Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 1/2017

01-01-2017 | Original Article

Treatment response evaluation with 18F-FDG PET/CT and 18F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation

Authors: Christos Sachpekidis, J. Hillengass, H. Goldschmidt, B. Wagner, U. Haberkorn, K. Kopka, A. Dimitrakopoulou-Strauss

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2017

Login to get access

Abstract

Aim

The aim of this study was to assess the combined use of the radiotracers 18F-FDG and 18F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT).

Patients and methods

Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with 18F-FDG and 18F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD).

Results

An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, 18F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, 18F-FDG PET/CT-based treatment response revealed CR in 14 patients (18F-FDG PET/CT CR), PR in 11 patients (18F-FDG PET/CT PR) and progressive disease in four patients (18F-FDG PET/CT PD). In terms of 18F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, 18F-NaF PET/CT depicted 56 of the 129 18F-FDG positive lesions (43 %). Follow-up 18F-NaF PET/CT showed persistence of 81.5 % of the baseline 18F-NaF positive MM lesions after treatment, despite the fact that 64.7 % of them had turned to 18F-FDG negative. Treatment response according to 18F-NaF PET/CT revealed CR in one patient (18F-NaF PET/CT CR), PR in five patients (18F-NaF PET/CT PR), SD in 12 patients (18F-NaF PET/CT SD), and PD in seven patients (18F-NaF PET/CT PD). Dynamic 18F-FDG and 18F-NaF PET/CT studies showed that SUVaverage, SUVmax, as well as the kinetic parameters K1, influx and FD from reference bone marrow and skeleton responded to therapy with a significant decrease (p < 0.001).

