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01-11-2013 | Magnetic Resonance

Defining predictors for long progression-free survival after radioembolisation of hepatic metastases of neuroendocrine origin

Authors: Wieland H. Sommer, Felix Ceelen, Xabier García-Albéniz, Philipp M. Paprottka, Christoph J. Auernhammer, Marco Armbruster, Konstantin Nikolaou, Alexander R. Haug, Maximilian F. Reiser, Daniel Theisen

Published in: European Radiology | Issue 11/2013

Abstract

Objectives

To define predictive parameters of long progression-free survival (PFS) in patients undergoing radioembolisation of neuroendocrine liver metastases.

Methods

The following clinical and magnetic resonance imaging (MRI) parameters of 45 radioembolised patients (median age, 62 years; range, 43–75) were reviewed: age, gender, levels of chromogranin A and neuron-specific enolase (NSE), primary tumour site, Ki-67 proliferation index, hepatic tumour load, number of metastases, signal intensity characteristics, vascularisation, haemorrhagic and necrotic transformation and fluid–fluid levels. PFS was assessed according to RECIST 1.0. Statistical analysis included univariate Cox regression, Kaplan–Meier and multivariate regression.

Results

Median PFS was 727 days (95 % CI, 378–964). In the univariate regression analysis, hypovascular metastases progressed earlier (111 vs 727 days; P < 0.05). A Ki-67 ≤2 % was associated with a longer PFS than a Ki-67 of 3–20 % or >20 % (911 vs 727 vs 210 days, respectively; P < 0.05). Low NSE predicted longer PFS (911 vs 378 days; P < 0.05). In the adjusted multivariate analysis, vascularisation (hypervascularisation vs. no hypervascularisation; P = 0.0009) and NSE level (low vs high; P = 0.0119) had the strongest influence on PFS.

Conclusion

Response to radioembolisation in patients with neuroendocrine liver metastases can be predicted by the metastatic vascularisation pattern, the NSE level and the Ki-67.

Key Points

• Radioembolisation is an effective treatment in hepatic metastases of neuroendocrine origin.

• Pre-therapeutic vascularisation patterns of metastases on MRI can predict long progression-free survival.

• Assessment of pre-therapeutic markers provides better therapy planning.

Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD (2005) Current status of gastrointestinal carcinoids. Gastroenterology 128:1717–1751PubMedCrossRef

Schimmack S, Svejda B, Lawrence B, Kidd M, Modlin IM (2011) The diversity and commonalities of gastroenteropancreatic neuroendocrine tumours. Langenbecks Arch Surg 396:273–298PubMedCrossRef

Auernhammer CJ, Goke B (2011) Therapeutic strategies for advanced neuroendocrine carcinomas of jejunum/ileum and pancreatic origin. Gut 60:1009–1021PubMedCrossRef

Modlin IM, Oberg K, Chung DC et al (2008) Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 9:61–72PubMedCrossRef

Steinmuller T, Kianmanesh R, Falconi M et al (2008) Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumours: foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 87:47–62PubMedCrossRef

Pavel M, Baudin E, Couvelard A et al (2012) ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 95:157–176PubMedCrossRef

Saxena A, Chua TC, Bester L, Kokandi A, Morris DL (2010) Factors predicting response and survival after yttrium-90 radioembolization of unresectable neuroendocrine tumour liver metastases: a critical appraisal of 48 cases. Ann Surg 251:910–916PubMedCrossRef

Gupta S, Johnson MM, Murthy R et al (2005) Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumours: variables affecting response rates and survival. Cancer 104:1590–1602PubMedCrossRef

Ho AS, Picus J, Darcy MD et al (2007) Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumours. AJR Am J Roentgenol 188:1201–1207PubMedCrossRef

10.

Osborne DA, Zervos EE, Strosberg J et al (2006) Improved outcome with cytoreduction versus embolization for symptomatic hepatic metastases of carcinoid and neuroendocrine tumours. Ann Surg Oncol 13:572–581PubMedCrossRef

11.

O'Toole D, Hentic O, Corcos O, Ruszniewski P (2004) Chemotherapy for gastro-enteropancreatic endocrine tumours. Neuroendocrinology 80:79–84PubMedCrossRef

12.

Sun W, Lipsitz S, Catalano P, Mailliard JA, Haller DG (2005) Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumours: Eastern Cooperative Oncology Group Study E1281. J Clin Oncol 23:4897–4904PubMedCrossRef

13.

Turner NC, Strauss SJ, Sarker D et al (2010) Chemotherapy with 5-fluorouracil, cisplatin and streptozocin for neuroendocrine tumours. Br J Cancer 102:1106–1112PubMedCrossRef

14.

Kwekkeboom DJ, de Herder WW, Kam BL et al (2008) Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 26:2124–2130PubMedCrossRef

15.

Kwekkeboom DJ, de Herder WW, van Eijck CH et al (2010) Peptide receptor radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumours. Semin Nucl Med 40:78–88PubMedCrossRef

16.

Kennedy AS, Dezarn WA, McNeillie P et al (2008) Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: early results in 148 patients. Am J Clin Oncol 31:271–279PubMedCrossRef

17.

Manfe AZ, Norberto L, Marchesini M, Lumachi F (2011) Usefulness of chromogranin A, neuron-specific enolase and 5-hydroxyindolacetic acid measurements in patients with malignant carcinoids. In Vivo 25:1027–1029PubMed

18.

Rhee TK, Lewandowski RJ, Liu DM et al (2008) 90Y Radioembolization for metastatic neuroendocrine liver tumours: preliminary results from a multi-institutional experience. Ann Surg 247:1029–1035PubMedCrossRef

19.

