Skip to main content
Top
Published in: European Radiology 2/2015

01-02-2015 | Hepatobiliary-Pancreas

Volumetric assessment of tumour response using functional MR imaging in patients with hepatocellular carcinoma treated with a combination of doxorubicin-eluting beads and sorafenib

Authors: Celia Pamela Corona-Villalobos, Vivek Gowdra Halappa, Jean-Francois H. Geschwind, Susanne Bonekamp, Diane Reyes, David Cosgrove, Timothy M Pawlik, Ihab R Kamel

Published in: European Radiology | Issue 2/2015

Login to get access

Abstract

Objective

To prospectively assess treatment response using volumetric functional magnetic resonance imaging (MRI) metrics in patients with hepatocellular carcinoma (HCC) treated with the combination of doxorubicin-eluting bead–transarterial chemoembolization (DEB TACE) and sorafenib.

Methods

A single center study enrolled 41 patients treated with systemic sorafenib, 400 mg twice a day, combined with DEB TACE. All patients had a pre-treatment and 3–4 week post-treatment MRI. Anatomic response criteria (RECIST, mRECIST and EASL) and volumetric functional response (ADC, enhancement) were assessed. Statistical analyses included paired Student’s t-test, Kaplan-Meier curves, Cohen’s Kappa, and multivariate cox proportional hazard model.

Results

Median tumour size by RECIST remained unchanged post-treatment (8.3 ± 4.1 cm vs. 8.1 ± 4.3 cm, p = 0.44). There was no significant survival difference for early response by RECIST (p = 0.93). EASL and mRECIST could not be analyzed in 12 patients. Volumetric ADC increased significantly (1.32 × 10−3 mm2/sec to 1.60 × 10−3 mm2/sec, p < 0.001), and volumetric enhancement decreased significantly in HAP (38.2 % to 17.6 %, p < 0.001) and PVP (76.6 % to 41.2 %, p < 0.005). Patients who demonstrated ≥ 65 % decrease PVP enhancement had significantly improved overall survival compared to non-responders (p < 0.005).

Conclusion

Volumetric PVP enhancement was demonstrated to be significantly correlated with survival in the combination of DEB TACE and sorafenib for patients with HCC, enabling precise stratification of responders and non-responders.

