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Published in: European Journal of Nuclear Medicine and Molecular Imaging 2/2015

01-02-2015 | Original Article

Favourable outcomes of 177Lu-octreotate peptide receptor chemoradionuclide therapy in patients with FDG-avid neuroendocrine tumours

Authors: Raghava Kashyap, Michael S. Hofman, Michael Michael, Grace Kong, Timothy Akhurst, Peter Eu, Diana Zannino, Rodney J. Hicks

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2015

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Abstract

Purpose

Increased glycolytic activity on FDG PET/CT defines a subgroup of patients with metastatic gastroenteropancreatic neuroendocrine tumour (NET) with a poor prognosis. A limited range of systemic treatment options exist for more aggressive NET. The role of peptide receptor chemoradionuclide therapy (PRCRT) in such patients is, however, unclear. This retrospective study assessed the outcomes of patients with FDG-avid NET treated with PRCRT.

Methods

Clinical, biochemical and imaging response was assessed after completion of induction treatment of PRCRT with 5-fluorouracil in 52 patients selected for treatment on the basis of somatostatin-receptor imaging without spatially discordant FDG-avid disease. Of the cohort, 67 % had received prior chemotherapy. Overall survival (OS) and progression-free survival (PFS) were also analysed.

Results

PRCRT was well tolerated with negligible grade 3/4 toxicities. After a median follow-up period of 36 months, the median OS was not achieved with a median PFS of 48 months. At 3 months after completion of PRCRT 2 % of patients showed a complete anatomical response, 28 % a partial response, 68 % stable disease, and only 2 % progression. On FDG PET/CT, 27 % achieved a complete metabolic response during the follow-up period. A biochemical response (>25 % fall in chromogranin-A levels) was seen in 45 %.

