Effect of peptide receptor radionuclide therapy (PRRT) with tandem isotopes — [90Y]Y/[177Lu]Lu-DOTATATE in patients with disseminated neuroendocrine tumours depending on [18F]FDG PET/CT qualification in Polish multicentre experience — do we need [18F]FDG PET/CT for qualification to PRRT?
Abstract
Introduction: Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues is a treatment option for patients with disseminated neuroendocrine tumours (NET). The aim of the study was the evaluation of the role of [18F]FDG PET/CT in predicting response, progression-free survival (PFS) and overall survival (OS) after tandem therapy [90Y]Y/[177Lu]Lu-DOTATATE.
Material and methods: Seventy-five patients with histopathologically proven NET G1 and G2 were included in the study. Before treatment [68Ga]Ga-DOTATATE PET/CT and [18F]FDG PET/CT was performed. Patients were treated with [90Y]Y/[177Lu]Lu-DOTATATE (1:1) with mixed amino-acid infusion for kidney protection.
Results: Progression-free survival was 22.2 months for [18F]FDG-positive patients and 59.3 months for [18F]FDG-negative patients (p = 0.003). The OS from diagnosis (OS-D) and from the start of PRRT (OS-T) was not reached in [18F]FDG-negative patients, and in [18F]FDG-positive patients it was 71.8 months and 55.8 months, respectively. The observed overall one-year survival in [18F]FDG-positive vs. [18F]FDG-negative patients was 96.8% vs. 99.1%, two-year survival was 88.9% vs. 96%, and five-year survival was 58.8% vs. 88%, respectively. The one-year and two-year risk of progression was 15% vs. 58.9% in [18F]FDG-positive patients and 11% vs. 32% in [18F]FDG-negative patients. The objective response rate (ORR) [18F]FDG-positive vs. [18F]FDG-negative patients was 41.7% vs. 17%.
Conclusions: [18F]FDG-positive patients have statistically significant shorter survival parameters than [18F]FDG-negative patients. The risk of progression in [18F]FDG-positive vs. [18F]FDG-negative patients in one-year follow-up is comparable, whereas in two-year follow-up it is nearly two times higher for [18F]FDG PET/CT-positive patients.
Keywords: PRRT[90Y]Y/[177Lu]Lu-DOTATATE[18F]FDG PET/CTtandem therapyneuroendocrine tumours
References
- Kos-Kudła B, Blicharz-Dorniak J, Strzelczyk J, et al. Consensus Conference, Polish Network of Neuroendocrine Tumours. Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours). Endokrynol Pol. 2013; 64(6): 418–443.
- Plöckinger U, Rindi G, Arnold R, et al. European Neuroendocrine Tumour Society. 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(6): 394–424.
- Ramage JK, Ahmed A, Ardill J, et al. UK and Ireland Neuroendocrine Tumour Society. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut. 2012; 61(1): 6–32.
- 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(18): 3063–3072.
- Ramage JK, De Herder WW, Delle Fave G, et al. Vienna Consensus Conference participants. ENETS Consensus Guidelines Update for Colorectal Neuroendocrine Neoplasms. Neuroendocrinology. 2016; 103(2): 139–143.
- Kvols LK, Brendtro KL. North American Neuroendocrine Tumor Society (NANETS). The North American Neuroendocrine Tumor Society (NANETS) guidelines: mission, goals, and process. Pancreas. 2010; 39(6): 705–706.
- Maroun J, Kocha W, Kvols L, et al. Guidelines for the diagnosis and management of carcinoid tumours. Part 1: the gastrointestinal tract. A statement from a Canadian National Carcinoid Expert Group. Curr Oncol. 2006; 13(2): 67–76.
- Amin MB, Edge S, Greene F. AJCC Cancer Staging Manual. Eighth Edition. Springer 2017.
- Brierley JD, Gospodarowicz MK, Wittekind CT. TNM Classification of Malignant Tumours. Eighth Edition. Wiley Blackwell 2017.
- Binderup T, Knigge U, Loft A, 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(5): 704–712.
- Severi S, Nanni O, Bodei L, et al. Role of 18FDG PET/CT in patients treated with 177Lu-DOTATATE for advanced differentiated neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2013; 40(6): 881–888.
