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 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 11/2019

01-10-2019 | Neuroendocrine Tumor | Original Article

Prognostic value of somatostatin receptor expressing tumor volume calculated from 68Ga-DOTATATE PET/CT in patients with well-differentiated neuroendocrine tumors

Authors: Akira Toriihara, Lucia Baratto, Tomomi Nobashi, Sonya Park, Negin Hatami, Guido Davidzon, Pamela L. Kunz, Andrei Iagaru

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2019

Login to get access

Abstract

Purpose

To evaluate the prognostic value of volumetric parameters calculated from 68Ga-1,4,7,10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Thr3-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated neuroendocrine tumor (WD-NET).

Methods

Ninety-two patients (44 men and 48 women, mean age of 59.5-year-old) with pathologically confirmed WD-NET (grades 1 or 2) were enrolled in a prospective expanded access protocol. Selected data was analyzed retrospectively for this project. Maximum standardized uptake value (SUVmax) in the lesion with the highest 68Ga-DOTATATE uptake was measured and recorded for each patient. In addition, two volumetric parameters, namely, somatostatin receptor expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE), were calculated in each 68Ga-DOTATATE-avid lesion. SRETV was defined as tumor volume with higher 68Ga-DOTATATE uptake than the 50% of SUVmax within the volume of interest (VOI) for each lesion. TLSRE was calculated by multiplying SRETV and mean SUV within the same VOI. Thereafter, the sum of SRETV (ΣSRETV) and TLSRE (ΣTLSRE) for all detected lesions per patient were calculated. Progression-free survival (PFS) was set as primary endpoint. Kaplan-Meier survival analysis, log-rank test, and Cox’s proportional hazard model were used for statistical analysis.

Results

Univariate analyses revealed significant difference of PFS for WHO tumor grade and ΣSRETV (P < 0.05), while there were no significant differences in age, sex, SUVmax, and ΣTLSRE (P > 0.05). Multivariate analysis identified WHO tumor grade and ΣSRETV as independent predictors of PFS.

