Novel imaging biomarkers of response to transcatheter arterial chemoembolization in hepatocellular carcinoma patients
Commentary

Novel imaging biomarkers of response to transcatheter arterial chemoembolization in hepatocellular carcinoma patients

Sylvain Favelier, Louis Estivalet, Pierre Pottecher, Romaric Loffroy

Department of Vascular, Oncologic and Interventional Radiology, University of Dijon School of Medicine, Bocage Teaching Hospital, Dijon Cedex, France

Correspondence to: Prof. Romaric Loffroy, MD, PhD. Department of Vascular, Oncologic and Interventional Radiology, Le2i UMR CNRS 6306, University of Dijon School of Medicine, Bocage Teaching Hospital, 14 Rue Gaffarel, BP 77908, 21079 Dijon Cedex, France. Email: romaric.loffroy@chu-dijon.fr; romaric.loffroy@gmail.com.

Submitted Jun 15, 2015. Accepted for publication Jun 30, 2015.

doi: 10.3978/j.issn.1000-9604.2015.07.02


Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide (1). Most patients present with intermediate or advanced disease that is not amenable to curative treatment, and the median survival in this group is 6-8 months (2). Several studies and well-designed randomized trials have shown a positive effect of transcatheter arterial chemoembolization (TACE) on patient outcome and survival (3-8). As nicely described in the present article from Wáng et al., assessment of tumor response is of extreme importance in patients undergoing locoregional treatments of liver cancer (9). Early assessment of the effectiveness of TACE and monitoring of tumor response are paramount to the identification of treatment failure, guidance of future therapy, and determination of the interval for repeat treatment. Wáng et al. confirm in this article that imaging evaluation of HCC response to therapy is generally and widely performed with cross-sectional imaging [computed tomography (CT) and magnetic resonance imaging (MRI)] by using the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria and the European Association for the Study of the Liver (EASL) criteria which have been introduced in the past decade (9). It is interesting to note that these criteria are not based on experimental or observational studies, but are proposed as revised versions of World Health Organization (WHO) and RECIST criteria (10-13). Initial reports showed that they were better than the latter for assessment of response, and both have been shown to be independent prognostic factors (14-19). Nevertheless, these criteria have been shown to have several limitations, mainly the lack of standardization, and there are concerns about applicability and reproducibility that have been raised. Indeed, they may be difficult to use, especially in heterogeneous lesions, and their use is dependent on operator experience. Although recent guidelines have acknowledged the potential value of these new criteria, they are not considered robust enough to replace older morphological criteria in trials (18). As a result, since they were first introduced, numerous studies have been published to better define the type and optimal number of target lesions, the ideal imaging technique, and the follow-up schedule. At present most teams perform one-dimensional mRECIST or two-dimensional EASL measurement of the enhanced portion of a maximum of two target lesions (18,19). Nevertheless, very recent data have suggested that three-dimensional (3D) evaluation of the whole tumor burden using specific software, functional imaging or cone-beam CT (CBCT) imaging may be of interest as novel imaging biomarkers to predict future tumor response to TACE in HCC patients (10,20-27).


Three-dimensional (3D) evaluation

The anatomic imaging biomarkers assume that tumors are spherical before and after treatment (28). In both RECIST and mRECIST, a 30% decrease in diameter of tumor, defined as the threshold for partial response, is presumed to correspond to a 65% decrease in tumor volume. Similarly, a 20% increase in diameter of viable tumor, which defines the threshold for defining disease progression, corresponds to an approximately 73% increase in spherical volume. These cut points are rather arbitrary and may not be applicable to all therapies. Furthermore, both RECIST and modified RECIST measurements are only estimates of the tumor volume and are prone to inter-observer measurement variability. In a retrospective study of 45 HCCs, diameter based on 3D measurements was significantly different than diameter based on conventional bidimensional (2D) measurements (29). Volumetric evaluation of HCC and its necrotic component eliminates this limitation and, when available, offers the most comprehensive anatomic evaluation for determining treatment response (30). Voxel-by-voxel volumetric analysis of tumor density and necrosis has been shown to be more reproducible than 2D analysis (29,31). Volumetric quantification is particularly helpful in cases in which necrosis is heterogeneously distributed in HCC and cannot be assessed using modified RECIST. Volumetric evaluation of HCC and its degree of necrosis is a very promising tool because it is more accurate and reproducible than the currently used 2D measurement. However, volumetric measurement is not easily feasible in the routine clinical setting and is still not included in tumor response criteria.


