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

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 4/2020

Open Access 01-04-2020 | Radionuclide Therapy | Original Article

Tandem peptide receptor radionuclide therapy using 90Y/177Lu-DOTATATE for neuroendocrine tumors efficacy and side-effects - polish multicenter experience

Authors: Jolanta Kunikowska, Anna Zemczak, Maciej Kołodziej, Paweł Gut, Izabela Łoń, Dariusz Pawlak, Renata Mikołajczak, Grzegorz Kamiński, Marek Ruchała, Beata Kos-Kudła, Leszek Królicki

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 4/2020

Login to get access

Abstract

Introduction

One of the concepts of theranostics in nuclear medicine is peptide receptor radionuclide therapy (PRRT), whereby labeled somatostatin analogs are used for imaging and treating inoperable or disseminated neuroendocrine tumors (NET).

Aim

The aim of the study was to determine the therapeutic efficacy and toxicity of tandem 90Y /177Lu-DOTATATE in patients with disseminated NET in a multicenter trial.

Materials and methods

103 patients with NET G1/G2 treated with 90Y/177Lu-DOTATATE (1:1) with amino-acid infusion for nephroprotection were included in the study.

Results

Overall survival from the disease diagnosis (OS-D) was 127.4 months and from the time of PRRT (OS-T) was 89.5 months. Progression-free survival (PFS) was 29.9 months. An analysis based on the proliferation index revealed a statistically significant impact on PFS and OS-T (PFS G1 vs G2, 59.3 vs 24.3 months; OS-T G1 vs G2, not reached vs 79.9 months). The effect of the primary disease site was also analyzed. For pancreatic vs small bowel vs large bowel, the PFS was 30.8 vs 30.3 vs 40.6 months, the OS-T was 94 vs 61.9 vs 131.2 months and OS-D was 130.4 vs 89.2 vs not reached months, respectively. The 2-year risk of progression was 42%. The probability of 2-year and 5-year overall survival was 89% and 62%, respectively. PRRT was well tolerated by all patients. One patient (1%) developed myelodysplastic syndrome. No other grade 3 and 4 hematological or renal toxicity was observed.

