The Experts below are selected from a list of 9270 Experts worldwide ranked by ideXlab platform
Evangelos Terpos - One of the best experts on this subject based on the ideXlab platform.
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Myeloma Bone Disease from biology findings to treatment approaches
Blood, 2019Co-Authors: Evangelos Terpos, Ioannis Ntanasisstathopoulos, Meletios A DimopoulosAbstract:Bone Disease is a cardinal complication of multiple Myeloma that affects quality of life and survival. Osteocytes have emerged as key players in the development of Myeloma-related Bone Disease. Along with other factors, they participate in increased osteoclast activity, decreased osteoblast function, and immunosuppressed marrow microenvironment, which deregulate Bone turnover and result in Bone loss and skeletal-related events. Denosumab is a novel alternative to bisphosphonates against Myeloma Bone Disease. Special considerations in this constantly evolving field are thoroughly discussed.
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biology and treatment of Myeloma related Bone Disease
Metabolism-clinical and Experimental, 2017Co-Authors: Evangelos Terpos, Dimitrios Christoulas, Maria GavriatopoulouAbstract:Myeloma Bone Disease (MBD) is the most common complication of multiple Myeloma (MM), resulting in skeleton-related events (SREs) such as severe Bone pain, pathologic fractures, vertebral collapse, hypercalcemia, and spinal cord compression that cause significant morbidity and mortality. It is due to an increased activity of osteoclasts coupled to the suppressed Bone formation by osteoblasts. Novel molecules and pathways that are implicated in osteoclast activation and osteoblast inhibition have recently been described, including the receptor activator of nuclear factor-kB ligand/osteoprotegerin pathway, activin-A and the wingless-type signaling inhibitors, dickkopf-1 (DKK-1) and sclerostin. These molecules interfere with tumor growth and survival, providing possible targets for the development of novel drugs for the management of lytic Disease in Myeloma but also for the treatment of MM itself. Currently, bisphosphonates are the mainstay of the treatment of Myeloma Bone Disease although several novel agents such as denosumab and sotatercept appear promising. This review focuses on recent advances in MBD pathophysiology and treatment, in addition to the established therapeutic guidelines.
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impact of denosumab dmb compared with zoledronic acid za on renal function in the treatment of Myeloma Bone Disease
Journal of Clinical Oncology, 2017Co-Authors: Noopur Raje, David G Roodman, Ramon Garciasanz, Wolfgang Willenbacher, Kazuyuki Shimizu, Brian G M Durie, Li Zhu, Paul Cheng, Sumita Bhatta, Evangelos TerposAbstract:8005Background: Osteolytic Bone Disease and renal dysfunction are complications of multiple Myeloma. ZA, used for the prevention and treatment of Bone complications, can be nephrotoxic. DMB inhibit...
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comparison of modern and conventional imaging techniques in establishing multiple Myeloma related Bone Disease a systematic review
British Journal of Haematology, 2013Co-Authors: Josien C Regelink, Evangelos Terpos, Monique C Minnema, Marjolein H Kamphuis, Pieter G Raijmakers, Indra Pietersvan Den C Bos, Ben G F Heggelman, Rutgerjan Nievelstein, Rene H J Otten, Danielle Van Lammeren VenemaAbstract:This systematic review of studies compared magnetic resonance imaging (MRI), (18) F-fluorodeoxyglucose positron emission tomography (FDG-PET), FDG-PET with computerized tomography (PET-CT) and CT with whole body X-Ray (WBXR) or (whole body) CT in order to provide evidence-based diagnostic guidelines in multiple Myeloma Bone Disease. A comprehensive search of 3 bibliographic databases was performed; methodological quality was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria (score 1-14). Data from 32 directly comparative studies were extracted. The mean QUADAS score was 7·1 (3-11), with quality hampered mainly by a poor description of selection and execution criteria. All index tests had a higher detection rate when compared to WBXR, with up to 80% more lesions detected by the newer imaging techniques; MRI (1·12-1·82) CT (1·04-1·33), PET (1·00-1·58) and PET-CT (1·27-1·45). However, the modern imaging techniques detected fewer lesions in the skull and ribs. In a direct comparison CT and MRI performed equally with respect to detection rate and sensitivity. This systematic review supports the International Myeloma Working Group guidelines, which recommend that WBCT can replace WBXR. In our opinion, the equal performance of MRI also indicates that it is a valuable alternative. As lesions of the skull and ribs are underdiagnosed by modern imaging techniques we advise additional X-rays of these regions. The consequences of this approach are discussed.
