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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Preliminary qualification of a novel, hypoxic-based radiologic signature for trans-arterial chemoembolization in hepatocellular carcinoma

Authors: David J. Pinato, Madhava Pai, Isabella Reccia, Markand Patel, Alexandros Giakoustidis, Georgios Karamanakos, Azelea Rushd, Shiraz Jamshaid, Alberto Oldani, Glenda Grossi, Mario Pirisi, Paul Tait, Rohini Sharma

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Survival advantage following trans-arterial chemoembolization (TACE) is variable in patients with hepatocellular carcinoma (HCC). We combined pre-TACE radiologic features to derive a novel prognostic signature in HCC.

Methods

A multi-institutional dataset of 98 patients was generated from two retrospective cohorts from United Kingdom (65%) and Italy (36%). The prognostic impact of a number baseline imaging parameters was assessed and factors significant on univariate analysis were combined to create a novel radiologic signature on multivariable analyses predictive of overall survival (OS) following TACE.

Results

Median OS was 15.4 months. Tumour size > 7 cm (p < 0.001), intra-tumour necrosis (ITN) (p = 0.02) and arterial ectatic neovascularisation (AEN) (p = 0.03) emerged as individual prognostic factors together with radiologic response (p < 0.001) and elevated alpha-fetoprotein (AFP) (p = 0.01). Combination of tumour size > 7 cm, ITN and AEN identified patients with poor prognosis (p < 0.001).

