Skip to main content
Top
Published in: Annals of Hematology 10/2017

01-10-2017 | Original Article

Dynamic contrast-enhanced magnetic resonance imaging parameters correlate with advanced revised-ISS and angiopoietin-1/angiopoietin-2 ratio in patients with multiple myeloma

Authors: Evangelos Terpos, Dimitris Matsaridis, Vassilis Koutoulidis, Flora Zagouri, Dimitrios Christoulas, Sophia Fontara, Evangelia Panourgias, Maria Gavriatopoulou, Efstathios Kastritis, Meletios A. Dimopoulos, Lia A. Moulopoulos

Published in: Annals of Hematology | Issue 10/2017

Login to get access

Abstract

The aim of the study was to assess the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with newly diagnosed multiple myeloma (MM) who were treated with novel anti-myeloma agents. We studied 60 previously untreated MM patients at diagnosis, 14 with smoldering MM (SMM) and 5 with MGUS. All patients underwent MRI of the thoracolumbar spine and pelvis before the administration of any kind of therapy, and DCE-MRI was performed. The MRI perfusion parameters evaluated were wash-in (WIN), washout (WOUT), time-to-peak (TTPK), time-to-maximum slope (TMSP), and the WIN/TMSP ratio. The following serum levels of angiogenic cytokines were measured on the day of MRI: VEGF, angiogenin (Ang), angiopoietin-1 (Angp-1), and −2 (Angp-2). Symptomatic MM patients had increased WIN compared to SMM (p < 0.05) and MGUS patients (p = 0.001). TTPK was decreased, and WIN/TMSP was increased in both symptomatic and SMM patients compared to MGUS patients (p < 0.05). Symptomatic MM patients had decreased TMSP compared to MGUS patients. The Angp-1/Angp-2 ratio was reduced in symptomatic MM compared to SMM (p = 0.017) and MGUS patients (p < 0.001). TTPK correlated with Angp-1/Angp-2 ratio and importantly with R-ISS. Patients with R-ISS-3 had lower TTPK median value (23 s, range 18–29 s) compared to patients with R-ISS-2 (48 s, range 27–68 s) and patients with R-ISS-1 MM (54 s, range 42–76 s; p ANOVA = 0.01). A subset of patients with low TTPK (lower quartile) had shorter time to progression compared to all other patients. These data suggest that certain DCE-MRI parameters correlate with R-ISS and adverse prognostic features of angiogenesis, such as the ratio of Angp-1/Angp-2.
Literature
1.
go back to reference Landgren O, Kyle RA, Rajkumar SV (2011) From myeloma precursor disease to multiple myeloma: new diagnostic concepts and opportunities for early intervention. Clin Cancer Res 17:1243–1252CrossRefPubMed Landgren O, Kyle RA, Rajkumar SV (2011) From myeloma precursor disease to multiple myeloma: new diagnostic concepts and opportunities for early intervention. Clin Cancer Res 17:1243–1252CrossRefPubMed
2.
go back to reference Dhodapkar MV, Sexton R, Waheed S, Usmani S, Papanikolaou X, Nair B et al (2014) Clinical, genomic, and imaging predictors of myeloma progression from asymptomatic monoclonal gammopathies (SWOG S0120). Blood 123:78–85CrossRefPubMedPubMedCentral Dhodapkar MV, Sexton R, Waheed S, Usmani S, Papanikolaou X, Nair B et al (2014) Clinical, genomic, and imaging predictors of myeloma progression from asymptomatic monoclonal gammopathies (SWOG S0120). Blood 123:78–85CrossRefPubMedPubMedCentral
3.
go back to reference Ludwig C, Williams DS, Bartlett DB, Essex SJ, McNee G, Allwood JW et al (2015) Alterations in bone marrow metabolism are an early and consistent feature during the development of MGUS and multiple myeloma. Blood Cancer J 5:e359CrossRefPubMedPubMedCentral Ludwig C, Williams DS, Bartlett DB, Essex SJ, McNee G, Allwood JW et al (2015) Alterations in bone marrow metabolism are an early and consistent feature during the development of MGUS and multiple myeloma. Blood Cancer J 5:e359CrossRefPubMedPubMedCentral