Key Points

PVP enhancement is significantly correlated with survival in responders (p < 0.005).
There was no significant survival difference for early response using RECIST (p = 0.93).
mRECIST or EASL could not assess tumour response in 29 % of patients.
Literature
1.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153–156PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153–156PubMedCrossRef
2.
go back to reference Befeler AS, Di Bisceglie AM (2002) Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology 122:1609–1619PubMedCrossRef Befeler AS, Di Bisceglie AM (2002) Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology 122:1609–1619PubMedCrossRef
3.
go back to reference Bruix J, Llovet JM (2002) Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 35:519–524PubMedCrossRef Bruix J, Llovet JM (2002) Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 35:519–524PubMedCrossRef
4.
go back to reference Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390PubMedCrossRef Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390PubMedCrossRef
5.
go back to reference Camma C, Schepis F, Orlando A et al (2002) Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 224:47–54PubMedCrossRef Camma C, Schepis F, Orlando A et al (2002) Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 224:47–54PubMedCrossRef
6.
go back to reference Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37:429–442PubMedCrossRef Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37:429–442PubMedCrossRef
7.
go back to reference Reyes DK, Vossen JA, Kamel IR et al (2009) Single-center phase II trial of transarterial chemoembolization with drug-eluting beads for patients with unresectable hepatocellular carcinoma: initial experience in the United States. Cancer J 15:526–532PubMedCrossRef Reyes DK, Vossen JA, Kamel IR et al (2009) Single-center phase II trial of transarterial chemoembolization with drug-eluting beads for patients with unresectable hepatocellular carcinoma: initial experience in the United States. Cancer J 15:526–532PubMedCrossRef
8.
go back to reference Wilhelm SM, Carter C, Tang L et al (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099–7109PubMedCrossRef Wilhelm SM, Carter C, Tang L et al (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099–7109PubMedCrossRef
9.
go back to reference Wang B, Xu H, Gao ZQ, Ning HF, Sun YQ, Cao GW (2008) Increased expression of vascular endothelial growth factor in hepatocellular carcinoma after transcatheter arterial chemoembolization. Acta Radiol 49:523–529PubMedCrossRef Wang B, Xu H, Gao ZQ, Ning HF, Sun YQ, Cao GW (2008) Increased expression of vascular endothelial growth factor in hepatocellular carcinoma after transcatheter arterial chemoembolization. Acta Radiol 49:523–529PubMedCrossRef
10.
go back to reference Li X, Feng GS, Zheng CS, Zhuo CK, Liu X (2004) Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level. World J Gastroenterol 10:2878–2882PubMed Li X, Feng GS, Zheng CS, Zhuo CK, Liu X (2004) Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level. World J Gastroenterol 10:2878–2882PubMed
11.
go back to reference Pawlik TM, Reyes DK, Cosgrove D, Kamel IR, Bhagat N, Geschwind JF (2011) Phase II trial of sorafenib combined with concurrent transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma. J Clin Oncol 29:3960–3967PubMedCrossRef Pawlik TM, Reyes DK, Cosgrove D, Kamel IR, Bhagat N, Geschwind JF (2011) Phase II trial of sorafenib combined with concurrent transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma. J Clin Oncol 29:3960–3967PubMedCrossRef
12.
go back to reference Lencioni R, de Baere T, Burrel M et al (2012) Transcatheter treatment of hepatocellular carcinoma with doxorubicin-loaded DC bead (DEBDOX): technical recommendations. Cardiovasc Intervent Radiol 35:980–985PubMedCentralPubMedCrossRef Lencioni R, de Baere T, Burrel M et al (2012) Transcatheter treatment of hepatocellular carcinoma with doxorubicin-loaded DC bead (DEBDOX): technical recommendations. Cardiovasc Intervent Radiol 35:980–985PubMedCentralPubMedCrossRef
13.
go back to reference Kamel IR, Liapi E, Reyes DK, Zahurak M, Bluemke DA, Geschwind JF (2009) Unresectable hepatocellular carcinoma: serial early vascular and cellular changes after transarterial chemoembolization as detected with MR imaging. Radiology 250:466–473PubMedCrossRef Kamel IR, Liapi E, Reyes DK, Zahurak M, Bluemke DA, Geschwind JF (2009) Unresectable hepatocellular carcinoma: serial early vascular and cellular changes after transarterial chemoembolization as detected with MR imaging. Radiology 250:466–473PubMedCrossRef
