Current Management Strategies for Patients With Gastrointestinal and Pulmonary Neuroendocrine Tumors
- 作者: Mikheeva Y.V.1, Rumyantsev P.O.2, Puzakov K.K.1, Slashchuk K.Y.3, Omelchuk D.D.4, Potapenko A.V.2, Medvedev S.P.1
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隶属关系:
- National Medical Research Centre "Treatment and Rehabilitation Centre", Moscow, Russia
- BELOOSTROV Clinic of High Technologies, Saint Petersburg, Russia
- Endocrinology Research Centre, Moscow, Russia
- Doctor 03, Moscow, Russia
- 栏目: Reviews
- ##submission.dateSubmitted##: 10.12.2024
- ##submission.dateAccepted##: 23.05.2025
- ##submission.datePublished##: 26.05.2025
- URL: https://rjonco.com/1028-9984/article/view/642734
- DOI: https://doi.org/10.17816/onco642734
- ID: 642734
如何引用文章
详细
Neuroendocrine tumors (NETs) of the gastrointestinal tract and lungs are rare yet clinically significant neoplasms characterized by heterogeneous progression and diverse manifestations. This article systematizes current management strategies based on the latest recommendations and scientific advances. Epidemiological trends are a key focus, including an increase in NET incidence rates over the past few decades (6.4 times in the USA from 1973 to 2012) and the predominance of gastroenteropancreatic NETs (62–70%) and bronchopulmonary NETs (25%). The following key clinical aspects are highlighted, including hormonally active conditions (carcinoid syndrome, gastrinomas, insulinomas) and their complications (carcinoid heart disease and crises). Current approaches to diagnose, treatment, and monitoring of NETs are discussed using recent guidelines and scientific data. Molecular genetic testing is emphasized because of its ability to improve risk stratification and personalize treatment. The following treatment options are discussed: surgery (resection, liver transplantation); pharmacotherapy (somatostatin analogues, telotristat, and targeted therapies such as sunitinib and everolimus); chemotherapy; peptide receptor radionuclide therapy. The key study outcomes are presented. The article also addresses challenges in early diagnosis and the need for a multidisciplinary approach and personalized treatment. Promising areas of using novel biomarkers and imaging techniques are mentioned, and the importance of follow-up is emphasized, including follow-up intervals and watch and wait strategies for small tumors. The article discusses the challenges of early diagnosis and the importance of thorough tumor evaluations and explores prospects for further research to optimize treatment strategies.
全文:

作者简介
Yulia Mikheeva
National Medical Research Centre "Treatment and Rehabilitation Centre", Moscow, Russia
Email: yuliya.mikheeva64@gmail.com
ORCID iD: 0009-0009-2644-3102
SPIN 代码: 2298-1810
MD, Cand. Sci. (Medicine), Head of the Oncology Department
俄罗斯联邦, Moscow, RussiaPavel Rumyantsev
BELOOSTROV Clinic of High Technologies, Saint Petersburg, Russia
Email: pavelrum@gmail.com
ORCID iD: 0000-0002-7721-634X
SPIN 代码: 7085-7976
MD, Dr. Sci. (Medicine)
俄罗斯联邦, Saint Petersburg, RussiaKonstantin Puzakov
National Medical Research Centre "Treatment and Rehabilitation Centre", Moscow, Russia
Email: k_kovalchik@mail.ru
ORCID iD: 0009-0001-6869-1579
SPIN 代码: 5800-6834
俄罗斯联邦, Moscow, Russia
Konstantin Slashchuk
Endocrinology Research Centre, Moscow, Russia
Email: slashuk911@gmail.com
ORCID iD: 0000-0002-3220-2438
SPIN 代码: 3079-8033
MD, Cand. Sci. (Medicine), Oncologist, endocrinologist of the Radionuclide Therapy Department
俄罗斯联邦, Moscow, RussiaDaniil Omelchuk
Doctor 03, Moscow, Russia
Email: lebedev1dd@gmail.com
ORCID iD: 0000-0002-2788-2352
SPIN 代码: 6398-0656
MD, Cand. Sci. (Medicine)
俄罗斯联邦, Moscow, RussiaAnastasiya Potapenko
BELOOSTROV Clinic of High Technologies, Saint Petersburg, Russia
Email: osipchukanastasiia@gmail.com
ORCID iD: 0000-0001-8903-7325
SPIN 代码: 6774-4710
俄罗斯联邦, Saint Petersburg, Russia
Sergey Medvedev
National Medical Research Centre "Treatment and Rehabilitation Centre", Moscow, Russia
编辑信件的主要联系方式.
