A Glimpse into Lutetium 177 Therapy in Malignant Insulinoma: Case Report and Review of Literature

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Published: 2023-12-27

Page: 190-203


Kholoud Alqasem *

Department of Internal Medicine, King Hussein Cancer Center, Queen Rania Al Abdullah Street, P.O. Box: 1269, Amman-11941, Jordan.

Raya Alawneh *

School of Medicine, The University of Jordan, Amman-11942, Jordan

Yaqin Alzagareet

School of Medicine, The University of Jordan, Amman-11942, Jordan.

Haya Mesmar

Department of Pathology and Laboratory Medicine, King Hussein Cancer Center, Amman-11941, Jordan.

Zaid Omari

Department of Radiology, King Hussein Cancer Center, Amman-11941, Jordan.

Maissoune Hajir

Department of Internal Medicine, King Hussein Cancer Center, Queen Rania Al Abdullah Street, P.O. Box: 1269, Amman-11941, Jordan.

Marwa Al-Shatti

Department of Pathology and Laboratory Medicine, King Hussein Cancer Center, Amman-11941, Jordan.

*Author to whom correspondence should be addressed.


Abstract

Background: Insulinomas are a rare type of pancreatic neuroendocrine tumors, characterized by their frequent benign nature and propensity to induce hypoglycemia through excessive insulin secretion. This case report underscores the importance of timely diagnosis and the advantages of a multifaceted therapeutic strategy for treating metastatic malignant insulinomas. This report highlights the promise of somatostatin analogs, chemotherapy, and peptide receptor radionuclide therapy (PRRT) in achieving better patient outcomes.

Case Presentation: A 37-year-old previously healthy woman presented with recurrent hypoglycemia and severe neurological symptoms. Initially misdiagnosed and treated with prednisolone, the patient was eventually admitted to the intensive care unit because of hypoglycemia and hypoxia. Computed tomography revealed a 5.7 cm pancreatic tumor with multifocal liver and spleen metastases. Liver biopsy confirmed a well-differentiated neuroendocrine tumor grade 2. Treatment commenced with continuous glucose infusion and lanreotide and short-acting octreotide injections, followed by palliative chemotherapy (capecitabine and temozolomide). The patient experienced significant clinical improvement, and the subsequent follow-up showed partial resolution of the liver lesions. Further management included peptide receptor radionuclide therapy (PRRT) with Lutetium-177-DOTATATE, which remarkably reduced tumor size and symptoms. The patient maintained euglycemia and clinical stability, with progression-free survival (PFS) exceeding 30 months.

Conclusions: This case highlights the successful management of metastatic malignant insulinoma using a combination of somatostatin analogs, chemotherapy, and PRRT. Sustained clinical improvement and progression-free survival demonstrated the potential of this multimodal approach in controlling the disease and enhancing the patient's quality of life. Further research and guidelines are required to improve the management of metastatic insulinoma. This report emphasizes the importance of considering diverse treatment modalities to provide effective and personalized care for rare and complex endocrine tumors such as malignant insulinoma.

Keywords: Insulinoma, NET, malignant, metastatic, PRRT, lutetium 177, capecitabine, lanreotide


How to Cite

Alqasem, Kholoud, Raya Alawneh, Yaqin Alzagareet, Haya Mesmar, Zaid Omari, Maissoune Hajir, and Marwa Al-Shatti. 2023. “A Glimpse into Lutetium 177 Therapy in Malignant Insulinoma: Case Report and Review of Literature”. Asian Journal of Research and Reports in Endocrinology 6 (1):190-203. https://journalajrre.com/index.php/AJRRE/article/view/84.

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References

Marek B, Kajdaniuk D, Kos-Kudła B, Foltyn W, Borgiel-Marek H, Matyja V, Pakuła D. Insulinoma--diagnostyka i leczenie [Insulinoma--diagnosis and treatment]. Endokrynologia Polska. 2007;58(1):58–62.

Mittendorf EA, Liu YC, McHenry CR. Giant insulinoma: case report and review of literature. The Journal of Clinical Endocrinology and Metabolism. 2005; 90(1):575–580. Available:https://doi.org/10.1210/jc.2004-0825

Shao Y, Qu YQ, Wang XL, Song ZG, Guo QH, Dou JT, Ba JM, Lü ZH, Mu YM. Malignant insulinoma: Report of 6 patients and literature review. Neuro Endocrinology Letters. 2016;37(3):189–192.

De Herder WW, Hofland J. Insulinoma. In K. R. Feingold (Eds.) et al., Endotext. MDText.com, Inc; 2023.

