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

[PURPOSE] SABR therapy in the setting of interstitial lung disease (ILD) is associated with higher toxicity risks. This dosimetric analysis of the ASPIRE-ILD trial evaluates doses delivered to targets and organs at risk, and correlations between baseline factors and outcomes, to better inform patient selection and treatment planning.

[METHODS AND MATERIALS] Radiation plans were centrally reviewed, and descriptive statistics were used to assess doses to targets and organs at risk. Unadjusted Cox proportional hazards and logistic regression were performed to identify predictors of overall survival, local control, and related adverse events. Linear regression was performed to identify significant predictors of the Functional Assessment of Cancer Therapy: Lung.

[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 and planning target volume (PTV) were 12.0 ± 11.2 cc and 33.9 ± 22.0 cc, respectively. The mean ± SD maximum dose was 64.2 ± 6.3 Gy. On unadjusted analyses, local control decreased with increasing tumor size [measured as either internal gross tumor volume size (P = .038) or PTV size (P = .033)]. The risk of grade ≥2 adverse events increased with higher heart maximum dose (P = .020) and heart D15cc (P = .025), and with increasing fibrosis surrounding the tumor [measured as the Hounsfield unit density of lung immediately surrounding the PTV (P = .006)]. Worse overall survival was associated with ILD subtype, previous or current ILD treatment, home oxygen use, and larger target sizes. Smoking cessation and a diagnosis of idiopathic pulmonary fibrosis were associated with improved Functional Assessment of Cancer Therapy: Lung scores at 6 months.

[CONCLUSIONS] 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 the lung was associated with higher toxicity. Smoking cessation may be important in preserving quality of life after treatment.