Email: feelyou2017@mail.ru
ORCID iD: 0009-0008-2395-3169
SPIN 代码: 7382-5729
俄罗斯联邦, Moscow, Russia
参考
- Klöppel G. Neuroendocrine Neoplasms: Dichotomy, Origin and Classifications. Visc Med. 2017;33(5):324–330. doi: 10.1159/000481390
- Fraenkel M, Faggiano A, Valk GD. Epidemiology of Neuroendocrine Tumors. Frontiers of Hormone Research. 2015;44:1–23. doi: 10.1159/000381970
- Ito T, Lee L, Jensen RT. Carcinoid-syndrome: recent advances, current status and controversies. Current Opinion in Endocrinology & Diabetes and Obesity. 2018;25(1):22–35. doi: 10.1097/MED.0000000000000376
- Fang JM, Li J, Shi J. An update on the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. World J Gastroenterol. 2022;28(10):1009–1023. doi: 10.3748/wjg.v28.i10.1009
- Dasari A, Shen C, Halperin D, et al. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. JAMA Oncol. 2017;3(10):1335–1342. doi: 10.1001/jamaoncol.2017.0589
- Xu Z, Wang L, Dai S, et al. Epidemiologic Trends of and Factors Associated With Overall Survival for Patients With Gastroenteropancreatic Neuroendocrine Tumors in the United States. JAMA Netw Open. 2021;4(9):e2124750. doi: 10.1001/jamanetworkopen.2021.24750
- Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97(4):934–59. doi: 10.1002/cncr.11105
- Clift AK, Kidd M, Bodei L, et al. Neuroendocrine Neoplasms of the Small Bowel and Pancreas. Neuroendocrinology. 2020;110(6):444–476. doi: 10.1159/000503721
- Halperin DM, Shen C, Dasari A, et al. Frequency of carcinoid syndrome at neuroendocrine tumour diagnosis: a population-based study. Lancet Oncol. 2017;18:525–534. doi: 10.1016/S1470-2045(17)30110-9
- Oronsky B, Ma PC, Morgensztern D, Carter CA. Nothing But NET: A Review of Neuroendocrine Tumors and Carcinomas. Neoplasia. 2017;19(12):991–1002. doi: 10.1016/j.neo.2017.09.002
- Russo S, Nielen MM, Boon JC, et al. Neuropsychological investigation into the carcinoid syndrome. Psychopharmacology (Berl). 2003;168:324–328. doi: 10.1007/s00213-003-1455-5
- Jin C, Sharma AN, Thevakumar B, et al. Pathophysiology, Pathology, Clinical Manifestations, and Management. Cardiology. 2021;146(1):65–73. doi: 10.1159/000507847
- Xu A, Suz P, Reljic T, et al. Perioperative Carcinoid Crisis: A Systematic Review and Meta-Analysis. Cancers (Basel). 2022;14(12):2966. doi: 10.3390/cancers14122966
- Ito T, Lee L, Jensen RT. Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies. Expert Opin Pharmacother. 2016;17(16):2191–2205. doi: 10.1080/14656566.2016.1236916
- Landry JP, Clemente-Gutierrez U, Pieterman CRC, et al. Management of adrenocorticotropic hormone-secreting neuroendocrine tumors and the role of bilateral adrenalectomy in ectopic Cushing syndrome. Surgery. 2022;172(2):559–566. doi: 10.1016/j.surg.2022.03.014
- Gibril F, Chen YJ, Schrump DS, et al. Prospective study of thymic carcinoids in patients with multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 2003;88(3):1066–1081. doi: 10.1210/jc.2002-021314
- Fang JM, Li J, Shi J. An update on the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. World J Gastroenterol. 2022;28(10):1009–1023. doi: 10.3748/wjg.v28.i10.1009
- Rooper LM, Sharma R, Li QK, et al. INSM1 Demonstrates Superior Performance to the Individual and Combined Use of Synaptophysin, Chromogranin and CD56 for Diagnosing Neuroendocrine Tumors of the Thoracic Cavity. Am J Surg Pathol. 2017;41(11):1561–1569. doi: 10.1097/PAS.0000000000000916
- Hankus J, Tomaszewska R. Neuroendocrine neoplasms and somatostatin receptor subtypes expression. Nucl Med Rev Cent East Eur. 2016;19(2):111–117. doi: 10.5603/NMR.2016.0022
