Repeated Stereotactic Body Radiotherapy With CyberKnife® in Lung Cancer: Toxicity Can Be Reduced by Sparing Irradiation to the Lungs

Background: Data of multiple courses of stereotactic body radiotherapy (SBRT) for lung malignancies is scarce. We aimed to investigate the efficacy and safety of repeated SBRT with CyberKnife and to identify predictors of lung toxicity.Methods: We reviewed patients with primary or metastatic lung cancer who underwent repeated SBRT with CyberKnife® between December 2013 and April 2021. Local control (LC), overall survival (OS) and adverse events were analyzed. We generated a composite plan and investigated the mean lung dose (MLD), V5–V30 of the bilateral lungs, and absolute lung volumes spared from 5–30 Gy (VS5–VS30), based on equivalent dose in 2.0-Gy fractions (α / β = 3). Clinical and dosimetric predictors of Grade 2+ radiation pneumonitis (RP) were examined.Results: Twenty patients underwent repeated SBRT for 27 lesions. The most predominant dose fractionation was 60 Gy in five fractions. The median follow-up duration from the last SBRT was 18.0 months (range, 3–55 months). The 1-year and 2-year LC of lung lesions in repeated courses were 95.2% and 95.2%, respectively. The 1-year and 2-year OS rates after repeated SBRT were 88.4% and 49.7%, respectively. Five patients (25%) developed Grade 2+ RP, including a Grade 5 RP. There was no association between clinical factors and Grade 2+ RP. The Grade 2+ RP group showed higher composite MLD (p = 0.042) and lower composite VS5 (p = 0.042), VS10 (p = 0.015), VS15 (p = 0.008), and VS20 (p = 0.025), compared with the Grade 0–1 RP group.Conclusions: Repeated SBRT with CyberKnife® showed favorable LC and OS, but a high rate of Grade 2+ RP. Analysis of the composite plans showed that MLD and VS5–VS20 may predict lung toxicity of multicourse SBRT.