Conclusion

PRCRT is an effective treatment in patients with FDG-avid NET, even in patients who have failed conventional therapies. Given apparently higher response rates than with alternative therapeutic options and low toxicity, further research is needed to establish whether PRCRT should be used as a first-line treatment modality in this patient population.
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Literature
2.
go back to reference Sorbye H, Welin S, Langer SW, Vestermark LW, Holt N, Osterlund P, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol. 2013;24:152–60. doi:10.1093/annonc/mds276.PubMedCrossRef Sorbye H, Welin S, Langer SW, Vestermark LW, Holt N, Osterlund P, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol. 2013;24:152–60. doi:10.​1093/​annonc/​mds276.PubMedCrossRef
4.
go back to reference Pavel M, Baudin E, Couvelard A, Krenning E, Oberg K, Steinmuller T, et al. ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2012;95:157–76. doi:10.1159/000335597.PubMedCrossRef Pavel M, Baudin E, Couvelard A, Krenning E, Oberg K, Steinmuller T, et al. ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2012;95:157–76. doi:10.​1159/​000335597.PubMedCrossRef
5.
go back to reference Hofman MS, Hicks RJ. Changing paradigms with molecular imaging of neuroendocrine tumors. Discov Med. 2012;14:71–81.PubMed Hofman MS, Hicks RJ. Changing paradigms with molecular imaging of neuroendocrine tumors. Discov Med. 2012;14:71–81.PubMed
6.
go back to reference Adams S, Baum R, Rink T, Schumm-Drager PM, Usadel KH, Hor G. Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. Eur J Nucl Med. 1998;25:79–83.PubMedCrossRef Adams S, Baum R, Rink T, Schumm-Drager PM, Usadel KH, Hor G. Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. Eur J Nucl Med. 1998;25:79–83.PubMedCrossRef
7.
go back to reference Kayani I, Bomanji JB, Groves A, Conway G, Gacinovic S, Win T, et al. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1, Tyr3-octreotate) and 18F-FDG. Cancer. 2008;112:2447–55. doi:10.1002/cncr.23469.PubMedCrossRef Kayani I, Bomanji JB, Groves A, Conway G, Gacinovic S, Win T, et al. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1, Tyr3-octreotate) and 18F-FDG. Cancer. 2008;112:2447–55. doi:10.​1002/​cncr.​23469.PubMedCrossRef
8.
go back to reference Pasquali C, Rubello D, Sperti C, Gasparoni P, Liessi G, Chierichetti F, et al. Neuroendocrine tumor imaging: can 18F-fluorodeoxyglucose positron emission tomography detect tumors with poor prognosis and aggressive behavior? World J Surg. 1998;22:588–92.PubMedCrossRef Pasquali C, Rubello D, Sperti C, Gasparoni P, Liessi G, Chierichetti F, et al. Neuroendocrine tumor imaging: can 18F-fluorodeoxyglucose positron emission tomography detect tumors with poor prognosis and aggressive behavior? World J Surg. 1998;22:588–92.PubMedCrossRef
9.
11.
go back to reference Claringbold PG, Brayshaw PA, Price RA, Turner JH. Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2011;38:302–11. doi:10.1007/s00259-010-1631-x.PubMedCrossRef Claringbold PG, Brayshaw PA, Price RA, Turner JH. Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2011;38:302–11. doi:10.​1007/​s00259-010-1631-x.PubMedCrossRef
12.
go back to reference Hubble D, Kong G, Michael M, Johnson V, Ramdave S, Hicks RJ. 177Lu-octreotate, alone or with radiosensitising chemotherapy, is safe in neuroendocrine tumour patients previously treated with high-activity 111In-octreotide. Eur J Nucl Med Mol Imaging. 2010;37:1869–75. doi:10.1007/s00259-010-1483-4.PubMedCrossRef Hubble D, Kong G, Michael M, Johnson V, Ramdave S, Hicks RJ. 177Lu-octreotate, alone or with radiosensitising chemotherapy, is safe in neuroendocrine tumour patients previously treated with high-activity 111In-octreotide. Eur J Nucl Med Mol Imaging. 2010;37:1869–75. doi:10.​1007/​s00259-010-1483-4.PubMedCrossRef
13.
go back to reference Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26:2124–30. doi:10.1200/JCO.2007.15.2553.PubMedCrossRef Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26:2124–30. doi:10.​1200/​JCO.​2007.​15.​2553.PubMedCrossRef
14.
16.
go back to reference Kong G, Thompson M, Collins M, Herschtal A, Hofman MS, Johnston V. Assessment of predictors of response and long-term survival of patients with neuroendocrine tumour treated with peptide receptor chemoradionuclide therapy (PRCRT). Eur J Nucl Med Mol Imaging. 2014. doi:10.1007/s00259-014-2788-5.PubMedCentral Kong G, Thompson M, Collins M, Herschtal A, Hofman MS, Johnston V. Assessment of predictors of response and long-term survival of patients with neuroendocrine tumour treated with peptide receptor chemoradionuclide therapy (PRCRT). Eur J Nucl Med Mol Imaging. 2014. doi:10.​1007/​s00259-014-2788-5.PubMedCentral
17.
go back to reference Krenning EP, Valkema R, Kooij PP, Breeman WA, Bakker WH, de Herder WW. Scintigraphy and radionuclide therapy with [indium-111-labelled-diethyl triamine penta-acetic acid-D-Phe1]-octreotide. Ital J Gastroenterol Hepatol. 1999;31 Suppl 2:S219–223.PubMed Krenning EP, Valkema R, Kooij PP, Breeman WA, Bakker WH, de Herder WW. Scintigraphy and radionuclide therapy with [indium-111-labelled-diethyl triamine penta-acetic acid-D-Phe1]-octreotide. Ital J Gastroenterol Hepatol. 1999;31 Suppl 2:S219–223.PubMed