Okabayashi T, Shima Y, Sumiyoshi T, Kozuki A, Ito S, Ogawa Y, Kobayashi M, Hanazaki K. Diagnosis and management of insulinoma. World Journal of Gastroenterology. 2013;19(6):829–837.

Available:https://doi.org/10.3748/wjg.v19.i6.829

Sanli Y, Garg I, Kandathil A, Kendi T, Zanetti MJB, Kuyumcu S, Subramaniam RM. Neuroendocrine Tumor Diagnosis and Management: 68Ga-DOTATATE PET/CT. American Journal of Roentgenology. 2018;211(2):267–277.

Available: https://doi.org/10.2214/ajr.18.19881

Lee C, Lee G, Kim D, Kim N, Kim SW, Song KH. A Large Malignant Insulinoma: Case Report with Endosonographic, Immunohistochemical and Ultrastructural Features. The Korean Journal of Internal Medicine.2003;18(1):45-49.

Available:https://doi.org/10.3904/kjim.2003.18.1.45

Giannis D, Moris D, Karachaliou GS, Tsilimigras DI, Karaolanis G, Papalampros A, Felekouras E. Insulinomas: from diagnosis to treatment. A review of the literature. Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology. 2020;25(3):1302–1314.

De Herder WW, Van Schaik E, Kwekkeboom DJ, Feelders RA. New therapeutic options for metastatic malignant insulinomas. Clinical Endocrinology. 2011;75(3):277–284.

Available:https://doi.org/10.1111/j.1365-2265.2011.04145.x

Arrivi G, Verrico M, Roberto M, Barchiesi G, Faggiano A, Marchetti P, Mazzuca F, & Tomao S. Capecitabine and Temozolomide (CAPTEM) in Advanced Neuroendocrine Neoplasms (NENs): A Systematic Review and Pooled Analysis. Cancer Management and Research. 2022;14:3507–3523.

Available:https://doi.org/10.2147/CMAR.S372776

Kunz PL, Graham NT, Catalano PJ, Nimeiri HS, Fisher GA, Longacre TA, Suarez CJ, Martin BA, Yao JC, Kulke MH, Hendifar AE, Shanks JC, Shah MH, Zalupski MM, Schmulbach EL, Reidy-Lagunes DL, Strosberg JR, O'Dwyer PJ, Benson AB. 3rd. Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients with Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211). Journal of Clinical Oncology: Official Journal of The American Society of Clinical Oncology. 2023;41(7):1359–1369. Available:https://doi.org/10.1200/JCO.22.01013

Reubi JC, Kvols LK, Waser B, Nagorney DM, Heitz PU, Charboneau JW, Reading CC, Moertel C. Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. Cancer Research. 1990;50(18):5969–5977.

Eriksson B, Renstrup J, Imam H, Oberg K. High-dose treatment with lanreotide of patients with advanced neuroendocrine gastrointestinal tumors: clinical and biological effects. Annals of Oncology : Official Journal of the European Society for Medical Oncology. 1997;8(10):1041–1044.

Available:https://doi.org/10.1023/a:1008205415035

Tomassetti P, Migliori M, Gullo L. Slow release lanreotide treatment in endocrine gastrointestinal tumors. The American Journal of Gastroenterology. 1998;93(9): 1468–1471. Available:https://doi.org/10.1111/j.1572-0241.1998.465_q.x

Toumpanakis C, Caplin ME. Update on the role of somatostatin analogs for the treatment of patients with gastro-enteropancreatic neuroendocrine tumors. Seminars in Oncology. 2013;40(1):56–68. Available:https://doi.org/10.1053/j.seminoncol.2012.11.006

Romeo S, Milione M, Gatti A, Fallarino M, Corleto V, Morano S, Baroni MG. Complete clinical remission and disappearance of liver metastases after treatment with somatostatin analogue in a 40-year-old woman with a malignant insulinoma positive for somatostatin receptors type 2. Hormone Research. 2006;65(3):120–125. Available:https://doi.org/10.1159/000091408

Okamoto M, Kishimoto M, Takahashi Y, Osame K, Noto H, Yamamoto-Honda R, Kajio H, Tokuhara M, Edamoto Y, Endo H, Igari T, Kubota K, Noda M. A case of malignant insulinoma: successful control of glycemic fluctuation by replacing octreotide injections with octreotide LAR injections. Endocrine Journal. 2013; 60(8):951–957. Available:https://doi.org/10.1507/endocrj.ej13-0025

Hirshberg B, Cochran C, Skarulis MC, Libutti SK, Alexander HR, Wood BJ, Chang R, Kleiner DE, Gorden P. Malignant insulinoma: spectrum of unusual clinical features. Cancer. 2005;104(2):264– 272. Available:https://doi.org/10.1002/cncr.21179

Healy ML, Dawson SJ, Murray RM, Zalcberg J, Jefford M. Severe hypoglycaemia after long-acting octreotide in a patient with an unrecognized malignant insulinoma. Internal Medicine Journal. 2007;37(6):406–409.

