181
Views
5
CrossRef citations to date
0
Altmetric
Review

Therapeutic strategies for patients with neuroendocrine neoplasms: current perspectives

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 389-403 | Received 03 Mar 2022, Accepted 06 Jul 2022, Published online: 13 Jul 2022

References

  • Ameri P, Ferone D. Diffuse endocrine system, neuroendocrine tumors and immunity: what’s new? Neuroendocrinology. 2012;95(4):267–276.
  • Rosai J. The origin of neuroendocrine tumors and the neural crest saga. Mod Pathol. 2011;24(Suppl 2):S53–7.
  • 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.
  • O’Shea T, Druce M. When should genetic testing be performed in patients with neuroendocrine tumours? Rev Endocr Metab Disord. 2017;18(4):499–515.
  • Ida A, Okubo Y, Kasajima R, et al. Clinicopathological and genetic analyses of small cell neuroendocrine carcinoma of the prostate: histological features for accurate diagnosis and toward future novel therapies. Pathol Res Pract. 2022;229:153731.
  • Massironi S, Campana D, Pusceddu S, et al. Second primary neoplasms in patients with lung and gastroenteropancreatic neuroendocrine neoplasms: data from a retrospective multi-centric study. Dig Liver Dis. 2021;53(3):367–374.
  • Feola T, Puliani G, Sesti F, et al. Risk factors for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a three-centric case-control study. J Endocrinol Invest. 2022;45(4):849–857.
  • Barrea L, Muscogiuri G, Modica R, et al. Cardio-metabolic indices and metabolic syndrome as predictors of clinical severity of gastroenteropancreatic neuroendocrine tumors. Front Endocrinol (Lausanne). 2021;12:649496.
  • Ito T, Lee L, Jensen RT. Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies. Expert Opin Pharmacother. 2016;17(16):2191–2205.
  • Riihimäki M, Hemminki A, Sundquist K, et al. The epidemiology of metastases in neuroendocrine tumors. Int J Cancer. 2016;139(12):2679–2686.
  • Das S, Dasari A. Epidemiology, incidence, and prevalence of neuroendocrine neoplasms: are there global differences? Curr Oncol Rep. 2021;23(4):43.
  • Zatelli MC, Guadagno E, Messina E, et al. Open issues on G3 neuroendocrine neoplasms: back to the future. Endocr Relat Cancer. 2018;25(6):R375–R384.
  • Board. WCoTE. Digestive system tumours. Lyon (France):International Agency for Research on cancer;2019. WHO classification of tumours seires tev.
  • Travis WD, Brambilla E, Burke AP, et al. Introduction to the 2015 World Health Organization classification of tumors of the lung, pleura, thymus, and heart. J Thorac Oncol. 2015;10(9):1240–1242.
  • 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.
  • Pavel M, Valle JW, Eriksson B, et al. ENETS consensus guidelines for the standards of care in neuroendocrine neoplasms: systemic therapy - biotherapy and novel targeted agents. Neuroendocrinology. 2017;105(3):266–280.
  • Del Prete M, Fiore F, Modica R, et al. Hepatic arterial embolization in patients with neuroendocrine tumors. J Exp Clin Cancer Res. 2014;33(1):43.
  • Faggiano A, Di Maio S, Mocerino C, et al. Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group. Endocrine. 2019;66(2):417–424.
  • [cited 2022 Feb 1]. https://www.nccn.org/login?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf .
  • Scandurra C, Modica R, Maldonato NM, et al. Quality of life in patients with neuroendocrine neoplasms: the role of severity, clinical heterogeneity, and resilience. J Clin Endocrinol Metab. 2021;106(1):e316–e327.
  • Faggiano A, Lo Calzo F, and Pizza G, et al. The safety of available treatments options for neuroendocrine tumors. Expert Opin Drug Saf. 2017;16(10): 1149–1161. .
  • Modlin IM, Pavel M, Kidd M, et al. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol Ther. 2010;31(2):169–188.
  • Oberg K. Future aspects of somatostatin-receptor-mediated therapy. Neuroendocrinology. 2004;80(Suppl 1):57–61.
