Dosimetric predictors of radiation-induced lung injury in stereotactic body radiation therapy

Materials and methods. The aim was to retrospectively investigate correlations between potential predictive parameters and the occurrence of radiation-induced lung injury in patients with primary or secondary lung tumours treated with stereotactic body radiation therapy (SBRT). Sixty patients (63 tumours) underwent SBRT, with a dose of 45 Gy in 3 fractions over 5 days or 26 Gy in single fraction. The following parameters were tested for correlation with Radiation Therapy Oncology Group (RTOG) lung toxicity score: planning target volume (PTV), tumour location, primary vs. metastatic tumour, and Mean Lung Dose (in 2 Gy fractions, MLD2). Normal Tissue Complication Probability (NTCP) values were then estimated. Results. The median follow-up time was 30.9 months (range 6.7-56.7). RTOG grade 0-1 toxicity was observed in 54/63 (85.7%) and grade 2-3 in 9/63 (14.3%) cases. Mean values of MLD2 for RTOG grade 0-1 and 2-3 were respectively 11.2 Gy (95% Confidence Interval (CI) 10.1-12.3 Gy) and 20.3 Gy (95% CI 16.6-23.9 Gy). NTCP mean values for RTOG grade 0-1 and 2-3 were respectively 4% (95% CI 2-5.9%) and 37% (95% CI 11.6-62.3%). Univariate analysis, performed with t-Student test, showed a statistically significant difference between MLD2 values in the two groups (t = 5.93 and p 0.001). Logistic regression analysis showed a good correlation between MLD2 and toxicity scores 2-3 (p = 0.008, odds ratio 1.5). From logistic regression relationship between the observed rates of grade 2-3 and MLD2, a D50=19.8 Gy and a 50=2.2 were obtained. From the sigmoid-shaped dose-response relationship between NTCP and MLD2, a D50=22.4 Gy and 50=2.2 were derived. Discussion. MLD2 is strongly associated to the risk of lung injury. Higher NTCP values are associated with a higher risk, but when comparing the expected to the observed toxicity rate, NTCP seems to underestimate the risk.