Conclusion

F-FDG PET/CT demonstrated a sensitivity of 57.7 % and a specificity of 100 % in treatment response evaluation of MM. Despite its limited sensitivity, the performance of 18F-FDG PET/CT was satisfactory, given that 6/9 false negative patients in follow-up scans (66.7 %) were clinically characterized as nCR, a disease stage with very low tumor mass. On the other hand, 18F-NaF PET/CT does not seem to add significantly to 18F-FDG PET/CT in treatment response evaluation of MM patients undergoing HDT and ASCT, at least shortly after therapy.
Literature
1.
Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomised trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergrouppe Francais du Myelome. N Engl J Med. 1996;335:91–7.CrossRefPubMed
2.
Harousseau JL. Autologous transplantation for multiple myeloma. Ann Oncol. 2008;19 Suppl 7:vii128–33.PubMed
3.
Bladé J, Rosiñol L, Cibeira MT, Rovira M, Carreras E. Hematopoietic stem cell transplantation for multiple myeloma beyond 2010. Blood. 2010;115:3655–63.CrossRefPubMed
4.
5.
Engelhardt M, Terpos E, Kleber M, European Myeloma Network, et al. European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma. Haematologica. 2014;99:232–42.CrossRefPubMedPubMedCentral
6.
Cavo M, Tacchetti P, Patriarca F, GIMEMA Italian Myeloma Network, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010;376:2075–85.CrossRefPubMed
7.
Cavo M, Rajkumar SV, Palumbo A, International Myeloma Working Group, et al. International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. Blood. 2011;117:6063–73.CrossRefPubMedPubMedCentral
8.
Bladé J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998;102:1115–23.CrossRefPubMed
9.
Durie BG, Harousseau JL, Miguel JS, International Myeloma Working Group, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467–73.CrossRefPubMed
10.
Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538–48.CrossRefPubMed
11.
Zamagni E, Nanni C, Gay F, et al. 18F-FDG PET/CT focal, but not osteolytic, lesions predict the progression of smoldering myeloma to active disease. Leukemia. 2016;30:417–22.CrossRefPubMed
12.
Bartel TB, Haessler J, Brown TL, et al. F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma. Blood. 2009;114:2068–76.CrossRefPubMedPubMedCentral
13.
Zamagni E, Patriarca F, Nanni C, et al. Prognostic relevance of 18F-FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation. Blood. 2011;118:5989–95.CrossRefPubMed
14.
Derlin T, Weber C, Habermann CR, et al. 18F-FDG PET/CT for detection and localization of residual or recurrent disease in patients with multiple myeloma after stem cell transplantation. Eur J Nucl Med Mol Imaging. 2012;39:493–500.CrossRefPubMed
15.
Caers J, Withofs N, Hillengass J, et al. The role of positron emission tomography-computed tomography and magnetic resonance imaging in diagnosis and follow up of multiple myeloma. Haematologica. 2014;99:629–37.CrossRefPubMedPubMedCentral
16.
Zamagni E, Nanni C, Mancuso K, et al. PET/CT improves the definition of complete response and allows to detect otherwise unidentifiable skeletal progression in multiple myeloma. Clin Cancer Res. 2015;21:4384–90.CrossRefPubMed
17.
18.
Hawkins RA, Choi Y, Huang SC, et al. Evaluation of the skeletal kinetics of fluorine-18-fluoride ion with PET. J Nucl Med. 1992;33:633–42.PubMed
19.
Even-Sapir E, Mishani E, Flusser G, et al. 18F-Fluoride positron emission tomography and positron emission tomography/computed tomography. Semin Nucl Med. 2007;37:462–9.CrossRefPubMed
20.
Grant FD, Fahey FH, Packard AB, et al. Skeletal PET with 18 F-fluoride: applying new technology to an old tracer. J Nucl Med. 2008;49:68–78.CrossRefPubMed
21.
Hillner BE, Siegel BA, Hanna L, Duan F, Quinn B, Shields AF. 18F-fluoride PET used for treatment monitoring of systemic cancer therapy: results from the National Oncologic PET Registry. J Nucl Med. 2015;56:222–8.CrossRefPubMed
22.
Beheshti M, Mottaghy FM, Payche F, et al. (18)F-NaF PET/CT: EANM procedure guidelines for bone imaging. Eur J Nucl Med Mol Imaging. 2015;42:1767–77.CrossRefPubMed
23.
Lecouvet FE, Talbot JN, Messiou C, Bourguet P, Liu Y, de Souza NM, et al. Monitoring the response of bone metastases to treatment with Magnetic Resonance Imaging and nuclear medicine techniques: a review and position statement by the European Organisation for Research and Treatment of Cancer imaging group. Eur J Cancer. 2014;50:2519–31.CrossRefPubMed