Conclusions

We identified a coherent signature based on commonly available imaging biomarkers likely to be reflective of differential patterns of relative hypoxia and neovascularisation. Large tumours displaying AEN and ITN are characterised by a shorter survival after TACE.
Literature
1.
go back to reference Dufour JF, Bargellini I, De Maria N, De Simone P, Goulis I, Marinho RT. Intermediate hepatocellular carcinoma: current treatments and future perspectives. Ann Oncol. 2013;24(Suppl 2):ii24–9.CrossRefPubMed Dufour JF, Bargellini I, De Maria N, De Simone P, Goulis I, Marinho RT. Intermediate hepatocellular carcinoma: current treatments and future perspectives. Ann Oncol. 2013;24(Suppl 2):ii24–9.CrossRefPubMed
2.
go back to reference Bolondi L, Burroughs A, Dufour JF, Galle PR, Mazzaferro V, Piscaglia F, Raoul JL, Sangro B. Heterogeneity of patients with intermediate (BCLC B) hepatocellular carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis. 2012;32(4):348–59.PubMed Bolondi L, Burroughs A, Dufour JF, Galle PR, Mazzaferro V, Piscaglia F, Raoul JL, Sangro B. Heterogeneity of patients with intermediate (BCLC B) hepatocellular carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis. 2012;32(4):348–59.PubMed
3.
go back to reference Camma C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, Andreone P, Craxi A, Cottone M. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology. 2002;224(1):47–54.CrossRefPubMed Camma C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, Andreone P, Craxi A, Cottone M. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology. 2002;224(1):47–54.CrossRefPubMed
4.
go back to reference Kudo M, Matsui O, Izumi N, Kadoya M, Okusaka T, Miyayama S, Yamakado K, Tsuchiya K, Ueshima K, Hiraoka A, et al. Transarterial chemoembolization failure/refractoriness: JSH-LCSGJ criteria 2014 update. Oncology. 2014;87(Suppl 1):22–31.CrossRefPubMed Kudo M, Matsui O, Izumi N, Kadoya M, Okusaka T, Miyayama S, Yamakado K, Tsuchiya K, Ueshima K, Hiraoka A, et al. Transarterial chemoembolization failure/refractoriness: JSH-LCSGJ criteria 2014 update. Oncology. 2014;87(Suppl 1):22–31.CrossRefPubMed
5.
go back to reference Hucke F, Sieghart W, Pinter M, Graziadei I, Vogel W, Müller C, Heinzl H, Waneck F, Trauner M, Peck-Radosavljevic M. The ART-strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE. J Hepatol. 2014;60(1):118-26. Hucke F, Sieghart W, Pinter M, Graziadei I, Vogel W, Müller C, Heinzl H, Waneck F, Trauner M, Peck-Radosavljevic M. The ART-strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE. J Hepatol. 2014;60(1):118-26.
6.
go back to reference Kudo M, Arizumi T, Ueshima K. Assessment for retreatment (ART) score for repeated transarterial chemoembolization in patients with hepatocellular carcinoma. Hepatology. 2014;59(6):2424–5.CrossRefPubMed Kudo M, Arizumi T, Ueshima K. Assessment for retreatment (ART) score for repeated transarterial chemoembolization in patients with hepatocellular carcinoma. Hepatology. 2014;59(6):2424–5.CrossRefPubMed
7.
go back to reference European Association for Study of L, European Organisation for R, Treatment of C. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. Eur J Cancer. 2012;48(5):599–641.CrossRef European Association for Study of L, European Organisation for R, Treatment of C. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. Eur J Cancer. 2012;48(5):599–641.CrossRef
8.
go back to reference Kim BK, Kim KA, An C, Yoo EJ, Park JY, Kim do Y, Ahn SH, Han KH, Kim SU, Kim MJ. Prognostic role of magnetic resonance imaging vs. computed tomography for hepatocellular carcinoma undergoing chemoembolization. Liver Int. 2015;35(6):1722–30.CrossRefPubMed Kim BK, Kim KA, An C, Yoo EJ, Park JY, Kim do Y, Ahn SH, Han KH, Kim SU, Kim MJ. Prognostic role of magnetic resonance imaging vs. computed tomography for hepatocellular carcinoma undergoing chemoembolization. Liver Int. 2015;35(6):1722–30.CrossRefPubMed
9.
go back to reference Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30(1):52–60.CrossRefPubMed Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30(1):52–60.CrossRefPubMed
10.
go back to reference Yang CF, Ho YZ, Chang JM, Chiang RH, Lai KH, Lee SD, Tsai YT, Lui WY, Liu TJ, Chen GH. Transcatheter arterial chemoembolization for hepatocellular carcinoma. Cancer Chemother Pharmacol. 1989;23(Suppl):S26–8.CrossRefPubMed Yang CF, Ho YZ, Chang JM, Chiang RH, Lai KH, Lee SD, Tsai YT, Lui WY, Liu TJ, Chen GH. Transcatheter arterial chemoembolization for hepatocellular carcinoma. Cancer Chemother Pharmacol. 1989;23(Suppl):S26–8.CrossRefPubMed
11.