Conclusion

ΣSRETV calculated from 68Ga-DOTATATE PET/CT may have prognostic value of PFS in WD-NET patients.
Literature
1.
Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017;3:1335–42.CrossRefPubMedPubMedCentral
2.
Chai SM, Brown IS, Kumarasinghe MP. Gastroenteropancreatic neuroendocrine neoplasms: selected pathology review and molecular updates. Histopathology. 2018;72:153–67.CrossRefPubMed
3.
Binderup T, Knigge U, Mellon Mogensen A, Palnaes Hansen C, Kjaer A. Quantitative gene expression of somatostatin receptors and noradrenaline transporter underlying scintigraphic results in patients with neuroendocrine tumors. Neuroendocrinology. 2008;87:223–32.CrossRefPubMed
4.
Geijer H, Breimer LH. Somatostatin receptor PET/CT in neuroendocrine tumours: update on systemic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2013;40:1770–80.CrossRefPubMed
5.
Hope TA, Bergsland EK, Bozkurt MF, Graham M, Heaney AP, Herrmann K, et al. Appropriate use criteria for somatostatin receptor PET imaging in neuroendocrine tumors. J Nucl Med. 2018;59:66–74.CrossRefPubMedPubMedCentral
6.
Bozkurt MF, Virgolini I, Balogova S, Beheshti M, Rubello D, Decristoforo C, et al. Guideline for PET/CT imaging of neuoroendocrine neoplasms with 68Ga-DOTA-conjugated somatostatin receptor targeting peptides and 18F-DOPA. Eur J Nucl Med Mol Imaging. 2017;44:1588–601.CrossRefPubMed
7.
Chan DL, Pavlakis N, Schembri GP, Bernard EJ, Hsiao E, Hayes A, et al. Dual somatostatin receptor/FDG PET/CT imaging in metastatic neuroendocrine tumours: proposal for a novel grading scheme with prognostic significance. Theranostics. 2017;7:1149–58.CrossRefPubMedPubMedCentral
8.
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 18FDG. Cancer. 2008;112:2447–55.CrossRefPubMed
9.
Lococo F, Perotti G, Cardillo G, De Waure C, Filice A, Graziano P, et al. Multicenter comparison of 18F-FDG and 68Ga-DOTA-peptide PET/CT for pulmonary carcinoid. Clin Nucl Med. 2015;40:e183–9.CrossRefPubMed
10.
Panagiotidis E, Alshammari A, Michopoulou S, Skoura E, Naik K, Maragkoudakis E, et al. Comparison of the impact of 68Ga-DOTATATE and 18F-FDG PET/CT on clinical management in patients with neuroendocrine tumors. J Nucl Med. 2017;58:91–6.CrossRefPubMed
11.
Sampathirao N, Basu S. MIB-1 index-stratified assessment of dual-tracer PET/CT with 68Ga-DOTATATE and 18F-FDG and multimodality anatomic imaging in metastatic neuroendocrine tumors of unknown primary in a PRRT workup setting. J Nucl Med Technol. 2017;45:34–41.CrossRefPubMed
12.
Bahri H, Laurence L, Edeline J, Leghzali H, Devillers A, Raoul JL, et al. High prognostic value of 18F-FDG PET for metastatic gastroenteropancreatic neuroendocrine tumors: a long-term evaluation. J Nucl Med. 2014;55:1786–90.CrossRefPubMed
13.
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.CrossRefPubMed
14.
Ezziddin S, Adler L, Sabet A, Poppel TD, Grabellus F, Yuce A, et al. Prognostic stratification of metastatic gastroenteropancreatic neuroendocrine neoplasms by 18F-FDG PET: feasibility of a metabolic grading system. J Nucl Med. 2014;55:1260–6.CrossRefPubMed
15.
Garin E, Le Jeune F, Devillers A, Cuggia M, de Lajarte-Thirouard AS, Bouriel C, et al. Predictive value of 18F-FDG PET and somatostatin receptor scintigraphy in patients with metastatic endocrine tumors. J Nucl Med. 2009;50:858–64.CrossRefPubMed
16.
Johnbeck CB, Knigge U, Langer SW, Loft A, Berthelsen AK, Federspiel B, et al. Prognostic value of 18F-FLT PET in patients with neuroendocrine neoplasms: a prospective head-to-head comparison with 18F-FDG PET and Ki-67 in 100 patients. J Nucl Med. 2016;57:1851–7.CrossRefPubMed
17.
Kim HS, Choi JY, Choi DW, Lim HY, Lee JH, Hong SP, et al. Prognostic value of volume-based metabolic parameters measured by 18F-FDG PET/CT of pancreatic neuroendocrine tumors. Nucl Med Mol Imaging. 2014;48:180–6.CrossRefPubMedPubMedCentral
18.
Koch W, Auernhammer CJ, Geisler J, Spitzweg C, Cyran CC, Ilhan H, et al. Treatment with octreotide in patients with well-differentiated neuroendocrine tumors of the ileum: prognostic stratification with Ga-68-DOTA-TATE positron emission tomography. Mol Imaging. 2014;13:1–10.CrossRefPubMed
19.
Campana D, Ambrosini V, Pezzilli R, Fanti S, Labate AM, Santini D, et al. Standardized uptake values of 68Ga-DOTANOC PET: a promising prognostic tool in neuroendocrine tumors. J Nucl Med. 2010;51:353–9.CrossRefPubMed
20.
