Mackenzie Colleen McGee BS, Presenter: Nothing to Disclose

Shannon Rosati BA, Abstract Co-Author: Nothing to Disclose

John Blair Hamner MD, Abstract Co-Author: Nothing to Disclose

Thomas Sims, Abstract Co-Author: Nothing to Disclose

Catherine Ng MS, Abstract Co-Author: Nothing to Disclose

Andrew Davidoff, Abstract Co-Author: Nothing to Disclose

In this study we tested the hypothesis that administration of bevacizumab followed by radiation therapy (RT) would improve tumor response to ionizing radiation in heterotopic glioma xenografts, but that dose schedule would be of critical importance.

Fifty-five SCID mice with size-matched subcutaneous U87 glioma xenografts were divided into six treatment groups: (1) controls, (2) bevacizumab alone, (3) RT alone, (4) bevacizumab, with RT given the same day, (5) bevacizumab, with RT given two days later, and (6) bevacizumab, with RT given five days later. Mice in RT groups received a single dose of 8 Gy to the tumor site. In addition to size, tumors were evaluated for differences in oxygenation using Oxylab Probe measurement.

Bevacizumab treated tumors had improved oxygenation 48 hours after therapy (19.08+/-29.13mmHg) versus controls (6.192+/-8.141mmHg). Five days after therapy there was a trend towards return to control oxygenation measurements (7.475+/-8.740mmHg). Bevacizumab treated tumors, with RT given two days later, had the smallest average volume 21 days post therapy (770.8+/-414.6 mm3) compared to each of the following groups: control (2090+/-838.3mm3), bevacizumab alone (1058+/-663.9mm3), RT alone (1066+/-517.3mm3), bevacizumab, with RT five days later (1078+/-512.9mm3), and bevacizumab, with RT given the same day (804.4+/- 533.2mm3).

In our model, bevacizumab improved tumor oxygenation transiently with maximal levels occurring 48 hours after one dose of bevacizumab was given. The brief reduction in tumor hypoxia coincided with the maximum anti-tumor activity of RT.

Our study suggests that maximizing the benefits of bevacizumab as adjuvant therapy will be heavily reliant on appropriate scheduling of RT.

McGee, M, Rosati, S, Hamner, J, Sims, T, Ng, C, Davidoff, A, Importance of Dose Schedule When Combining Bevacizumab and Ionizing Radiation for the Treatment of Glioma Xenografts.  Radiological Society of North America 2007 Scientific Assembly and Annual Meeting, November 25 - November 30, 2007 ,Chicago IL. http://archive.rsna.org/2007/5006125.html