Jerrold L. Boxerman MD, PhD, Presenter: Medical Advisor, Imaging Biometrics, LLC

Zheng Zhang PhD, Abstract Co-Author: Nothing to Disclose

Kathleen M. Schmainda PhD, Abstract Co-Author: Owner, Imaging Biometrics, LLC

Bradley S. Snyder MS, Abstract Co-Author: Nothing to Disclose

Melissa Prah BS, MS, Abstract Co-Author: Nothing to Disclose

Yair Safriel MBBCh, Abstract Co-Author: Principal, PharmaScan Clinical Trials

A. Gregory Sorensen MD, Abstract Co-Author: CEO, Siemens USA Consultant, sanofi-aventis Group Research support, sanofi-aventis Group Consultant, Bayer AG Research support, Exelixis, Inc Research support, Schering-Plough Corporation Consultant, Mitsubishi Corporation Consultant, Biogen Idec Inc Research support, Takeda Pharmaceutical Company Limited

Mark Gilbert, Abstract Co-Author: Nothing to Disclose

Daniel Paul Barboriak MD, Abstract Co-Author: Advisory Board, General Electric Company

ACRIN 6677/RTOG 0625 is a multi-center randomized phase II trial of bevacizumab with irinotecan or temozolomide in recurrent GBM. Pseudoresponse in patients receiving VEGF blockade has raised concerns that conventional MRI may not predict overall (OS) and progression-free survival (PFS). We compared the ability of relative cerebral blood volume (rCBV) from DSC-MRI and post-Gd 2D-T1 MRI after 2 weeks of treatment to predict OS and PFS.

37/123 patients enrolled consented to DSC-MRI plus conventional MRI, 13 (mean age 54±14 years, 7 men) with DSC-MRI at baseline plus 2 weeks after start of treatment. Two central readers determined response status at 2 weeks using 2D-T1 enhancement and Macdonald threshold criteria with adjudication if necessary. Enhancing ROIs were also defined semi-automatically from thresholded 2D-T1 difference images and used to extract mean GRE (TE=30-40ms) or SE (TE=60-105ms) rCBV (EPI, pre-load, 90° flip angle, post-processing leakage correction) normalized to normal-appearing white matter. Kaplan-Meier survival estimates and log rank test (2-sided) were used to determine if response status on 2D-T1 MRI and rCBV changes on DSC-MRI are predictive of PFS and OS, respectively. Fisher’s exact test (2-sided) was used to determine association between change in rCBV and response status on 2D-T1 MRI.

At 2 weeks, there were 3 responders and 10 non-responder/non-progressors (NR-NPs) on 2D-T1, and 4 positive and 9 negative changes from baseline in rCBV. One patient (NR-NP, positive rCBV change) had progressed clinically before week 2 and was excluded from PFS analyses. PFS was significantly worse for patients with increasing vs. decreasing rCBV (p=0.0034), but not for responders vs. NR-NPs (p=0.44). Similarly, survival time was significantly shorter for patients with increasing vs. decreasing rCBV (p=0.0015) but not for responders vs. NR-NPs (p=0.92). There was no significant association between positive vs. negative change in rCBV and responders vs. NR-NPs on 2D-T1 MRI (p=1.0).

After 2 weeks of anti-VEGF therapy, change in rCBV from baseline has highly significant prognostic value for PFS and OS, whereas 2D-T1 response status does not.

Early increase in rCBV may be a useful MRI biomarker for the failure of anti-VEGF therapy, permitting a timely switch to alternative trials when necessary. Funded through NCI U01-CA079778 and U01-CA080098.

Boxerman, J, Zhang, Z, Schmainda, K, Snyder, B, Prah, M, Safriel, Y, Sorensen, A, Gilbert, M, Barboriak, D, Early Post-Bevacizumab Change in rCBV from DSC-MRI Predicts Overall Survival in Recurrent Glioblastoma Whereas 2D-T1 Response Status Does not: Results from the ACRIN 6677/RTOG 0625 Multi-Center Study.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14005217.html