Subscribe to RSS

DOI: 10.5935/2526-8732.20190018
Prognostic Factors Associated with the Efficacy of Hepatic Transarterial Embolization in Patients with Neuroendocrine Tumors
Fatores Prognósticos Associados à Eficácia da Embolização Transarterial Hepática em Pacientes com Tumores Neuroendócrinos
Financial support: none to declare.

ABSTRACT
Introduction: To evaluate the safety and efficacy of hepatic transarterial embolization (TAE) or transarterial chemoembolization (TACE) in patients with irresectable liver metastases from neuroendocrine tumors (NETs) treated at two Brazilian cancer centers. Methods: Retrospective multicenter analysis of patients (pts) with histological diagnosis of neuroendocrine tumor of any origin with unresectable and measurable hepatic metastases who underwent at least one procedure of TAE or TACE. Endpoints: Hepatic progression free survival (HPFS), overall survival (OS), tumor response and toxicity assessment. Results: Thirty-six pts were evaluated. Primary tumors were as follow: midgut 20 pts, pancreas 7 pts, others 9 pts. Most of patients had grade (G) 1-2 tumors (93.3%). In patients with functioning NETs, clinically significant symptomatic control was 41.7%. Concerning type of embolization (TAE vs TACE), there were no significant differences in the proportion of patients achieving reduction of at least 50% of 5HIAA (45.5% vs 50%) and radiological disease control rate (91.3% vs 92.3%), respectively. In a median follow up of 40.8 months (m), median HPFS was 38.9m, and mean OS was 98m (median not reached). No significant differences were found in HPFS or OS by type of embolization procedure. Pancreatic primary tumor and G3 tumor by WHO classification were associated with significantly shorter HPFS. Tumor G3 was also associated with shorter OS. Adverse events of any grade were: abdominal pain (13.8%), fever (5.5%), and 2 pts developed biloma. Conclusion: Our study is the first in our region reporting results of TAE/TACE in patients with irresectable liver metastases from NETs. We observed that pts with pancreatic or G3 NET derive less benefit from these procedures. In pts with G1-2 NETs, both techniques offer similar results.
RESUMO
Resumo Introdução: Avaliar a segurança e eficácia da embolização transarterial hepática (TAE) ou quimioembolização transarterial (TACE) em pacientes com metástases hepáticas de tumores neuroendócrinos (TNEs) irressecáveis tratados em dois centros brasileiros de câncer. Métodos: retrospectiva analítica multicêntrica de pacientes (pts) com diagnóstico histológico de tumor neuroendócrino de qualquer origem com metástases hepáticas irressecáveis e mensuráveis que foram submetidas a pelo menos um procedimento de TAE ou TACE. Parâmetros: Sobrevida livre de progressão hepática (SLPH), sobrevida geral (SG), resposta tumoral e avaliação de toxicidade. Resultados: Trinta e seis pts foram avaliados. Os tumores primários foram os seguintes: 20 pts intestino médio, 7 pts pâncreas, 9 pts outros. A maioria dos pacientes apresentava tumores grau (G) 1-2 (93.3%). Em pacientes com TNEs funcionais, clinicamente o controle sintomático foi significativo foi 41.7%. Em relação ao tipo de embolização (TAE vs TACE), não houve diferenças significativas na proporção de pacientes que obtiveram redução de pelo menos 50% do 5HIAA (45.5% vs 50%) e a taxa de controle radiológico da doença (91.3% vs 92.3%), respectivamente. Em um acompanhamento médio de 40.8 meses (m), a SLPH intermediário foi de 38.9m, e a SG média foi de 98m (média não atingida). Não foram encontradas diferenças significativas na SLPH ou na SG pelo tipo de procedimento de embolização. Tumor primário pancreático e tumor G3, pela classificação da OMS, foram também associados com significativa redução da SLPH. O tumor G3 também foi associado com SG reduzida. Os eventos adversos de qualquer grau foram: dor abdominal (13.8%), febre (5.5%) e 2 pts desenvolveram biloma. Conclusão: Nosso estudo é o primeiro em nossa área que relata resultados de TAE/TACE em pacientes com metástases hepáticas irressecáveis de TNEs. Observamos que os pacientes com TNE G3 ou pancreático obtêm menos benefícios destes procedimentos. Em pts com TNEs G1-2, ambas as técnicas oferecem resultados similares.
