Prospective study of serial18F-FDG PET and18F-fluoride PET to predict time to skeletal-related events, time to progression, and survival in patients with bone-dominant metastatic breast cancer

Abstract

Assessing therapy response of breast cancer bone metastases is challenging. In retrospective studies, serial18F-FDG PET was predictive of time to skeletal-related events (tSRE) and time to progression (TTP).18F-NaF PET improves bone metastasis detection compared with bone scanning. We prospectively tested18F-FDG PET and18F-NaF PET to predict tSRE, TTP, and overall survival (OS) in patients with bone-dominant metastatic breast cancer (MBC). Methods: Patients with bone-dominant MBC were imaged with18F-FDG PET and18F-NaF PET before starting new therapy (scan1) and again at a range of times centered around approximately 4 mo later (scan2). Maximum standardized uptake value (SUVmax) and lean body mass adjusted standardized uptake (SULpeak) were recorded for a single index lesion and up to 5 most dominant lesions for each scan. tSRE, TTP, and OS were assessed exclusive of the PET images. Univariate Cox regression was performed to test the association between clinical endpoints and18F-FDG PET and18F-NaF PET measures. mPERCIST (Modified PET Response Criteria in Solid Tumors) were also applied. Survival curves for mPERCIST compared response categories of complete respon-se1partial response1stable disease versus progressive disease for tSRE, TTP, and OS. Results: Twenty-eight patients were evaluated. Higher18F-FDG SULpeak at scan2 predicted shorter time to tSRE (P 5,0.001) and TTP (P 5 0.044). Higher18F-FDG SUVmax at scan2 predicted a shorter time to tSRE (P 5,0.001). A multivariable model using18F-FDG SUVmax of the index lesion at scan1 plus the difference in SUVmax of up to 5 lesions between scans was predictive for tSRE and TTP. Among 24 patients evaluable by18F-FDG PET mPERCIST, tSRE and TTP were longer in responders (complete response, partial response, or stable disease) than in nonresponders (progressive disease) (P 5 0.007, 0.028, respectively), with a trend toward improved survival (P 5 0.1). An increase in the uptake between scans of up to 5 lesions by18F-NaF PET was associated with longer OS (P 5 0.027). Conclusion: Changes in18F-FDG PET parameters during therapy are predictive of tSRE and TTP, but not OS. mPERCIST evaluation in bone lesions may be useful in assessing response to therapy and is worthy of evaluation in multicenter, prospective trials. Serial18F-NaF PET was associated with OS but was not useful for predicting TTP or tSRE in bone-dominant MBC.