- Strosberg JR, Halfdanarson TR, Bellizzi AM, et al. The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors. Pancreas. 2017;46(6):707–714. doi: 10.1097/MPA.0000000000000850
- McCall CM, Shi C, Cornish TC, et al. Grading of well-differentiated pancreatic neuroendocrine tumors is improved by the inclusion of both Ki67 proliferative index and mitotic rate. Am J Surg Pathol. 2013;37(11):1671–1677. doi: 10.1097/PAS.0000000000000089
- Rindi G, Klimstra DS, Abedi-Ardekani B, et al. A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod Pathol. 2018;31(12):1770–1786. doi: 10.1038/s41379-018-0110-y
- Tang LH, Untch BR, Reidy DL, et al. Well-Differentiated Neuroendocrine Tumors with a Morphologically Apparent High-Grade Component: A Pathway Distinct from Poorly Differentiated Neuroendocrine Carcinomas. Clin Cancer Res. 2016;22(4):1011–1017. doi: 10.1158/1078-0432.CCR-15-0548
- Simbolo M, Mafficini A, Sikora KO, et al. Lung neuroendocrine tumours: deep sequencing of the four World Health Organization histotypes reveals chromatin-remodelling genes as major players and a prognostic role for TERT, RB1, MEN1 and KMT2D. J Pathol. 2017;241(4):488–500. doi: 10.1002/path.4853
- Wang F, Xu X, Ye Z, et al. Prognostic Significance of Altered ATRX/DAXX Gene in Pancreatic Neuroendocrine Tumors: A Meta-Analysis. Front. Endocrinol. 2021;12:691557. doi: 10.3389/fendo.2021.691557
- Bellizzi A.M. Immunohistochemistry in the diagnosis and classification of neuroendocrine neoplasms: what can brown do for you? Hum Pathol. 2020;96:8–33. doi: 10.1016/j.humpath.2019.12.002
- Niederst MJ, Sequist LV, Poirier JT, et al. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun. 2015;6:6377. doi: 10.1038/ncomms7377
- Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med. 2011;3(75):75ra26. doi: 10.1126/scitranslmed.3002003
- Leonetti A, Sharma S, Minari R, et al. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br J Cancer. 2019;121(9):725–737. doi: 10.1038/s41416-019-0573-8
- Kulke MH. Clinical presentation and management of carcinoid tumors. Hematol Oncol Clin North Am. 2007;21(3):433–455. doi: 10.1016/j.hoc.2007.04.004
- Di Giacinto P, Rota F, Rizza L, et al. Chromogranin A: From Laboratory to Clinical Aspects of Patients with Neuroendocrine Tumors. Int J Endocrinol. 2018;8126087. doi: 10.1155/2018/8126087
- Bhattacharyya S, Toumpanakis C, Chilkunda D, et al. Risk Factors for the Development and Progression of Carcinoid Heart Disease. Am. J. Cardiol. 2011;107:1221–1226. doi: 10.1016/j.amjcard.2010.12.025
- Kalligeros M, Diamantopoulos L, Toumpanakis C. Biomarkers in Small Intestine NETs and Carcinoid Heart Disease: A Comprehensive Review. Biology (Basel). 2021;10(10):950. doi: 10.3390/biology10100950
- Isgrò MA, Bottoni P, Scatena R. Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. Adv Exp Med Biol. 2015;867:125–143. doi: 10.1007/978-94-017-7215-0_9
- Ma ZY, Gong YF, Zhuang HK, et al. Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management. World J Gastroenterol. 2020;26(19):2305–2322. doi: 10.3748/wjg.v26.i19.2305
- Puli SR, Kalva N, Bechtold ML, et al. Diagnostic accuracy of endoscopic ultrasound in pancreatic neuroendocrine tumors: a systematic review and meta analysis. World J Gastroenterol. 2013;19(23):3678–3684. doi: 10.3748/wjg.v19.i23.3678
- James PD, Tsolakis AV, Zhang M, et al. Incremental benefit of preoperative EUS for the detection of pancreatic neuroendocrine tumors: a meta-analysis. Gastrointest Endosc. 2015;81:848–856.e1. doi: 10.1016/j.gie.2014.12.031
- Partelli S, Muffatti F, Andreasi V, et al. A Single-center Prospective Observational Study Investigating the Accuracy of Preoperative Diagnostic Procedures in the Assessment of Lymph Node Metastases in Nonfunctioning Pancreatic Neuroendocrine Tumors. Ann Surg. 2022;276(5):921–928. doi: 10.1097/SLA.0000000000005615