14.
go back to reference Kamel IR, Bluemke DA, Eng J et al (2006) The role of functional MR imaging in the assessment of tumor response after chemoembolization in patients with hepatocellular carcinoma. J Vasc Interv Radiol 17:505–512PubMedCrossRef Kamel IR, Bluemke DA, Eng J et al (2006) The role of functional MR imaging in the assessment of tumor response after chemoembolization in patients with hepatocellular carcinoma. J Vasc Interv Radiol 17:505–512PubMedCrossRef
15.
go back to reference Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52–60PubMedCrossRef Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52–60PubMedCrossRef
16.
go back to reference Halappa VG, Bonekamp S, Corona-Villalobos CP et al (2012) Intrahepatic cholangiocarcinoma treated with local-regional therapy: quantitative volumetric apparent diffusion coefficient maps for assessment of tumor response. Radiology 264:285–294PubMedCrossRef Halappa VG, Bonekamp S, Corona-Villalobos CP et al (2012) Intrahepatic cholangiocarcinoma treated with local-regional therapy: quantitative volumetric apparent diffusion coefficient maps for assessment of tumor response. Radiology 264:285–294PubMedCrossRef
17.
go back to reference Gowdra Halappa V, Corona-Villalobos CP, Bonekamp S et al (2013) Neuroendocrine liver metastasis treated by using intraarterial therapy: Volumetric functional imaging biomarkers of early tumor response and survival. Radiology 266:502–513PubMedCrossRef Gowdra Halappa V, Corona-Villalobos CP, Bonekamp S et al (2013) Neuroendocrine liver metastasis treated by using intraarterial therapy: Volumetric functional imaging biomarkers of early tumor response and survival. Radiology 266:502–513PubMedCrossRef
18.
go back to reference Bonekamp S, Jolepalem P, Lazo M, Gulsun MA, Kiraly AP, Kamel IR (2011) Hepatocellular carcinoma: response to TACE assessed with semiautomated volumetric and functional analysis of diffusion-weighted and contrast-enhanced MR imaging data. Radiology 260:752–761PubMedCrossRef Bonekamp S, Jolepalem P, Lazo M, Gulsun MA, Kiraly AP, Kamel IR (2011) Hepatocellular carcinoma: response to TACE assessed with semiautomated volumetric and functional analysis of diffusion-weighted and contrast-enhanced MR imaging data. Radiology 260:752–761PubMedCrossRef
19.
go back to reference Bonekamp S, Halappa VG, Geschwind JF et al (2013) Unresectable hepatocellular carcinoma: MR imaging after intraarterial therapy. part II. response stratification using volumetric functional criteria after intraarterial therapy. Radiology. doi:10.1148/radiol.13121637 Bonekamp S, Halappa VG, Geschwind JF et al (2013) Unresectable hepatocellular carcinoma: MR imaging after intraarterial therapy. part II. response stratification using volumetric functional criteria after intraarterial therapy. Radiology. doi:10.​1148/​radiol.​13121637
20.
go back to reference Galizia MS, Tore HG, Chalian H, McCarthy R, Salem R, Yaghmai V (2012) MDCT necrosis quantification in the assessment of hepatocellular carcinoma response to yttrium 90 radioembolization therapy: comparison of two-dimensional and volumetric techniques. Acad Radiol 19:48–54PubMedCrossRef Galizia MS, Tore HG, Chalian H, McCarthy R, Salem R, Yaghmai V (2012) MDCT necrosis quantification in the assessment of hepatocellular carcinoma response to yttrium 90 radioembolization therapy: comparison of two-dimensional and volumetric techniques. Acad Radiol 19:48–54PubMedCrossRef
21.
go back to reference Liapi E, Geschwind JF (2011) Transcatheter arterial chemoembolization for liver cancer: is it time to distinguish conventional from drug-eluting chemoembolization? Cardiovasc Intervent Radiol 34:37–49PubMedCrossRef Liapi E, Geschwind JF (2011) Transcatheter arterial chemoembolization for liver cancer: is it time to distinguish conventional from drug-eluting chemoembolization? Cardiovasc Intervent Radiol 34:37–49PubMedCrossRef
22.
go back to reference Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247PubMedCrossRef Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247PubMedCrossRef
23.
go back to reference Bruix J, Sherman M, Llovet JM et al (2001) Clinical management of hepatocellular carcinoma. Conclusions of the barcelona-2000 EASL conference. European association for the study of the liver. J Hepatol 35:421–430PubMedCrossRef Bruix J, Sherman M, Llovet JM et al (2001) Clinical management of hepatocellular carcinoma. Conclusions of the barcelona-2000 EASL conference. European association for the study of the liver. J Hepatol 35:421–430PubMedCrossRef
