Abstract

ObjectivesTo generate and validate state-of-the-art radiomics models for prediction of radiation-induced lung injury and oncologic outcome in non-small cell lung cancer (NSCLC) patients treated with robotic stereotactic body radiation therapy (SBRT).MethodsRadiomics models were generated from the planning CT images of 110 patients with primary, inoperable stage I/IIa NSCLC who were treated with robotic SBRT using a risk-adapted fractionation scheme at the University Hospital Cologne (training cohort). In total, 199 uncorrelated radiomic features fulfilling the standards of the Image Biomarker Standardization Initiative (IBSI) were extracted from the outlined gross tumor volume (GTV). Regularized models (Coxnet and Gradient Boost) for the development of local lung fibrosis (LF), local tumor control (LC), disease-free survival (DFS) and overall survival (OS) were built from either clinical/ dosimetric variables, radiomics features or a combination thereof and validated in a comparable cohort of 71 patients treated by robotic SBRT at the Radiosurgery Center in Northern Germany (test cohort).ResultsOncologic outcome did not differ significantly between the two cohorts (OS at 36 months 56% vs. 43%, p = 0.065; median DFS 25 months vs. 23 months, p = 0.43; LC at 36 months 90% vs. 93%, p = 0.197). Local lung fibrosis developed in 33% vs. 35% of the patients (p = 0.75), all events were observed within 36 months. In the training cohort, radiomics models were able to predict OS, DFS and LC (concordance index 0.77–0.99, p < 0.005), but failed to generalize to the test cohort. In opposite, models for the development of lung fibrosis could be generated from both clinical/dosimetric factors and radiomic features or combinations thereof, which were both predictive in the training set (concordance index 0.71– 0.79, p < 0.005) and in the test set (concordance index 0.59–0.66, p < 0.05). The best performing model included 4 clinical/dosimetric variables (GTV-Dmean, PTV-D95%, Lung-D1ml, age) and 7 radiomic features (concordance index 0.66, p < 0.03).ConclusionDespite the obvious difficulties in generalizing predictive models for oncologic outcome and toxicity, this analysis shows that carefully designed radiomics models for prediction of local lung fibrosis after SBRT of early stage lung cancer perform well across different institutions.

Highlights

  • Stereotactic body radiation therapy (SBRT) is an effective therapy for early-stage, node-negative, medically inoperable non-small cell lung cancer (NSCLC)

  • Despite the obvious difficulties in generalizing predictive models for oncologic outcome and toxicity, this analysis shows that carefully designed radiomics models for prediction of local lung fibrosis after SBRT of early stage lung cancer perform well across different institutions

  • A set of volumetric and dosimetric parameters was extracted from the planning system including gross tumor volume (GTV), planning target volume (PTV), GTV-Dmax, GTV-Dmean, GTV-D95%, PTV-D95% and lung doses Lung-D1ml, LungD10ml, Lung-D50ml, Lung-D100ml [13, 37,38,39,40], see Table 1

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Summary

Introduction

Stereotactic body radiation therapy (SBRT) is an effective therapy for early-stage, node-negative, medically inoperable non-small cell lung cancer (NSCLC). After irradiation, about 10–15% of the tumors will recur locally, up to 50% of the patients will experience systemic disease progression despite PET-based staging before SBRT [5], and 25–30% of the patients will develop radiation-induced lung injury (RILI) on follow-up chest imaging. Several studies have applied radiomic analysis in SBRT of NSCLC [21,22,23,24,25,26,27,28,29,30,31,32,33,34], but so far, the clinical impact of the developed algorithms has been low due to low reproducibility of the results [35], lack of standardization of the extracted radiomic features and lack of external validation on data from other institutions

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