Prospective Study of Serial 18F-FDG PET and 18F-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, serial ¹⁸F-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 tested ¹⁸F-FDG PET and ¹⁸F-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 with ¹⁸F-FDG PET and ¹⁸F-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 (SUV_max) and lean body mass adjusted standardized uptake (SUL_peak) 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 and ¹⁸F-FDG PET and ¹⁸F-NaF PET measures. mPERCIST (Modified PET Response Criteria in Solid Tumors) were also applied. Survival curves for mPERCIST compared response categories of complete response+partial response+stable disease versus progressive disease for tSRE, TTP, and OS. Results: Twenty-eight patients were evaluated. Higher ¹⁸F-FDG SUL_peak at scan2 predicted shorter time to tSRE (P = <0.001) and TTP (P = 0.044). Higher ¹⁸F-FDG SUV_max at scan2 predicted a shorter time to tSRE (P = <0.001). A multivariable model using ¹⁸F-FDG SUV_max of the index lesion at scan1 plus the difference in SUV_max of up to 5 lesions between scans was predictive for tSRE and TTP. Among 24 patients evaluable by ¹⁸F-FDG PET mPERCIST, tSRE and TTP were longer in responders (complete response, partial response, or stable disease) than in nonresponders (progressive disease) (P = 0.007, 0.028, respectively), with a trend toward improved survival (P = 0.1). An increase in the uptake between scans of up to 5 lesions by ¹⁸F-NaF PET was associated with longer OS (P = 0.027). Conclusion: Changes in ¹⁸F-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. Serial ¹⁸F-NaF PET was associated with OS but was not useful for predicting TTP or tSRE in bone-dominant MBC.

Keywords: 18F-FDG PET; 18F-NaF PET; bone dominant breast cancer; response to therapy.

FIGURE 1.

Sagittal images of a 43-y-old woman: scan1 (A) and scan2 (B). Index lesions (not same lesions) decreased 58% by ¹⁸F-FDG PET and 2% by ¹⁸F-NaF PET. Response was considered partial by mPERCIST. Bone metastases were considered stable by ¹⁸F-NaF PET.

FIGURE 2.

Kaplan–Meier plots for ¹⁸F-FDG mPERCIST response criteria. Responders by mPERCIST (CR, PR, or stable disease) (n = 13) and nonresponders (n = 11). (A) tSRE. (B) TTP. (C) OS.