Available:https://doi.org/10.1111/j.1445-5994.2007.01371.x

Stehouwer CD, Lems WF, Fischer HR, Hackeng WH, Naafs MA. Aggravation of hypoglycemia in insulinoma patients by the long-acting somatostatin analogue octreotide (Sandostatin). Acta Endocrinologica. 1989;121(1):34–40.

Available:https://doi.org/10.1530/acta.0.1210034

Jawiarczyk A, Bolanowski M, Syrycka J, Bednarek-Tupikowska G, Kałużny M, Kołodziejczyk A, Domosławski P. Effective therapy of insulinoma by using long-acting somatostatin analogue. A case report and literature review. Experimental and Clinical Endocrinology & Diabetes: Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2012; 120(2):68–72. Available:https://doi.org/10.1055/s-0031-1287792

Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, Mayer C, Aminossadati B., Pape UF, Bläker M, Harder J, Arnold C, Gress T, Arnold R. PROMID Study Group. 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 from the PROMID Study Group. Journal of Clinical Oncology: official journal of the American Society of Clinical Oncology. 2009;27(28):4656–4663.

Available:https://doi.org/10.1200/JCO.2009.22.8510

Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P. CLARINET Investigators. Lanreotide is in metastatic enteropancreatic neuroendocrine tumors. The New England Journal of Medicine. 2014;371(3):224–233. Available:https://doi.org/10.1056/NEJMoa1316158

Michael M, Garcia-Carbonero R, Weber MM, Lombard-Bohas C, Toumpanakis C, Hicks RJ. The Antiproliferative Role of Lanreotide in Controlling Growth of Neuroendocrine Tumors: A Systematic Review. The Oncologist. 2017;22(3):272–285. Available:https://doi.org/10.1634/theoncologist.2016-0305

Arnold R, Wied M, Behr TH. Somatostatin analogues in the treatment of endocrine tumors of the gastrointestinal tract. Expert Opinion on Pharmacotherapy. 2002;3(6): 643–656.

Available:https://doi.org/10.1517/14656566.3.6.643

Lamberts SW, Van Der Lely AJ, De Herder WW, Hofland LJ. Octreotide. The New England Journal of Medicine. 1996; 334(4):246–254. Available:https://doi.org/10.1056/NEJM199601253340408

Newman CB, Melmed S, Snyder PJ, Young WF, Boyajy LD, Levy R, Stewart WN, Klibanski A, Molitch ME, Gagel RF. Safety and efficacy of long-term octreotide therapy of acromegaly: results of a multicenter trial in 103 patients--a clinical research center study. The Journal of Clinical Endocrinology and Metabolism. 1995;80(9):2768–2775. Available:https://doi.org/10.1210/jcem.80.9.7673422

Bongiovanni A, Nicolini S, Ibrahim T, Foca F, Sansovini M, Di Paolo A, Grassi I, Liverani C, Calabrese C, Ranallo N, Matteucci F, Paganelli G, Severi S. 177Lu-DOTATATE Efficacy and Safety in Functioning Neuroendocrine Tumors: A Joint Analysis of Phase II Prospective Clinical Trials. Cancers. 2022; 14(24) :6022.

Available:https://doi.org/10.3390/cancers14246022

De Herder WW, Van Schaik E, Kwekkeboom DJ, Feelders RA. New therapeutic options for metastatic malignant insulinomas. Clinical Endocrinology. 2011b;75(3):277–284.

Available: https://doi.org/10.1111/j.1365-2265.2011.04145.x

Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A. NETTER-1 Trial Investigators. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. The New England Journal of Medicine. 2017; 376(2):125–135. Available:https://doi.org/10.1056/NEJMoa1607427

Brabander T, Van Der Zwan WA, Teunissen JJM, Kam BLR, Feelders RA, De Herder WW, Van Eijck CHJ, Franssen GJH, Krenning EP, Kwekkeboom DJ. Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3] octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research. 2017;23(16):4617–4624.

