Tumor Specific Growth Rate as a Predictor of Outcomes in Oligo-Progressive Disease Treated with Stereotactic Body Radiotherapy

Abstract

<h3>Purpose/Objective(s)</h3> Histologic classification alone does not fully represent the distribution of tumor behaviors due to within histology heterogeneity. The aim of this study is to assess the variation and the impact of pre- and post- tumor specific growth rate (SGR) on outcomes of metastatic patients with oligo-progressive (OP) disease treated with SBRT. <h3>Materials/Methods</h3> Patients with known metastatic disease and ≤3 radiologically OP were enrolled in a prospective phase II study. For the purpose of this analysis, treated metastases were retrospectively contoured on pre-SBRT diagnostic images (GTV1 - within 3-months), at time of SBRT (GTV2) and post-SBRT (GTV3 -within 3-months). SGR was calculated using the time interval (t=days) and volume changes (GTVx/GTVy) for each metastasis (<i>ln</i>(GTV2/GTV1)/t). Pre-SBRT growth (SGR1) was defined as <i>GTV2 – GTV1</i>, and post-SBRT (SGR2) as <i>GTV3 – GTV2</i>. High SGR was defined as greater than the median SGR value for each population. Progression was defined as local failure (LF) or distant progression. The impact of SGR1 and SGR2 (as continuous variables) on LF and progression was evaluated using a subdistribution hazards model to account for the competing risk of death. Cox Proportional Hazard was used to assess the association of SGR1 and SGR2 with overall survival (OS). For patients with multiple lesions, the highest SGR was used for progression and OS analyses. <h3>Results</h3> Thirty-five patients with 55 metastases from breast (29%), gastro-intestinal (GI) (40%) and genito-urinary (GU) (31%) cancers were analyzed. Median follow-up was 11.74 (interquartile range (IQR): 8.05-15.65 months). The median volume of GTV1, GTV2 and GTV3 was 3.91 (IQR 0.94 - 6.71)cc, 7.68 (IQR 2.04-15.43)cc and 2.72 (IQR 0.8-8.08)cc respectively. Median SGR1 and SGR2 was 0.007 (IQR 0.004 - 0.013) and -0.009 (IQR -0.01 to -0.002), with median SGR1/SGR2 per histology 0.005 (IQR 0.003 - 0.007)/-0.010 (IQR -0.019 to -0.006) breast, 0.011 (IQR 0.007 - 0.014)/-0.010 (IQR-0.013 to -0.002) GI and 0.006 (IQR 0.001 - 0.015)/-0.009 (IQR-0.012 to -0.001) GU. There was no statistically significant difference seen between histologies and SGR1 (p 0.15) and SGR2 (p 0.98). 48% of cases had a high SGR1 and 50% a high SGR2. At 12 months the LF and distant progression was11% and 76.8% respectively, while the probability of OS was 59%. There was a trend significant association between SGR1 and the probability of progression (p 0.055) while no significant association was found with the LF (p 0.28) or OS (p=0.35). Patients with low vs. high SGR1 had a higher probability of being alive but the difference did not reach statistical significance [SGR1 71% vs. 47% (p 0.35)]. SGR2 did not have a significant impact LF (p=0.59) or OS (p 0.39). <h3>Conclusion</h3> Lower SGR measurements seems to have better response after SBRT and may be used in the future for patient selection. These findings require validation in a larger cohort.