18.
go back to reference Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.PubMedCrossRef Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.PubMedCrossRef
19.
go back to reference Krenning EP, Kooij PP, Pauwels S, Breeman WA, Postema PT, De Herder WW, et al. Somatostatin receptor: scintigraphy and radionuclide therapy. Digestion. 1996;57 Suppl 1:57–61.PubMedCrossRef Krenning EP, Kooij PP, Pauwels S, Breeman WA, Postema PT, De Herder WW, et al. Somatostatin receptor: scintigraphy and radionuclide therapy. Digestion. 1996;57 Suppl 1:57–61.PubMedCrossRef
20.
go back to reference Kong G, Johnston V, Ramdave S, Lau E, Rischin D, Hicks RJ. High-administered activity In-111 octreotide therapy with concomitant radiosensitizing 5FU chemotherapy for treatment of neuroendocrine tumors: preliminary experience. Cancer Biother Radiopharm. 2009;24:527–33. doi:10.1089/cbr.2009.0644.PubMedCrossRef Kong G, Johnston V, Ramdave S, Lau E, Rischin D, Hicks RJ. High-administered activity In-111 octreotide therapy with concomitant radiosensitizing 5FU chemotherapy for treatment of neuroendocrine tumors: preliminary experience. Cancer Biother Radiopharm. 2009;24:527–33. doi:10.​1089/​cbr.​2009.​0644.PubMedCrossRef
21.
go back to reference Claringbold PG, Price RA, Turner JH. Phase I-II study of radiopeptide 177Lu-octreotate in combination with capecitabine and temozolomide in advanced low-grade neuroendocrine tumors. Cancer Biother Radiopharm. 2012;27:561–9. doi:10.1089/cbr.2012.1276.PubMedCrossRef Claringbold PG, Price RA, Turner JH. Phase I-II study of radiopeptide 177Lu-octreotate in combination with capecitabine and temozolomide in advanced low-grade neuroendocrine tumors. Cancer Biother Radiopharm. 2012;27:561–9. doi:10.​1089/​cbr.​2012.​1276.PubMedCrossRef
22.
go back to reference Cwikla JB, Sankowski A, Seklecka N, Buscombe JR, Nasierowska-Guttmejer A, Jeziorski KG, et al. Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study. Ann Oncol. 2010;21:787–94. doi:10.1093/annonc/mdp372.PubMedCrossRef Cwikla JB, Sankowski A, Seklecka N, Buscombe JR, Nasierowska-Guttmejer A, Jeziorski KG, et al. Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study. Ann Oncol. 2010;21:787–94. doi:10.​1093/​annonc/​mdp372.PubMedCrossRef
23.
go back to reference Horsch D, Ezziddin S, Haug A, Gratz KF, Dunkelmann S, Krause BJ, et al. Peptide receptor radionuclide therapy for neuroendocrine tumors in Germany: first results of a multi-institutional cancer registry. Recent Results Cancer Res. 2013;194:457–65. doi:10.1007/978-3-642-27994-2_25.PubMedCrossRef Horsch D, Ezziddin S, Haug A, Gratz KF, Dunkelmann S, Krause BJ, et al. Peptide receptor radionuclide therapy for neuroendocrine tumors in Germany: first results of a multi-institutional cancer registry. Recent Results Cancer Res. 2013;194:457–65. doi:10.​1007/​978-3-642-27994-2_​25.PubMedCrossRef
24.
go back to reference Romer A, Seiler D, Marincek N, Brunner P, Koller MT, Ng QK, et al. Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2014;41:214–22. doi:10.1007/s00259-013-2559-8.PubMedCrossRef Romer A, Seiler D, Marincek N, Brunner P, Koller MT, Ng QK, et al. Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2014;41:214–22. doi:10.​1007/​s00259-013-2559-8.PubMedCrossRef
25.
go back to reference Villard L, Romer A, Marincek N, Brunner P, Koller MT, Schindler C, et al. Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers. J Clin Oncol. 2012;30:1100–6. doi:10.1200/JCO.2011.37.2151.PubMedCrossRef Villard L, Romer A, Marincek N, Brunner P, Koller MT, Schindler C, et al. Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers. J Clin Oncol. 2012;30:1100–6. doi:10.​1200/​JCO.​2011.​37.​2151.PubMedCrossRef
26.
go back to reference Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol. 2011;29:2416–23. doi:10.1200/JCO.2010.33.7873.PubMedCrossRef Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol. 2011;29:2416–23. doi:10.​1200/​JCO.​2010.​33.​7873.PubMedCrossRef
27.
go back to reference van Essen M, Krenning EP, Kam BL, de Herder WW, van Aken MO, Kwekkeboom DJ. Report on short-term side effects of treatments with 177Lu-octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2008;35:743–8. doi:10.1007/s00259-007-0688-7.PubMedCentralPubMedCrossRef van Essen M, Krenning EP, Kam BL, de Herder WW, van Aken MO, Kwekkeboom DJ. Report on short-term side effects of treatments with 177Lu-octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2008;35:743–8. doi:10.​1007/​s00259-007-0688-7.PubMedCentralPubMedCrossRef
28.
go back to reference Kesavan M, Claringbold PG, Turner JH. Hematological toxicity of combined Lu-octreotate radiopeptide chemotherapy of gastroenteropancreatic neuroendocrine tumors in long-term follow-up. Neuroendocrinology. 2014;99:108–17. doi:10.1159/000362558.PubMedCrossRef Kesavan M, Claringbold PG, Turner JH. Hematological toxicity of combined Lu-octreotate radiopeptide chemotherapy of gastroenteropancreatic neuroendocrine tumors in long-term follow-up. Neuroendocrinology. 2014;99:108–17. doi:10.​1159/​000362558.PubMedCrossRef