  • Grozinsky-Glasberg S, Shimon I, Korbonits M, et al. Somatostatin analogues in the control of neuroendocrine tumours: efficacy and mechanisms. Endocr Relat Cancer. 2008;15(3):701–720.
  • Narayanan S, Kunz PL. Role of somatostatin analogues in the treatment of neuroendocrine tumors. J Natl Compr Canc Netw. 2015;13(1):109–117. quiz 117.
  • Bruns C, Lewis I, Briner U, et al. SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol. 2002;146(5):707–716.
  • Toumpanakis C, Garland J, Marelli L, et al. Long-term results of patients with malignant carcinoid syndrome receiving octreotide LAR. Aliment Pharmacol Ther. 2009;30(7):733–740.
  • Vinik AI, Wolin EM, Liyanage N, et al. Evaluation of lanreotide depot/autogel efficacy and safety as a carcinoid syndrome treatment (elect): a randomized, double-blind, placebo-controlled trial. Endocr Pract. 2016;22(9):1068–1080.
  • Fisher GA, Wolin EM, Liyanage N, et al. Patient-reported symptom control of diarrhea and flushing in patients with neuroendocrine tumors treated with lanreotide depot/autogel: results from a randomized, placebo-controlled, double-blind and 32-Week Open-Label Study. Oncologist. 2018;23(1):16–24.
  • Susini C, Buscail L. Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol. 2006;17(12):1733–1742.
  • Florio T. Molecular mechanisms of the antiproliferative activity of somatostatin receptors (SSTRs) in neuroendocrine tumors. Front Biosci. 2008;13(13):822–840.
  • Chan DL, Ferone D, Albertelli M, et al. Escalated-dose somatostatin analogues for antiproliferative effect in GEPNETS: a systematic review. Endocrine. 2017;57(3):366–375.
  • Rinke A, Müller -H-H, Schade-Brittinger C, et al. 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. J Clin Oncol. 2009;27(28):4656–4663.
  • Caplin ME, Pavel M, Ćwikła JB, et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371(3):224–233.
  • Rinke A, Wittenberg M, Schade-Brittinger C, et al. 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.
  • Caplin ME, Pavel M, Ćwikła JB, et al. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study. Endocr Relat Cancer. 2016;23(3):191–199.
  • Caplin ME, Pavel M, Phan AT, et al. Lanreotide autogel/depot in advanced enteropancreatic neuroendocrine tumours: final results of the CLARINET open-label extension study. Endocrine. 2021;71(2):502–513.
  • Brighi N, Panzuto F, Modica R, et al. Biliary stone disease in patients with neuroendocrine tumors treated with somatostatin analogs: a Multicenter Study. Oncologist. 2020;25(3):259–265.
  • 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.
  • Lamberti G, Faggiano A, Brighi N, et al. Nonconventional doses of somatostatin analogs in patients with progressing well-differentiated neuroendocrine tumor. J Clin Endocrinol Metab. 2020;105(1):194–200.
  • Hofland LJ, Lamberts SWJ. The pathophysiological consequences of somatostatin receptor internalization and resistance. Endocr Rev. 2003;24(1):28–47.
  • Pavel M, Ćwikła 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.
  • Pavel M, O’Toole D, Costa F, et al. ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (Nen) and nen of unknown primary site. Neuroendocrinology. 2016;103(2):172–185.
  • Baudin E, Caplin M, and Garcia-Carbonero R, et al., Lung and thymic carcinoids: ESMO clinical practice guidelines for diagnosis, treatment and follow-up☆. Ann Oncol. 2021;32(4): 439–451. .
  • Laskaratos F-M, Walker M, Naik K, et al. Predictive factors of antiproliferative activity of octreotide LAR as first-line therapy for advanced neuroendocrine tumours. Br J Cancer. 2016;115(11):1321–1327.
  • Faggiano A, Carratù AC, Guadagno E, et al. Somatostatin analogues according to Ki67 index in neuroendocrine tumours: an observational retrospective-prospective analysis from real life. Oncotarget. 2016;7(5):5538–5547.
