of development of pneumonitis. Six patients were dead from this pneumonitis without improvement after injection of antibiotics and steroid.Mouse lung induced by combined radiation and antitumor agents was histologically investigated. Mice were irradiated 2000 R or 4000 R to the left hemithorax. CPM, Adriamycin (ADM) and Rinderon (RD) were given to them intraperitoneally.Both CPM and ADM could enhance the lung damage. Histopathologic pictures induced by combined radiation and antitumor agents were characterized not only by alveolar thickening with cellular accumulation, but also by exudate into alveolar lumen. RD was effective in controlling exudate into alveolar lumen at the time of 4 weeks after radiation.In view of the low incidence of pulmonary toxicity and the benefit of improving tumor response, combined radiotherapy and chemotherapy should be carried out. However, it should be kept in mind that fatal pneumonitis could be occurred as a complication of combination therapy.