Real-world acute toxicity and 90-day mortality in patients with stage I non-small cell lung cancer treated with stereotactic body radiotherapy

INTRODUCTION: Stereotactic body radiotherapy (SBRT) has firmly established its role in stage I non-small cell lung cancer (NSCLC). Clinical trial results may not fully apply to real-world scenarios. This study aimed to uncover the real-world incidence of acute toxicity and 90-day mortality in SBRT-treated stage I NSCLC patients and develop prediction models for these outcomes. METHODS: Prospective data from the Dutch Lung Cancer Audit for Radiotherapy (DLCA-R) were collected nationally. Patients with stage I NSCLC (cT1-2aN0M0) treated with SBRT in 2017-2021 were included. Acute toxicity was assessed, defined as grade =2 radiation-pneumonitis or grade =3 non-hematologic toxicity =90 days after SBRT. Prediction models for acute toxicity and 90-day mortality were developed and internally validated. RESULTS: Among 7,279 patients, the mean age was 72.5 years, with 21.6% being >80 years. Most were female (50.7%), had WHO scores 0-1 (73.3%), and cT1a-b tumors (64.6%), predominantly in upper lobes (65.2%). Acute toxicity was observed in 280 (3.8%) of patients and 90-day mortality in 122 (1.7%). Predictors for acute toxicity included WHO =2, lower FEV1 and DLCO, no pathology confirmation, middle/lower lobe tumor location, cT1c-cT2a stage, and higher mean lung dose (c-statistic 0.68). Female gender, WHO =2, and acute toxicity predicted higher 90-day mortality (c-statistic 0.73). CONCLUSIONS: This nationwide study revealed a low rate of acute toxicity and an acceptable 90-day mortality rate in SBRT-treated stage I NSCLC patients. Notably, advanced age did not increase acute toxicity or mortality risk. Our predictive models, with satisfactory performance, offer valuable tools for identifying high-risk patients.