  • Haug AR, Rominger A, Mustafa M, et al. Treatment with octreotide does not reduce tumor uptake of 68 Ga-DOTATATE as measured by PET/CT in patients with neuroendocrine tumors. J Nucl Med. 2011;52(11):1679–1683.
  • Yordanova A, Wicharz MM, Mayer K, et al. The role of adding somatostatin analogues to peptide receptor radionuclide therapy as a combination and maintenance therapy. Clin Cancer Res. 2018;24(19):4672–4679.
  • Syguła A, Ledwon A, Hasse-Lazar K, et al. In patients with well-differentiated neuroendocrine tumours, there is no apparent benefit of somatostatin analogues after disease control by peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2022. DOI:10.1007/s00259-022-05792-y.
  • [cited 2022 Feb 1] https://doi.org/10.1016/j.annonc.2020.08.1374
  • Faggiano A, Modica R, and Lo Calzo F, et al. Lanreotide therapy vs active surveillance in MEN1-related pancreatic neuroendocrine tumors < 2 centimeters. J Clin Endocrinol Metab. 2020;105(1):dgz007. DOI: 10.1210/clinem/dgz007.
  • Sandostatin LAR and Axitinib vs Pbo in Pnts with advanced well-differentiated non-pancreatic neuroendocrine carcinomas. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT01744249
  • Non-functioning pancreatic neuroendocrine tumors in MEN1: somatostatin Analogs Versus NO Treatment. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT02705651
  • A Phase II Study of ramucirumab with somatostatin analog therapy in patients with advanced PCTPIS of RWSAT in PWAPCT. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT02795858
  • Study of lanreotide in patients with metastatic gastrointestinal neuroendocrine tumors who are undergoing liver-directed radioembolization with Yttrium-90 microspheres. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT02859064
  • A trial aiming to assess the safety and activity of the combination of cabozantinib plus lanreotide in GEP. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT04427787
  • Study to assess the efficacy and safety of lanreotide Autogel® in Chinese participants with GEP-NETs. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT04852679
  • Cabozantinib and lanreotide as treatment for gastroenteropancreatic neuroendocrine tumors. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT05048901
  • A trial to assess efficacy and safety of octreotide subcutaneous depot in patients with GEP-NET. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT05050942
  • van Fraeyenhove F, Meireson N, Terriere L, et al. High-dose lanreotide in the treatment of poorly differentiated pancreatic neuroendocrine carcinoma: a case report. Case Rep Oncol. 2014;7(1):155–163.
  • Pavel M, Öberg K, and Falconi M, et al., Gastroenteropancreatic neuroendocrine neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(7): 844–860. .
  • Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):514–523.
  • Raymond E, Dahan L, Raoul J-L, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):501–513.
  • Yao JC, Fazio N, Singh S, et al. 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.
  • Wolin EM. PI3K/Akt/mTOR pathway inhibitors in the therapy of pancreatic neuroendocrine tumors. Cancer Lett. 2013;335(1):1–8.
  • Grozinsky-Glasberg S, Franchi G, Teng M, et al. Octreotide and the mTOR inhibitor RAD001 (everolimus) block proliferation and interact with the Akt-mTOR-p70S6K pathway in a neuro-endocrine tumour cell Line. Neuroendocrinology. 2008;87(3):168–181.
  • 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):4311–4318.
  • Pavel ME, Hainsworth JD, Baudin E, et al. 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.
  • Pavel ME, Baudin E, Öberg KE, et al. Efficacy of everolimus plus octreotide LAR in patients with advanced neuroendocrine tumor and carcinoid syndrome: final overall survival from the randomized, placebo-controlled phase 3 RADIANT-2 study. Ann Oncol. 2017;28(7):1569–1575.
  • Faggiano A, Malandrino P, Modica R, et al. Efficacy and safety of everolimus in extrapancreatic neuroendocrine tumor: a comprehensive review of literature. Oncologist. 2016;21(7):875–886.
  • Lee L, Ito T, Jensen RT. Everolimus in the treatment of neuroendocrine tumors: efficacy, side-effects, resistance, and factors affecting its place in the treatment sequence. Expert Opin Pharmacother. 2018;19(8):909–928.