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advances in imaging and the management of Myeloma Bone Disease
Journal of Clinical Oncology, 2011Co-Authors: Evangelos Terpos, Lia A Moulopoulos, Meletios A DimopoulosAbstract:Osteolytic Disease is a major complication of multiple Myeloma that may lead to devastating skeletal-related events (SREs). Conventional radiography remains the gold standard for the evaluation of Bone Disease in patients with Myeloma. However, whole-body magnetic resonance imaging (MRI) is recommended in patients with normal conventional radiography and should be performed as part of staging in all patients with a solitary plasmacytoma of Bone. Urgent MRI is also the diagnostic procedure of choice to assess suspected cord compression, whereas computed tomography can guide tissue biopsy. Positron emission tomography with computed tomography can provide complementary information to MRI, but its use in multiple Myeloma must be better defined by further studies. The incorporation of abnormal MRI findings into the definition of symptomatic Myeloma also needs to be clarified. Bisphosphonates remain the cornerstone for the management of Myeloma Bone Disease. Intravenous pamidronate and zoledronic acid are equally effective in reducing SREs, whereas zoledronic acid seems to offer survival benefits in symptomatic patients. Caution is needed to avoid adverse events, such as renal impairment and osteonecrosis of the jaw. Novel antiresorptive agents, such as denosumab, have given encouraging results, but further studies are needed before their approval for managing Myeloma Bone Disease. Combination approaches with novel antiMyeloma agents, such as bortezomib (which has anabolic effects on Bone) with bisphosphonates or with drugs that enhance osteoblast function, such as antidickkopf-1 agents, antisclerostin drugs, or sotatercept, may favorably alter our way of managing Myeloma Bone Disease in the near future.
Peter I Croucher - One of the best experts on this subject based on the ideXlab platform.
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the use of bisphosphonates in multiple Myeloma recommendations of an expert panel on behalf of the european Myeloma network
Annals of Oncology, 2009Co-Authors: Orhan Sezer, Evangelos Terpos, Peter I Croucher, Ramon Garciasanz, Mario Boccadoro, J San F Miguel, J Ashcroft, J Blade, Michele CavoAbstract:Background: Bisphosphonates (BPs) prevent, reduce, and delay multiple Myeloma (MM)-related skeletal complications. Intravenous pamidronate and zoledronic acid, and oral clodronate are used for the management of MM Bone Disease. The purpose of this paper is to review the current evidence for the use of BPs in MM and provide European Union-specific recommendations to support the clinical practice of treating Myeloma Bone Disease. Design and methods: An interdisciplinary, expert panel of specialists on MM and Myeloma-related Bone Disease convened for a face-to-face meeting to review and assess the evidence and develop the recommendations. The panel reviewed and graded the evidence available from randomized clinical trials, clinical practice guidelines, and the body of published literature. Where published data were weak or unavailable, the panel used their own clinical experience to put forward recommendations based solely on their expert opinions. Results: The panel recommends the use of BPs in MM patients suffering from lytic Bone Disease or severe osteoporosis. Intravenous administration may be preferable; however, oral administration can be considered for patients unable to make hospital visits. Dosing should follow approved indications with adjustments if necessary. In general, BPs are well tolerated, but preventive steps should be taken to avoid renal impairment and osteonecrosis of the jaw (ONJ). The panel agrees that BPs should be given for 2 years, but this may be extended if there is evidence of active Myeloma Bone Disease. Initial therapy of ONJ should include discontinuation of BPs until healing occurs. BPs should be restarted if there is Disease progression. Conclusions: BPs are an essential component of MM therapy for minimizing skeletal morbidity. Recent retrospective data indicate that a modified dosing regimen and preventive measures can greatly reduce the incidence of ONJ.
