Radiation Pneumonitis and Change of Pulmonary Function after Stereotactic Body Radiotherapy for T1N0M0 Non-Small Cell Lung Cancer and Their Impact on Survival in a Supplementary Analysis of Japan Clinical Oncology Group (JCOG) Study JCOG0403

Abstract

The purpose of this study was to investigate the frequency of radiation pneumonitis and change of pulmonary function and their impact on survival after stereotactic body radiotherapy (SBRT) for T1N0M0 non-small cell lung cancer (NSCLC) as a supplementary analysis of Japan Clinical Oncology Group (JCOG) study JCOG0403. Radiation pneumonitis was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. The test of pulmonary function included forced expiratory volume in 1.0 second (FEV1.0) and oxygen saturation of peripheral artery (SpO2). These were measured before the start of SBRT and every 6 months after it. In a total of 169 pts (65 medically operable and 104 inoperable; median age,78) enrolled in the phase II study of SBRT with 48Gy in 4 fractions for T1N0M0 pathology-proven NSCLC (JCOG0403), 146 pts and 153 pts whose FEV1.0 and SpO2 were measured before the start of SBRT and at least once after the start of SBRT without events that might affect their pulmonary function, such as local recurrence, regional lymph node metastases, or lung metastases were included in the analysis of FEV1.0 and in the analysis of SpO2, respectively. The worst grade of radiation pneumonitis and the maximum change of pulmonary function were determined based on each record during the first 1 year after the start of SBRT. Hazard ratios (HR) and their 95% confidence intervals (CI) for overall survival (OS) between subgroups were estimated by the Cox proportional hazards model and the landmark analysis was applied to OS counted from 1 year and 30 days after the start of SBRT. Radiation pneumonitis grade 2 or more was observed in 33 (20%) of 169 pts, 14 (22%) of 65 inoperable pts, and 19 (18%) of 104 operable pts. The pts with the factor of older age or tumor located in the middle or lower lobe had grade 2 or more radiation pneumonitis more frequently in the total of 169 pts (Fisher’s exact test p=0.033, p=0.048). FEV1.0 was decreased by 10% or more in 46 (32%) in total, 18 (32%) of inoperable pts, and 28 (32%) of operable pts. Larger tumor size was associated with 10% or more decrease of FEV1.0 in the total pts (p=0.010) and inoperable pts (p=0.016). Absolute % of SpO2 decreased by 5% or more in 5 (3%) of the total of 153 pts, 2 (3%) of 59 inoperable pts, and 3 (3%) of 94 operable pts. Grade 2 or more radiation pneumonitis and 10% or more decrease of FEV1.0 were not associated with OS in any groups, but 5% or more absolute % of SpO2 decrease was a worse factor for OS in the total pts (HR = 3.28: 95%CI, 1.31-8.20, log-rank test p=0.007) and inoperable pts (3.63: 95%CI, 1.10-11.94, p=0.023). The study suggested that more attention should be paid in the pts with the factor of older age, and tumor located in the middle or lower lobe for radiation pneumonitis, and the pts with larger tumor size for deteriorating pulmonary function. Decrease of absolute % of SpO2 5% or more might be a poor prognostic factor.