For patients receiving lung stereotactic ablative radiotherapy (SABR), evidence suggests that high peritumor density predicts an increased risk of microscopic disease (MDE) and local-regional failure, but only if there is low or heterogenous
199 patients treated in a routine setting were collated from a single institution for training, and 76 patients from an external institution for validation. Three density metrics (mean, 90th percentile, standard deviation (SD)) were studied in 1mm annuli between 0.5cm inside and 2cm outside the GTV boundary. Dose SD and fraction of volume receiving less than 30Gy were studied in annuli 0.5-2cm outside the GTV to describe
Local relapse occurred at a rate of 6.5% in the training cohort, and 18% in the validation cohort, which included larger and more centrally located tumors. High peritumor density in combination with high dose variability (0.5 - 1.6cm) predicts LR. No interactions predicted RF. The LR interaction improved the predictive ability compared to using clinical variables alone (optimism-adjusted C-index; 0.82 vs 0.76). Re-fitting model coefficients in external data confirmed the importance of this interaction (C-index; 0.86 vs 0.76). Dose variability in the 0.5-1.6 cm annular region strongly correlates with heterogeneity inside the target volume (SD; ρ = 0.53 training, ρ = 0.65 validation).
In these real-world cohorts, the combination of relatively high peritumor density and high dose variability predicts increase in LR, but not RF, following lung SABR. This external validation justifies potential use of the model to increase low-dose CTV margins for high-risk patients.