4.
go back to reference Botta C, Di Martino MT, Ciliberto D, Cucè M, Correale P, Rossi M et al (2016) A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival. Blood Cancer J 6:e511CrossRefPubMedPubMedCentral Botta C, Di Martino MT, Ciliberto D, Cucè M, Correale P, Rossi M et al (2016) A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival. Blood Cancer J 6:e511CrossRefPubMedPubMedCentral
5.
go back to reference Rajkumar SV, Leong T, Roche PC, Fonseca R, Dispenzieri A, Lacy MQ et al (2000) Prognostic value of bone marrow angiogenesis in multiple myeloma. Clin Cancer Res 6:3111–3116PubMed Rajkumar SV, Leong T, Roche PC, Fonseca R, Dispenzieri A, Lacy MQ et al (2000) Prognostic value of bone marrow angiogenesis in multiple myeloma. Clin Cancer Res 6:3111–3116PubMed
6.
go back to reference Hillengass J, Zechmann C, Bauerle T, Wagner-Gund B, Heiss C, Benner A et al (2009) Dynamic contrast-enhanced magnetic resonance imaging identifies a subgroup of patients with asymptomatic monoclonal plasma cell disease and pathologic microcirculation. Clin Cancer Res 15:3118–3125CrossRefPubMed Hillengass J, Zechmann C, Bauerle T, Wagner-Gund B, Heiss C, Benner A et al (2009) Dynamic contrast-enhanced magnetic resonance imaging identifies a subgroup of patients with asymptomatic monoclonal plasma cell disease and pathologic microcirculation. Clin Cancer Res 15:3118–3125CrossRefPubMed
7.
go back to reference Savvopoulou V, Maris TG, Koureas A, Gouliamos A, Moulopoulos LA (2011) Degenerative endplate changes of the lumbosacral spine: dynamic contrast-enhanced MRI profiles related to age, sex, and spinal level. J Magn Reson Imaging 33:382–389CrossRefPubMed Savvopoulou V, Maris TG, Koureas A, Gouliamos A, Moulopoulos LA (2011) Degenerative endplate changes of the lumbosacral spine: dynamic contrast-enhanced MRI profiles related to age, sex, and spinal level. J Magn Reson Imaging 33:382–389CrossRefPubMed
8.
go back to reference Lang N, Su MY, Yu HJ, Lin M, Hamamura MJ, Yuan H (2013) Differentiation of myeloma and metastatic cancer in the spine using dynamic contrast-enhanced MRI. Magn Reson Imaging 31:1285–1291CrossRefPubMedPubMedCentral Lang N, Su MY, Yu HJ, Lin M, Hamamura MJ, Yuan H (2013) Differentiation of myeloma and metastatic cancer in the spine using dynamic contrast-enhanced MRI. Magn Reson Imaging 31:1285–1291CrossRefPubMedPubMedCentral
9.
go back to reference Consolino L, Longo DL, Dastrù W, Cutrin JC, Dettori D, Lanzardo S et al (2016) Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging. Int J Cancer 139:404–413CrossRefPubMed Consolino L, Longo DL, Dastrù W, Cutrin JC, Dettori D, Lanzardo S et al (2016) Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging. Int J Cancer 139:404–413CrossRefPubMed
10.
go back to reference Nosàs-Garcia S, Moehler T, Wasser K, Kiessling F, Bartl R, Zuna I et al (2005) Dynamic contrast-enhanced MRI for assessing the disease activity of multiple myeloma: a comparative study with histology and clinical markers. J Magn Reson Imaging 22:154–162CrossRefPubMed Nosàs-Garcia S, Moehler T, Wasser K, Kiessling F, Bartl R, Zuna I et al (2005) Dynamic contrast-enhanced MRI for assessing the disease activity of multiple myeloma: a comparative study with histology and clinical markers. J Magn Reson Imaging 22:154–162CrossRefPubMed
11.
go back to reference Dutoit JC, Vanderkerken MA, Verstraete KL (2013) Value of whole body MRI and dynamic contrast enhanced MRI in the diagnosis, follow-up and evaluation of disease activity and extent in multiple myeloma. Eur J Radiol 82:1444–1452CrossRefPubMed Dutoit JC, Vanderkerken MA, Verstraete KL (2013) Value of whole body MRI and dynamic contrast enhanced MRI in the diagnosis, follow-up and evaluation of disease activity and extent in multiple myeloma. Eur J Radiol 82:1444–1452CrossRefPubMed