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an osteoprotegerin like peptidomimetic inhibits osteoclastic Bone resorption and osteolytic Bone Disease in Myeloma
Cancer Research, 2007Co-Authors: Deborah J Heath, Karin Vanderkerken, Xin Cheng, Orla Gallagher, Matthew Prideaux, Ramachandran Murali, Peter I CroucherAbstract:Multiple Myeloma is a B-cell malignancy characterized by the uncontrolled growth of plasma cells in the Bone marrow and the development of osteolytic Bone Disease. Myeloma cells express the receptor activator of nuclear factor kappaB ligand (RANKL), induce RANKL expression in the Bone marrow, and down-regulate expression of the decoy receptor osteoprotegerin, thereby promoting Bone resorption. Targeting this system in Myeloma has clear therapeutic potential. However, osteoprotegerin also binds tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and prevents TRAIL-induced apoptosis of Myeloma cells. Whether or not osteoprotegerin can bind TRAIL and prevent apoptosis in vivo and the relative importance of osteoprotegerin binding to TRAIL and RANKL are unclear. In the present study, we have investigated the ability of an osteoprotegerin-like peptidomimetic (OP3-4), designed to block the RANKL/RANK interaction, to inhibit osteoclastic Bone resorption and TRAIL-induced apoptosis in vitro and Myeloma Bone Disease in vivo. OP3-4 inhibited osteoclast formation (P < 0.01) and Bone resorption (P < 0.01) in vitro. However, OP3-4 had no effect on TRAIL-induced apoptosis of RPMI 8226 Myeloma cells. Treatment of 5T2MM Myeloma-bearing mice with OP3-4 decreased osteoclast number and the proportion of Bone surface covered by osteoclasts (P < 0.05). Treatment also prevented the tumor-induced decrease in cancellous Bone area and the development of osteolytic lesions (P < 0.05). OP3-4 also reduced tumor burden when compared with the control (P < 0.05). These data suggest that OP3-4 and the selective inhibition of RANKL, but not TRAIL activity, are effective in preventing Myeloma Bone Disease and offer a novel therapeutic approach to treating this aspect of Myeloma. [Cancer Res 2007;67(1):202-8].
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serum concentrations of dickkopf 1 protein are increased in patients with multiple Myeloma and reduced after autologous stem cell transplantation
International Journal of Cancer, 2006Co-Authors: Marianna Politou, Meletios A Dimopoulos, Deborah J Heath, Amin Rahemtulla, Richard Szydlo, Athanasios Anagnostopoulos, Peter I Croucher, Evangelos TerposAbstract:Dickkopf-1 (DKK-1) protein, a soluble inhibitor of Wnt signalling, has been implicated in the pathogenesis of Myeloma Bone Disease through the suppression of osteoblast differentiation. In this study, serum concentrations of DKK-1 were measured in 50 Myeloma patients (32 at diagnosis and 18 before and after autologous stem cell transplantation (ASCT), 18 patients with monoclonal gammopathy of undetermined significance (MGUS), and 22 healthy controls. Serum DKK-1 levels were increased in MM at diagnosis compared with MGUS (mean ± SD: 67 ± 54 ng/mL vs. 38 ± 13 ng/mL; p = 0.006) and controls (31 ± 11 ng/mL; p = 0.02), while there was no difference between MGUS patients and controls. Although patients with stage 2 and 3 Myeloma had higher DKK-1 values than stage 1 patients (79 ± 63 vs. 40 ± 13; p = 0.005), no significant correlation between serum DKK-1 and Myeloma Bone Disease was observed. Myeloma patients before ASCT also had increased levels of DKK-1 (63 ± 77 ng/mL; p = 0.03) compared with controls, supporting the notion that DKK-1 may be responsible for the suppressed osteoblast activity even in patients with low tumor burden. After ASCT, there was a sustained decrease in DKK-1 levels over time, while Bone formation markers elevated, suggesting that the reduction of DKK-1 levels after ASCT may correlate with the normalization of osteoblast function. These results could provide the basis for developing agents that block DKK-1, thus restoring osteoblast function and counteracting the increased osteoclastogenesis observed in Myeloma. © 2006 Wiley-Liss, Inc.