Available:https://doi.org/10.1158/1078-0432.CCR-16-2743

Cives M, Strosberg J. Radionuclide Therapy for Neuroendocrine Tumors. Current Oncology Reports. 2017; 19(2):9. Available:https://doi.org/10.1007/s11912-017-0567-8

Asti M, Tegoni M, Farioli D, Iori M, Guidotti C, Cutler CS, Mayer P, Versari A, Salvo D. Influence of cations on the complexation yield of DOTATATE with yttrium and lutetium: a perspective study for enhancing the 90Y and 177Lu labeling conditions. Nuclear Medicine and Biology. 2012; 39(4):509–517. Available:https://doi.org/10.1016/j.nucmedbio.2011.10.015

De Araújo EB, Caldeira Filho JS, Nagamati LT, Muramoto, E, Colturato MT, Couto RM, Pujatti PB, Mengatti J, Silva CP. A comparative study of 131I and 177Lu labeled somatostatin analogues for therapy of neuroendocrine tumours. Applied Radiation and Isotopes: Including Data, Instrumentation and Methods for use in Agriculture, Industry and Medicine. 2009; 67(2):227–233. Available:https://doi.org/10.1016/j.apradiso.2008.09.009

Cives M, Strosberg JR. Treatment Strategies for Metastatic Neuroendocrine Tumors of the Gastrointestinal Tract. Current Treatment Options in Oncology. 2017;18(3).

Available:https://doi.org/10.1007/s11864-017-0461-5

Hofland J, Brabander T, Verburg FA, Feelders RA, De Herder WW. Peptide Receptor Radionuclide Therapy. The Journal of Clinical Endocrinology and Metabolism. 2022;107(12):3199–3208.

Available:https://doi.org/10.1210/clinem/dgac574

Bergsma H, Konijnenberg M, Kam BLR, Teunissen JJ, Kooij PPM, De Herder WWW, Franssen GJH, Van Eijck CH, Krenning EP, Kwekkeboom DJ. Subacute haematotoxicity after PRRT with 177Lu-DOTA-octreotate: prognostic factors, incidence and course. European Journal of Nuclear Medicine and Molecular Imaging. 2016;43(3):453–463.

Available:https://doi.org/10.1007/s00259-015-3193-4

Bergsma H, Van Lom K, Raaijmakers MH, Konijnenberg MW, Kam BBL, Teunissen JJ, De Herder WW, Krenning EP, Kwekkeboom DJ. Persistent Hematologic Dysfunction after Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE: Incidence, Course, and Predicting Factors in Patients with Gastroenteropancreatic Neuroendocrine Tumors. The Journal of Nuclear Medicine. 2018;59(3):452–458.

Available:https://doi.org/10.2967/jnumed.117.189712

Kwekkeboom DJ, De Herder WW, Kam BL, Van Eijck CH, Van Essen M, Kooij PP, Feelders RA, Van Aken MO, Krenning EP. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3] octreotate: Toxicity, efficacy, and survival. Journal of Clinical Oncology : Official Journal of The American Society of Clinical Oncology. 2008;26(13):2124–2130. Available:https://doi.org/10.1200/JCO.2007.15.2553

Ong GS, Henley DE, Hurley D, Turner JH, Claringbold PG, Fegan PG. Therapies for the medical management of persistent hypoglycaemia in two cases of inoperable malignant insulinoma. European Journal of Endocrinology. 2010;162(5):1001–1008.

Available:https://doi.org/10.1530/EJE-09-1010

Zandee WT, Brabander T, Blažević A, Kam BLR, Teunissen JJM, Feelders RA, Hofland J, De Herder WW. Symptomatic and Radiological Response to 177Lu-DOTATATE for the Treatment of Functioning Pancreatic Neuroendocrine Tumors. The Journal of Clinical Endocrinology and Metabolism. 2019; 104(4):1336–1344. Available:https://doi.org/10.1210/jc.2018-01991

Kumar S, Melek M, Rohl PJ. Case Report: Hypoglycemia Due to Metastatic Insulinoma in Insulin-Dependent Type 2 Diabetes Successfully Treated With 177 Lu-DOTATATE. Frontiers in Endocrinology. 2022:13. Available:https://doi.org/10.3389/fendo.2022.906012

Magalhães D, Sampaio IL, Ferreira G, Bogalho P, Martins-Branco D, Santos RL, Duarte H. Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE as a promising treatment of malignant insulinoma: A series of case reports and literature review. Journal of Endocrinological Investigation. 2019;42(3): 249–260.

Available:https://doi.org/10.1007/s40618-018-0911-3