Functional imaging

Functional imaging, unlike anatomic imaging, provides information on tumor viability, cellularity, vascularity, and metabolism (32-34). These changes can be detected earlier than anatomic changes and are more applicable in assessing treatment response after TACE.

Diffusion-weighted imaging (DWI)

DWI has recently shown potential for HCC detection compared to or combined to contrast-enhanced T1-weighted imaging (35,36). DWI is also increasingly used to evaluate tumor response to locoregional therapy (37). There are several reports about the use of DWI to evaluate HCC response to TACE (23,25,38). These studies have shown differences in apparent diffusion coefficient (ADC) values between viable and necrotic portions of HCCs after treatment and measurable differences before and after treatment. In a prospective study, Kamel et al. (25) observed an increase in tumor ADC value that was significant 1-2 weeks after initial TACE, borderline significant 3 weeks after therapy, and insignificant 24 h and 4 weeks after therapy. They also showed that the maximum difference in tumor enhancement was present 1-2 weeks after TACE. Thus, they recommend the use of contrast-enhanced T1-weighted imaging and DWI 1-2 weeks after TACE. In an explant correlation study, investigators observed that ADC had a significant correlation with tumor necrosis assessed with histopathology (39). For prediction of complete tumor necrosis after TACE, an area under the curve (AUC) of 0.85 was observed for ADC compared with an AUC of 0.82-0.89 for image subtraction, without significant difference between the two techniques (39). The use of DWI in combination with conventional MRI shows promising results in increasing the sensitivity for detecting viable tumor (38). Diffusion restriction (hyperintensity on imaging performed with high b values and low ADC values) suggests viable tumor components (39). However, a study showed lower performance of DWI compared with contrast-enhanced imaging, with lower sensitivity for detection of local HCC recurrence (60.7% vs. 82%, respectively) (40). Regarding the use of pretreatment ADC as a marker of response to TACE, the data are limited, and two studies published to date report conflicting results (41,42). In a prospective study by Yuan et al. (41), non-responding HCCs had a significantly higher pretreatment ADC than HCCs that responded. On the other hand, a recently published retrospective study showed that HCCs with poor or incomplete response to TACE had significantly lower pretreatment ADC and lower post-TACE ADC values than HCCs with good or complete response (42). Both studies showed an increase in ADC in HCC with good response compared with HCC with poor response (41,42). Given the conflicting results from these two studies, the value of pre-TACE ADC in predicting response should be verified in a large prospective study. The limitations of DWI relate to image quality, with possible echo-planar imaging-related artifacts, and to limited knowledge on ADC reproducibility in liver tumors (43-45). In other words, despite promising results, DWI cannot still replace contrast-enhanced T1-weighted imaging and subtraction for assessment of HCC response. The role of baseline ADC and early changes in ADC values as markers of tumor response and time to tumor progression should be determined in a large prospective study.

Perfusion imaging

Dynamic contrast-enhanced MRI (DCE-MRI) (46) and perfusion CT (47) involve the use of contrast agents with high-temporal-resolution imaging to capture changes in MR signal intensity or CT attenuation as a function of time. These changes are used to quantify tissue and tumor vascular characteristics. Perfusion CT has the advantage of a direct linear relation between enhancement change and iodine concentration, whereas the relationship between MR signal intensity and gadolinium concentration is not necessarily linear depending on the dose of contrast injected, sequence parameters, and concentration reached in the target tissue. Although linearity can be assumed in DCE-MRI at certain concentrations, it is preferable to determine gadolinium concentration using unenhanced baseline T1 measurement. In contrast, perfusion CT is limited by the risk of radiation exposure, especially when follow-up studies are needed, and the lack of multipara-metric imaging. Multipara-metric imaging is possible only with MRI in which DCE-MRI can be combined with DWI. Recent studies using perfusion CT or DCE-MRI have shown potential for quantifying perfusion of malignant liver lesions and for monitoring treatment response to antiangiogenic drugs in HCC (48-51). Antiangiogenic agents are thought to induce an antipermeability effect while TACE reduces tumor blood volume (52). These effects result in a significant decrease in hepatic arterial fraction and perfusion in tumors effectively treated by TACE. In conclusion, as with DWI, it will be interesting to determine the role of pretreatment and early changes in tumor perfusion parameters as predictors of subsequent response to therapy and time to tumor progression. In addition, clinical utility, reproducibility, accuracy, proper modeling, and validation of perfusion CT and MRI techniques must be established.