  • Yao JC, Lombard-Bohas C, Baudin E, et al. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol. 2010;28(1):69–76.
  • Bajetta E, Catena L, Fazio N, et al. Everolimus in combination with octreotide long-acting repeatable in a first-line setting for patients with neuroendocrine tumors: an ITMO group study. Cancer. 2014;120(16):2457–2463.
  • Chan JA, Ryan DP, Zhu AX, et al. Phase I study of pasireotide (SOM 230) and everolimus (RAD001) in advanced neuroendocrine tumors. Endocr Relat Cancer. 2012;19(5):615–623.
  • Ferolla P, Brizzi MP, Meyer T, et al. Efficacy and safety of long-acting pasireotide or everolimus alone or in combination in patients with advanced carcinoids of the lung and thymus (LUNA): an open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2017;18(12):1652–1664.
  • Baudin E, Berruti A, Mario G, et al. First long-term results on efficacy and safety of long-acting pasireotide in combination with everolimus in patients with advanced carcinoids (NET) of the lung/thymus: phase II LUNA trial. J Clin Oncol. 2021 May 28;39(15_suppl):8574.
  • Panzuto F, Rinzivillo M, Fazio N, et al. Real-world study of everolimus in advanced progressive neuroendocrine tumors. Oncologist. 2014;19(9):966–974.
  • Gallo M, Malandrino P, Fanciulli G, et al. Everolimus as first line therapy for pancreatic neuroendocrine tumours: current knowledge and future perspectives. J Cancer Res Clin Oncol. 2017;143(7):1209–1224.
  • Kulke MH, Bergsland EK, Yao JC. Glycemic control in patients with insulinoma treated with everolimus. N Engl J Med. 2009;360(2):195–197.
  • Meric-Bernstam F, Akcakanat A, Chen H, et al. PIK3CA/PTEN mutations and Akt activation as markers of sensitivity to allosteric mTOR inhibitors. Clin Cancer Res. 2012;18(6):1777.
  • Martins D, Spada F, Lambrescu I, et al. Predictive markers of response to everolimus and sunitinib in neuroendocrine tumors. Target Oncol. 2017;12(5):611–622.
  • Scoazec J-Y. Angiogenesis in neuroendocrine tumors: therapeutic applications. Neuroendocrinology. 2013;97(1):45–56.
  • Faivre S, Delbaldo C, Vera K, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol. 2006;24(1):25–35.
  • Kulke MH, Lenz H-J, Meropol NJ, et al. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol. 2008;26(20):3403–3410.
  • 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.
  • Bassler D, Briel M, Montori VM, et al. Stopping randomized trials early for benefit and estimation of treatment effects systematic review and meta-regression analysis. JAMA. 2010;303(12):1180–1187.
  • Mathew A, Führer D, Lahner H. Sunitinib-induced hypothyroidism and survival in pancreatic neuroendocrine tumors. Hormone Metab Res. 2021;53(12):794–800.
  • Rinzivillo M, Fazio N, Pusceddu S, et al. Sunitinib in patients with pre-treated pancreatic neuroendocrine tumors: a real-world study. Pancreatology. 2018;18(2):198–203.
  • Gao H, Dong J, Zhang W, et al. Sequential capecitabine/temozolomide and sunitinib treatment in patients with metastatic well-differentiated grade 1/grade 2 pancreatic neuroendocrine tumors. Endocr Pract. 2022;28(3):292–297.
  • Zurita AJ, Khajavi M, H-K W, et al. Circulating cytokines and monocyte subpopulations as biomarkers of outcome and biological activity in sunitinib-treated patients with advanced neuroendocrine tumours. Br J Cancer. 2015;112(7):1199–1205.
