Skip to main content
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 8/2013

01.08.2013 | Original Article

Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence

verfasst von: Davide Campana, Gabriele Capurso, Stefano Partelli, Francesca Nori, Francesco Panzuto, Domenico Tamburrino, Giulia Cacciari, Gianfranco Delle Fave, Massimo Falconi, Paola Tomassetti

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 8/2013

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment modality for patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs). The aim of this study was to determine the time to progression of patients treated with PRRT and to identify the prognostic factors related to treatment response.

Methods

Patients with sporadic GEP NETs prospectively treated with PRRT were retrospectively analysed. The primary end point was progression-free survival (PFS).

Results

A total of 69 patients (37 men and 32 women; 45 with pancreatic and 24 with gastrointestinal lesion; 22 NET G1 and 41 NET G2) were treated with 90Y or 177Lu. The objective response rate was 27.5 % (partial response, PR), while 50.7 % had stable disease and 23.2 % had progressive disease. Significant differences in PFS were observed in relationship to the stage of the disease (44 months for stage III, 23 months for stage IV), the evidence of a PR 6 months after the end of the PRRT (39 months in patients with a PR, 22 months in patients without a PR) and previous transarterial chemoembolization (TACE, yes 13 months vs no 31 months). Stage IV, NET G2 and previous TACE were found to be significant factors for tumour progression at multivariate analysis.