Keywords:
Embolization, Therapeutic - Chemoembolization, Therapeutic - Neuroendocrine tumors - Neoplasm metastasis.Descritores:
Embolização terapêutica - Quimioembolização terapêutica - Tumores neuroendócrinos - Metástases neoplásicas.AUTHOR'S CONTRIBUTION
Jose Eduardo Nuñez: Collection and assembly of data, Conception and design, Data analysis and interpretation, Final approval of manuscript, Manuscript writing, Provision of study materials or patient.
Charles Zurstrassen: Collection and assembly of data, Data analysis and interpretation, Final approval of manuscript, Manuscript writing, Provision of study materials or patient.
Milton Barros: Collection and assembly of data, Data analysis and interpretation, Final approval of manuscript, Manuscript writing, Provision of study materials or patient.
Deise Uema: Collection and assembly of data, Data analysis and interpretation, Final approval of manuscript, Manuscript writing, Provision of study materials or patient.
Rossana Lopez: Collection and assembly of data, Data analysis and interpretation, Final approval of manuscript, Manuscript writing, Provision of study materials or patient.
Rachel Riechelmann: Collection and assembly of data, Conception and design, Data analysis and interpretation, Final approval of manuscript, Manuscript writing, Provision of study materials or patient.
Publication History
Received: 30 December 2018
Accepted: 04 July 2019
Article published online:
01 October 2019
© 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil
Jose Eduardo Nuñez, Charles Zurstrassen, Milton Barros, Deise Uema, Rossana Lopez, Rachel Riechelmann. Prognostic Factors Associated with the Efficacy of Hepatic Transarterial Embolization in Patients with Neuroendocrine Tumors. Brazilian Journal of Oncology 2019; 15: e-20190018.
DOI: 10.5935/2526-8732.20190018
-
REFERENCES
-
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; Jun; 26 (18) 3063-3072
MissingFormLabel
-
Rindi G,
D'Adda T,
Froio E,
Fellegara G,
Bordi C..
Prognostic factors in gastrointestinal endocrine tumors. Endocr Pathol 2007; Feb;
18 (03) 145-149
MissingFormLabel
-
Dasari A,
Shen C,
Halperin D,
Zhao B,
Zhou S,
Xu Y.
et al
Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine
tumors in the United States. JAMA Oncol 2017; Oct; 3 (10) 1335-1342
MissingFormLabel
-
Pape UF,
Berndt U,
Müller-Nordhorn J,
Böhmig M,
Roll S,
Koch M.
et al
Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours.
Endocr Relat Cancer 2008; Dec; 15 (04) 1083-1097
MissingFormLabel
-
Kennedy A,
Bester L,
Salem R,
Sharma RA,
Parks RW,
Ruszniewski P..
Role of hepatic intra-arterial therapies in metastatic neuroendocrine tumours (NET):
guidelines from the net-liver-metastases consensus conference. HPB (Oxford) 2015;
Jan; 17 (01) 29-37
MissingFormLabel
-
Ruszniewski P,
Rougier P,
Roche A,
Legmann P,
Sibert A,
Hochlaf S.
et al
Hepatic arterial chemoembolization in patients with liver metastases of endocrine
tumors a prospective phase II study in 24 patients. Cancer 1993; Apr; 71 (08) 2624-2630
MissingFormLabel
-
King J,
Quinn R,
Glenn DM,
Janssen J,
Tong D,
Liaw W.
et al
Radioembolization with selective internal radiation microspheres for neuroendocrine
liver metastases. Cancer 2008; Sep; 113 (05) 921-929
MissingFormLabel
-
Arrese D,
McNally ME,
Chokshi R,
Feria-Arias E,
Schmidt C,
Klemanski D.
