Distinguishing radiation fibrosis from tumour recurrence after stereotactic ablative radiotherapy (SABR) for lung cancer: A quantitative analysis of CT density changes

Background. For patients treated with stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer, benign computed tomography (CT) changes due to radiation-induced lung injury (RILI) can be difficult to differentiate from recurrence. We measured the utility of CT image feature analysis in differentiating RILI from recurrence, compared to Response Evaluation Criteria In Solid Tumours (RECIST). Materials and methods. Twenty-two patients with 24 lesions treated with SABR were selected (11 with recurrence, 13 with substantial RILI). On each follow-up CT, consolidative changes and ground glass opacities (GGO) were contoured. For each lesion, contoured regions were analysed for mean and variation in Hounsfield units (HU), 3D volume, and RECIST size during follow-up. Results. One hundred and thirty-six CT scans were reviewed, with a median imaging follow-up of 26 months. The 3D volume and RECIST measures of consolidative changes could significantly distinguish recurrence from RILI, but not until 15 months post-SABR; mean volume at 15 months [all values +/- 95% confidence interval (CI)] of 30.1 +/- 19.3 cm(3) vs. 5.1 +/- 3.6 cm(3) (p = 0.030) and mean RECIST size at 15 months of 4.34 +/- 1.13 cm vs. 2.63 +/- 0.84 cm (p = 0.028) respectively for recurrence vs. RILI. At nine months post-SABR, patients with recurrence had significantly higher-density consolidative changes (mean at nine months of -96.4 +/- 32.7 HU vs. -143.2 +/- 28.4 HU for RILI; p = 0.046). They also had increased variability of HU, an image texture metric, measured as the standard deviation (SD) of HU, in the GGO areas (SD at nine months of 210.6 +/- 14.5 HU vs. 175.1 +/- 18.7 HU for RILI; p = 0.0078). Conclusions. Quantitative changes in mean HU and GGO textural analysis have the potential to distinguish RILI from recurrence as early as nine months post-SABR, compared to 15 months with RECIST and 3D volume. If validated, this approach could allow for earlier detection and salvage of recurrence, and result in fewer unnecessary investigations of benign RILI.