Sharma P, Naswa N, Kc SS, Alvarado LA, Dwivedi AK, Yadav Y, et al. Comparison of the prognostic values of 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT in patients with well-differentiated neuroendocrine tumor. Eur J Nucl Med Mol Imaging. 2014;41:2194–202.CrossRefPubMed
21.
Ambrosini V, Campana D, Polverari G, Peterle C, Diodato S, Ricci C, et al. Prognostic value of 68Ga-DOTANOC PET/CT SUVmax in patients with neuroendocrine tumors of the pancreas. J Nucl Med. 2015;56:1843–8.CrossRefPubMed
22.
Abdulrezzak U, Kurt YK, Kula M, Tutus A. Combined imaging with 68Ga-DOTA-TATE and 18F-FDG PET/CT on the basis of volumetric parameters in neuroendocrine tumors. Nucl Med Commun. 2016;37:874–81.CrossRefPubMed
23.
Tirosh A, Papadakis GZ, Millo C, Hammoud D, Sadowski SM, Herscovitch P, et al. Prognostic utility of total 68Ga-DOTATATE-avid tumor volume in patients with neuroendocrine tumors. Gastroenterology. 2018;154:998–1008.CrossRefPubMed
24.
Moradi F, Jamali M, Barkhodari A, Schneider B, Chin F, Quon A, et al. Spectrum of 68Ga-DOTA TATE uptake in patients with neuroendocrine tumors. Clin Nucl Med. 2016;41:e281–7.CrossRefPubMed
25.
Thompson HM, Minamimoto R, Jamali M, Barkhodari A, von Eyben R, Iagaru A. A prospective, matched comparison study of SUV measurements from time-of-flight versus non-time-of-flight PET/CT scanners. Clin Nucl Med. 2016;41:e323–6.CrossRefPubMed
26.
Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.CrossRefPubMed
27.
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.CrossRefPubMed
28.
Kratochwil C, Stefanova M, Mavriopoulou E, Holland-Letz T, Dimitrakopoulou-Strauss A, Afshar-Oromieh A, et al. SUV of [68Ga]DOTATOC-PET/CT predicts response probability of PRRT in neuroendocrine tumors. Mol Imaging Biol. 2014;17:313–8.CrossRef
29.
Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376:125–35.CrossRefPubMedPubMedCentral
30.
Yang Z, Tang LH, Klimstra DS. Effect of tumor heterogeneity on the assessment of Ki67 labeling index in well-differentiated neuroendocrine tumors metastatic to the liver: implications for prognostic stratification. Am J Surg Pathol. 2011;35:853–60.CrossRefPubMed
31.
Adesoye T, Daleo MA, Loeffler AG, Winslow ER, Weber SM, Cho CS. Discordance of histologic grade between primary and metastatic neuroendocrine carcinomas. Ann Sur Oncol. 2015;22(suppl 3):S817–21.CrossRef
32.
Richards-Taylor S, Tilley C, Jaynes E, Hu H, Armstrong T, Pearce NW, et al. Clinically significant differences in Ki-67 proliferation index between primary and metastases in resected pancreatic neuroendocrine tumors. Pancreas. 2017;46:1354–8.CrossRefPubMed
33.
Haug AR, Auernhammer CJ, Wangler B, Schmidt GP, Uebleis C, Goke B, et al. 68Ga-DOTATATE PET/CT for the early prediction of response to somatostatin receptor-mediated radionuclide therapy in patients with well-differentiated neuroendocrine tumors. J Nucl Med. 2010;51:1349–56.CrossRefPubMed
34.
Tirosh A, Papadakis GZ, Millo C, Sadowski SM, Herscovitch P, Pacak K, et al. Association between neuroendocrine tumors biomarkers and primary tumor site and disease type based on total 68Ga-DOTATATE-avid tumor volume measurements. Eur J Endocrinol. 2017;176:575–82.CrossRefPubMedPubMedCentral
Metadata
Title
Prognostic value of somatostatin receptor expressing tumor volume calculated from 68Ga-DOTATATE PET/CT in patients with well-differentiated neuroendocrine tumors
Authors
Akira Toriihara
Lucia Baratto
Tomomi Nobashi
Sonya Park
Negin Hatami
Guido Davidzon
Pamela L. Kunz
Andrei Iagaru
Publication date
01-10-2019
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2019
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-019-04455-9

Other articles of this Issue 11/2019

European Journal of Nuclear Medicine and Molecular Imaging 11/2019 Go to the issue

Letter to the Editor

Scan preparation for patients with type I diabetes treated with continuous sub-cutaneous insulin infusion (CSII) pumps

Original Article

Introducing FDG PET/CT-guided chemoradiotherapy for stage III NSCLC in low- and middle-income countries: preliminary results from the IAEA PERTAIN trial

Original Article

Quality of life in patients with midgut NET following peptide receptor radionuclide therapy

Original Article

Enlarged perivascular spaces and florbetapir uptake in patients with intracerebral hemorrhage

Original Article

Comparison of PSMA-ligand PET/CT and multiparametric MRI for the detection of recurrent prostate cancer in the pelvis

Original Article

A multiparametric analysis based on DCE-MRI to improve the accuracy of parotid tumor discrimination