Experimental and Clinical Therapeutics

Monday, October 17, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP123) Changes in serum vascular endothelial growth factor (VEGF) levels following stereotactic body radiation therapy (SBRT) to liver and lung tumors.

Kavanagh, Brian*,, Schefter, Tracey1, Gaspar, Laurie1, Zaemisch, Rebekah1, Gravdahl, Daniel1, Raben, David1, Frederick, Barbara1, 1 University of Colorado, Aurora, CO, USA

ABSTRACT- Purpose/Objective: Vascular endothelial growth factor (VEGF) is an important cytokine linked to tumor development and progression. Stereotactic body radiation therapy (SBRT) involves focused, high-dose radiation therapy to discrete extracranial tumor sites as primary treatment or as systemic cytoreductive therapy. We investigated patterns of serum VEGF levels in patients receiving SBRT to determine a possible role for anti-VEGF therapy combined with SBRT. Materials/Methods: An IRB-approved translational/clinical protocol was conducted. Eligible patients were scheduled to receive SBRT, defined as a 3-fraction regimen of at least 10 Gy per fraction, to 1 or more extracranial tumors. Serum samples were obtained at 3 timepoints: within 1 week prior to SBRT, on the day of final SBRT fraction, and 30-60 days later. Samples were stored at -70C until analysis. Serum VEGF concentrations were determined by enzyme-linked immunosorbent assay (R&D Systems, Minneapolis, MN). Quantitative changes were analyzed with respect to tumor site, gross tumor volume (GTV, cc), planning target volume (PTV, cc), and prescription dose (Gy). Results: Fifteen patients who received SBRT to lesions in the lung (N=9) or liver (N=6) were studied. Histologies included squamous cancer(6), adenocarcinoma(3), renal cell cancer(3), small cell cancer(2), and thymoma(1). No patient received any systemic therapy during the observation period. Median GTV was 25 cc (range 3-100); median PTV was 22cc (93-250 cc). The SBRT dose prescribed to the PTV ranged from 45-60 Gy in 3 fractions. One liver SBRT patient with baseline levels above the reliably measurable range was excluded from analysis. Pre-SBRT serum VEGF levels averaged 213 pg/ml and were lower among liver SBRT patients(p=ns). In the entire group of patients, serum VEGF was significantly increased immediately after the third fraction of SBRT by an average of 32%(p=0.01) but returned to baseline 30 days later (see poster). Further analysis revealed the increase was predominantly due to patients treated to lung tumors, who had an average 49% increase immediately after SBRT(p=0.003) that remained elevated by 33% thirty days later(p=0.11). VEGF levels and change in VEGF were not correlated with GTV, PTV, or dose. Conclusions: Although VEGF secretion after SBRT to the liver appears to be widely variable, serum VEGF is significantly increased immediately following SBRT to lung tumors. Increased levels appear to be sustained for at least one month after treatment. The VEGF expression in this setting is likely a stress response that might promote tumor progression. These observations suggest a possible benefit for a treatment strategy combining anti-VEGF therapy for systemic tumor inhibition with SBRT for cytoreduction in sites of gross disease.

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2005 RRS