OT2-05-03: ACRIN 6688 Phase II Study of Fluorine-18 3′-Deoxy-3′ Fluorothymidine (FLT) in Invasive Breast Cancer.

Abstract

Abstract Background Neoadjuvant chemotherapy (NAC) prior to surgery provides enhanced options for locoregional management and has become an integral component of primary breast cancer management. Initial tumor response in patients receiving NAC is generally determined at therapy completion. This evaluation is determined by either the presence/absence of palpable tumor as a clinical response and/or presence/absence of invasive tumor cells in the breast and nodes as a pathological response. The ability to evaluate the effectiveness of neoadjuvant therapy early during treatment would be of significant importance. FDG PET imaging has been shown to be predictive of subsequent tumor response, but the tendency of FDG to accumulate in inflammatory tissues can complicate image interpretation. MRI changes have also been touted as predictors of response. Preliminary data suggest that early FLT PET is better able to predict response to therapy, as FLT uptake has been shown to correlate with cellular proliferation, and does not significantly accumulate in inflammatory tissue (Kenny et al, Eur J Nucl Med Mol Imaging 2007:1339–1347). The analysis of these data may provide a better understanding of early treatment response and improve the clinical management of breast cancer in the future. Trial design and eligibility: In this phase II multi-institutional study, breast cancer patients with locally advanced disease with a tumor size ≥2cm (measured on imaging or estimated by physical exam) are eligible. Participants will receive standard of care NAC at their respective institutions. Participants will have 3 FLT imaging sessions to evaluate therapy response: at baseline, early-treatment (5-10 days after initiating treatment), and post-treatment prior to surgery. Specific aims: The primary objective is to correlate the percentage change in the standardized uptake value between baseline and early therapy FLT in the primary tumor with pathologic response. Correlatively, FLT PET parameters will be compared with proliferative indices from the initial biopsy and residual tumor surgical samples using Ki-67 staining, mitotic index, and residual cancer burden. Potential safety issues and the physiologic effects associated with FLT administration will also be evaluated. Statistical methods: To evaluate the relationship between an uptake parameter and pathologic complete response, a ROC curve will be estimated and the area under the curve, along with its 95% confidence interval, will be determined. Accrual: Currently, 45/67 patients have accrued to the study. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-05-03.