Possible changes in glucose metabolism induced by radioligand therapy in patients with neuroendocrine neoplasms
, 1, 1, 2, 3, 1, 1, 1, 1
Abstract
Introductiom: Neuroendocrine neoplasms (NENs) belong to a heterogeneous group of tumours originating from neuroendocrine cells. Primary tumours most commonly occur in the gastrointestinal tract, although they can arise in any part of the human body. Radioligand therapy (RLT) is recommended for progressive or inoperable cases in subsequent lines of the therapy. Our study aimed to investigate glucose metabolism alterations during and after radioligand therapy in patients with neuroendocrine neoplasms undergoing radioligand therapy.
Material and methods: The study was performed on 41 patients with inoperable neuroendocrine tumours, who underwent one cycle (4 courses) of radioligand therapy with [177Lu]Lu-DOTA-TATE alone or tandem therapy with [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE with a standardised nephroprotection protocol. Laboratory parameters were analysed during the first and fourth courses and one year
after the last course of treatment.
Results: The study showed a statistically insignificant increase in fasting glucose concentration during and after radioligand therapy, accompanied by a parallel increase in insulin concentration. In patients treated with tandem therapy, the increase in fasting glucose was higher, but the results were still statistically insignificant. No glycaemic severe adverse events [Common Terminology Criteria for
Adverse Events (CTCAE) G3–G5] were observed.
Conclusions: Radioligand therapy potentially increases fasting glucose concentrations, probably due to changes in peripheral glucose metabolism. However, it remains a safe treatment method for patients with neuroendocrine neoplasms and does not cause severe glycaemic adverse events related to glucose metabolism.
Keywords: RLTPRRTglucoseglycaemiainsulinHbA1c177-Lu90-Y
References
- Leotlela PD, Jauch A, Holtgreve-Grez H, et al. Genetics of neuroendocrine and carcinoid tumours. Endocr Relat Cancer. 2003; 10(4): 437–450.
- Imperiale A. Neuroendocrine Tumors: Treatment and Management. Cancers (Basel). 2022; 14(16).
- Rossi RE, Massironi S. The Increasing Incidence of Neuroendocrine Neoplasms Worldwide: Current Knowledge and Open Issues. J Clin Med. 2022; 11(13).
- Kos-Kudła B, Foltyn W, Malczewska A, et al. Update of the diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours). Endokrynol Pol. 2022; 73(3): 387–454.
- Ohmoto A, Rokutan H, Yachida S. Pancreatic Neuroendocrine Neoplasms: Basic Biology, Current Treatment Strategies and Prospects for the Future. Int J Mol Sci. 2017; 18(1).
- Juhlin CC, Zedenius J, Höög A. Metastatic Neuroendocrine Neoplasms of Unknown Primary: Clues from Pathology Workup. Cancers (Basel). 2022; 14(9).
- Rindi G, Mete O, Uccella S, et al. Overview of the 2022 WHO Classification of Neuroendocrine Neoplasms. Endocr Pathol. 2022; 33(1): 115–154.
- Kaçmaz E, Heidsma CM, Besselink MGH, et al. Treatment of Liver Metastases from Midgut Neuroendocrine Tumours: A Systematic Review and Meta-Analysis. J Clin Med. 2019; 8(3).
- Ahmadi Bidakhvidi N, Goffin K, Dekervel J, et al. Peptide Receptor Radionuclide Therapy Targeting the Somatostatin Receptor: Basic Principles, Clinical Applications and Optimization Strategies. Cancers (Basel). 2021; 14(1).
- Kaliszewski K, Ludwig M, Greniuk M, et al. Advances in the Diagnosis and Therapeutic Management of Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs). Cancers (Basel). 2022; 14(8).
- Carlsen EA, Fazio N, Granberg D, et al. Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: a multicenter cohort study. Endocr Relat Cancer. 2019; 26(2): 227–239.
- 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.
- Sjögreen Gleisner K, Spezi E, Solny P, et al. Variations in the practice of molecular radiotherapy and implementation of dosimetry: results from a European survey. EJNMMI Phys. 2017; 4(1): 28.
- 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.
- Kolasińska-Ćwikła A, Łowczak A, Maciejkiewicz KM, et al. Peptide Receptor Radionuclide Therapy for Advanced Gastroenteropancreatic Neuroendocrine Tumors - from oncology perspective. Nucl Med Rev Cent East Eur. 2018; 21(2).
