Effects of radiotherapy and chemotherapy on lung function in patients with non-small-cell lung cancer

Purpose: To evaluate the effects of chemoradiation on objective tests of pulmonary function. Methods and materials: One hundred lung cancer patients treated in five protocols between 1992 and 2000 with combinations of thoracic radiotherapy (RT) and chemotherapy were evaluated with pre- and post-RT pulmonary function tests. The pulmonary function tests were analyzed for changes in measures of obstruction (forced expiratory volume in 1 s per unit of vital capacity [FEV₁/VC]), restriction (total lung capacity [TLC]), and diffusing capacity (diffusing capacity for carbon monoxide [DLCO]). The use and timing of chemotherapy and RT, as well as patient, tumor, and treatment factors, were evaluated using univariate and multivariate analyses. Results: No treatment or patient factors were significantly associated with changes in FEV₁/VC. Chemotherapy with RT, compared with RT alone, was associated with a lower post-RT TLC (92% vs. 107%, p = 0.002). Nodal status (N2-N3 vs. N1),tumor location (central vs. peripheral), use of ≥6 treatment fields, and tumor volume ≥100 cm³ were also associated with a significantly lower post-RT TLC. On univariate analysis, the use of any chemotherapy (p = 0.029) and the use of concurrent vs. sequential chemotherapy (p = 0.028) were predictive of a lower post-RT DLCO. Patient age ≥60 years, nodal status (N2-N3 vs. N0-N1), tumor volume ≥100 cm³, tumor location (central vs. peripheral), and use of ≥6 treatment fields were also associated with a significantly lower post-RT DLCO. The fractional volume of irradiated normal lung correlated with the decrease in DLCO (p <0.001), with a 1.3% DLCO decline for each 1% of total lung volume that received >20 Gy. Conclusion: The addition of chemotherapy to RT significantly exacerbates the post-RT decrease in TLC and DLCO. The greatest decrease in DLCO occurs in patients treated with concurrent chemoradiation.