Abstract
PurposeTo establish whether first-order statistical features from [18F]fluoride and 2-deoxy-2-[18F] fluoro-d-glucose ([18F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) demonstrate incremental value in skeletal metastasis response assessment compared with maximum standardised uptake value (SUVmax).ProceduresSixteen patients starting endocrine treatment for de novo or progressive breast cancer bone metastases were prospectively recruited to undergo [18F]fluoride and [18F]FDG PET/CT scans before and 8 weeks after treatment. Percentage changes in SUV parameters, metabolic tumour volume (MTV), total lesion metabolism (TLM), standard deviation (SD), entropy, uniformity and absolute changes in kurtosis and skewness, from the same ≤ 5 index lesions, were measured. Clinical response to 24 weeks, assessed by two experienced oncologists blinded to PET/CT imaging findings, was used as a reference standard and associations were made between parameters and progression free and overall survival.Results[18F]fluoride PET/CT: In four patients (20 lesions) with progressive disease (PD), TLM and kurtosis predicted PD better than SUVmax on a patient basis (4, 4 and 3 out of 4, respectively) and TLM, entropy, uniformity and skewness on a lesion basis (18, 16, 16, 18 and 15 out of 20, respectively). Kurtosis was independently associated with PFS (p = 0.033) and OS (p = 0.008) on Kaplan-Meier analysis. [18F]FDG PET: No parameter provided incremental value over SUVmax in predicting PD or non-PD. TLM was significantly associated with OS (p = 0.041) and skewness with PFS (p = 0.005). Interlesional heterogeneity of response was seen in 11/16 and 8/16 patients on [18F]fluoride and [18F]FDG PET/CT, respectively.ConclusionWith [18F]fluoride PET/CT, some first-order features, including those that take into account lesion volume but also some heterogeneity parameters, provide incremental value over SUVmax in predicting clinical response and survival in breast cancer patients with bone metastases treated with endocrine therapy. With [18F]FDG PET/CT, no first-order parameters were more accurate than SUVmax although TLM and skewness were associated with OS and PFS, respectively. Intra-patient heterogeneity of response occurs commonly between metastases with both tracers and most parameters.
Highlights
Skeletal metastases are common in patients with advanced breast cancer and are associated with significant morbidity [1]
This is the first report that has evaluated several first-order statistical features, including some heterogeneity parameters, for early treatment response assessment of breast cancer bone metastases compared to standard Standardised uptake value (SUV) measures using [18F]fluoride and [18F]FDG positron emission tomography/computed tomography (PET/CT)
Our exploratory data demonstrate that certain first-order statistical features from [18F]fluoride and [18F]FDG PET, related to volume and heterogeneity, may provide incremental value over SUVmax in the prediction of treatment response and survival in breast cancer bone metastases treated with endocrine therapy, a finding that deserves confirmation in further prospective evaluation in future studies
Summary
Skeletal metastases are common in patients with advanced breast cancer and are associated with significant morbidity [1]. Varied tumour response to treatment is undoubtedly an important factor in the clinical outcome, accentuating the need to have reliable measures to monitor patients for early disease progression in order to allow timely discontinuation of ineffective treatment. Measuring volumetric parameters or heterogeneity of tracer activity has been shown to have incremental predictive or prognostic value in a number of cancers [10,11,12,13,14,15,16,17,18,19,20,21]. First-order statistics measure global properties of a tumour from individual voxel values and can be obtained from the histogram of voxel intensities and are most commonly used [22], but there are no reports on the use of first-order heterogeneity parameters in evaluating treatment response assessment of breast cancer bone metastases using [18F]fluoride or [18F]FDG PET
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