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zoledronic acid treatment of 5t2mm bearing mice inhibits the development of Myeloma Bone Disease evidence for decreased osteolysis tumor burden and angiogenesis and increased survival
Journal of Bone and Mineral Research, 2003Co-Authors: Peter I Croucher, C M Shipman, Hendrik De Raeve, Mark Perry, Anja Hijzen, Jennifer Lippitt, Jonathan Green, Eric Van Marck, Ben Van Camp, Karin VanderkerkenAbstract:Multiple Myeloma is characterized by the growth of plasma cells in the Bone marrow and the development of osteolytic Bone Disease. Myeloma cells are found closely associated with Bone, and targeting this environment may therefore affect both the Bone Disease and the growth of Myeloma cells. We have investigated the effect of the potent bisphosphonate, zoledronic acid, on the development of Bone Disease, tumor burden, and Disease-free survival in the 5T2MM model of Myeloma. 5T2MM murine Myeloma cells were injected intravenously into C57BL/KaLwRij mice. After 8 weeks, all animals had a paraprotein. Animals were treated with zoledronic acid (120 μg/kg, subcutaneously, twice weekly) or vehicle, from the time of tumor cell injection or from paraprotein detection for 12 or 4 weeks, respectively. All animals injected with tumor cells developed osteolytic lesions, a decrease in cancellous Bone volume, an increase in osteoclast perimeter, and a decrease in Bone mineral density. Zoledronic acid prevented the formation of lesions, prevented cancellous Bone loss and loss of Bone mineral density, and reduced osteoclast perimeter. Zoledronic acid also decreased paraprotein concentration, decreased tumor burden, and reduced angiogenesis. In separate experiments, Kaplan-Meier analysis demonstrated a significant increase in survival after treatment with zoledronic acid when compared with control (47 vs. 35 days). A single dose of zoledronic acid was also shown to be effective in preventing the development of osteolytic Bone Disease. These data show that zoledronic acid is able to prevent the development of osteolytic Bone Disease, decrease tumor burden in Bone, and increase survival in a model of established Myeloma.
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recombinant osteoprotegerin decreases tumor burden and increases survival in a murine model of multiple Myeloma
Cancer Research, 2003Co-Authors: Karin Vanderkerken, Evy De Leenheer, C M Shipman, Kewal Asosingh, Angelo Willems, Ben Van Camp, Peter I CroucherAbstract:The aim of the present study was to determine whether modifying the local Bone environment with osteoprotegerin (OPG), the soluble decoy receptor for receptor activator of nuclear factor-κB (RANK) ligand, could affect tumor burden and survival in the 5T33MM murine model of multiple Myeloma. Treatment of mice, injected with 5T33MM cells, with recombinant OPG (Fc-OPG) caused a significant decrease in serum paraprotein and tumor burden and a significant increase in time to morbidity. This was associated with a decrease in osteoclast number in vivo but had no effect on apoptosis and proliferation of 5T33MM cells in vitro. These data indicate that targeting the Bone microenvironment by inhibiting the interaction between RANK ligand and RANK with Fc-OPG not only inhibits the development of Myeloma Bone Disease but also decreases tumor growth and increases survival.
Karin Vanderkerken - One of the best experts on this subject based on the ideXlab platform.