29.
go back to reference Binderup T, Knigge U, Loft A, Mortensen J, Pfeifer A, Federspiel B, et al. Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET. J Nucl Med. 2010;51:704–12. doi:10.2967/jnumed.109.069765.PubMedCrossRef Binderup T, Knigge U, Loft A, Mortensen J, Pfeifer A, Federspiel B, et al. Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET. J Nucl Med. 2010;51:704–12. doi:10.​2967/​jnumed.​109.​069765.PubMedCrossRef
31.
go back to reference Sun W, Lipsitz S, Catalano P, Mailliard JA, Haller DG; Eastern Cooperative Oncology Group. Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281. J Clin Oncol. 2005;23:4897–904.PubMedCrossRef Sun W, Lipsitz S, Catalano P, Mailliard JA, Haller DG; Eastern Cooperative Oncology Group. Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281. J Clin Oncol. 2005;23:4897–904.PubMedCrossRef
32.
go back to reference Strosberg JR, Fine RL, Choi J, Nasir A, Coppola D, Chen DT, et al. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer. 2011;117:268–75. doi:10.1002/cncr.25425.PubMedCrossRef Strosberg JR, Fine RL, Choi J, Nasir A, Coppola D, Chen DT, et al. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer. 2011;117:268–75. doi:10.​1002/​cncr.​25425.PubMedCrossRef
33.
go back to reference Rinke A, Muller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009;27:4656–63. doi:10.1200/JCO.2009.22.8510.PubMedCrossRef Rinke A, Muller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009;27:4656–63. doi:10.​1200/​JCO.​2009.​22.​8510.PubMedCrossRef
34.
go back to reference Brizzi MP, Berruti A, Ferrero A, Milanesi E, Volante M, Castiglione F. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte oncology network. BMC Cancer. 2009;9:388. doi:10.1186/1471-2407-9-388.PubMedCentralPubMedCrossRef Brizzi MP, Berruti A, Ferrero A, Milanesi E, Volante M, Castiglione F. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte oncology network. BMC Cancer. 2009;9:388. doi:10.​1186/​1471-2407-9-388.PubMedCentralPubMedCrossRef
35.
go back to reference Delpassand ES, Samarghandi A, Mourtada JS, Zamanian S, Espenan GD, Sharif R, et al. Long-term survival, toxicity profile, and role of F-18 FDG PET/CT scan in patients with progressive neuroendocrine tumors following peptide receptor radionuclide therapy with high activity In-111 pentetreotide. Theranostics. 2012;2:472–80. doi:10.7150/thno.3739.PubMedCentralPubMedCrossRef Delpassand ES, Samarghandi A, Mourtada JS, Zamanian S, Espenan GD, Sharif R, et al. Long-term survival, toxicity profile, and role of F-18 FDG PET/CT scan in patients with progressive neuroendocrine tumors following peptide receptor radionuclide therapy with high activity In-111 pentetreotide. Theranostics. 2012;2:472–80. doi:10.​7150/​thno.​3739.PubMedCentralPubMedCrossRef
36.
go back to reference Yao JC, Pavel M, Phan AT, Kulke MH, Hoosen S, St Peter J, et al. Chromogranin A and neuron-specific enolase as prognostic markers in patients with advanced pNET treated with everolimus. J Clin Endocrinol Metab. 2011;96:3741–9. doi:10.1210/jc.2011-0666.PubMedCrossRef Yao JC, Pavel M, Phan AT, Kulke MH, Hoosen S, St Peter J, et al. Chromogranin A and neuron-specific enolase as prognostic markers in patients with advanced pNET treated with everolimus. J Clin Endocrinol Metab. 2011;96:3741–9. doi:10.​1210/​jc.​2011-0666.PubMedCrossRef
37.
go back to reference Pape UF, Berndt U, Muller-Nordhorn J, Bohmig M, Roll S, Koch M, et al. Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours. Endocrinol Relat Cancer. 2008;15:1083–97. doi:10.1677/ERC-08-0017.CrossRef Pape UF, Berndt U, Muller-Nordhorn J, Bohmig M, Roll S, Koch M, et al. Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours. Endocrinol Relat Cancer. 2008;15:1083–97. doi:10.​1677/​ERC-08-0017.CrossRef
38.
39.
go back to reference Kipritidis J, Siva S, Hofman MS, Callahan J, Hicks RJ, Keall PJ. Validating and improving CT ventilation imaging by correlating with ventilation 4D-PET/CT using 68Ga-labeled nanoparticles. Med Phys. 2014;41:011910. doi:10.1118/1.4856055.PubMedCrossRef Kipritidis J, Siva S, Hofman MS, Callahan J, Hicks RJ, Keall PJ. Validating and improving CT ventilation imaging by correlating with ventilation 4D-PET/CT using 68Ga-labeled nanoparticles. Med Phys. 2014;41:011910. doi:10.​1118/​1.​4856055.PubMedCrossRef
Metadata
Title
Favourable outcomes of 177Lu-octreotate peptide receptor chemoradionuclide therapy in patients with FDG-avid neuroendocrine tumours
Authors
Raghava Kashyap
Michael S. Hofman
Michael Michael
Grace Kong
Timothy Akhurst
Peter Eu
Diana Zannino
Rodney J. Hicks
Publication date
01-02-2015
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2015
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-014-2906-4

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