Cone-beam CT (CBCT) imaging

Assessing treatment success during TACE is critically important as it affects treatment endpoints and consequently tumor response, local progression-free, and overall survival (53,54). The objective of post-treatment CBCT is to provide immediate assessment of tumor coverage and offer the possibility to change catheter positioning to ensure complete treatment of tumor burden and even predict tumor response (11,18,26). Incomplete tumor treatment negatively impacts survival (55,56). The imaging characteristics of different chemo-embolic agents differ substantially, thus requiring different post-treatment CBCT techniques. Lipiodol is a radiopaque contrast agent, which has also been used as a biomarker for HCC (55). Lipiodol deposition in the tumor is a prognostic factor affecting local recurrence of HCC and may be determined directly during the procedure using unenhanced CBCT, which offers equivalent lipiodol detection accuracy to unenhanced MDCT imaging (55-58). Drug-eluting beads (DEB), commonly loaded with doxorubicin, are radiolucent and so are mixed with contrast agent during delivery. These beads occlude tumor-feeding arteries from where the chemotherapy diffuses locally into the tumor (59). Assessment of DEB-TACE therefore requires the visualization of tumor-feeding vessel devascularization or tumor contrast agent saturation features on CBCT images (26,60,61). The value of immediate post-procedural CBCT scanning has been explored in several studies.

Lipiodol-CBCT (Lip-CBCT)

Lip-CBCT is a technique used to assess the lipiodol deposition into the tumor after drug delivery. This technique involves the acquisition of a CBCT scan without contrast medium injection immediately after conventional TACE treatment. Incomplete deposition of lipiodol into the tumor may be indicative of extrahepatic supply or incomplete delivery (62). Lip-CBCT imaging provides immediate feedback to the operator with lipiodol conspicuity equivalent to unenhanced multidetector CT and is predictive of tumor response when compared with 1-month follow-up multiphasic multidetector CT or contrast-enhanced MR imaging (57,58,62). The use of Lip-CBCT helps to achieve complete iodized oil filling of tumor(s) and therefore improves therapeutic effects by optimizing the embolization endpoint (62). Intra-procedural Lip-CBCT depicts HCC with 100% sensitivity compared with preprocedural diagnostic imaging (54,55).

Drug-eluting bead-CBCT (DEB-CBCT)

DEB-CBCT is a technique that involves a single non-contrast-enhanced CBCT scan after DEB-TACE to assess treatment success by visually estimating the degree of marginal contrast material saturation of the entire tumor volume, which is used as a surrogate for the beads deposition location and can help in determining the embolization endpoint. With DEB-CBCT, the positive predictive value of tumor response for marginal contrast agent saturation above 75% on DEB-CBCT images is 85% (60).

Dual-phase-CBCT (DP-CBCT)

The aim of DP-CBCT after DEB-TACE is to assess treatment success by displaying the changes in contrast enhancement of the target tumor(s) on both phases owing to tumor feeding vessel devascularization. The same protocol of the DP-CBCT technique as described elsewhere is used also after treatment ensuring that the same microcatheter positioning and contrast agent injection protocols are used (26,27). DP-CBCT helps to assess the lack of contrast agent uptake in the tumor whereas DEB-CBCT depicts the contrast agent uptake of the tumor margins, in both cases indicating successful tumor coverage with DEB-TACE. DP-CBCT has also shown to be predictive of tumor response according to the EASL and the RECIST guidelines at 1-month follow-up contrast-enhanced MR imaging. Limited tumor enhancement changes on DP-CBCT images after DEB-TACE may suggest to the operator either the need for retreatment or to search for additional feeding arteries. Commonly, the post-DEB-TACE DP-CBCT technique displays an arterial tumor enhancement and tumor-feeding arteries on the first scan (arterial phase, 3-15-second acquisition delay), and then parenchymal tumor enhancement on the second (parenchymal phase, 28-second acquisition delay).


