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 F-FDG PET was predictive of time to skeletal-related events (tSRE) and time to progression (TTP).F-NaF PET improves bone metastasis detection compared with bone scanning. We prospectively tested F-FDG PET andF-NaF PET to predict tSRE, TTP, and overall survival (OS) in patients with bone-dominant metastatic breast cancer (MBC). Patients with bone-dominant MBC were imaged withF-FDG PET and F-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) and lean body mass adjusted standardized uptake (SUL) 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 F-FDG PET andF-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. Twenty-eight patients were evaluated. HigherF-FDG SUL at scan2 predicted shorter time to tSRE ( = <0.001) and TTP ( = 0.044). Higher F-FDG SUV at scan2 predicted a shorter time to tSRE ( = <0.001). A multivariable model using F-FDG SUV of the index lesion at scan1 plus the difference in SUV of up to 5 lesions between scans was predictive for tSRE and TTP. Among 24 patients evaluable by F-FDG PET mPERCIST, tSRE and TTP were longer in responders (complete response, partial response, or stable disease) than in nonresponders (progressive disease) ( = 0.007, 0.028, respectively), with a trend toward improved survival ( = 0.1). An increase in the uptake between scans of up to 5 lesions by F-NaF PET was associated with longer OS ( = 0.027). Changes inF-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 F-NaF PET was associated with OS but was not useful for predicting TTP or tSRE in bone-dominant MBC.

A comparison of prostate cancer bone metastases on 18F-Sodium Fluoride and Prostate Specific Membrane Antigen (18F-PSMA) PET/CT: Discordant uptake in the same lesion

“…High PSMA PET uptake in areas suspicious for metastasis is considered highly reliable for prostate cancer and discordance with NaF can be interpreted to suggest there is an invasive component not driven by osteoblastic reaction. This parallels bone findings in metastatic breast cancer, where predominately osteolytic mechanisms are suspected to underlay observed discordance between NaF PET/CT and FDG PET/CT [25, 26].…”

Application of PET Tracers in Molecular Imaging for Breast Cancer

“…In general, a negative [ 18 F]-NaF-PET/CT can be used to exclude bone metastases, but in case of positive findings, [ 18 F]-NaF-PET/CT should be carefully interpreted and correlated with CT findings. With regard to the prognostic value of [ 18 F]-NaF-PET/ CT, one prospective study was performed in 28 BC patients with bone-dominant disease, showing no correlation between baseline SUV max and skeletal-related events, time-to-progression or overall survival (OS) [41]. However, ΔSUV max of 5 lesions between baseline and 4 months of systemic treatment was associated with OS [41].…”

“…With regard to the prognostic value of [ 18 F]-NaF-PET/ CT, one prospective study was performed in 28 BC patients with bone-dominant disease, showing no correlation between baseline SUV max and skeletal-related events, time-to-progression or overall survival (OS) [41]. However, ΔSUV max of 5 lesions between baseline and 4 months of systemic treatment was associated with OS [41]. With regard to the predictive value of [ 18 F]-NaF-PET/CT, two small studies showed that lack of endocrine treatment efficacy was related to an increase in metabolic flux to mineral bone or SUV max in BC patients with bone only disease (see Table 1) [42,44].…”

Clinical utility of circulating tumor DNA as a response and follow-up marker in cancer therapy

“…Finally, response assessment can be difficult in certain settings regardless the therapy given. In a bone-dominant disease such as prostate cancer and hormone-positive breast cancer, response assessment is hampered as bone lesions are considered non-evaluable by RECIST [5].…”