Conclusion

Low tumour burden and a low proliferation index represent independent prognostic factors for long PFS, while previous chemoembolization techniques represent independent prognostic factors for early tumour progression and shorter PFS. Our data suggest that chemoembolization techniques to reduce the hepatic tumour burden should be avoided.
Literatur
1.
Zurück zum Zitat Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, 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;26:3063–72.PubMedCrossRef Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, 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;26:3063–72.PubMedCrossRef
2.
Zurück zum Zitat Reubi JC, Laissue JA. Multiple actions of somatostatin in neoplastic disease. Trends Pharmacol Sci 1995;16:110–5.PubMedCrossRef Reubi JC, Laissue JA. Multiple actions of somatostatin in neoplastic disease. Trends Pharmacol Sci 1995;16:110–5.PubMedCrossRef
3.
Zurück zum Zitat Reubi JC, Waser B, Liu Q, Laissue JA, Schonbrunn A. Subcellular distribution of somatostatin sst2A receptors in human tumors of the nervous and neuroendocrine systems: membranous versus intracellular location. J Clin Endocrinol Metab 2000;85:3882–91.PubMedCrossRef Reubi JC, Waser B, Liu Q, Laissue JA, Schonbrunn A. Subcellular distribution of somatostatin sst2A receptors in human tumors of the nervous and neuroendocrine systems: membranous versus intracellular location. J Clin Endocrinol Metab 2000;85:3882–91.PubMedCrossRef
4.
Zurück zum Zitat Arnold R, Benning R, Neuhaus C, Rolwage M, Trautmann ME. Gastroenteropancreatic endocrine tumours: effect of Sandostatin on tumour growth. The German Sandostatin Study Group. Digestion 1993;54 Suppl 1:72–5.PubMedCrossRef Arnold R, Benning R, Neuhaus C, Rolwage M, Trautmann ME. Gastroenteropancreatic endocrine tumours: effect of Sandostatin on tumour growth. The German Sandostatin Study Group. Digestion 1993;54 Suppl 1:72–5.PubMedCrossRef
5.
Zurück zum Zitat Janson ET, Oberg K. Long-term management of the carcinoid syndrome. Treatment with octreotide alone and in combination with alpha-interferon. Acta Oncol 1993;32:225–9.PubMedCrossRef Janson ET, Oberg K. Long-term management of the carcinoid syndrome. Treatment with octreotide alone and in combination with alpha-interferon. Acta Oncol 1993;32:225–9.PubMedCrossRef
6.
Zurück zum Zitat Ducreux M, Ruszniewski P, Chayvialle JA, Blumberg J, Cloarec D, Michel H, et al. The antitumoral effect of the long-acting somatostatin analog lanreotide in neuroendocrine tumors. Am J Gastroenterol 2000;95:3276–81.PubMedCrossRef Ducreux M, Ruszniewski P, Chayvialle JA, Blumberg J, Cloarec D, Michel H, et al. The antitumoral effect of the long-acting somatostatin analog lanreotide in neuroendocrine tumors. Am J Gastroenterol 2000;95:3276–81.PubMedCrossRef
7.
Zurück zum Zitat Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, 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;27:4656–63.PubMedCrossRef Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, 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;27:4656–63.PubMedCrossRef
8.
Zurück zum Zitat Bodei L, Cremonesi M, Zoboli S, Grana C, Bartolomei M, Rocca P, et al. Receptor-mediated radionuclide therapy with 90Y-DOTATOC in association with amino acid infusion: a phase I study. Eur J Nucl Med Mol Imaging 2003;30:207–16.PubMedCrossRef Bodei L, Cremonesi M, Zoboli S, Grana C, Bartolomei M, Rocca P, et al. Receptor-mediated radionuclide therapy with 90Y-DOTATOC in association with amino acid infusion: a phase I study. Eur J Nucl Med Mol Imaging 2003;30:207–16.PubMedCrossRef
9.
Zurück zum Zitat Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J. The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol 2001;12:941–5.PubMedCrossRef Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J. The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol 2001;12:941–5.PubMedCrossRef
10.
Zurück zum Zitat Waldherr C, Pless M, Maecke HR, Schumacher T, Crazzolara A, Nitzsche EU, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med 2002;43:610–6.PubMed Waldherr C, Pless M, Maecke HR, Schumacher T, Crazzolara A, Nitzsche EU, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med 2002;43:610–6.PubMed
11.
Zurück zum Zitat Valkema R, Pauwels S, Kvols LK, Barone R, Jamar F, Bakker WH, et al. Survival and response after peptide receptor radionuclide therapy with [90Y-DOTA0, Tyr3]octreotide in patients with advanced gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 2006;36:147–56.PubMedCrossRef Valkema R, Pauwels S, Kvols LK, Barone R, Jamar F, Bakker WH, et al. Survival and response after peptide receptor radionuclide therapy with [90Y-DOTA0, Tyr3]octreotide in patients with advanced gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 2006;36:147–56.PubMedCrossRef
12.
Zurück zum Zitat Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008;26:2124–30.PubMedCrossRef Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008;26:2124–30.PubMedCrossRef
13.
Zurück zum Zitat Kwekkeboom DJ, de Herder WW, van Eijck CH, Kam BL, van Essen M, Teunissen JJ, et al. Peptide receptor radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 2010;40:78–88.PubMedCrossRef Kwekkeboom DJ, de Herder WW, van Eijck CH, Kam BL, van Essen M, Teunissen JJ, et al. Peptide receptor radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 2010;40:78–88.PubMedCrossRef
14.