Shaheen M, Hassanain M, Aljiffry M et al (2012) Predictors of response to radio-embolization (TheraSphere®) treatment of neuroendocrine liver metastasis. HPB (Oxford) 14:60–66CrossRef

20.

Memon K, Lewandowski RJ, Mulcahy MF et al (2012) Radioembolization for neuroendocrine liver metastases: safety, imaging, and long-term outcomes. Int J Radiat Oncol Biol Phys 83:887–894PubMedCrossRef

21.

Paprottka PM, Hoffmann RT, Haug A et al (2012) Radioembolization of symptomatic, unresectable neuroendocrine hepatic metastases using yttrium-90 microspheres. Cardiovasc Intervent Radiol 35:334–342PubMedCrossRef

22.

Paprottka PM, Jakobs TF, Reiser MF, Hoffmann RT (2012) Practical vascular anatomy in the preparation of radioembolization. Cardiovasc Intervent Radiol 35:454–462PubMedCrossRef

23.

Kennedy A, Nag S, Salem R et al (2007) Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. Int J Radiat Oncol Biol Phys 68:13–23PubMedCrossRef

24.

Sommer WH, Zech CJ, Bamberg F et al (2012) Fluid-fluid level in hepatic metastases: a characteristic sign of metastases of neuroendocrine origin. Eur J Radiol 81:2127–2132PubMedCrossRef

25.

Yao JC, Shah MH, Ito T et al (2011) Everolimus for advanced pancreatic neuroendocrine tumours. N Engl J Med 364:514–523PubMedCrossRef

26.

Kloppel G (2011) Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms. Endoc Relat Cancer 18:S1–S16CrossRef

27.

King J, Quinn R, Glenn DM et al (2008) Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer 113:921–929PubMedCrossRef

28.

Ramage JK, Ahmed A, Ardill J et al (2012) Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut 61:6–32PubMedCrossRef

29.

Raymond E, Dahan L, Raoul JL et al (2011) Sunitinib malate for the treatment of pancreatic neuroendocrine tumours. N Engl J Med 364:501–513PubMedCrossRef

30.

Yao JC, Pavel M, Phan AT et al (2011) Chromogranin A and neuron-specific enolase as prognostic markers in patients with advanced pNET treated with everolimus. J Clin Endocrinol Metab 96:3741–3749PubMedCrossRef

31.

Proye C (2001) Natural history of liver metastasis of gastroenteropancreatic neuroendocrine tumours: place for chemoembolization. World J Surg 25:685–688PubMedCrossRef

32.

Venook AP (1999) Embolization and chemoembolization therapy for neuroendocrine tumours. Curr Opin Oncol 11:38–41PubMedCrossRef

33.

Sato KT, Omary RA, Takehana C et al (2009) The role of tumor vascularity in predicting survival after yttrium-90 radioembolization for liver metastases. J Vasc Interv Radiol 20:1564–1569PubMedCrossRef

34.

Jamali M, Chetty R (2008) Predicting prognosis in gastroentero-pancreatic neuroendocrine tumours: an overview and the value of Ki-67 immunostaining. Endocr Pathol 19:282–288PubMedCrossRef

35.

Lawrence B, Gustafsson BI, Kidd M, Pavel M, Svejda B, Modlin IM (2011) The clinical relevance of chromogranin A as a biomarker for gastroenteropancreatic neuroendocrine tumours. Endocrinol Metab Clin North Am 40:111–134, viiiPubMedCrossRef

36.

Lindholm DP, Oberg K (2011) Biomarkers and molecular imaging in gastroenteropancreatic neuroendocrine tumours. Horm Metab Res 43:832–837PubMedCrossRef

37.

Engelman S, Leon-Ferre R, Naraev BG (2012) Clinical outcomes and predictive value of chromogranin A (CgA) and pancreastatin (PcSt) in liver-directed therapies (LDTs) for well-differentiated metastatic neuroendocrine tumours. ASCO Annual Meeting, June 5–12, 2012, Chicago, IL

38.

O’Toole D, Grossman A, Gross D et al (2009) ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumours: biochemical markers. Neuroendocrinology 90:194–202PubMedCrossRef

39.

Cao C, Yan TD, Morris DL, Bester L (2010) Radioembolization with yttrium-90 microspheres for pancreatic cancer liver metastases: results from a pilot study. Tumouri 96:955–958

40.

Dunfee BL, Riaz A, Lewandowski RJ et al (2010) Yttrium-90 radioembolization for liver malignancies: prognostic factors associated with survival. J Vasc Interv Radiol 21:90–95PubMedCrossRef

41.

Rinke A, Muller HH, Schade-Brittinger C et al (2009) Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumour growth in patients with metastatic neuroendocrine midgut tumours: a report from the PROMID Study Group. J Clin Oncol 27:4656–4663PubMedCrossRef

42.

Atassi B, Bangash AK, Bahrani A et al (2008) Multimodality imaging following 90Y radioembolization: a comprehensive review and pictorial essay. Radiographics 28:81–99PubMedCrossRef

Title: Defining predictors for long progression-free survival after radioembolisation of hepatic metastases of neuroendocrine origin
Authors: Wieland H. Sommer
Felix Ceelen
Xabier García-Albéniz
Philipp M. Paprottka
Christoph J. Auernhammer
Marco Armbruster
Konstantin Nikolaou
Alexander R. Haug
Maximilian F. Reiser
Daniel Theisen
Publication date: 01-11-2013
Publisher: Springer Berlin Heidelberg
Published in: European Radiology / Issue 11/2013
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-013-2925-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Defining predictors for long progression-free survival after radioembolisation of hepatic metastases of neuroendocrine origin

Abstract

Objectives

Methods

Results

Conclusion

Key Points

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Methods

Results

Conclusion

Key Points

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