A Collaborative Analysis of Stereotactic Lung Radiotherapy Outcomes for Early-Stage Non-Small-Cell Lung Cancer Using Daily Online Cone-Beam Computed Tomography Image-Guided Radiotherapy

Introduction: We report lung stereotactic-body radiotherapy (SBRT) outcomes for a large pooled cohort treated using daily online cone-beam computed tomography. Methods: Five hundred and five stage I-IIB (T1-3N0M0) non-small-cell lung cancer (NSCLC) cases underwent SBRT using cone-beam computed tomography image guidance at five international institutions from 1998 to 2010. Median age was 74 years (range, 42-92) whereas median forced expiratory volume in 1 second/diffusing lung capacity for carbon monoxide were 1.4 liter (65%) and 10.8 ml/min/mmHg (53%). Of the 505 cases, 64% were biopsy proven and 87% medically inoperable. Staging was: IA 63%, IB 33%, IIA 2%, and recurrent 1%. Median max tumor dimension was 2.6 cm (range, 0.9-8.5). Median heterogeneously calculated volumetric prescription dose (PD) was 54 Gy (range, 20-64 Gy) in three fractions (range, 1-15) over 8 days (range, 1-27). Median biologically equivalent PD biological equivalent doses (BED10) was 132 Gy (range, 60-180). Results: With a median follow-up of 1.6 years (range, 0.1-7.3), the 2-year Kaplan-Meier local control (LC), regional control, and distant metastasis (DM) rates were 94%, 89%, and 20%, respectively, whereas cause-specific and overall survival were 87% and 60% (78% operable, 58% inoperable, p = 0.01), respectively. Stage, gross-tumor volume size (>= 2.7 cm) and PD(BED10) predicted local relapse (LR) and DM. LR was 15% for BED10 less than 105 Gy versus 4% for BED10 of 105 Gy or more (p < 0.001); DM was 31% versus 18% for BED10 less than 105 versus 105 Gy or more (p = 0.01). On multivariate analysis, PD(BED10) and elapsed days during radiotherapy predicted LR; gross-tumor volume size predicted DM. Grade 2 or higher pneumonitis, rib fracture, myositis, and dermatitis were 7%, 3%, 1%, and 2%, respectively. Conclusions: In the largest early-stage NSCLC SBRT data set to date, a high rate of local control was achieved, which was correlated with a PD(BED10) of 105 Gy or more. Failures were primarily distant, severe toxicities were rare, and overall survival was encouraging in operable patients.