- Tafuto S, von Arx C, Capozzi M, et al. Safety and Activity of Metronomic Temozolomide in Second-Line Treatment of Advanced Neuroendocrine Neoplasms. J Clin Med. 2019; 8(8).
- Zappi A, Persano I, Galvani L, et al. Chemotherapy in Well Differentiated Neuroendocrine Tumors (NET) G1, G2, and G3: A Narrative Review. J Clin Med. 2023; 12(2).
- Ricci C, Lamberti G, Ingaldi C, et al. Treatment of advanced gastro-entero-pancreatic neuro-endocrine tumors: A systematic review and network meta-analysis of phase III randomized controlled trials. Cancers (Basel). 2021; 13(2): 358.
- Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011; 364(6): 514–523.
- Yao JC, Fazio N, Singh S, et al. RAD001 in Advanced Neuroendocrine Tumours, Fourth Trial (RADIANT-4) Study Group. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016; 387(10022): 968–977.
- Raymond E, Dahan L, Raoul JL, et al. Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine Tumors. N Engl J Med. 2011; 364(6): 501–513.
- Spada F, Campana D, Lamberti G, et al. [Lu]Lu-DOTA-TATE versus standard of care in adult patients with gastro-enteropancreatic neuroendocrine tumours (GEP-NETs): a cost-consequence analysis from an Italian hospital perspective. Eur J Nucl Med Mol Imaging. 2022; 49(6): 2037–2048.
- de Vathaire F, El-Fayech C, Ben Ayed FF, et al. Radiation dose to the pancreas and risk of diabetes mellitus in childhood cancer survivors: a retrospective cohort study. Lancet Oncol. 2012; 13(10): 1002–1010.
- Denoyer D, Lobachevsky P, Jackson P, et al. Analysis of 177Lu-DOTA-octreotate therapy-induced DNA damage in peripheral blood lymphocytes of patients with neuroendocrine tumors. J Nucl Med. 2015; 56(4): 505–511.
- Eberlein U, Nowak C, Bluemel C, et al. DNA damage in blood lymphocytes in patients after (177)Lu peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2015; 42(11): 1739–1749.
- Saracyn M, Durma AD, Bober B, et al. Long-Term Complications of Radioligand Therapy with Lutetium-177 and Yttrium-90 in Patients with Neuroendocrine Neoplasms. Nutrients. 2022; 15(1).
- Bodei L, Kidd M, Paganelli G, et al. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors. Eur J Nucl Med Mol Imaging. 2015; 42(1): 5–19.
- Bober B, Saracyn M, Zaręba K, et al. Early Complications of Radioisotope Therapy with Lutetium-177 and Yttrium-90 in Patients with Neuroendocrine Neoplasms-A Preliminary Study. J Clin Med. 2022; 11(4).
- Teunissen JJM, Krenning EP, de Jong FH, et al. Effects of therapy with [177Lu-DOTA 0,Tyr 3]octreotate on endocrine function. Eur J Nucl Med Mol Imaging. 2009; 36(11): 1758–1766.
- Mikołajczak R, Maecke HR. Radiopharmaceuticals for somatostatin receptor imaging. Nucl Med Rev Cent East Eur. 2016; 19(2): 126–132.
- Bevere M, Gkountakos A, Martelli FM, et al. An Insight on Functioning Pancreatic Neuroendocrine Neoplasms. Biomedicines. 2023; 11(2).
- Gomes-Porras M, Cárdenas-Salas J, Álvarez-Escolá C. Somatostatin Analogs in Clinical Practice: a Review. Int J Mol Sci. 2020; 21(5).
- Panzuto F, Ricci C, Rinzivillo M, et al. The Antiproliferative Activity of High-Dose Somatostatin Analogs in Gastro-Entero-Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis. J Clin Med. 2022; 11(20).
- Stueven AK, Kayser A, Wetz C, et al. Somatostatin Analogues in the Treatment of Neuroendocrine Tumors: Past, Present and Future. Int J Mol Sci. 2019; 20(12).
- Patel KR, Nahar A, Elhassan YS, et al. The effects of somatostatin analogues on glycaemia in the treatment of neuroendocrine tumours. J Neuroendocrinol. 2022; 34(4): e13064.
