A study of the association of the diagnosis to treatment initiation duration and overall survival in stage I non-small cell lung cancer treated with stereotactic body radiation therapy

Abstract

Background: Lung cancer is one of the most common cancers in the world, and the leading cause of cancer-related death in Ontario. It is clinically relevant to understand the association between the diagnosis to treatment initiation (DTI) duration and overall survival (OS) in lung cancer, yet prior studies have been limited by poor validity and inconsistent methodologies. Consensus-based recommendations were developed to address these limitations. This study aimed to apply the consensus-based recommendations to investigate the association between DTI duration and OS in stage I non-adenocarcinoma non-small cell lung cancer (NSCLC) patients who received stereotactic body radiation therapy (SBRT) in Ontario. No prior study has addressed this common lung cancer treatment. Methods: A population-based retrospective cohort study was conducted using administrative health data from ICES. The cohort included Ontario patients with pathologically diagnosed stage I NSCLC between January 1, 2010, and June 30, 2019, who received curative SBRT. Patients with adenocarcinomas were excluded from the cohort due to their heterogeneity, uncontrollable within the available data. Kaplan Meier analysis and multivariable Cox proportional hazards models were used to assess the association between DTI duration and OS. Cubic splines were used to assess the linearity of the exposure. Results: 532 patients were included in the cohort. The median DTI duration was 61 (interquartile range: 46-79) days. The Kaplan Meier analysis suggested a trend with longer DTI durations being associated with worse OS. There was no evidence to support a non-linear association between DTI duration and OS. In multivariable Cox proportional hazards models, every 1-week and 4-week increase in DTI duration was associated with a 4% (aHR = 1.04 (95% CI = 1.01-1.08 p = 0.022)) and 19% (aHR = 1.19 (95% CI = 1.03-1.38 p = 0.022)) increased rate of all-cause death respectively. Findings were robust in sensitivity analysis. Conclusions: This thesis advances the understanding of cancer DTI duration and OS, while demonstrating the effective application of the consensus-based recommendations. Longer DTI durations were associated with worse OS in stage I non-adenocarcinoma NSCLC patients who received SBRT in Ontario. These findings can inform clinical decision-making and health policy to improve patient outcomes.