Zurück zum Zitat Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol 2011;29:2416–23.PubMedCrossRef Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol 2011;29:2416–23.PubMedCrossRef
15.
Zurück zum Zitat Bosman FT, Carneiro F, Hruban RH, et al. WHO classification of tumours of the digestive system. 4th ed. Lyon: IARC; 2010. Bosman FT, Carneiro F, Hruban RH, et al. WHO classification of tumours of the digestive system. 4th ed. Lyon: IARC; 2010.
16.
Zurück zum Zitat Rindi G, Klöppel G, Couvelard A, Komminoth P, Körner M, Lopes JM, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2007;451:757–62.PubMedCrossRef Rindi G, Klöppel G, Couvelard A, Komminoth P, Körner M, Lopes JM, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2007;451:757–62.PubMedCrossRef
17.
Zurück zum Zitat Rindi G, Klöppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2006;449:395–401.PubMedCrossRef Rindi G, Klöppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2006;449:395–401.PubMedCrossRef
18.
Zurück zum Zitat Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205–16.PubMedCrossRef Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205–16.PubMedCrossRef
19.
Zurück zum Zitat Bajetta E, Catena L, Procopio G, De Dosso S, Bichisao E, Ferrari L, et al. Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours? Cancer Chemother Pharmacol 2007;59:637–42.PubMedCrossRef Bajetta E, Catena L, Procopio G, De Dosso S, Bichisao E, Ferrari L, et al. Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours? Cancer Chemother Pharmacol 2007;59:637–42.PubMedCrossRef
20.
Zurück zum Zitat Sun W, Lipsitz S, Catalano P, Mailliard JA, Haller DG, Eastern Cooperative Oncology Group. Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281. J Clin Oncol 2005;23:4897–904.PubMedCrossRef Sun W, Lipsitz S, Catalano P, Mailliard JA, Haller DG, Eastern Cooperative Oncology Group. Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281. J Clin Oncol 2005;23:4897–904.PubMedCrossRef
21.
Zurück zum Zitat Kouvaraki MA, Ajani JA, Hoff P, Wolff R, Evans DB, Lozano R, et al. Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol 2004;22:4762–71.PubMedCrossRef Kouvaraki MA, Ajani JA, Hoff P, Wolff R, Evans DB, Lozano R, et al. Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol 2004;22:4762–71.PubMedCrossRef
22.
Zurück zum Zitat Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 2011;364:501–13.PubMedCrossRef Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 2011;364:501–13.PubMedCrossRef
23.
Zurück zum Zitat Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 2011;364:514–23.PubMedCrossRef Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 2011;364:514–23.PubMedCrossRef
24.
Zurück zum Zitat Panzuto F, Boninsegna L, Fazio N, Campana D, Pia Brizzi M, Capurso G, et al. Metastatic and locally advanced pancreatic endocrine carcinomas: analysis of factors associated with disease progression. J Clin Oncol 2011;29:2372–7.PubMedCrossRef Panzuto F, Boninsegna L, Fazio N, Campana D, Pia Brizzi M, Capurso G, et al. Metastatic and locally advanced pancreatic endocrine carcinomas: analysis of factors associated with disease progression. J Clin Oncol 2011;29:2372–7.PubMedCrossRef
25.
Zurück zum Zitat Panzuto F, Campana D, Fazio N, Brizzi MP, Boninsegna L, Nori F, et al.: Risk factors for disease progression in advanced jejunoileal neuroendocrine tumors. Neuroendocrinology 2012;96:32–40. Panzuto F, Campana D, Fazio N, Brizzi MP, Boninsegna L, Nori F, et al.: Risk factors for disease progression in advanced jejunoileal neuroendocrine tumors. Neuroendocrinology 2012;96:32–40.
26.
Zurück zum Zitat Bettini R, Boninsegna L, Mantovani W, Capelli P, Bassi C, Pederzoli P, et al. Prognostic factors at diagnosis and value of WHO classification in a mono-institutional series of 180 non-functioning pancreatic endocrine tumours. Ann Oncol 2008;19:903–8.PubMedCrossRef Bettini R, Boninsegna L, Mantovani W, Capelli P, Bassi C, Pederzoli P, et al. Prognostic factors at diagnosis and value of WHO classification in a mono-institutional series of 180 non-functioning pancreatic endocrine tumours. Ann Oncol 2008;19:903–8.PubMedCrossRef
27.
Zurück zum Zitat Panzuto F, Nasoni S, Falconi M, Corleto VD, Capurso G, Cassetta S, et al. Prognostic factors and survival in endocrine tumor patients: comparison between gastrointestinal and pancreatic localization. Endocr Relat Cancer 2005;12:1083–92.PubMedCrossRef Panzuto F, Nasoni S, Falconi M, Corleto VD, Capurso G, Cassetta S, et al. Prognostic factors and survival in endocrine tumor patients: comparison between gastrointestinal and pancreatic localization. Endocr Relat Cancer 2005;12:1083–92.PubMedCrossRef
28.
Zurück zum Zitat Scarpa A, Mantovani W, Capelli P, Beghelli S, Boninsegna L, Bettini R, et al. Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients. Mod Pathol 2010;23:824–33.PubMedCrossRef Scarpa A, Mantovani W, Capelli P, Beghelli S, Boninsegna L, Bettini R, et al. Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients. Mod Pathol 2010;23:824–33.PubMedCrossRef
Metadaten
Titel
Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence
verfasst von
Davide Campana
Gabriele Capurso
Stefano Partelli
Francesca Nori
Francesco Panzuto
Domenico Tamburrino
Giulia Cacciari
Gianfranco Delle Fave
Massimo Falconi
Paola Tomassetti
Publikationsdatum
01.08.2013
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 8/2013
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-013-2402-2

Weitere Artikel der Ausgabe 8/2013

European Journal of Nuclear Medicine and Molecular Imaging 8/2013 Zur Ausgabe