Association between Inter-Fraction Tumor Volume Changes and Patient Outcomes from Stereotactic Ablative Radiotherapy for Early-Stage Lung Cancer.

Several studies have noted an increase in the volume of lung tumors treated with stereotactic ablative radiotherapy (SABR) through the course of treatment. The prevalence of such changes and the effect on disease control have not been well studied. Tumor swelling could improve control through immune effects, or worsen it due to geographic miss of the radiotherapy. This is the first study investigating the association between inter-fraction volume changes during lung SABR and clinical outcomes. Patients with AJCC 7th ed. T1-2N0M0 non-small cell lung cancer (NSCLC), who had 4-5 fraction SABR from 4/2009-7/2019 were included in this retrospective study. A planning target volume (PTV) of 5mm was used with motion management as needed. Using cone-beam CT (CBCT) images obtained before each treatment, we contoured each tumor with a standardized procedure in commercially available software. Tumor volumes were assessed prior to initial, midway (third fraction), and last fraction. To explore the relationships between volumetric changes and baseline characteristics, univariable and multivariable linear regression was used. To assess relationship of volume change with outcomes, Fine-Gray models were used with outcomes of local, regional, and distant recurrence, with death as a competing risk. The analysis plan was specified prior to data collection. 121 patients were included. The median ratio of tumor volume at the middle of treatment to start of treatment (Start-Mid) was 1.18 (IQR 1.08, 1.27); the ratio of end of treatment to start (Start-End) was 1.15 (IQR 1.04, 1.28). There was a negative correlation between initial tumor volume and both Start-Mid and Start-End values (p = 0.004 and 0.005, respectively) on univariable analysis. Tumors treated with 50 Gy in 4 fractions (BED 10 112.5 Gy) exhibited larger Start-Mid values compared to those treated with 50 Gy in 5 fractions (BED 10 100 Gy, p = 0.038). Other examined characteristics had no significant correlation with inter-fraction tumor volume changes. Multivariable linear regression analysis reaffirmed a strong correlation between initial tumor volume and both Start-Mid and Start-End changes (p = 0.004 and 0.009, respectively). Fine-Gray models showed no significant correlation between tumor volume changes and local or regional recurrence but found a negative association between Start-Mid change and distant recurrence (p<0.001). Tumor volume often increases during lung SABR. This phenomenon did not appear to adversely affect locoregional control. Increased tumor volume was correlated with reduced distant recurrence, possibly representing an immune effect. Our findings suggest volume changes are likely a consequence of acute inflammatory reactions rather than tumor growth, and modest PTV expansions may be sufficient for tumor coverage. [ABSTRACT FROM AUTHOR]