DCE-MRI and dynamic FDG PET to monitor breast cancer response to neoadjuvant sunitinib in patients with locally-advanced breast cancer.

Abstract Abstract #6006 Background: We are enrolling patients with locally-advanced (LABC) or inflammatory breast cancer on a phase II trial of neoadjuvant sunitinib and metronomic chemotherapy. The addition of sunitinib is hypothesized to increase rate of pathologic complete response (pCR) via its effect on tumor vasculature. Measurement of FDG PET and MRI parameters of metabolism and blood flow (BF) after a one week run-in of sunitinib alone provides an opportunity to evaluate in vivo pharmacodynamics of sunitinib which may be predictive of response and provide insight into mechanism of sunitinib activity. Materials and Methods: Patients with HER2 negative LABC participated in an imaging trial with pre-therapy [18F]-FDG PET and DCE-MRI (T0) followed by a one-week run-in of sunitinib 37.5 mg orally daily with a second PET and MRI on day 7 (T1). FDG metabolic rate (MRFDG), transport (FDG K1) and MR indices of tumor perfusion (peak enhancement (PE), signal enhancement ratio (SER), and washout volume(WV)) were assessed. Results: Metabolism and perfusion parameters are available for the first 3 patients treated on this trial. All patients presented with grade 3, HER2 negative LABC. DCI-MRI (left) and PET images (right) pre-therapy (T0, top) and after one week sunitinib (T1, bottom) are illustrated in Figure 1. DCE-MRI studies show gray-scale images with color-coded regional perfusion (SER) superimposed; red indicates high levels of perfusion and blue lower levels. Three different responses were observed and expressed as percent change T0 to T1: patient 1 had no significant change in metabolism (MRFDG) or perfusion (K1,SER, PE); patient 2 showed a decline in perfusion with decreases in K1 (-55%), SER (-19%), PE (-10%), and WV (-56%), but minimal change in MRFDG (+ 5.9%); while patient 3 had marked declines in perfusion K1 (-41%), SER (-25%), WV (-78%) and MRFDG (-59%). Discussion: These early data demonstrate the ability to measure changes in tumor metabolism and blood flow by PET and MRI and illustrate heterogeneity in tumor response to sunitinib. As patients complete neoadjuvant chemotherapy (NC), metabolism and perfusion parameters from mid-therapy (T2) and end-therapy (T3) imaging will be evaluated in the context of pCR versus other with the goal of exploiting functional imaging parameters to predict response to NC and elucidate mechanism of response to sunitinib and metronomic chemotherapy. Supported by grant from NCCN, SI11. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6006.