- July M, Santhanam P, Giovanella L, et al. Role of positron emission tomography imaging in Multiple Endocrine Neoplasia syndromes. Clin Physiol Funct Imaging. 2018; 38(1): 4–9.
- Sansovini M, Severi S, Ianniello A, et al. Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with Lu-D OTATATE. Eur J Nucl Med Mol Imaging. 2017; 44(3): 490–499.
- Binderup T, Knigge U, Loft A, et al. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res. 2010; 16(3): 978–985.
- Kunikowska J, Zemczak A, Górska M, et al. TeleNEN as a telemedicine model for neuroendocrine neoplasm management in case of Meckel's diverticulum NET. Endokrynol Pol. 2018; 69(3): 313–317.
- 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(1): 9–15.
- Kunikowska J, Królicki L, Hubalewska-Dydejczyk A, et al. 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(10): 1788–1797.
- Kunikowska J, Pawlak D, Bąk MI, et al. Long-term results and tolerability of tandem peptide receptor radionuclide therapy with Y/Lu-DOTATATE in neuroendocrine tumors with respect to the primary location: a 10-year study. Ann Nucl Med. 2017; 31(5): 347–356.
- Kunikowska J, Zemczak A, Kołodziej M, et al. Tandem peptide receptor radionuclide therapy using Y/Lu-DOTATATE for neuroendocrine tumors efficacy and side-effects - polish multicenter experience. Eur J Nucl Med Mol Imaging. 2020; 47(4): 922–933.
- 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(13): 2124–2130.
- Delpassand ES, Samarghandi A, Zamanian S, et al. Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience. Pancreas. 2014; 43(4): 518–525.
- Parghane RV, Talole S, Prabhash K, et al. Clinical Response Profile of Metastatic/Advanced Pulmonary Neuroendocrine Tumors to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE. Clin Nucl Med. 2017; 42(6): 428–435.
- Sabet A, Dautzenberg K, Haslerud T, et al. Specific efficacy of peptide receptor radionuclide therapy with (177)Lu-octreotate in advanced neuroendocrine tumours of the small intestine. Eur J Nucl Med Mol Imaging. 2015; 42(8): 1238–1246.
- Bodei L, Cremonesi M, Grana CM, et al. Peptide receptor radionuclide therapy with ¹⁷⁷Lu-DOTATATE: the IEO phase I-II study. Eur J Nucl Med Mol Imaging. 2011; 38(12): 2125–2135.
- van Essen M, Krenning EP, Bakker WH, et al. Peptide receptor radionuclide therapy with 177Lu-octreotate in patients with foregut carcinoid tumours of bronchial, gastric and thymic origin. Eur J Nucl Med Mol Imaging. 2007; 34(8): 1219–1227.
- Bodei L, Cremonesi M, Kidd M, et al. Peptide receptor radionuclide therapy for advanced neuroendocrine tumors. Thorac Surg Clin. 2014; 24(3): 333–349.
- Nicolini S, Severi S, Ianniello A, et al. Investigation of receptor radionuclide therapy with Lu-DOTATATE in patients with GEP-NEN and a high Ki-67 proliferation index. Eur J Nucl Med Mol Imaging. 2018; 45(6): 923–930.
- Ianniello A, Sansovini M, Severi S, et al. Peptide receptor radionuclide therapy with (177)Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and (18)F-FDG PET. Eur J Nucl Med Mol Imaging. 2016; 43(6): 1040–1046.
- Strosberg J, El-Haddad G, Wolin E, et al. NETTER-1 Trial Investigators. Phase 3 Trial of Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med. 2017; 376(2): 125–135.
- Ezziddin S, Khalaf F, Vanezi M, et al. Outcome of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2014; 41(5): 925–933.
- Zhang J, Kulkarni HR, Singh A, et al. Peptide Receptor Radionuclide Therapy in Grade 3 Neuroendocrine Neoplasms: Safety and Survival Analysis in 69 Patients. J Nucl Med. 2019; 60(3): 377–385.
- Rogowski W, Wachuła E, Gorzelak A, et al. Capecitabine and temozolomide combination for treatment of high-grade, well-differentiated neuroendocrine tumour and poorly-differentiated neuroendocrine carcinoma - retrospective analysis. Endokrynol Pol. 2019; 70(4): 313–317.
