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

• 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
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0123877

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.