go back to reference Sieghart W, Hucke F, Peck-Radosavljevic M. Transarterial chemoembolization: modalities, indication, and patient selection. J Hepatol. 2015;62(5):1187–95.CrossRefPubMed Sieghart W, Hucke F, Peck-Radosavljevic M. Transarterial chemoembolization: modalities, indication, and patient selection. J Hepatol. 2015;62(5):1187–95.CrossRefPubMed
12.
go back to reference Cabibbo G, Maida M, Genco C, Parisi P, Peralta M, Antonucci M, Brancatelli G, Camma C, Craxi A, Di Marco V. Natural history of untreatable hepatocellular carcinoma: a retrospective cohort study. World J Hepatol. 2012;4(9):256–61.CrossRefPubMedPubMedCentral Cabibbo G, Maida M, Genco C, Parisi P, Peralta M, Antonucci M, Brancatelli G, Camma C, Craxi A, Di Marco V. Natural history of untreatable hepatocellular carcinoma: a retrospective cohort study. World J Hepatol. 2012;4(9):256–61.CrossRefPubMedPubMedCentral
13.
go back to reference Woodall CE, Scoggins CR, Loehle J, Ravindra KV, McMasters KM, Martin RC. Hepatic imaging characteristics predict overall survival in hepatocellular carcinoma. Ann Surg Oncol. 2007;14(10):2824–30.CrossRefPubMed Woodall CE, Scoggins CR, Loehle J, Ravindra KV, McMasters KM, Martin RC. Hepatic imaging characteristics predict overall survival in hepatocellular carcinoma. Ann Surg Oncol. 2007;14(10):2824–30.CrossRefPubMed
14.
go back to reference Chen YW, Pan HB, Tseng HH, Hung YT, Huang JS, Chou CP. Assessment of blood flow in hepatocellular carcinoma: correlations of computed tomography perfusion imaging and circulating angiogenic factors. Int J Mol Sci. 2013;14(9):17536–52.CrossRefPubMedPubMedCentral Chen YW, Pan HB, Tseng HH, Hung YT, Huang JS, Chou CP. Assessment of blood flow in hepatocellular carcinoma: correlations of computed tomography perfusion imaging and circulating angiogenic factors. Int J Mol Sci. 2013;14(9):17536–52.CrossRefPubMedPubMedCentral
15.
go back to reference Pinato DJ, Pirisi M, Maslen L, Sharma R. Tissue biomarkers of prognostic significance in hepatocellular carcinoma. Adv Anat Pathol. 2014;21(4):270–84.CrossRefPubMed Pinato DJ, Pirisi M, Maslen L, Sharma R. Tissue biomarkers of prognostic significance in hepatocellular carcinoma. Adv Anat Pathol. 2014;21(4):270–84.CrossRefPubMed
16.
go back to reference Bishayee A, Darvesh AS. Angiogenesis in hepatocellular carcinoma: a potential target for chemoprevention and therapy. Curr Cancer Drug Targets. 2012;12(9):1095–118.PubMed Bishayee A, Darvesh AS. Angiogenesis in hepatocellular carcinoma: a potential target for chemoprevention and therapy. Curr Cancer Drug Targets. 2012;12(9):1095–118.PubMed
17.
go back to reference Luo D, Wang Z, Wu J, Jiang C, Wu J. The role of hypoxia inducible factor-1 in hepatocellular carcinoma. Biomed Res Int. 2014;2014:409272.PubMedPubMedCentral Luo D, Wang Z, Wu J, Jiang C, Wu J. The role of hypoxia inducible factor-1 in hepatocellular carcinoma. Biomed Res Int. 2014;2014:409272.PubMedPubMedCentral
18.
go back to reference Ngan H, Peh WC. Arteriovenous shunting in hepatocellular carcinoma: its prevalence and clinical significance. Clin Radiol. 1997;52(1):36–40.CrossRefPubMed Ngan H, Peh WC. Arteriovenous shunting in hepatocellular carcinoma: its prevalence and clinical significance. Clin Radiol. 1997;52(1):36–40.CrossRefPubMed
19.
20.
go back to reference Kadalayil L, Benini R, Pallan L, O'Beirne J, Marelli L, Yu D, Hackshaw A, Fox R, Johnson P, Burroughs AK, et al. A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer. Ann Oncol. 2013;24(10):2565–70.CrossRefPubMedPubMedCentral Kadalayil L, Benini R, Pallan L, O'Beirne J, Marelli L, Yu D, Hackshaw A, Fox R, Johnson P, Burroughs AK, et al. A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer. Ann Oncol. 2013;24(10):2565–70.CrossRefPubMedPubMedCentral
21.
go back to reference Sinn DH, Cho JY, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC. Different survival of barcelona clinic liver cancer stage C hepatocellular carcinoma patients by the extent of portal vein invasion and the type of extrahepatic spread. PLoS One. 2015;10(4):e0124434.CrossRefPubMedPubMedCentral Sinn DH, Cho JY, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC. Different survival of barcelona clinic liver cancer stage C hepatocellular carcinoma patients by the extent of portal vein invasion and the type of extrahepatic spread. PLoS One. 2015;10(4):e0124434.CrossRefPubMedPubMedCentral
Metadata
Title
Preliminary qualification of a novel, hypoxic-based radiologic signature for trans-arterial chemoembolization in hepatocellular carcinoma
Authors
David J. Pinato
Madhava Pai
Isabella Reccia
Markand Patel
Alexandros Giakoustidis
Georgios Karamanakos
Azelea Rushd
Shiraz Jamshaid
Alberto Oldani
Glenda Grossi
Mario Pirisi
Paul Tait
Rohini Sharma
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4120-4

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