Conclusions

This multicenter trial showed that tandem 90Y/177Lu-DOTATATE is highly effective and safe therapy for patients with disseminated NET.
Literature
1.
2.
3.
Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26:3063–72.CrossRef
4.
Öberg K, Knigge U, Kwekkeboom D, et al. On behalf of the ESMO guidelines working group. Neuroendocrine gastro-enteropancreatic tumors: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23:124–30.CrossRef
5.
Trofimiuk-Muldner M, Lewkowicz E, Wysocka K, et al. Epidemiology of gastroenteropancreatic neuroendocrine neoplasms in Krakow and Krakow district in 2007-2011. Endokrynol Pol. 2017;68:42–6.CrossRef
6.
Caplin ME, Pavel M, Ruszniewski P. Lanreotide in metastatic Enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371:224–33.CrossRef
7.
Rinke A, Müller HH, Schade-Brittinger C, 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 fromthe PROMID study group. J Clin Oncol. 2009;27:4656–63.CrossRef
8.
Delle Fave GF, O'Toole D, Sundin A, et al. ENETS consensus guidelines update for Gastroduodenal neuroendocrine neoplasms. Neuroendocrinology. 2016;103:119–24.CrossRef
9.
Valkema R, de Jong M, Bakker WH, et al. Phase I study of peptide receptor radionuclide therapy with [111In-DTPA0]octreotide: the Rotterdam experience. Semin Nucl Med. 2002;32:110–22.CrossRef
10.
Anthony LB, Woltering EA, Espanan GD, Cronin MD, Maloney TJ, McCarthy KE. Indium-111-pentetreotide prolongs survival in gastroenteropancreatic malignancies. Semin Nucl Med. 2002;32:123–32.CrossRef
11.
Waldherr C, Pless M, Maecke HR, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4GBq 90Y-DOTATOC. J Nucl Med. 2002;43:610–6.PubMed
12.
Bodei L, Cremonesi M, Grana C, et al. Receptor radionuclide therapy with 90Y[DOTA]0-Tyr3-octerotide(90Y- DOTATOC) in neuroendocrine tumors. Eur J Nucl Med Mol Imaging. 2004;31:1038–46.CrossRef
13.
Kwekkeboom DJ, Mueller-Brand J, Paganelli G, et al. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J Nucl Med. 2005;46:62S–6S.PubMed
14.
Kwekkeboom D, Bakker W, Kam BLR, et al. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate. Eur J Nucl Med. 2003;30:417–22.CrossRef
15.
Kwekkeboom DJ, de Herder WW, Kam BL, et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26:2124–30.CrossRef
16.
17.
De Jong M, Bernard HF, Breeman WA, et al. Combination of 90Y- and 177Lu- labeled somatostatin analogs is superior for radionuclide therapy compared to 90Y- or 177Lu-labeled analogs only. J Nucl Med. 2002;43:123P–4P.
18.
de Jong M, Breeman WA, Valkema R, Bernard BF, Krenning EP. Combination radionuclide therapy using 177Lu- and 90Y-labeled somatostatin analogs. J Nucl Med. 2005;46:13S–7S.PubMed
19.
Kunikowska J, Królicki L, Hubalewska-Dydejczyk A, Mikołajczak R, Sowa-Staszczak A, Pawlak D. Clinical results of radionuclide therapy of neuroendocrine tumours with 90Y-DOTATATE and tandem 90Y/177Lu-DOTATATE: which is a better therapy option? Eur J Nucl Med Mol Imaging. 2011;38:1788–97.CrossRef
20.
Kunikowska J, Pawlak D, Bąk MI, Kos-Kudła B, Mikołajczak R, Królicki L. Long-term results and tolerability of tandem peptide receptor radionuclide therapy with 90Y/177Lu-DOTATATE in neuroendocrine tumors with respect to the primary location: a 10-year study. Ann Nucl Med. 2017;31:347–56. https://​doi.​org/​10.​1007/​s12149-017-1163-6.CrossRefPubMed
21.
Kos-Kudła B, Blicharz-Dorniak J, Handkiewicz-Junak D, et al. Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the polish network of neuroendocrine Tumours). Endokrynol Pol. 2013;64:418–43.CrossRef
22.
Rolleman EJ, Valkema R, de Jong M, et al. Safe and effective inhibition of renal uptake of radiolabelled octreotide by a combination of lysine and arginine. Eur J Nucl Med Mol Imaging. 2003;30:9–15.CrossRef
23.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.CrossRef
24.
Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:501–13 Errata w: N Engl J Med 2011; 364:1082.CrossRef
25.
Yao JC, Shah MH, Ito T, et al. RAD001 in advanced neuroendocrine tumors, third trial (RADIANT-3) study group. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:514–23.CrossRef
26.
27.
Cieciera M, Kratochwil C, Moltz J, et al. Semi-automatic 3D-volumetry of liver metastases from neuroendocrine tumors to improve combination therapy with 177Lu-DOTATOC and 90Y-DOTATOC. Diagn Interv Radiol. 2016;22:201–6.CrossRef
28.
Siegel JA, Stabin MG. Absorbed fractions for electrons and beta particles in spheres of various sizes. J Nucl Med. 1994;35:152–6.PubMed
29.
Villard L, Romer A, Marincek N, 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.CrossRef
30.
Dumont RA, Seiler D, Marincek N, et al. Survival after somatostatin based radiopeptide therapy with (90)Y-DOTATOC vs. (90)Y-DOTATOC plus (177)Lu-DOTATOC in metastasized gastrinoma. Am J Nucl Med Mol Imaging. 2014;5:46–55.PubMedPubMedCentral
31.
Horsch D, Ezziddin S, Haug A, et al. Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: A multi-institutional registry study with prospective follow-up. Eur J Cancer. 2016;58:41–51.CrossRef
32.
Baum R, Kulkarni H, Singh A, et al. Results and adverse events of personalized peptide receptor radionuclide therapy with 90Yttrium and 177Lutetium in 1048 patients with neuroendocrine neoplasms. Oncotarget. 2018;9:16932–50.CrossRef
33.
Seregni E, Maccauro M, Chiesa C, et al. Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy. Eur J Nucl Med Mol Imaging. 2014;41:223–30.CrossRef
34.
Radojewski P, Dumont R, Marincek N, et al. Towards tailored radiopeptide therapy. Eur J Nucl Med Mol Imaging. 2015;42:1231–7.CrossRef
35.
Binderup T, Knigge U, Loft A, Federspiel B, Kjaer A. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res. 2010;16:978–85.CrossRef
36.
Severi S, Nanni O, Bodei L. Role of 18FDG PET/CT in patients treated with 177Lu-DOTATATE for advanced differentiated neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2013;40:881–8.CrossRef
37.
38.
39.
Kunikowska J, Królicki L, Sowa-Staszczak A, Pawlak D, Hubalewska-Dydejczyk A, Mikołajczak R. Nephrotoxicity after PRRT - still a serious clinical problem? Renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATATE and 90Y/177Lu-DOTATATE. Endokrynol Pol. 2013;64:13–20.PubMed
Metadata
Title
Tandem peptide receptor radionuclide therapy using 90Y/177Lu-DOTATATE for neuroendocrine tumors efficacy and side-effects - polish multicenter experience
Authors
Jolanta Kunikowska
Anna Zemczak
Maciej Kołodziej
Paweł Gut
Izabela Łoń
Dariusz Pawlak
Renata Mikołajczak
Grzegorz Kamiński
Marek Ruchała
Beata Kos-Kudła
Leszek Królicki
Publication date
01-04-2020
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 4/2020
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-020-04690-5

Other articles of this Issue 4/2020

European Journal of Nuclear Medicine and Molecular Imaging 4/2020 Go to the issue

Original Article

Staging FDG PET-CT changes management in patients with gastric adenocarcinoma who are eligible for radical treatment

Original Article

Hypoxia-induced modulation of glucose transporter expression impacts 18F-fluorodeoxyglucose PET-CT imaging in hepatocellular carcinoma

Original Article

Dose escalation of an Evans blue–modified radiolabeled somatostatin analog 177Lu-DOTA-EB-TATE in the treatment of metastatic neuroendocrine tumors

Original Article

Comparative dosimetry between 99mTc-MAA SPECT/CT and 90Y PET/CT in primary and metastatic liver tumors

Letter to the Editor

Availability of both [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTATATE as PRRT agents for neuroendocrine tumors: can we evolve a rational sequential duo-PRRT protocol for large volume resistant tumors?

Image of the Month

A case of abdominal wall percutaneous endoscopic gastrostomy site metastatic disease from primary oropharyngeal squamous cell carcinoma