Top

Published in:

01-12-2015 | Endocrine Tumors

Feasibility of Radio-Guided Surgery with ⁶⁸Gallium-DOTATATE in Patients with Gastro-Entero-Pancreatic Neuroendocrine Tumors

Authors: Samira M. Sadowski, MD, Corina Millo, MD, Vladimir Neychev, MD, PhD, Rachel Aufforth, MD, Xavier Keutgen, MD, Joanne Glanville, MD, Meghna Alimchandani, MD, Naris Nilubol, MD, FACS, Peter Herscovitch, MD, Martha Quezado, MD, Electron Kebebew, MD, FACS

Published in: Annals of Surgical Oncology | Special Issue 3/2015

Abstract

Background

Surgery is the only definitive therapy for gastro-entero-pancreatic neuroendocrine tumors (GEPNETs), and achieving complete tumor resection is an important prognostic factor. Radiopharmaceuticals such as ⁶⁸Ga-DOTA peptides have been developed that offer superior accuracy for localization of GEPNETs. The study aim was to determine the feasibility of radio-guided surgery (RGS) using ⁶⁸Ga-DOTATATE in patients with primary and recurrent GEPNETs.

Methods

Fourteen patients with GEPNETs were enrolled onto a prospective study to determine the feasibility of RGS with ⁶⁸Ga-DOTATATE. Findings from preoperative imaging, intraoperative exploration, RGS, and pathology were analyzed.

Results

The median decay corrected target count rate was 172.6 (range 28.15–2341) for tumors, with a tumor-to-background ratio (TBR) of 4.46 (range 1.6–43.56). The median lesion size was 1.55 (range 0.5–15) cm. There was no significant correlation between preoperative imaging maximum standardized uptake value (SUV_max) of the lesions and TBR (Spearman r = − 0.01, p = 0.9), TBR and tumor size (Spearman r = 0.29, p = 0.14), and SUV_max and tumor size (Spearman r = 0.22, p = 0.28). The probe showed correct identification for gastric and small intestine neuroendocrine tumor (NET), including lymph node metastasis in 17 (81.0 %) of 21 cases, with a median TBR of 3.5 (1.6–40.2). For pancreatic NETs and lymph node metastasis, 16 (66.7 %) of 24 were correctly identified by RGS.

Conclusions

Our study shows that RGS with ⁶⁸Ga-DOTATATE is feasible and correctly confirms bowel NETs and metastatic mesenteric lymph nodes. Further studies are needed to determine the benefit of RGS with ⁶⁸Ga-DOTATATE.

Tsikitis VL, Wertheim BC, Guerrero MA. Trends of incidence and survival of gastrointestinal neuroendocrine tumors in the United States: a SEER analysis. J Cancer. 2012;3:292–302.PubMedPubMedCentralCrossRef

Lawrence B, Gustafsson BI, Chan A, Svejda B, Kidd M, Modlin IM. The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am. 2011;40:1–18.PubMedCrossRef

Plockinger U, Rindi G, Arnold R, et al. Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology. 2004;80:394–424.PubMedCrossRef

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.PubMedCrossRef

Ramage JK, Davies AH, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut. 2005;54(suppl 4):iv1–16.PubMedPubMedCentral

Wang YZ, Diebold A, Woltering E, et al. Radioguided exploration facilitates surgical cytoreduction of neuroendocrine tumors. J Gastrointest Surg. 2012;16:635–40.PubMedCrossRef

Hodolic M, Fettich J, Repse S, Peitl P, Lezaic L, Hojker S. Factors influencing radioguided surgery of neuroendocrine tumours using ^99mTc-ethylenediamine N,N′-diacetic acid/6-hydrazinopyridine-3-carboxylic acid-d-Phe1-Tyr3-octreotide. Nucl Med Commun. 2008;29:311–7.PubMedCrossRef

Grossrubatscher E, Vignati F, Dalino P, et al. Use of radioguided surgery with [¹¹¹In]-pentetreotide in the management of an ACTH-secreting bronchial carcinoid causing ectopic Cushing’s syndrome. J Endocrinol Invest. 2005;28:72–8.PubMedCrossRef

Albertario S, Forti P, Bianchi C, et al. Radioguided surgery for gastrinoma: a case report. Tumori. 2002;88:S41–3.PubMed

10.

Reubi JC, Kvols L, Krenning E, Lamberts SW. Distribution of somatostatin receptors in normal and tumor tissue. Metabolism. 1990;39(9 suppl 2):78–81.PubMedCrossRef

11.

de Herder WW, Hofland LJ, van der Lely AJ, Lamberts SW. Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours. Endocr Relat Cancer. 2003;10:451–8.PubMedCrossRef

12.

Reubi JC. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev. 2003;24:389–427.PubMedCrossRef

13.

Falconi M, Bartsch DK, Eriksson B, et al. ENETS Consensus guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic non-functioning tumors. Neuroendocrinology. 2012;95:120–34.PubMedCrossRef

14.

Yang J, Kan Y, Ge BH, Yuan L, Li C, Zhao W. Diagnostic role of gallium-68 DOTATOC and gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis. Acta Radiol. 2014;55:389–98.PubMedCrossRef

15.

