Abstract P4-01-01: Serial FDG and 18F-fluoride PET predict response to therapy in patients with breast cancer bone metastases
Authors: Montgomery SK , Barlow WE , Linden HM , Gralow JR , Ellis GK , Gadi VK , Schubert EK , Peterson LM , Novakova A , Doot R , Dunnwald LK , Mankoff DA , Specht JM 
Published: August 2014

Abstract
Background: Assessing response to therapy in patients (pts) with bone-dominant (BD) metastatic breast cancer is challenging by conventional imaging such as CT and bone scintigraphy. In prior retrospective analyses, measures of FDG uptake by FDG PET were predictive of both time to progression (TTP) and the risk of skeletal related events (SRE). Studies have also shown that 18F-fluoride PET improves bone metastasis detection compared to bone scintigraphy and, as a quantitative study, may be better suited to evaluate therapeutic response. We evaluated the utility of serial FDG PET and 18F-fluoride PET to prospectively assess response to therapy in BD metastatic breast cancer.
Methods: Pts with BD metastatic breast cancer were evaluated with FDG PET and 18F-fluoride PET prior to starting a new systemic therapy and after approximately 3 months. Serum markers (CA27.29 and CEA) were obtained at baseline and during treatment close to the time of PET imaging. In this analysis, static images from skull base to mid-thighs were analyzed quantitatively using the maximum standardized uptake value (SUV) of up to 5 most prominent lesions. Tumor locations were confirmed by CT and regions-of-interest were drawn on both FDG and 18F-fluoride images. Assessment of clinical endpoints including TTP and time to SRE was determined by independent review of clinical data and analyzed by Cox regression. PET imaging results were reported clinically, but not used to determine endpoints in this analysis.
Results: 47 pts (mean age 55, range 39-91) enrolled between 2004 and 2012. Most pts 43/47 (91%) had hormone receptor positive disease (primary or metastatic). 9/47 (19%) of pts had HER2+ disease. Systemic therapy during study was chemotherapy in 20/47 (43%) and endocrine therapy in 31/47 (66%). Most pts 30/47 (64%) received bisphosphonates. Mean time between baseline and follow up FDG and 18F-fluoride PET scans was 4.6 months. 42/47 (89%) pts had disease progression during study follow up (median TTP 5.9 months, 95% CI 4-9.2). Among 24 pts with 2 FDG and 2 18F-fluoride scans, percent change in FDG (&gt;-9% vs ≤-9%) was predictive of TTP, HR = 0.317, p = 0.038. Percent change (&gt;-19% vs ≤-19%) in 18F-fluoride SUV did not predict TTP, HR = 1.05, p = 0.914. Median time to SRE was 48 months. Absolute SUV for baseline FDG and 18F-Fluoride PET were both predictive of time to SRE (FDG SUV &gt;6 vs &lt;6; HR = 4.61, p = 0.002 and 18F-fluoride SUV &gt;25 vs &lt;25; HR = 4.5, p = 0.008).
Conclusions: Changes in FDG SUV over the course of treatment were a robust predictor of TTP, while changes in 18F-fluoride PET did not predict response. Both baseline high FDG and 18F-fluoride SUV were associated with earlier SRE occurrence. These results indicate a role for PET, particularly FDG PET, in assessing BD breast cancer and support a role for PET in future clinical trials. Funding support 5R01CA124573-05.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-01.