- Giri S, Afzalpurkar S, Angadi S, et al. Mucosal incision-assisted biopsy versus endoscopic ultrasound-assisted tissue acquisition for subepithelial lesions: a systematic review and meta-analysis. Clin Endosc. 2022;55(5):615–625. doi: 10.5946/ce.2022.133
- Iabichino G, Di Leo M, Arena M, et al. Diagnosis, treatment, and current concepts in the endoscopic management of gastroenteropancreatic neuroendocrine neoplasms. World J Gastroenterol. 2022;28(34):4943–4958. doi: 10.3748/wjg.v28.i34.4943
- Sundin A, et al. ENETS 2017 Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Radiological, Nuclear Medicine and Hybrid Imaging. Neuroendocrinology. 2017;105(3):212–245. doi: 10.1159/000471879
- Lee ST, Kulkarni HR, Singh A, Baum RP. Theranostics of Neuroendocrine Tumors. Visc Med. 2017;33(5):358–366. doi: 10.1159/000480383
- Saponjski J, Macut D, Petrovic N, et al. Diagnostic and prognostic value of 99mTc-Tektrotyd scintigraphy and 18F-FDG PET/CT in a single-center cohort of neuroendocrine tumors. Arch Med Sci. 2021;19(6):1753–1759. doi: 10.5114/aoms/130996
- Artiko V, Afgan A, Petrović J, et al. Evaluation of neuroendocrine tumors with 99mTc-EDDA/HYNIC TOC. Nucl Med Rev Cent East Eur. 2016;19(2):99–103. doi: 10.5603/NMR.2016.0020
- Sharma P, Singh H, Bal C, Kumar R. PET/CT imaging of neuroendocrine tumors with (68)Gallium-labeled somatostatin analogues: An overview and single institutional experience from India. Indian J Nucl Med. 2014;29(1):2–12. doi: 10.4103/0972-3919.125760
- Kunikowska J, Lewington V, Krolicki L. Optimizing Somatostatin Receptor Imaging in Patients With Neuroendocrine Tumors: The Impact of 99mTc-HYNICTOC SPECT/SPECT/CT Versus 68Ga-DOTATATE PET/CT Upon Clinical Management. Clin Nucl Med. 2017;42(12):905–911. doi: 10.1097/RLU.0000000000001877
- Wang R, Zheng-Pywell R, Chen HA, et al. Management of Gastrointestinal Neuroendocrine Tumors. Clin Med Insights Endocrinol Diabetes. 2019;12. doi: 10.1177/1179551419884058
- Hendifar AE, Marchevsky AM, Tuli R. Neuroendocrine Tumors of the Lung: Current Challenges and Advances in the Diagnosis and Management of Well-Differentiated Disease. J Thorac Oncol. 2017;12(3):425–436. doi: 10.1016/j.jtho.2016.11.2222
- Hofland J, Falconi M, Christ E, et al. European Neuroendocrine Tumor Society 2023 guidance paper for functioning pancreatic neuroendocrine tumour syndromes. J Neuroendocrinol. 2023;35(8):e13318. doi: 10.1111/jne.13318
- Dumlu EG, Karakoc D, Ozdemir A. Nonfunctional Pancreatic Neuroendocrine Tumors: Advances in Diagnosis, Management, and Controversies. Int Surg. 2015;100(6):1089–1097. doi: 10.9738/INTSURG-D-14-00204.1
- Hensley ML, Hagerty KL, Kewalramani T, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27(1):127–145. doi: 10.1200/JCO.2008.17.2627
- Sallinen V, Le Large TY, Galeev S, et al. Surveillance strategy for small asymptomatic non-functional pancreatic neuroendocrine tumors - a systematic review and meta-analysis. HPB (Oxford). 2017;19(4):310–320. doi: 10.1016/j.hpb.2016.12.010
- Lesurtel M, Nagorney DM, Mazzaferro V, et al. When should a liver resection be performed in patients with liver metastases from neuroendocrine tumours? A systematic review with practice recommendations. HPB (Oxford). 2015;17(1):17–22. doi: 10.1111/hpb.12225
- Gurusamy KS, Ramamoorthy R, Sharma D, et al. Liver resection versus other treatments for neuroendocrine tumours in patients with resectable liver metastases. Cochrane Database Syst Rev. 2009;2009(2):CD007060. doi: 10.1002/14651858
