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AbstractPurpose. Anti-angiogenic therapies are known to cause high radiographic response rates due to reduction in vascular permeability resulting in a lower degree of contrast extravasation. In the current study, we investigate the prognostic ability for model-derived parameters describing enhancing tumor volumetric dynamics to predict survival in recurrent glioblastoma treated with anti-angiogenic therapy. Experimental Design. N=276 patients in two phase II trials were used as training data, including bevacizumab +/- irinotecan (NCT00345163) and cabozantinib (NCT00704288), and N=74 patients in the bevacizumab arm of a phase III trial (NCT02511405) were used for validation. Enhancing volumes were estimated using T1 subtraction maps, and a biexponential model was used to estimate regrowth (g) and regression (d) rates, time to tumor regrowth (TTG), and the depth of response (DpR). Response characteristics were compared to diffusion MR phenotypes previously shown to predict survival. Results: Optimized thresholds occurred at g=0.07months-1 (phase II:HR=0.2579,P=5x10-20; phase III:HR=0.2197, P=5x10-5); d=0.11months-1 (HR=0.3365, P); TTG=3.8 months (HR=0.2702,P=6x10-17;HR=0.2061,P=2x10-5); and DpR=11.3% (HR=0.6326,P=0.0028;HR=0.4785, P=0.0206). Multivariable Cox regression controlling for age and baseline tumor volume confirmed these factors as significant predictors of survival. Patients with a favorable pre-treatment diffusion MRI phenotype had a significantly longer TTG and slower regrowth. Conclusions: Recurrent glioblastoma patients with a large, durable radiographic response to anti-angiogenic agents have significantly longer survival. This information is useful for interpreting activity of anti-angiogenic agents in recurrent glioblastoma.
Ellingson et al. (Mon,) studied this question.