The Expression of Adhesion Molecules on BAL Cells and Serum Soluble ICAM-1Level after the Radiotherapy for the Lung Cancer and Its Relationship to theDevelopment of of Radiation Pneumonitis and Fibrosis

Kim, Dong Soon; Paik, Sang Hoon; Choi, Eun Kyung; Chang, Hyesook; Lim, Chae Man; Koh, Yunsuck; Lee, Sang Do; Kim, Woo Sung; Kim, Won Dong

Abstract

BACKGROUND
Lung cancer is the second most frequent malignacy in man in Korea. Surgery is the best treatment modality for non-small cell lung cancer, but most patients were presented in far advanced stage. So radiation therapy(RT) with or without chemotherapy is the next choice and radiation-induced pneumonitis and pulmonary fibrosis is the major limiting factor for the curative RT. Radiation pneumonitis is manifested with fever, cough and dyspnea, 2~3 months after the termination of radiotherpy. Chest X ray shows infiltration, typically limited to the radiation field, but occasionally bilateral infiltration was reported. Also Gibson et al reported that BAL lymphocytosis was found in both lungs, even though the radiation was confined to one lung. The aim of this study is to investigate the change of adhesion molecules expression on BAL cells and serum soluble ICAM-1 (sICAM-1) level after the RT and its relationship to the development of radiation pneumonitis. The second aim is to confirm the bilaterality of change of BAL cell pattern and adhesion molecule expression. SUBJECTS: BAL and the measurement of sICAM level in serum and BALF were done on 29 patients with lung cancer who received RT with curative intention. The BAL was done before the RT in 16 patients and 1~2 month after RT in 18 patients. 5 patients performed BAL before and after RT. RESULT: Clinically significant radiation pneumonitis deveoped in 7 patients. After RT, total cell count in BAL was significantly increased from (20.2+/-10.2)X106 cells/ml to (35.3+/-21.6)X106 cells/ml (p=0.0344) and % lymphocyte was also increased from 5.3 +/- 4.2% to 39.6 +/- 23.4% (p=0.0001) in all patient group. There was no difference between ipsilateral and contraleteral side to RT, and between the patients with and without radiation-pneumonitis. In whole patient group, the level of sICAM-1 showed no significant change after RT(in serum: 378 +/-148, 411 +/-150 ng/ml, BALF: 20.2 +/- 12.2, 45.1 +/-34.8 ng/ml,respectively), but there was a significant difference between the patients with pneumonitis and without pneumonitis (serum: 505 +/- 164 vs 345 +/- 102 ng/ml, p=0.0253, BALF: 67.9+/-36.3 vs 25.2+/-17.9ng/ml,p= 0.0112). The expression of ICAM-1 on alveolar macrophages (AM) tends to increase after RT (RMFI: from 1.28 +/-0.479 to 1.63 +/-0.539, p=0.0605), but it was significantly high in patients with pneumonitis (2.10+/-0.390) compared to the patinets without pneumonitis (1.28+/-0.31,p=0.0002). ICAM-1 expression on lymphocytes and CD 18 (beta2-integrin) expression tended to be high in the patients with pneumonitis but the difference was statiastically not significant.
CONCLUSION
Subclinical alveolitis on the basis of BAL finding developed bilaterally in all patients after RT. But clinically significant pneumonitis occurred in much smaller fraction and the ICAM-1 expression on AM and the sICAM-1 level in serum were good indicator of it.