Acknowledgements

None.


Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.


References

  1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557-76. [PubMed]
  2. Bosch FX, Ribes J, Díaz M, et al. Primary liver cancer: worldwide incidence and trends. Gastroenterology 2004;127:S5-S16. [PubMed]
  3. Llovet JM, Real MI, Montaña X, et al. Arterial embolisation or chemoembolization versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial. Lancet 2002;359:1734-9. [PubMed]
  4. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 2002;35:1164-71. [PubMed]
  5. Poon RT, Tso WK, Pang RW, et al. A phase I/II trial of chemoembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead. Clin Gastroenterol Hepatol 2007;5:1100-8. [PubMed]
  6. Malagari K, Alexopoulou E, Chatzimichail K, et al. Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments: midterm results of doxorubicin-loaded DC bead. Abdom Imaging 2008;33:512-9. [PubMed]
  7. Reyes DK, Vossen JA, Kamel IR, et al. 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 2009;15:526-32. [PubMed]
  8. Lammer J, Malagari K, Vogl T, et al. Prospective randomized study of doxorubicineluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 2010;33:41-52. [PubMed]
  9. Wáng YX, De Baere T, Idée JM, et al. Transcatheter embolization therapy in liver cancer: an update of clinical evidences. Chin J Cancer Res 2015;27:96-121. [PubMed]
  10. Yaghmai V, Besa C, Kim E, et al. Imaging assessment of hepatocellular carcinoma response to locoregional and systemic therapy. AJR Am J Roentgenol 2013;201:80-96. [PubMed]
  11. Therasse P, Arbuck SG, Eisenhauer EA, 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. [PubMed]
  12. Eisenhauer EA, Therasse P, Bogaerts J, et al. New Response Evaluation Criteria in Solid Tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. [PubMed]
  13. Llovet JM, Di Bisceglie AM, Bruix J, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 2008;100:698-711. [PubMed]
  14. Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma: conclusions of the Barcelona-2000 EASL conference-European Association for the Study of the Liver. J Hepatol 2001;35:421-30. [PubMed]
  15. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010;30:52-60. [PubMed]
  16. European Association for the Study of the Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012;56:908-43. [PubMed]
  17. Edeline J, Boucher E, Rolland Y, et al. Comparison of tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST in patients treated with sorafenib for hepatocellular carcinoma. Cancer 2012;118:147-56. [PubMed]
  18. Shim JH, Lee HC, Kim SO, et al. Which response criteria best help predict survival of patients with hepatocellular carcinoma following chemoembolization? A validation study of old and new models. Radiology 2012;262:708-18. [PubMed]
  19. Kim BK, Kim KA, Park JY, et al. Prospective comparison of prognostic values of modified Response Evaluation Criteria in Solid Tumours with European Association for the Study of the Liver criteria in hepatocellular carcinoma following chemoembolisation. Eur J Cancer 2013;49:826-34. [PubMed]
  20. Chapiro J, Duran R, Lin M, et al. Identifying Staging Markers for Hepatocellular Carcinoma before Transarterial Chemoembolization: Comparison of Three-dimensional Quantitative versus Non-three-dimensional Imaging Markers. Radiology 2015;275:438-47. [PubMed]
  21. Chapiro J, Lin M, Duran R, et al. Assessing tumor response after loco-regional liver cancer therapies: the role of 3D MRI. Expert Rev Anticancer Ther 2015;15:199-205. [PubMed]
  22. Lin M, Pellerin O, Bhagat N, et al. Quantitative and volumetric European Association for the Study of the Liver and Response Evaluation Criteria in Solid Tumors measurements: feasibility of a semiautomated software method to assess tumor response after transcatheter arterial chemoembolization. J Vasc Interv Radiol 2012;23:1629-37. [PubMed]