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an osteoprotegerin like peptidomimetic inhibits osteoclastic Bone resorption and osteolytic Bone Disease in Myeloma
Cancer Research, 2007Co-Authors: Deborah J Heath, Karin Vanderkerken, Xin Cheng, Orla Gallagher, Matthew Prideaux, Ramachandran Murali, Peter I CroucherAbstract:Multiple Myeloma is a B-cell malignancy characterized by the uncontrolled growth of plasma cells in the Bone marrow and the development of osteolytic Bone Disease. Myeloma cells express the receptor activator of nuclear factor kappaB ligand (RANKL), induce RANKL expression in the Bone marrow, and down-regulate expression of the decoy receptor osteoprotegerin, thereby promoting Bone resorption. Targeting this system in Myeloma has clear therapeutic potential. However, osteoprotegerin also binds tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and prevents TRAIL-induced apoptosis of Myeloma cells. Whether or not osteoprotegerin can bind TRAIL and prevent apoptosis in vivo and the relative importance of osteoprotegerin binding to TRAIL and RANKL are unclear. In the present study, we have investigated the ability of an osteoprotegerin-like peptidomimetic (OP3-4), designed to block the RANKL/RANK interaction, to inhibit osteoclastic Bone resorption and TRAIL-induced apoptosis in vitro and Myeloma Bone Disease in vivo. OP3-4 inhibited osteoclast formation (P < 0.01) and Bone resorption (P < 0.01) in vitro. However, OP3-4 had no effect on TRAIL-induced apoptosis of RPMI 8226 Myeloma cells. Treatment of 5T2MM Myeloma-bearing mice with OP3-4 decreased osteoclast number and the proportion of Bone surface covered by osteoclasts (P < 0.05). Treatment also prevented the tumor-induced decrease in cancellous Bone area and the development of osteolytic lesions (P < 0.05). OP3-4 also reduced tumor burden when compared with the control (P < 0.05). These data suggest that OP3-4 and the selective inhibition of RANKL, but not TRAIL activity, are effective in preventing Myeloma Bone Disease and offer a novel therapeutic approach to treating this aspect of Myeloma. [Cancer Res 2007;67(1):202-8].
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zoledronic acid treatment of 5t2mm bearing mice inhibits the development of Myeloma Bone Disease evidence for decreased osteolysis tumor burden and angiogenesis and increased survival
Journal of Bone and Mineral Research, 2003Co-Authors: Peter I Croucher, C M Shipman, Hendrik De Raeve, Mark Perry, Anja Hijzen, Jennifer Lippitt, Jonathan Green, Eric Van Marck, Ben Van Camp, Karin VanderkerkenAbstract:Multiple Myeloma is characterized by the growth of plasma cells in the Bone marrow and the development of osteolytic Bone Disease. Myeloma cells are found closely associated with Bone, and targeting this environment may therefore affect both the Bone Disease and the growth of Myeloma cells. We have investigated the effect of the potent bisphosphonate, zoledronic acid, on the development of Bone Disease, tumor burden, and Disease-free survival in the 5T2MM model of Myeloma. 5T2MM murine Myeloma cells were injected intravenously into C57BL/KaLwRij mice. After 8 weeks, all animals had a paraprotein. Animals were treated with zoledronic acid (120 μg/kg, subcutaneously, twice weekly) or vehicle, from the time of tumor cell injection or from paraprotein detection for 12 or 4 weeks, respectively. All animals injected with tumor cells developed osteolytic lesions, a decrease in cancellous Bone volume, an increase in osteoclast perimeter, and a decrease in Bone mineral density. Zoledronic acid prevented the formation of lesions, prevented cancellous Bone loss and loss of Bone mineral density, and reduced osteoclast perimeter. Zoledronic acid also decreased paraprotein concentration, decreased tumor burden, and reduced angiogenesis. In separate experiments, Kaplan-Meier analysis demonstrated a significant increase in survival after treatment with zoledronic acid when compared with control (47 vs. 35 days). A single dose of zoledronic acid was also shown to be effective in preventing the development of osteolytic Bone Disease. These data show that zoledronic acid is able to prevent the development of osteolytic Bone Disease, decrease tumor burden in Bone, and increase survival in a model of established Myeloma.