et al
MissingFormLabel
- Extrahepatic disease should not preclude transarterial chemoembolization for metastatic
neuroendocrine carcinoma. Annals of Surgical Oncology 2013; Mar; 20 (04) 1114-1120
. Gupta S, Yao JC, Ahrar K, Wallace, MJ, Morello, FA, Madoff, DC. Hepatic artery embolization
and chemoembolization for treatment of patients with metastatic carcinoid tumors:
The M.D. Anderson experience. Cancer J. 2003 Jul/Aug;9(4):261-7.
MissingFormLabel
-
Swärd C,
Johanson V,
Nieveen Van Dijkum E,
Jansson S,
Nilsson O,
Wängberg B.
et al
MissingFormLabel
- Prolonged survival after hepatic artery embolization in patients with midgut carcinoid
syndrome. Br J Surg 2009; May; 96 (05) 517-21 . Drougas, JG, Anthony, LB, Blair, TK,
Lopez, RR, Wright, JK, Chapman, WC. Hepatic artery chemoembolization for management
of patients with advanced metastatic carcinoid tumors. Am J Surg. 1998 May;175(5):408-12.
MissingFormLabel
-
Gupta S,
Johnson MM,
Murthy R,
Ahrar K,
Wallace MJ,
Madoff DC.
et al
Hepatic arterial embolization and chemoembolization for the treatment of patients
with metastatic neuroendocrine tumors: variables affecting response rates and survival.
Cancer 2005; Oct; 104 (08) 1590-1602
MissingFormLabel
-
Dong X.
Da, Carr BI. Hepatic artery chemoembolization for the treatment of liver metastases
from neuroendocrine tumors: a long-term follow-up in 123 patients. Med Oncol 2011;
Dec; 28 (Suppl 1): S286-90
MissingFormLabel
-
Pitt SC,
Knuth J,
Keily JM,
McDermott JC,
Weber SM,
Chen H.
et al
Hepatic neuroendocrine metastases: chemo- or bland embolization?. J Gastrointest Surg
2008; Nov; 12 (11) 1951-1960
MissingFormLabel
-
Ruutiainen AT,
Soulen MC,
Tuite CM,
Clark TWI,
Mondschein JI,
Stavropoulos SW.
et al
Chemoembolization and bland embolization of neuroendocrine tumor metastases to the
liver. J Vasc Interv Radiol 2007; Jul; 18 (07) 847-855
MissingFormLabel
-
Schell SR,
Camp ER,
Caridi JG,
Hawkins IF..
Hepatic artery embolization for control of symptoms, octreotide requirements, and
tumor progression in metastatic carcinoid tumors. J Gastrointest Surg 2002; Sep/Oct;
6 (05) 664-670
MissingFormLabel
-
Lewis MA,
Jaramillo S,
Roberts L,
Fleming CJ,
Rubin J,
Grothey A..
Hepatic artery embolization for neuroendocrine tumors: postprocedural management and
complications. Oncologist 2012; 17 (05) 725-731
MissingFormLabel
-
de Baere T,
Arai Y,
Lencioni R,
Geschwind JF,
Rilling W,
Salem R.
et al
Treatment of liver tumors with lipiodol TACE: technical recommendations from experts
opinion. Cardiovasc Intervent Radiol 2016; Mar; 39 (03) 334-343
MissingFormLabel
-
Pavel M,
O'Toole D,
Costa F,
Capdevila J,
Gross D,
Kianmanesh R.
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 (02) 172-185
MissingFormLabel
-
Harbert GM,
Brame RG,
McGaughey HS,
Thornton WN..
Fetomaternal water exchange. Obstet Gynecol 1968; Oct; 32 (02) 232-240
MissingFormLabel
-
Ruszniewski P,
Malka D..
Hepatic arterial chemoembolization in the management of advanced digestive endocrine
tumors. Digestion 2000; 62 (Suppl 1): 79-83
MissingFormLabel
-
Strosberg JR,
Choi J,
Cantor AB,
Kvols LK..
