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Woolf D.K.,Breast Cancer Research Unit | Padhani A.R.,Paul Strickland Scanner Center | Makris A.,Breast Cancer Research Unit
Annals of Oncology | Year: 2015

Bone is the most common site for breast cancer metastases, occurring in up to 70% of those with metastatic disease. In order to effectively manage these patients, it is essential to have consistent, reproducible and validated methods of assessing response to therapy. We present current clinical practice of imaging response assessment of bone metastases. We also review the biology of bone metastases and measures of response assessment including clinical assessment, tumour markers and imaging techniques; bone scans (BSs), computed tomography (CT), positron emission tomography, magnetic resonance imaging (MRI) and whole-body diffusion-weighted MRI (WB DW-MRI). The current standard of care of BSs and CT has significant limitations and are not routinely recommended for the purpose of response assessment in the bones. WB DW-MRI has the potential to address this unmet need and should be evaluated in clinical trials. © 2014 The Author.

There is an increasing awareness that anatomical approaches based on measurements of tumor size have significant limitations for assessing therapy response. Functional imaging techniques are increasing being used to monitor response to therapies with novel mechanisms of action, often predicting the success of therapy before conventional measurements have changed. Dynamic contrast-enhanced and diffusion magnetic resonance imaging (MRI) are the most advanced in their evidence base, and in this manuscript we focus on them as response parameters. Technology, data gathering methods, and current limitations for these techniques are addressed. With few exceptions, most studies shows that successful treatment is reflected by increases in tumor water diffusion values visible as increased apparent diffusion coefficient values. Most response assessment studies also show that successful treatment results in decreases in tumor vascularization and microvessel permeability.

Padhani A.R.,Paul Strickland Scanner Center | Koh D.-M.,Royal Marsden Hospital | Collins D.J.,Cancer Research UK Research Institute
Radiology | Year: 2011

Diffusion-weighted (DW) magnetic resonance (MR) imaging is emerging as a powerful clinical tool for directing the care of patients with cancer. Whole-body DW imaging is almost at the stage where it can enter widespread clinical investigations, because the technology is stable and protocols can be implemented for the majority of modern MR imaging systems. There is a continued need for further improvements in data acquisition and analysis and in display technologies. Priority areas for clinical research include clarification of histologic relationships between tissues of interest and DW MR imaging biomarkers at diagnosis and during therapy response. Because whole-body DW imaging excels at bone marrow assessments at diagnosis and for therapy response, it can potentially address a number of unmet clinical and pharmaceutical requirements. There are compelling needs to document and understand how common and novel treatments affect whole-body DW imaging results and to establish response criteria that can be tested in prospective clinical studies that incorporate measures of patient benefit. ©RSNA, 2001.

Zweifel M.,Mount Vernon Cancer Center | Padhani A.R.,Paul Strickland Scanner Center
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2010

Introduction: Classically, the first step in the clinical development of drugs in oncology involves assessments of dose limiting toxicity (DLT) and maximum tolerated dose (MTD). New paradigms are needed for antiangiogenic drugs and vascular disrupting agents (VDAs) as they are active at doses well below the MTD and as single agents their use might not translate into anti-tumour efficacy. MRI is able to assess the antivascular effects of antivascular drugs via changes in functional kinetic parameters; however, the usefulness of MRI in decision making has been questioned by many. Objectives: Our aim is to review the experience of using dynamic contrast-enhanced MRI (DCE-MRI) in early clinical development of vascular directed anticancer therapies over the last decade. Thirty-nine phase I and II studies including data on more than 700 patients have been published as abstracts and/or papers, documenting DCE-MRI changes after the administration of antiangiogenic drugs and VDAs. Discussion: Perfusion MRI is helpful in assessing whether mechanistic goals are achieved, in assisting dose selection for phase II studies, in selecting subpopulations enriched for response and in predicting patient benefit. Imaging tools are increasingly available. Future challenges for imaging include correlation with clinical measures of efficacy and determining relationships with blood and serum biomarkers. © 2010 Springer-Verlag.

Li S.P.,Academic Oncology Unit | Padhani A.R.,Paul Strickland Scanner Center
Journal of Magnetic Resonance Imaging | Year: 2012

There is an increasing awareness that the evaluation of tumor response to oncologic treatments based solely on anatomic imaging assessments face many limitations, particularly in this era of novel biologic targeted therapies. Functional imaging techniques such as diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) have the ability to depict important tumor biologic features and are able to predict therapy response based on assessments of cellularity and tumor vascularity, which often precede morphologic alterations. In this article we focus on DW-MRI and DCE-MRI as response parameters addressing the technologies involved, quantification methods, and validation for each technique and their current role in imaging response to conventional and novel therapies. We also discuss the challenges that lie ahead in the deployment of these imaging methods into the clinical environment. © 2011 Wiley Periodicals, Inc.

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