12.
go back to reference Merz M, Ritsch J, Kunz C, Wagner B, Sauer S, Hose D et al (2015) Dynamic contrast-enhanced magnetic resonance imaging for assessment of antiangiogenic treatment effects in multiple myeloma. Clin Cancer Res 21:106–112CrossRefPubMed Merz M, Ritsch J, Kunz C, Wagner B, Sauer S, Hose D et al (2015) Dynamic contrast-enhanced magnetic resonance imaging for assessment of antiangiogenic treatment effects in multiple myeloma. Clin Cancer Res 21:106–112CrossRefPubMed
13.
go back to reference Hillengass J, Wasser K, Delorme S, Kiessling F, Zechmann C, Benner A et al (2007) Lumbar bone marrow microcirculation measurements from dynamic contrast-enhanced magnetic resonance imaging is a predictor of event-free survival in progressive multiple myeloma. Clin Cancer Res 13:475–481CrossRefPubMed Hillengass J, Wasser K, Delorme S, Kiessling F, Zechmann C, Benner A et al (2007) Lumbar bone marrow microcirculation measurements from dynamic contrast-enhanced magnetic resonance imaging is a predictor of event-free survival in progressive multiple myeloma. Clin Cancer Res 13:475–481CrossRefPubMed
14.
go back to reference Merz M, Moehler TM, Ritsch J, Bäuerle T, Zechmann CM, Wagner B et al (2016) Prognostic significance of increased bone marrow microcirculation in newly diagnosed multiple myeloma: results of a prospective DCE-MRI study. Eur Radiol 26:1404–1411CrossRefPubMed Merz M, Moehler TM, Ritsch J, Bäuerle T, Zechmann CM, Wagner B et al (2016) Prognostic significance of increased bone marrow microcirculation in newly diagnosed multiple myeloma: results of a prospective DCE-MRI study. Eur Radiol 26:1404–1411CrossRefPubMed
15.
go back to reference Terpos E, Anargyrou K, Katodritou E, Kastritis E, Papatheodorou A, Christoulas D et al (2012) Circulating angiopoietin-1 to angiopoietin-2 ratio is an independent prognostic factor for survival in newly diagnosed patients with multiple myeloma who received therapy with novel antimyeloma agents. Int J Cancer 130:735–742CrossRefPubMed Terpos E, Anargyrou K, Katodritou E, Kastritis E, Papatheodorou A, Christoulas D et al (2012) Circulating angiopoietin-1 to angiopoietin-2 ratio is an independent prognostic factor for survival in newly diagnosed patients with multiple myeloma who received therapy with novel antimyeloma agents. Int J Cancer 130:735–742CrossRefPubMed
16.
go back to reference Moulopoulos LA, Maris TG, Papanikolaou N, Panagi G, Vlahos L, Dimopoulos MA (2003) Detection of malignant bone marrow involvement with dynamic contrast-enhanced magnetic resonance imaging. Ann Oncol 14:152–158CrossRefPubMed Moulopoulos LA, Maris TG, Papanikolaou N, Panagi G, Vlahos L, Dimopoulos MA (2003) Detection of malignant bone marrow involvement with dynamic contrast-enhanced magnetic resonance imaging. Ann Oncol 14:152–158CrossRefPubMed
17.
go back to reference Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV et al (2014) International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15:e538–e548CrossRefPubMed Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV et al (2014) International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15:e538–e548CrossRefPubMed
18.
go back to reference Hillengass J, Zechmann CM, Nadler A, Hose D, Cremer FW, Jauch A et al (2008) Gain of 1q21 and distinct adverse cytogenetic abnormalities correlate with increased microcirculation in multiple myeloma. Int J Cancer 122:2871–2875CrossRefPubMed Hillengass J, Zechmann CM, Nadler A, Hose D, Cremer FW, Jauch A et al (2008) Gain of 1q21 and distinct adverse cytogenetic abnormalities correlate with increased microcirculation in multiple myeloma. Int J Cancer 122:2871–2875CrossRefPubMed