Hofman MS, Kong G, Neels OC, Eu P, Hong E, Hicks RJ. High management impact of Ga-68 DOTATATE (GaTate) PET/CT for imaging neuroendocrine and other somatostatin expressing tumours. J Med Imag Radiat Oncol. 2012;56:40–7.CrossRef

16.

Ohrvall U, Westlin JE, Nilsson S, et al. Intraoperative gamma detection reveals abdominal endocrine tumors more efficiently than somatostatin receptor scintigraphy. Cancer. 1997;80(12 suppl):2490–4.PubMedCrossRef

17.

Adams S, Baum RP. Intraoperative use of gamma-detecting probes to localize neuroendocrine tumors. Q J Nucl Med. 2000;44:59–67.PubMed

18.

Gulec SA, Daghighian F, Essner R. PET-probe: evaluation of technical performance and clinical utility of a handheld high-energy gamma probe in oncologic surgery. Ann Surg Oncol. 2006. doi:10.1245/ASO.2006.05.047.PubMed

19.

Freesmeyer M, Wurst C, Uberrueck T, et al. Intraoperative identification of a neuroendocrine tumour diagnosed by ⁶⁸Ga-DOTATOC PET but undetectable by surgical palpation or conventional imaging. Nuklearmedizin. 2009;48:N50–1.PubMed

20.

Kunikowska J, Slodkowski M, Koperski L, et al. Radioguided surgery in patient with pancreatic neuroendocrine tumour followed by PET/CT scan as a new approach of complete resection evaluation—case report. Nucl Med Rev Cent East Eur. 2014;17:110–4.PubMed

21.

Kaemmerer D, Prasad V, Daffner W, et al. Radioguided surgery in neuroendocrine tumors using Ga-68-labeled somatostatin analogs: a pilot study. Clin Nucl Med. 2012;37:142–7.PubMedCrossRef

22.

Bosman F, Carneiro F, Hruban R, Theise N. WHO classification of tumors of the digestive system. 4th ed. Lyon: International Agency for Research on Cancer; 2010.

23.

Volante M, Brizzi MP, Faggiano A, et al. Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy. Mod Pathol. 2007;20:1172–82.PubMedCrossRef

24.

Hodul PJ, Strosberg JR, Kvols LK. Aggressive surgical resection in the management of pancreatic neuroendocrine tumors: when is it indicated? Cancer Control. 2008;15:314–21.PubMed

25.

Mayo SC, de Jong MC, Pulitano C, et al. Surgical management of hepatic neuroendocrine tumor metastasis: results from an international multi-institutional analysis. Ann Surg Oncol. 2010;17:3129–36.PubMedCrossRef

26.

van Hulsteijn LT, Corssmit EP, van der Hiel B, Smit JW, Stokkel MP. Is there a role for radioguided surgery with iodine-labeled metaiodobenzylguanidine in resection of neuroendocrine tumors? Clin Nucl Med. 2012;37:1083–8.PubMedCrossRef

27.

Prasad V, Baum RP. Biodistribution of the Ga-68 labeled somatostatin analogue DOTA-NOC in patients with neuroendocrine tumors: characterization of uptake in normal organs and tumor lesions. Q J Nucl Med Mol Imaging. 2010;54:61–7.PubMed

28.

Bilimoria KY, Bentrem DJ, Merkow RP, et al. Application of the pancreatic adenocarcinoma staging system to pancreatic neuroendocrine tumors. J Am Coll Surg. 2007;205:558–63.PubMedCrossRef

29.

Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual. 7th edition. New York: Springer, 2010.

Title: Feasibility of Radio-Guided Surgery with 68Gallium-DOTATATE in Patients with Gastro-Entero-Pancreatic Neuroendocrine Tumors
Authors: Samira M. Sadowski, MD
Corina Millo, MD
Vladimir Neychev, MD, PhD
Rachel Aufforth, MD
Xavier Keutgen, MD
Joanne Glanville, MD
Meghna Alimchandani, MD
Naris Nilubol, MD, FACS
Peter Herscovitch, MD
Martha Quezado, MD
Electron Kebebew, MD, FACS
Publication date: 01-12-2015
Publisher: Springer US
Published in: Annals of Surgical Oncology / Issue Special Issue 3/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-015-4857-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Feasibility of Radio-Guided Surgery with ⁶⁸Gallium-DOTATATE in Patients with Gastro-Entero-Pancreatic Neuroendocrine Tumors

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Special Issue 3/2015

Outcomes of Breast Cancer Patients Treated with Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience

Pattern of Lymphatic Spread of Esophageal Cancer at the Cervicothoracic Junction Based on the Tumor Location

Erratum to: The Ability to Diagnose Intrahepatic Cholangiocarcinoma Definitively Using Novel Branched DNA-Enhanced Albumin RNA In Situ Hybridization Technology

Suppression of SAMSN1 Expression is Associated with the Malignant Phenotype of Hepatocellular Carcinoma

Clinicopathologic Features and Outcomes of Non-B, Non-C Hepatocellular Carcinoma After Hepatectomy

The miR-506-Induced Epithelial–Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer