Stereotactic or Conventional Radiation for Early-Stage Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Stereotactic ablative radiotherapy (SABR) has been increasingly used for the treatment of inoperable early-stage non-small cell lung cancer (NSCLC). It has been shown to provide promising local control (LC) and toxicity in prospective trials. However, randomized trials have shown conflicting results in terms of whether SABR confers an overall survival (OS) advantage compared to conventionally fractionated radiotherapy (CFRT). A systematic review of Medline and Embase (inception to December 2020) was performed on early-stage NSCLC patients randomized to SABR versus CFRT. Two independent reviewers screened titles, abstracts, and manuscripts. A random-effects model was used to estimate treatment effects. Toxicity outcomes were compared by the Cochran-Mantel-Haenszel test. Individual patient data were digitally approximated and pooled as secondary analysis. The literature search identified 1494 studies, and 16 studies were included for full-text review. Two randomized trials were identified, including a total of 203 patients, of which 115 (57%) received SABR, and 88 (43%) received CFRT. The weighted mean age was 74 years and 48% of patients were male. Most patients had T1 cancers (67%). Stereotactic ablative radiotherapy was not associated with a significant improvement in OS (hazard ratio: 0.84; 95% confidence interval (CI) 0.34-2.08, p=0.71). There was no significant difference in LC between SABR and CFRT (relative risk: 0.59; CI 0.28-1.23, p=0.16). Of the commonly reported adverse events, one grade 4 toxicity of dyspnea was reported for SABR, while all others i.e., grade 3 or higher toxicities were similar. Stereotactic ablative radiotherapy demonstrated less esophagitis, dyspnea, and skin reaction of any grade. Despite widespread adoption and extensive single-arm prospective and retrospective studies suggesting its benefit, this systematic review and meta-analysis of randomized trials fail to confirm improvements in LC, OS, and toxicity profile of SABR over CFRT in early NSCLC. This small study is likely underpowered to detect clinically significant differences.