19.
go back to reference Anargyrou K, Dimopoulos MA, Sezer O, Terpos E (2008) Novel anti-myeloma agents and angiogenesis. Leuk Lymphoma 49:677–689CrossRefPubMed Anargyrou K, Dimopoulos MA, Sezer O, Terpos E (2008) Novel anti-myeloma agents and angiogenesis. Leuk Lymphoma 49:677–689CrossRefPubMed
20.
go back to reference Anargyrou K, Terpos E, Vassilakopoulos TP, Pouli A, Sachanas S, Tzenou T et al (2008) Normalization of the serum angiopoietin-1 to angiopoietin-2 ratio reflects response in refractory/resistant multiple myeloma patients treated with bortezomib. Haematologica 93:451–454CrossRefPubMed Anargyrou K, Terpos E, Vassilakopoulos TP, Pouli A, Sachanas S, Tzenou T et al (2008) Normalization of the serum angiopoietin-1 to angiopoietin-2 ratio reflects response in refractory/resistant multiple myeloma patients treated with bortezomib. Haematologica 93:451–454CrossRefPubMed
21.
go back to reference Gkotzamanidou M, Christoulas D, Souliotis VL, Papatheodorou A, Dimopoulos MA, Terpos E (2013) Angiogenic cytokines profile in smoldering multiple myeloma: no difference compared to MGUS but altered compared to symptomatic myeloma. Med Sci Monit 19:1188–1194CrossRefPubMedPubMedCentral Gkotzamanidou M, Christoulas D, Souliotis VL, Papatheodorou A, Dimopoulos MA, Terpos E (2013) Angiogenic cytokines profile in smoldering multiple myeloma: no difference compared to MGUS but altered compared to symptomatic myeloma. Med Sci Monit 19:1188–1194CrossRefPubMedPubMedCentral
22.
go back to reference Huang SY, Chen BB, Lu HY, Lin HH, Wei SY, Hsu SC, Shih TT (2012) Correlation among DCE-MRI measurements of bone marrow angiogenesis, microvessel density, and extramedullary disease in patients with multiple myeloma. Am J Hematol 87:837–839CrossRefPubMed Huang SY, Chen BB, Lu HY, Lin HH, Wei SY, Hsu SC, Shih TT (2012) Correlation among DCE-MRI measurements of bone marrow angiogenesis, microvessel density, and extramedullary disease in patients with multiple myeloma. Am J Hematol 87:837–839CrossRefPubMed
23.
go back to reference Fam NP, Verma S, Kutryk M, Stewart DJ (2003) Clinician guide to angiogenesis. Circulation 108:2613–2618CrossRefPubMed Fam NP, Verma S, Kutryk M, Stewart DJ (2003) Clinician guide to angiogenesis. Circulation 108:2613–2618CrossRefPubMed
24.
go back to reference Hillengass J, Ritsch J, Merz M, Wagner B, Kunz C, Hielscher T et al (2016) Increased microcirculation detected by dynamic contrast-enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma. Br J Haematol 174:127–135CrossRefPubMed Hillengass J, Ritsch J, Merz M, Wagner B, Kunz C, Hielscher T et al (2016) Increased microcirculation detected by dynamic contrast-enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma. Br J Haematol 174:127–135CrossRefPubMed
Metadata
Title
Dynamic contrast-enhanced magnetic resonance imaging parameters correlate with advanced revised-ISS and angiopoietin-1/angiopoietin-2 ratio in patients with multiple myeloma
Authors
Evangelos Terpos
Dimitris Matsaridis
Vassilis Koutoulidis
Flora Zagouri
Dimitrios Christoulas
Sophia Fontara
Evangelia Panourgias
Maria Gavriatopoulou
Efstathios Kastritis
Meletios A. Dimopoulos
Lia A. Moulopoulos
Publication date
01-10-2017
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 10/2017
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-017-3078-7

Other articles of this Issue 10/2017

Annals of Hematology 10/2017 Go to the issue