Pulmonary Interstitial Changes Is A Predictive Factor For Radiation Pneumonitis After Stereotactic Body Radiation Therapy For Lung Cancer Patients

Pulmonary interstitial changes (IC) are occasionally observed on the pretreatment computed tomography (CT) scans of lung cancer patients without clinical symptoms or diagnostic confirmation of interstitial pneumonia. The incidence of radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT) for lung cancer patients with IC is not known. The purpose of the present study was to evaluate the incidence of RP after SBRT for lung cancer patients with IC. Between November 2003 and August 2012, we selected 260 consecutive primary lung cancer patients who were treated with SBRT. According to the presence or absence of IC in the pretreatment CT, patients were divided into two groups: an IC group (n = 18) and a non-IC group (n = 242). The median age was 77 years old (range, 51-92 years), and there were 164 male and 96 female patients. SBRT was given with an isocenter dose of 48 Gy in 4 fractions in all patients. There were no significant differences in the dosimetric lung parameters between the IC and non-IC groups. The cumulative incidence of RP was calculated by the Kaplan-Meier method. Predictive factors of RP were evaluated by univariate and multivariate analysis in all cases and in the IC group, respectively. The median follow-up was 26.0 months (range, 2.7-104.6 months). Grade ≥2 RP was observed in 9 (50.0%) and 14 (6.7%) patients in the IC and non-IC group, respectively. In the IC group, 3 patients developed Grade 5 RP and died at 2.7, 4.3 and 8.5 months after SBRT. There were no cases of Grade ≥4 RP in the non-IC group. By multivariate analysis in all patients, presence of IC was the only significant predictive factor of Grade ≥2 RP. By univariate analysis in the IC group, pretreatment serum KL-6 (Krebs von den Lungen-6) levels, lung V5 and V10 (lung volume receiving ≥5, 10 Gy), and mean lung dose were significant predictive factors of Grade ≥2 RP (p = 0.017, 0.041, 0.038, and 0.038, respectively). Even in the IC group, patients with KL-6 levels of <600 U/mL did not develop Grade ≥4 RP. Overall survival rates at 2 years after SBRT in the IC and non-IC groups were 49.6% and 86.7%, respectively. The overall survival of the non-IC group was significantly longer than that of the IC group (p = 0.0005). Presence of IC in a pretreatment CT was a significant indicator of Grade ≥2 RP after SBRT for lung cancer patients. SBRT should not be considered for lung cancer patients with IC and high levels of KL-6 ≥600 U/mL.