Risk Factors for Radiation-Induced Lung Toxicity after Stereotactic Body Radiation Therapy in Patients with Non-Small Cell Lung Cancer

Abstract

Radiation-induced lung toxicity (RILT) is a potential fatal toxicity for stereotactic body radiation therapy (SBRT) for medically inoperable non-small cell lung cancer (NSCLC). This study aimed to examine the risk of RILT in a large institutional series of NSCLC patients and identify the dosimetric risk factors that predict RILT in order to help safe SBRT planning. Patients with early-stage or recurrent NSCLC who received lung SBRT between July 2002 and June 2015 formed the study population. The primary endpoint was RILT, including pneumonitis (RP) and fibrosis (RF), which was diagnosed and graded retrospectively according to RTOG1106. Onset time of RILT, either RP or RF, was calculated from the start of SBRT. Lungs were contoured consistently by one radiation oncologist according to RTOG atlas for organs at risk. Dosimetric factors were computed with exclusion of gross tumor volume (GTV) of either ipsilateral lung or total lungs. Risk factors of interest included age, gender, smoking status, pathological type, tumor stage, treatment history, baseline dyspnea, tumor location, prescription dose, history of previous treatment, GTV, planning target volume (PTV) and lung dosimetric parameters. A total of 276 patients with retrievable SBRT plans were eligible. The median follow-up was 47 months(95% CI: 41-53 months). There were 51(18.5%), 81(31.5%) and 110(39.9%) events of RP, RF and RILT, respectively. There were 74(26.8%), 27(9.7%), 8(2.9%) and 1(0.4%) for G1, G2, G3 and G4 RILT, respectively. Of the factors tested, previous radiation of thorax (OR:2.81; 95%CI:1.29-6.16; p=0.01) and V10 of total lungs (OR:1.06; 95%CI:1.01-1.11; p=0.019) were significant for G1+RP. History of lung surgery (OR:3.59; 95%CI:1.59-8.08; p=0.002) and baseline dyspnea (OR:1.99; 95%CI:1.11-3.59; p=0.022) were significant for G1+RF. Older age (OR:1.05; 95% CI:1.01-1.08; p=0.006), lung surgery (OR:3.00; 95%CI:1.27-7.11; p=0.012), baseline dyspnea (OR:2.43; 95% CI:1.35-4.37; p=0.003) and V10 of total lungs (OR:1.05; 95%CI:1.00-1.10; p=0.035) were significant for G1+RILT. Previous radiation of thorax (OR:5.51; 95%CI:2.34-12.96; p<0.001) and baseline dyspnea (OR:3.44; 95%CI:1.45-8.18; p=0.005) were significant for G2+RILT. Analysis of dosimetric parameters of ipsilateral lung demonstrated that none of lung dosimetric factors such as mean lung dose (MLD), V5, V10 and V20 were significantly associated with any grade of RILT(P>0.05). These simple lung dosimetric parameters were not significant for G2+RILT. RILT models will be presented at the meeting. Older age, lung surgery and baseline dyspnea are significant risk factors for RILT. Dosimetrically, V10 but not MLD and V20 of total lungs is a significant risk factor for RILT. This study represents one of the largest series reporting RILT after SBRT with comprehensive analysis of dosimetric risk factors for both ipsilateral lung and total lungs, with the lung organ consistently contoured per RTOG atlas.