- Phan AT. Metastatic pancreatic neuroendocrine tumors (pNET): placing current findings into perspective. Cancer Treat Rev. 2013;39(1):3–9. doi: 10.1016/j.ctrv.2012.02.010
- Al-Efraij K, Aljarma MA, Kennecke HF. Association of dose escalation of octreotide long-acting release on clinical symptoms and tumor markers and response among patients with neuroendocrine tumors. Cancer Med. 2015;4(6):864–870. doi: 10.1002/cam4.435
- Ferolla P, Faggiano A, Grimaldi F, et al. Shortened interval of long-acting octreotide administration is effective in patients with well-differentiated neuroendocrine carcinomas in progression on standard doses. J Endocrinol Invest. 2012;35(3):326–331. doi: 10.3275/7869
- Rinke A, Wittenberg M, Schade-Brittinger C, et al. 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 (PROMID): Results of Long-Term Survival. Neuroendocrinology. 2017;104(1):26–32. doi: 10.1159/000443612
- Caplin ME, Pavel M, Cwikla JB, et al. CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371(3):224–233. doi: 10.1056/NEJMoa1316158
- 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):3049. doi: 10.3390/ijms20123049
- Kiesewetter B, Pflugerr FF, Melhorn P, et al. Long-term experience with octreotide and lanreotide for the treatment of gastroenteropancreatic neuroendocrine tumors. Clin Transl Oncol. 2024. doi: 10.1007/s12094-024-03732-w
- Pavel M, Cwikla JB, Lombard-Bohas C, et al. Efficacy and safety of high-dose lanreotide autogel in patients with progressive pancreatic or midgut neuroendocrine tumours: CLARINET FORTE phase 2 study results. Eur J Cancer. 2021;157:403–414. doi: 10.1016/j.ejca.2021.06.056
- Diamantopoulos LN, Laskaratos FM, Kalligeros M, et al. Antiproliferative Effect of Above-Label Doses of Somatostatin Analogs for the Management of Gastroenteropancreatic Neuroendocrine Tumors. Neuroendocrinology. 2021;111(7):650–659. doi: 10.1159/000509420
- Caplin ME, Baudin E, Ferolla P, et al. ENETS consensus conference participants. Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids. Ann Oncol. 2015;26(8):1604–1620. doi: 10.1093/annonc/mdv041
- Ferolla P, Berruti A, Spada F, et al. Efficacy and Safety of Lanreotide Autogel and Temozolomide Combination Therapy in Progressive Thoracic Neuroendocrine Tumors (Carcinoid): Results from the Phase 2 ATLANT Study. Neuroendocrinology. 2023;113(3):332–342. doi: 10.1159/000526811
- Wolin EM, Jarzab B, Eriksson B, et al. Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues. Drug Des Devel Ther. 2015;9:5075–1586. doi: 10.2147/DDDT.S84177
- Cives M, et al. A phase II trial of pasireotide long-acting release in patients with metastatic neuroendocrine tumors refractory to octreotide LAR. European Journal of Cancer. 69.34–40. doi: 10.1016/j.ejca.2016.07.023
- Gadelha MR, et al. Hyperglycemia management in patients treated with pasireotide: consensus recommendations from a multidisciplinary expert panel. Endocrine Practice. 20(9),963–972. doi: 10.4158/EP13449.RA
- Strosberg J, et al. North American Neuroendocrine Tumor Society (NANETS) guidelines: Surveillance and management of recurrent or metastatic disease. Pancreas. 49(1),17–27. doi: 10.1097/MPA.0000000000001454
- Oberg K. Interferons in the management of neuroendocrine tumors and their possible mechanism of action. Yale J Biol Med. 1992;65(5):519–529
- Oberg K, Eriksson B, Janson ET. Interferons alone or in combination with chemotherapy or other biologicals in the treatment of neuroendocrine gut and pancreatic tumors. Digestion. 1994;55(3):64–69. doi: 10.1159/000201204
- Pavel M, Gross DJ, Benavent M, et al. Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial. Endocr Relat Cancer. 2018;25(3):309–322. doi: 10.1530/ERC-17-0455