24.
Tan E, Weiss BM, Mena E, Korde N, Choyke PL, Landgren O. Current and future imaging modalities for multiple myeloma and its precursor states. Leuk Lymphoma. 2011;52:1630–40.CrossRefPubMedPubMedCentral
25.
Kurdziel KA, Shih JH, Apolo AB, et al. The kinetics and reproducibility of 18F-sodium fluoride for oncology using current PET camera technology. J Nucl Med. 2012;53:1175–84.CrossRefPubMedPubMedCentral
26.
Nishiyama Y, Tateishi U, Shizukuishi K, et al. Role of 18F-fluoride PET/CT in the assessment of multiple myeloma: initial experience. Ann Nucl Med. 2013;27:78–83.CrossRefPubMed
27.
Xu F, Liu F, Pastakia B. Different lesions revealed by 18F-FDG PET/CT and 18F-NaF PET/CT in patients with multiple myeloma. Clin Nucl Med. 2014;39:e407–9.CrossRefPubMed
28.
Oral A, Yazici B, Ömür Ö, Comert M. Saydam G.18F-FDG and 18F-NaF PET/CT findings of a multiple myeloma patient with thyroid cartilage involvement. Clin Nucl Med. 2015;40:873–6.CrossRefPubMed
29.
Sachpekidis C, Goldschmidt H, Hose D, et al. PET/CT studies of multiple myeloma using (18) F-FDG and (18) F-NaF: comparison of distribution patterns and tracers’ pharmacokinetics. Eur J Nucl Med Mol Imaging. 2014;41:1343–53.CrossRefPubMed
30.
Ak I, Onner H, Akay OM. Is there any complimentary role of F-18 NaF PET/CT in detecting of osseous involvement of multiple myeloma? A comparative study of F-18 FDG PET/CT and F-18 FDG NaF PET/CT. Ann Hematol. 2015;94:1567–75.CrossRefPubMed
31.
Bhutani M, Turkbey B, Tan E, et al. Bone marrow abnormalities and early bone lesions in multiple myeloma and its precursor disease: a prospective study using functional and morphologic imaging. Leuk Lymphoma. 2015;21:1–23 (Epub ahead of print).
32.
International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003;121:749–57.CrossRef
33.
Sachpekidis C, Hillengass J, Goldschmidt H, et al. Comparison of (18)F-FDG PET/CT and PET/MRI in patients with multiple myeloma. Am J Nucl Med Mol Imaging. 2015;5:469–78.PubMedPubMedCentral
34.
Sokoloff L, Smith CB. Basic principles underlying radioisotopic methods for assay of biochemical processes in vivo. In: Greitz T, Ingvar DH, Widén L, editors. The metabolism of the human brain studied with positron emission tomography. New York: Raven; 1983. p. 123–48.
35.
Burger C, Buck A. Requirements and implementations of a flexible kinetic modeling tool. J Nucl Med. 1997;38:1818–23.PubMed
36.
Mikolajczyk K, Szabatin M, Rudnicki P, Grodzki M, Burger C. A Java environment for medical image data analysis: initial application for brain PET quantitation. Med Inf. 1998;23:207–14.
37.
Miyazawa H, Osmont A, Petit-Taboué MC, Tillet I, Travère JM, Young AR, et al. Determination of 18F-fluoro-2-deoxy-D-glucose rate constants in the anesthetized baboon brain with dynamic positron tomography. J Neurosci Methods. 1993;50:263–72.CrossRefPubMed
38.
Cheng C, Alt V, Dimitrakopoulou-Strauss A, Pan L, Thormann U, Schnettler R, et al. Evaluation of new bone formation in normal and osteoporotic rats with a 3-mm femur defect: functional assessment with dynamic PET-CT (dPET-CT) using a 2-deoxy-2 [(18)F] fluoro-D-glucose (18F-FDG) and 18F-fluoride. Mol Imaging Biol. 2013;15:336–44.CrossRefPubMed
39.
Sachpekidis C, Mai EK, Goldschmidt H, et al. (18)F-FDG dynamic PET/CT in patients with multiple myeloma: patterns of tracer uptake and correlation with bone marrow plasma cell infiltration rate. Clin Nucl Med. 2015;40:e300–7.CrossRefPubMed
40.
Ohtake T, Kosaka N, Watanabe T, Yokoyama I, Moritan T, Masuo M, et al. Noninvasive method to obtain input function for measuring tissue glucose utilization of thoracic and abdominal organs. J Nucl Med. 1991;32:1432–8.PubMed
41.
42.
Dimitrakopoulou-Strauss A, Strauss LG, Mikolajczyk K, et al. On the fractal nature of positron emission tomography (PET) studies. World J Nucl Med. 2003;4:306–13.
43.
Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, et al. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999;35:1773–82.CrossRefPubMed
44.
Nanni C, Zamagni E, Celli M, et al. The value of 18F-FDG PET/CT after autologous stem cell transplantation (ASCT) in patients affected by multiple myeloma (MM): experience with 77 patients. Clin Nucl Med. 2013;38:e74–9.CrossRefPubMed
