Dosimetric Outcomes for Stereotactic Radiotherapy in Early-Stage Non-Small Cell Lung Cancer and Interstitial Lung Disease: A Secondary Analysis of the ASPIRE-ILD Trial.

Abstract

Purpose: Stereotactic ablative radiotherapy (SABR) in the setting of interstitial lung disease (ILD) is associated with higher toxicity risks. This dosimetric analysis of the BLINDED-FOR-REVIEW trial evaluates doses delivered to targets and organs at risk (OARs), and correlations between baseline factors and outcomes, to better inform patient selection and treatment planning.

Methods: Radiation plans were centrally reviewed, and descriptive statistics were used to assess doses to targets and OARs. Unadjusted Cox proportional hazards and logistic regression were performed to identify predictors of overall survival (OS), local control (LC), and related adverse events. Linear regression was performed to identify significant predictors of the Functional Assessment of Cancer Therapy: Lung (FACT-L).

Results: The cohort included 39 patients with early-stage lung cancer and ILD treated with SABR (50 Gy in 5 fractions every other day). The mean internal gross tumor volume (iGTV) and planning target volume (PTV) were 12.0 ± 11.2 cc and 33.9 ± 22.0 cc, respectively. The mean ± SD Dmax was 64.2 ± 6.3 Gy. On unadjusted analyses, LC decreased with increasing tumour size (measured as either iGTV size [p=0.038] or PTV size [p=0.033]). The risk of grade ≥ 2 adverse events increased with higher heart Dmax (p=0.020) and heart D15cc (p=0.025), and with increasing fibrosis surrounding the tumour (measured as the Hounsfield unit density of lung immediately surrounding the PTV [p=0.006]). Worse OS was associated with ILD sub-type, previous or current ILD treatment, home oxygen use, and larger target sizes. Smoking cessation and a diagnosis of idiopathic pulmonary fibrosis (IPF) were associated with improved FACT-L scores at 6 months.

Conclusion: Several factors were associated with clinically relevant outcomes after SABR in patients with ILD, including radiation dose to the heart and smoking cessation. SABR delivered to highly fibrotic areas of lung was associated with higher toxicity. Smoking cessation may be important in preserving quality of life after treatment.