Abstract
Metastatic tumor deposits in bone marrow elicit differential bone responses that vary with the type of malignancy. This results in either sclerotic, lytic, or mixed bone lesions, which can change in morphology due to treatment effects and/or secondary bone remodeling. Hence, morphological imaging is regarded unsuitable for response assessment of bone metastases and in the current Response Evaluation Criteria In Solid Tumors 1.1 (RECIST1.1) guideline bone metastases are deemed unmeasurable. Nevertheless, the advent of functional and molecular imaging modalities such as whole-body magnetic resonance imaging (WB-MRI) and positron emission tomography (PET) has improved the ability for follow-up of bone metastases, regardless of their morphology. Both these modalities not only have improved sensitivity for visual detection of bone lesions, but also allow for objective measurements of bone lesion characteristics. WB-MRI provides a global assessment of skeletal metastases and for a one-step “all-organ” approach of metastatic disease. Novel MRI techniques include diffusion-weighted imaging (DWI) targeting highly cellular lesions, dynamic contrast-enhanced MRI (DCE-MRI) for quantitative assessment of bone lesion vascularization, and multiparametric MRI (mpMRI) combining anatomical and functional sequences. Recommendations for a homogenization of MRI image acquisitions and generalizable response criteria have been developed. For PET, many metabolic and molecular radiotracers are available, some targeting tumor characteristics not confined to cancer type (e.g. 18F-FDG) while other targeted radiotracers target specific molecular characteristics, such as prostate specific membrane antigen (PSMA) ligands for prostate cancer. Supporting data on quantitative PET analysis regarding repeatability, reproducibility, and harmonization of PET/CT system performance is available. Bone metastases detected on PET and MRI can be quantitatively assessed using validated methodologies, both on a whole-body and individual lesion basis. Both have the advantage of covering not only bone lesions but visceral and nodal lesions as well. Hybrid imaging, combining PET with MRI, may provide complementary parameters on the morphologic, functional, metabolic and molecular level of bone metastases in one examination. For clinical implementation of measuring bone metastases in response assessment using WB-MRI and PET, current RECIST1.1 guidelines need to be adapted. This review summarizes available data and insights into imaging of bone metastases using MRI and PET.
Highlights
Bone is a common site of secondary tumor deposits because, in addition to its rigid, calcified, outer cortex, it has a richly vascular inner marrow of bony trabeculae, stroma, haematopoeitic tissue and fat [1]
Based on the data and results referenced above, POSITRON EMISSION TOMOGRAPHY (PET)/MAGNETIC RESONANCE IMAGING (MRI) appears rather superior to PET/CT for the detection of metastatic bone lesions, but it lacks the morphologic information of bone and osteoblastic bone formation derived from the CT component, which might be mitigated some through innovative approaches as reported by Sonni and co-workers
Whole body MRI including modern techniques such as DWI, Dynamic contrast-enhanced MRI (DCE-MRI) and mpMRI can provide both detailed information on anatomical structures as well as functional information on individual lesions and whole body tumor burden
Summary
Bone is a common site of secondary tumor deposits because, in addition to its rigid, calcified, outer cortex, it has a richly vascular inner marrow of bony trabeculae, stroma, haematopoeitic tissue and fat [1]. Dynamic contrast-enhanced MRI (DCE-MRI) for quantitatively assessing vascularization within bone marrow in patients with multiple myeloma was found to be of prognostic significance for these patients [12, 13] While these techniques have their own limitations, they are not hampered by what makes bone lesions unmeasurable by RECIST 1.1 (i.e. radio-occult appearance, sclerotic response and persistent bone deformity on healing). The purpose of this manuscript is to review the MRI and PET techniques available for measuring bone metastases, their opportunities and challenges, and their applicability in various tumor types. Treatment with Radium-223, a calcium-mimetic and alphaemitter that selectively binds to areas of increased bone turnover, results in significantly prolonged OS in patients who had castration-resistant prostate cancer and bone metastases [30]
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