45.
Zamagni E, Cavo M. The role of imaging techniques in the management of multiple myeloma. Br J Haematol. 2012;159:499–513.PubMed
46.
Derlin T, Peldschus K, Münster S, et al. Comparative diagnostic performance of 18F-FDG PET/CT versus whole-body MRI for determination of remission status in multiple myeloma after stem cell transplantation. Eur Radiol. 2013;23:570–8.CrossRefPubMed
47.
Vij R, Fowler KJ, Shokeen M. New approaches to molecular imaging of multiple myeloma. J Nucl Med. 2016;57:1–4.CrossRefPubMed
48.
Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50 Suppl 1:122S–50.CrossRefPubMedPubMedCentral
49.
Janicek MJ, Hayes DF, Kaplan WD. Healing flare in skeletal metastases from breast cancer. Radiology. 1994;192:201–4.CrossRefPubMed
50.
Vogel CL, Schoenfelder J, Shemano I, Hayes DF, Gams RA. Worsening bone scan in the evaluation of antitumor response during hormonal therapy of breast cancer. J Clin Oncol. 1995;13:1123–8.PubMed
51.
Galasko CS. Diagnosis of skeletal metastases and assessment of response to treatment. Clin Orthop Relat Res. 1995;312:64–75.
52.
Cook GJ, Fogelman I. The role of nuclear medicine in monitoring treatment in skeletal malignancy. Semin Nucl Med. 2001;31:206–11.CrossRefPubMed
53.
Vassiliou V, Andreopoulos D, Frangos S, Tselis N, Giannopoulou E, Lutz S. Bone metastases: assessment of therapeutic response through radiological and nuclear medicine imaging modalities. Clin Oncol (R Coll Radiol). 2011;23:632–45.CrossRef
54.
García JR, Simó M, Soler M, Pérez G, López S, Lomeña F. Relative roles of bone scintigraphy and positron emission tomography in assessing the treatment response of bone metastases. Eur J Nucl Med Mol Imaging. 2005;32:1243–4.CrossRefPubMed
55.
Dimitrakopoulou-Strauss A, Hoffmann M, Bergner R, Uppenkamp M, Haberkorn U, Strauss LG. Prediction of progression-free survival in patients with multiple myeloma following anthracycline-based chemotherapy based on dynamic FDG-PET. Clin Nucl Med. 2009;34:576–84.CrossRefPubMed
56.
Laroche M, Lemaire O, Bourin P, et al. Dual-energy X-ray absorptiometry and biochemical markers of bone turnover after autologous stem cell transplantation in myeloma. Eur J Haematol. 2012;88:388–95.CrossRefPubMed
57.
Gandhi MK, Lekamwasam S, Inman I, et al. Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long-term follow-up of a prospective study. Br J Haematol. 2003;121:462–8.CrossRefPubMed
58.
Terpos E, Politou M, Szydlo R, et al. Autologous stem cell transplantation normalizes abnormal bone remodeling and sRANKL/osteoprotegerin ratio in patients with multiple myeloma. Leukemia. 2004;18:1420–6.CrossRefPubMed
59.
Installé J, Nzeusseu A, Bol A, Depresseux G, Devogelaer JP, Lonneux M. (18)F-fluoride PET for monitoring therapeutic response in Paget’s disease of bone. J Nucl Med. 2005;46:1650–8.PubMed
60.
Dey P. Basic principles and applications of fractal geometry in pathology: a review. Anal Quant Cytol Histol. 2005;27:284–90.PubMed
Metadata
Title
Treatment response evaluation with 18F-FDG PET/CT and 18F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation
Authors
Christos Sachpekidis
J. Hillengass
H. Goldschmidt
B. Wagner
U. Haberkorn
K. Kopka
A. Dimitrakopoulou-Strauss
Publication date
01-01-2017
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2017
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-016-3502-6

Other articles of this Issue 1/2017

European Journal of Nuclear Medicine and Molecular Imaging 1/2017 Go to the issue

Erratum

Erratum to: Characterization of the radiolabeled metabolite of tau PET tracer 18F-THK5351

Original Article

The value of 18F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma

Original Article

Metabolic tumor volume predicts overall survival and local control in patients with stage III non-small cell lung cancer treated in ACRIN 6668/RTOG 0235

Short Communication

Diagnostic potential of PET/CT using a 68Ga-labelled prostate-specific membrane antigen ligand in whole-body staging of renal cell carcinoma: initial experience

Original Article

Prognostic impact of tumour burden assessed by metabolic tumour volume on FDG PET/CT in anal canal cancer

Original Article

Evaluation of bone-seeking novel radiotracer 68Ga-NO2AP-Bisphosphonate for the detection of skeletal metastases in carcinoma breast