Integrated multimodal imaging of dynamic bone-tumor alterations associated with metastatic prostate cancer

Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellul...

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Published in:	PloS one Vol. 10; no. 4; p. e0123877
Main Authors:	Brisset, Jean-Christophe, Hoff, Benjamin A, Chenevert, Thomas L, Jacobson, Jon A, Boes, Jennifer L, Galbán, Stefanie, Rehemtulla, Alnawaz, Johnson, Timothy D, Pienta, Kenneth J, Galbán, Craig J, Meyer, Charles R, Schakel, Timothy, Nicolay, Klaas, Alva, Ajjai S, Hussain, Maha, Ross, Brian D
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 10-04-2015 Public Library of Science (PLoS)
Subjects:	Androgens Animal models Animals Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Biocompatibility Biomarkers Biomedical materials Bone cancer Bone Density Bone diseases Bone imaging Bone Neoplasms - diagnosis Bone Neoplasms - secondary Bone Neoplasms - therapy Bone turnover Brain cancer Cancer metastasis Cancer therapies Castration Computed tomography Development and progression Diagnosis Diagnostic imaging Diffusion Magnetic Resonance Imaging Diphosphonates - pharmacology Diphosphonates - therapeutic use Disease control Disease Models, Animal Docetaxel Feasibility studies Fractures Hematology Homeostasis Humans Insulin-like growth factors Magnetic resonance imaging Male Medical imaging Metastases Metastasis Mice Morbidity Multimodal Imaging - methods Oncology Osteoblasts - drug effects Osteoblasts - metabolism Osteolysis - diagnosis Osteoporosis Pain Patients Prostate cancer Prostatic Neoplasms - pathology Quality of life Taxoids - pharmacology Taxoids - therapeutic use Treatment Outcome Tumor Burden - drug effects Tumor Burden - radiation effects Tumors Netherlands Ann Arbor Michigan United States > US Michigan
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Summary:	Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM) of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (p<0.05). These studies suggest that PRM imaging biomarkers are useful for detection of the impact of prostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 Competing Interests: BDR, AR, TLC and CJG have a financial interest in the underlying technology which has been licensed to Imbio, LLC a company in which BDR and AR have a financial interest. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. Conceived and designed the experiments: BDR MH TLC JAJ AR TDJ KJP CJG. Performed the experiments: JCB BAH TLC JAJ SG TS ASA. Analyzed the data: JCB BAH TLC JLB TDJ KJP CJG CRM TS ASA MH BDR. Contributed reagents/materials/analysis tools: BAH TLC JAJ JLB SG AR TDJ KJP CJG CRM KN ASA MH BDR. Wrote the paper: JCB BAH TLC JAJ AR TDJ KJP CJG CRM TS KN ASA MH BDR. MH and BDR are co-senior authors on this work.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0123877