  • Testing Lutetium Lu 177 dotatate in patients with somatostatin receptor positive advanced bronchial neuroendocrine tumors. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT04665739
  • Lenvatinib and everolimus in treating patients with advanced UCT. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT03950609
  • A Study of LEE011 with everolimus in patients with advanced neuroendocrine tumors. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT03070301
  • Efficacy and safety of 177Lu-edotreotide PRRT in GEP-NET patients. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT03049189
  • Cisplatinum and everolimus in patients with metastatic or unresectable NEC of extrapulmonary origin. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT02695459
  • Efficacy and safety of everolimus and (STZ-5FU) given one upfront the other upon progression in advanced pancreatic neuroendocrine tumor (pNET). [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT02246127
  • antitumor efficacy of peptide receptor radionuclide therapy with 177lutetium -octreotate randomized vs sunitinib in unresectable progressive well-differentiated neuroendocrine pancreatic tumor: first randomized phase II. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT02230176
  • Everolimus and octreotide acetate with or without bevacizumab in treating patients with locally advanced or metastatic pancreatic neuroendocrine tumors that cannot be removed by surgery. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT01229943
  • Pellat A, Dreyer C, Couffignal C, et al. Clinical and biomarker evaluations of sunitinib in patients with grade 3 digestive neuroendocrine neoplasms. Neuroendocrinology. [cited 2022 Feb 1]. 2018;107(1):24–31.
  • Uccelli L, Boschi A, Cittanti C, et al. 90Y/177Lu-DOTATOC: from preclinical studies to application in humans. Pharmaceutics. [cited 2022 Feb 1]. 2021;13(9):1463.
  • Hicks RJ, Kwekkeboom DJ, Krenning E, et al. ENETS consensus guidelines for the standards of care in neuroendocrine neoplasia: peptide receptor radionuclide therapy with radiolabeled somatostatin analogues. Neuroendocrinology. 2017;105(3):295–309.
  • Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177 Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125–135.
  • Strosberg JR, Caplin ME, Kunz PL, et al. 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.
  • Sansovini M, Severi S, Ambrosetti A, et al. Treatment with the radiolabelled somatostatin analog 177Lu-DOTATATE for advanced pancreatic neuroendocrine tumors. Neuroendocrinology. 2013;97(4):347–354.
  • Haug AR. PRRT of neuroendocrine tumors: individualized dosimetry or fixed dose scheme? EJNMMI Res. 2020;10(1):35.
  • 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.
  • Strosberg J, Wolin E, Chasen B, et al. Health-related QUALITY of life in patients with progressive midgut neuroendocrine tumors treated with 177 Lu-Dotatate in the Phase III NETTER-1 trial. J Clin Oncol. 2018;36(25):2578–2584.
  • Ezziddin S, Attassi M, Yong-Hing CJ, et al. Predictors of long-term outcome in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors after peptide receptor radionuclide therapy with 177 Lu-Octreotate. J Nucl Med. 2014;55(2):183–190.
  • 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.
  • Pauwels E, van Binnebeek S, Vandecaveye V, et al. Inflammation-based index and 68 Ga-DOTATOC PET–derived uptake and volumetric parameters predict outcome in neuroendocrine tumor patients treated with 90 Y-DOTATOC. J Nucl Med. 2020;61(7):1014–1020.
  • Bodei L, Kidd M, Modlin IM, et al. Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors. Eur J Nucl Med Mol Imaging. 2016;43(5):839–851.
  • Albertelli M, Dotto A, Di Dato C, et al. PRRT: identikit of the perfect patient. Rev Endocr Metab Disord. 2021;22(3):563–579.
  • Mariniello A, Bodei L, Tinelli C, et al. Long-term results of PRRT in advanced bronchopulmonary carcinoid. Eur J Nucl Med Mol Imaging. 2016;43(3):441–452.
  • Lania A, Ferraù F, Rubino M, et al. Neoadjuvant Therapy for neuroendocrine neoplasms: recent progresses and future approaches. Front Endocrinol (Lausanne). 2021;12:651438.
  • 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.
  • Ostwal V, Basu S, Bhargava P, et al. Capecitabine-temozolomide in advanced grade 2 and grade 3 neuroendocrine neoplasms: benefits of chemotherapy in neuroendocrine neoplasms with significant 18FDG uptake. Neuroendocrinology. 2021;111(10):998–1004.
