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

Purpose:

The use of stereotactic ablative radiotherapy (SABR) 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 (OARs), and correlations between baseline factors and outcomes, to better inform patient selection and treatment planning.

Materials and Methods:

Radiation plans were centrally collected and reviewed, and descriptive statistics were used to assess doses to targets and OARs. Unadjusted Cox proportional hazards and logistic regression were performed, respectively, to identify predictors of overall survival (OS), local control (LC) and related adverse events Grade ≥2 based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Linear regression was performed to identify significant predictors of the Functional Assessment of Cancer Therapy: Lung (FACT-L), Cough Severity Scale, and pulmonary function testing (PFT) at 6 months.

Results:

The cohort included 39 patients treated with SABR (50 Gy in 5 fractions every other day). Thirty-five patients were treated with a volumetric modulated arc therapy (VMAT) technique, while the remaining four patients were treated using Cyberknife®. The mean internal gross tumour volume (iGTV) and planning target volume (PTV) for the entire cohort were 12.0 ± 11.2 cc and 33.9 ± 22.0 cc, respectively. The mean ± SD Dmax was 64.2 ± 6.3 Gy (128% of prescription). 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 primary tumour (measured as the Hounsfield unit density of lung immediately surrounding the PTV [p=0.006]). Worse OS was associated with ILD sub-type (specifically connective tissue disease-associated ILD [CT-ILD] and idiopathic pulmonary fibrosis [IPF]), previous ILD treatment, current ILD treatment, home oxygen use, and larger iGTV and PTV sizes. Smoking cessation, a diagnosis of IPF, and higher baseline forced vital capacity (FVC) were associated with improved FACT-L scores at 6 months. None of the examined OAR dosimetry and planning metrics were predictive of PFT values.

Conclusions:

Several factors were associated with clinically relevant outcomes after SABR in patients with ILD, including some that are modifiable (e.g. 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.