Selective hepatic artery embolization for treatment of patients with metastatic carcinoid
and pancreatic endocrine tumors. Cancer Control 2006; Jan; 13 (01) 72-78
MissingFormLabel
-
Eriksson BK,
Larsson EG,
Skogseid BM,
Löfberg AM,
Lörelius LE,
Öberg KE..
Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors.
Cancer 1998; Dec; 83 (11) 2293-2301
MissingFormLabel
-
Pericleous M,
Caplin ME,
Tsochatzis E,
Yu D,
Morgan-Rowe L,
Toumpanakis C..
Hepatic artery embolization in advanced neuroendocrine tumors: efficacy and long-term
outcomes. Asia Pac J Clin Oncol 2016; Mar; 12 (01) 61-69
MissingFormLabel
-
Sofocleous CT,
Petre EN,
Gonen M,
Reidy-Lagunes D,
Ip IK,
Alago W.
et al
Factors affecting periprocedural morbidity and mortality and long-term patient survival
after arterial embolization of hepatic neuroendocrine metastases. J Vasc Interv Radiol
2014; Jan; 25 (01) 22-30
MissingFormLabel
-
Ho AS,
Picus J,
Darcy MD,
Tan B,
Gould JE,
Pilgram TK.
et al
Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions
from neuroendocrine tumors. AJR Am J Roentgenol 2007; May; 188 (05) 1201-1207
MissingFormLabel
-
Kulke MH,
Shah MH,
Benson AB,
Bergsland E,
Berlin JD,
Blaszkowsky LS.
et al
Neuroendocrine tumors, version 1.2015. J Natl Compr Cancer Netw 2015; Jan; 13 (01)
78-108
MissingFormLabel
-
Gaba RC..
Chemoembolization practice patterns and technical methods among interventional radiologists:
results of an online survey. AJR Am J Roentgenol 2012; Mar; 198 (03) 692-699
MissingFormLabel
-
Fiore F,
Del Prete M,
Franco R,
Marotta V,
Ramundo V,
Marciello F.
et al
Transarterial embolization (TAE) is equally effective and slightly safer than transarterial
chemoembolization (TACE) to manage liver metastases in neuroendocrine tumors. Endocrine
2014; Sep; 47 (01) 177-182
MissingFormLabel
-
Bhagat N,
Reyes DK,
Lin M,
Kamel I,
Pawlik TM,
Frangakis C.
et al
Phase II study of chemoembolization with drug-eluting beads in patients with hepatic
neuroendocrine metastases: high incidence of biliary injury. Cardiovasc Intervent
Radiol 2013; 36 (02) 449-459
MissingFormLabel
-
de Baere T,
Deschamps F,
Teriitheau C,
Rao P,
Conengrapht K,
Schlumberger M.
et al
Transarterial chemoembolization of liver metastases from well differentiated gastroenteropancreatic
endocrine tumors with doxorubicin-eluting beads: preliminary results. J Vasc Interv
Radiol 2008; Jun; 19 (06) 855-861
MissingFormLabel
-
Gaur SK,
Friese JL,
Sadow CA,
Ayyagari R,
Binkert CA,
Schenker MP.
et al
Hepatic arterial chemoembolization using drug-eluting beads in gastrointestinal neuroendocrine
tumor metastatic to the liver. Cardiovasc Intervent Radiol 2011; Jun; 34 (03) 566-572
MissingFormLabel
-
Mota JM,
Sousa LG,
Riechelmann RP..
Complications from carcinoid syndrome: review of the current evidence. Ecancermedicalscience
2016; Aug; 10: 662
MissingFormLabel
-
Cao CQ,
Yan TD,
Bester L,
Liauw W,
Morris DL..
Radioembolization with yttrium microspheres for neuroendocrine tumour liver metastases.
Br J Surg 2010; Apr; 97 (04) 537-543
MissingFormLabel