  • Shah MH, Goldner WS, Benson AB, et al. Neuroendocrine and adrenal tumors,version 2.2021,NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2021;19(7):839–868.
  • Spada F, Antonuzzo L, Marconcini R, et al. Oxaliplatin-based chemotherapy in advanced neuroendocrine tumors: clinical outcomes and preliminary correlation with biological factors. Neuroendocrinology. 2016;103(6):806–814.
  • Capecitabine T and B for M or UPNT. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT01525082
  • Temozolomide with or without capecitabine in treating patients with advanced pancreatic neuroendocrine tumors. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT01824875.
  • Cisplatin C and E or T and C in TPWNC of the GT or PTIM or CBR by S. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT02595424
  • Assessment of the efficacy of bevacizumab in combination with folfiri as second-line treatment in patients suffering from an advanced inoperable poorly differentiated neuroendocrine carcinoma of an unknown or gastroentero-pancreatic primary cancer. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT02820857
  • Second-line therapy for patients with progressive poorly differentiated extra-pulmonary neuroendocrine carcinoma. Cited: 1 February 2022. https://ClinicalTrials.gov/show/NCT03837977
  • Platinum-doublet chemotherapy and nivolumab for the treatment of subjects with neuroendocrine neoplasms (NENs) of the gastroenteropancreatic (GEP) tract or of unknown (UK) origin. [cited 2022 Feb 1]. https://ClinicalTrials.gov/show/NCT03980925
  • Meyer T, Qian W, Caplin ME, et al. Capecitabine and streptozocin ± cisplatin in advanced gastroenteropancreatic neuroendocrine tumours. Eur J Cancer. 2014;50(5):902–911.
  • Kulke MH, Hornick JL, Frauenhoffer C, et al. O 6-methylguanine DNA methyltransferase deficiency and response to temozolomide-based therapy in patients with neuroendocrine tumors. Clin Cancer Res. 2009;15(1):338–345.
  • Ekeblad S, Sundin A, Janson ET, et al. Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Clin Cancer Res. 2007;13(10):2986–2991.
  • Crona J, Fanola I, Lindholm DP, et al. Effect of temozolomide in patients with metastatic bronchial carcinoids. Neuroendocrinology. 2013;98(2):151–155.
  • Tafuto S, von Arx C, and Capozzi M, et al. Safety and activity of metronomic temozolomide in second-line treatment of advanced neuroendocrine neoplasms. J Clin Med. 2019;8(8):1224. DOI: 10.3390/jcm8081224.
  • Ramirez RA, Beyer DT, Chauhan A, et al. The Role of Capecitabine/Temozolomide in metastatic neuroendocrine tumors. Oncologist. 2016;21(6):671–675.
  • Claringbold PG, Turner JH. Pancreatic neuroendocrine tumor control: durable objective response to combination 177Lu-Octreotate-Capecitabine-Temozolomide radiopeptide chemotherapy. Neuroendocrinology. 2016;103(5):432–439.
  • Cives M, Ghayouri M, Morse B, et al. Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors. Endocr Relat Cancer. 2016;23(9):759–767.
  • 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):152–160.
  • Garcia-Carbonero R, Rinke A, Valle JW, et al. ENETS consensus guidelines for the standards of care in neuroendocrine neoplasms. Systemic therapy 2: chemotherapy. Neuroendocrinology. 2017;105:281–294.
  • Frizziero M, Spada F, Lamarca A, et al. Carboplatin in combination with oral or intravenous etoposide for extra-pulmonary, poorly-differentiated neuroendocrine carcinomas. Neuro-endocrinology. 2019;109(2):100–112.
  • Fanciulli G, Di Molfetta S, and Dotto A, et al. Emerging therapies in pheochromocytoma and paraganglioma: immune checkpoint inhibitors in the starting blocks. J Clin Med. 2020;10(1):88. DOI: 10.3390/jcm10010088.
  • Colao A, de Nigris F, Modica R, et al. Clinical epigenetics of neuroendocrine tumors: the road ahead. Front Endocrinol (Lausanne). 2020;11:604341.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.