- Herrera-Martínez AD, Fuentes-Fayos AC, Sanchez-Sanchez R, et al. Does Telotristat Have a Role in Preventing Carcinoid Heart Disease? Int J Mol Sci. 2024;25(4):2036. doi: 10.3390/ijms25042036
- Morse MA, Liu E. Joish VN, et al. Antiproliferative Effects of Telotristat Ethyl in Patients with Neuroendocrine Tumors: The TELEACE Real-World Chart Review Study. Cancer Manag Res. 2020;12:6607–6614. doi: 10.2147/CMAR.S261257
- Faivre S, Niccoli P, Castellano D, et al. Sunitinib in pancreatic neuroendocrine tumors: updated progression-free survival and final overall survival from a phase III randomized study. Ann Oncol. 2017;28(2):339–343. doi: 10.1093/annonc/mdw561
- Yao JC, Phan AT, Chang DZ, et al. Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol. 2008;26(26):4311–8. doi: 10.1200/JCO.2008.16.7858
- Pavel ME, Hainsworth JD, Baudin E, et al. RADIANT-2 Study Group. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011;378(9808):2005–2012. doi: 10.1016/S0140-6736(11)61742-X
- Yao JC, Shah MH, Ito T, et al. RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study Group. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):514–523. doi: 10.1056/NEJMoa1009290
- Ishak KJ, Rael M, Hicks M, et al. Relative effectiveness of sunitinib versus everolimus in advanced pancreatic neuroendocrine tumors: an updated matching-adjusted indirect comparison. J Comp Eff Res. 2018;7(10):947–958. doi: 10.2217/cer-2018-0020
- 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. doi: 10.1016/S0140-6736(15)00817-X
- Ahn HK, Choi SH, Park SH, et al. Phase II study of pazopanib monotherapy in metastatic gastroenteropancreatic neuroendocrine tumours. Br J Cancer. 2013;109(6):1414–1419. doi: 10.1038/bjc.2013.470
- Bongiovanni A, Liverani C, Recine F, et al. Phase-II Trials of Pazopanib in Metastatic Neuroendocrine Neoplasia (mNEN): A Systematic Review and Meta-Analysis. Front Oncol. 2020;10:414. doi: 10.3389/fonc.2020.00414
- Fallah J, Brave MH, Weinstok C, et al. FDA Approval Summary: Belzutifan for von Hippel-Lindau Disease-Associated Tumors. Clin Cancer Res. 2022;28(22):4843–4848. doi: 10.1158/1078-0432.CCR-22-1054
- Sorbye H, Welin S, Langer SW, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol. 2013;24(1):152–60. doi: 10.1093/annonc/mds276
- Moertel CG, Hanley JA, Johnson LA. Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1980;303(21):1189–1194. doi: 10.1056/NEJM198011203032101
- Arrivi G, Verrico M, Roberto M, et al. Capecitabine and Temozolomide (CAPTEM) in Advanced Neuroendocrine Neoplasms (NENs): A Systematic Review and Pooled Analysis. Cancer Manag Res. 2022;14:3507–3523. doi: 10.2147/CMAR.S372776
- Borghesani M, Reni A, Lauricella E, et al. Efficacy and Toxicity Analysis of mFOLFIRINOX in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms. J Natl Compr Canc Netw. 2024;22(5):e247005. doi: 10.6004/jnccn.2024.7005
- Strosberg JR, Caplin ME, Kunz PL, et al. NETTER-1 investigators. 177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021;22(12):1752–1763. doi: 10.1016/S1470-2045(21)00572-6
- Singh S, Halperin D, Myrehaug S, et al. All the NETTER-2 Trial Investigators. [177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high‑dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2-3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised, phase 3 study. Lancet. 2024;403(10446):2807–2817. doi: 10.1016/S0140-6736(24)00701-3
- Strosberg JR, Halfdanarson TR, Bellizzi AM, et al. The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors. Pancreas. 2017;46(6):707–714. doi: 10.1097/MPA.0000000000000850
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