24.
go back to reference Grady L (2006) Random walks for image segmentation. IEEE Trans Pattern Anal Mach Intell 28:1768–1783PubMedCrossRef Grady L (2006) Random walks for image segmentation. IEEE Trans Pattern Anal Mach Intell 28:1768–1783PubMedCrossRef
25.
go back to reference Bonekamp S, Li Z, Geschwind JF et al (2013) Unresectable hepatocellular carcinoma: MR imaging after intraarterial therapy. Part I. identification and validation of volumetric functional response criteria. Radiology. doi:10.1148/radiol.13122307 Bonekamp S, Li Z, Geschwind JF et al (2013) Unresectable hepatocellular carcinoma: MR imaging after intraarterial therapy. Part I. identification and validation of volumetric functional response criteria. Radiology. doi:10.​1148/​radiol.​13122307
26.
go back to reference Lewin M, Fartoux L, Vignaud A, Arrive L, Menu Y, Rosmorduc O (2011) The diffusion-weighted imaging perfusion fraction f is a potential marker of sorafenib treatment in advanced hepatocellular carcinoma: a pilot study. Eur Radiol 21:281–290PubMedCrossRef Lewin M, Fartoux L, Vignaud A, Arrive L, Menu Y, Rosmorduc O (2011) The diffusion-weighted imaging perfusion fraction f is a potential marker of sorafenib treatment in advanced hepatocellular carcinoma: a pilot study. Eur Radiol 21:281–290PubMedCrossRef
27.
go back to reference Schraml C, Schwenzer NF, Martirosian P et al (2009) Diffusion-weighted MRI of advanced hepatocellular carcinoma during sorafenib treatment: initial results. AJR Am J Roentgenol 193:W301-7. doi:10.2214/AJR.08.2289 Schraml C, Schwenzer NF, Martirosian P et al (2009) Diffusion-weighted MRI of advanced hepatocellular carcinoma during sorafenib treatment: initial results. AJR Am J Roentgenol 193:W301-7. doi:10.​2214/​AJR.​08.​2289
28.
go back to reference Takayasu K, Arii S, Matsuo N et al (2000) Comparison of CT findings with resected specimens after chemoembolization with iodized oil for hepatocellular carcinoma. AJR Am J Roentgenol 175:699–704PubMedCrossRef Takayasu K, Arii S, Matsuo N et al (2000) Comparison of CT findings with resected specimens after chemoembolization with iodized oil for hepatocellular carcinoma. AJR Am J Roentgenol 175:699–704PubMedCrossRef
29.
go back to reference Li Z, Bonekamp S, Halappa VG et al (2012) Islet cell liver metastases: assessment of volumetric early response with functional MR imaging after transarterial chemoembolization. Radiology 264:97–109PubMedCrossRef Li Z, Bonekamp S, Halappa VG et al (2012) Islet cell liver metastases: assessment of volumetric early response with functional MR imaging after transarterial chemoembolization. Radiology 264:97–109PubMedCrossRef
30.
go back to reference European Association For The Study Of The Liver, European Organisation For Research And Treatment Of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943 European Association For The Study Of The Liver, European Organisation For Research And Treatment Of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943
31.
go back to reference Georgiades C, Geschwind JF, Harrison N et al (2012) Lack of response after initial chemoembolization for hepatocellular carcinoma: does it predict failure of subsequent treatment? Radiology 265:115–123PubMedCentralPubMedCrossRef Georgiades C, Geschwind JF, Harrison N et al (2012) Lack of response after initial chemoembolization for hepatocellular carcinoma: does it predict failure of subsequent treatment? Radiology 265:115–123PubMedCentralPubMedCrossRef
32.
33.
go back to reference Riaz A, Miller FH, Kulik LM et al (2010) Imaging response in the primary index lesion and clinical outcomes following transarterial locoregional therapy for hepatocellular carcinoma. JAMA 303:1062–1069PubMedCentralPubMedCrossRef Riaz A, Miller FH, Kulik LM et al (2010) Imaging response in the primary index lesion and clinical outcomes following transarterial locoregional therapy for hepatocellular carcinoma. JAMA 303:1062–1069PubMedCentralPubMedCrossRef
Metadata
Title
Volumetric assessment of tumour response using functional MR imaging in patients with hepatocellular carcinoma treated with a combination of doxorubicin-eluting beads and sorafenib
Authors
Celia Pamela Corona-Villalobos
Vivek Gowdra Halappa
Jean-Francois H. Geschwind
Susanne Bonekamp
Diane Reyes
David Cosgrove
Timothy M Pawlik
Ihab R Kamel
Publication date
01-02-2015
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 2/2015
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-014-3412-6

Other articles of this Issue 2/2015

European Radiology 2/2015 Go to the issue