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recombinant osteoprotegerin decreases tumor burden and increases survival in a murine model of multiple Myeloma
Cancer Research, 2003Co-Authors: Karin Vanderkerken, Evy De Leenheer, C M Shipman, Kewal Asosingh, Angelo Willems, Ben Van Camp, Peter I CroucherAbstract:The aim of the present study was to determine whether modifying the local Bone environment with osteoprotegerin (OPG), the soluble decoy receptor for receptor activator of nuclear factor-κB (RANK) ligand, could affect tumor burden and survival in the 5T33MM murine model of multiple Myeloma. Treatment of mice, injected with 5T33MM cells, with recombinant OPG (Fc-OPG) caused a significant decrease in serum paraprotein and tumor burden and a significant increase in time to morbidity. This was associated with a decrease in osteoclast number in vivo but had no effect on apoptosis and proliferation of 5T33MM cells in vitro. These data indicate that targeting the Bone microenvironment by inhibiting the interaction between RANK ligand and RANK with Fc-OPG not only inhibits the development of Myeloma Bone Disease but also decreases tumor growth and increases survival.
Suzanne Lentzsch - One of the best experts on this subject based on the ideXlab platform.
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whole body low dose computed tomography and advanced imaging techniques for multiple Myeloma Bone Disease
Clinical Cancer Research, 2014Co-Authors: M J Pianko, E Terpos, G D Roodman, Chaitanya Divgi, Sonja Zweegman, Jens Hillengass, Suzanne LentzschAbstract:Detection of lytic Bone lesions is a crucial in the work up for multiple Myeloma and very often dictates the decision to start treatment. Conventional radiography, despite decades of use, is often insufficient for detection of Bone Disease in multiple Myeloma. Modern imaging techniques such as magnetic resonance imaging (MRI), positron-emission tomography, and computed tomography offer superior detection of Myeloma Bone Disease and extramedullary manifestations of plasma cell dyscrasias. Novel whole-body low-dose computed tomography (WBLDCT) protocols allow for collection of superior image detail of the skeleton at doses of radiation similar to that of conventional planar radiography. Several studies have shown that WBLDCT has a superior detection rate for lytic Bone lesions compared to whole body X-ray (WBXR), potentially leading to restaging and changes in therapy. MRI and PET provide imaging data important for assessing Disease activity and prognostication. Due to several advantages over WBXR, WBLDCT is already the standard imaging technique for use in multiple Myeloma patients in many European institutions. However, the radiographic skeletal survey or WBXR is still initial study of choice used to screen for Myeloma Bone Disease in many institutions. In this review, we aim to explore the changing landscape of imaging for Myeloma Bone Disease through use of modern imaging techniques.
Nandita M Desouza - One of the best experts on this subject based on the ideXlab platform.
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assessing Myeloma Bone Disease with whole body diffusion weighted imaging comparison with x ray skeletal survey by region and relationship with laboratory estimates of Disease burden
Clinical Radiology, 2015Co-Authors: Sharon L Giles, Nandita M Desouza, David J Collins, Veronica A Morgan, S West, Faith E Davies, Gareth J Morgan, Christina MessiouAbstract:Aim To estimate and compare the extent of Myeloma Bone Disease by skeletal region using whole-body diffusion-weighted imaging (WB-DWI) and skeletal survey (SS) and record interobserver agreement, and to investigate differences in imaging assessments of Disease extent and apparent diffusion coefficient (ADC) between patients with pathological high versus low Disease burden. Materials and methods Twenty patients with relapsed Myeloma underwent WB-DWI and SS. Lesions were scored by number and size for each skeletal region by two independent observers using WB-DWI and SS. Observer scores, ADC, and ADC-defined volume of tumour-infiltrated marrow were compared between patients with high and low Disease burden (assessed by serum paraproteins and marrow biopsy). Results Observer scores were higher on WB-DWI than SS in every region ( p p = 0.06, p = 0.35). Conclusion WB-DWI demonstrated more lesions than SS in all regions except the skull with greater interobserver agreement. Sensitivity is not a limiting factor when considering WB-DWI in the management pathway of patients with Myeloma.
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whole body diffusion weighted mr imaging for assessment of treatment response in Myeloma
Radiology, 2014Co-Authors: Sharon L Giles, David J Collins, Veronica A Morgan, Faith E Davies, Gareth J Morgan, Christina Messiou, Catherine J Simpkin, Sharon West, Nandita M DesouzaAbstract:Our study demonstrates that whole-body diffusion-weighted imaging is a repeatable, quantifiable technique that can differentiate responders from nonresponders in Myeloma Bone Disease with high sensitivity and specificity.