  23. Chen CY, Li CW, Kuo YT, et al. Early response of hepatocellular carcinoma to transcatheter arterial chemoembolization: choline levels and MR diffusion constants-initial experience. Radiology 2006;239:448-56. [PubMed]
  24. Chung JC, Naik NK, Lewandowski RJ, et al. Diffusion-weighted magnetic resonance imaging to predict response of hepatocellular carcinoma to chemoembolization. World J Gastroenterol 2010;16:3161-7. [PubMed]
  25. Kamel IR, Liapi E, Reyes DK, et al. Unresectable hepatocellular carcinoma: serial early vascular and cellular changes after transarterial chemoembolization as detected with MR imaging. Radiology 2009;250:466-73. [PubMed]
  26. Loffroy R, Lin M, Yenokyan G, et al. Intraprocedural C-arm dual-phase cone-beam CT: can it be used to predict short-term response to TACE with drug-eluting beads in patients with hepatocellular carcinoma? Radiology 2013;266:636-48. [PubMed]
  27. Loffroy R, Favelier S, Cherblanc V, et al. C-arm dual-phase cone-beam CT: a revolutionary real-time imaging modality to assess drug-eluting beads TACE success in liver cancer patients. Quant Imaging Med Surg 2013;3:196-9. [PubMed]
  28. Tran LN, Brown MS, Goldin JG, et al. Comparison of treatment response classifications between unidimensional, bidimensional, and volumetric measurements of metastatic lung lesions on chest computed tomography. Acad Radiol 2004;11:1355-60. [PubMed]
  29. Galizia MS, Töre HG, Chalian H, et al. Evaluation of hepatocellular carcinoma size using two-dimensional and volumetric analysis: effect on liver transplantation eligibility. Acad Radiol 2011;18:1555-60. [PubMed]
  30. Yaghmai V, Miller FH, Rezai P, et al. Response to treatment series. Part 2. Tumor response assessment: using new and conventional criteria. AJR Am J Roentgenol 2011;197:18-27. [PubMed]
  31. Chalian H, Tochetto SM, Töre HG, et al. Hepatic tumors: region-of-interest versus volumetric analysis for quantification of attenuation at CT. Radiology 2012;262:853-61. [PubMed]
  32. Alonzi R, Hoskin P. Functional imaging in clinical oncology: magnetic resonance imaging-and computerised tomography-based techniques. Clin Oncol (R Coll Radiol) 2006;18:555-70. [PubMed]
  33. Wang YX, Ng CK. The impact of quantitative imaging in medicine and surgery: Charting our course for the future. Quant Imaging Med Surg 2011;1:1-3. [PubMed]
  34. Schouten CS, de Bree R, van der Putten L, et al. Diffusion-weighted EPI- and HASTE-MRI and 18F-FDG-PET-CT early during chemoradiotherapy in advanced head and neck cancer. Quant Imaging Med Surg 2014;4:239-50. [PubMed]
  35. Piana G, Trinquart L, Meskine N, et al. New MR imaging criteria with a diffusion-weighted sequence for the diagnosis of hepatocellular carcinoma in chronic liver diseases. J Hepatol 2011;55:126-32. [PubMed]
  36. Park MS, Kim S, Patel J, et al. Hepatocellular carcinoma: detection with diffusion-weighted versus contrast-enhanced magnetic resonance imaging in pretransplant patients. Hepatology 2012;56:140-8. [PubMed]
  37. Hamstra DA, Rehemtulla A, Ross BD. Diffusion magnetic resonance imaging: a biomarker for treatment response in oncology. J Clin Oncol 2007;25:4104-9. [PubMed]
  38. Kamel IR, Bluemke DA, Eng J, et al. The role of functional MR imaging in the assessment of tumor response after chemoembolization in patients with hepatocellular carcinoma. J Vasc Interv Radiol 2006;17:505-12. [PubMed]
  39. Mannelli L, Kim S, Hajdu CH, et al. Assessment of tumor necrosis of hepatocellular carcinoma after chemoembolization: diffusion-weighted and contrast-enhanced MRI with histopathologic correlation of the explanted liver. AJR Am J Roentgenol 2009;193:1044-52. [PubMed]
  40. Goshima S, Kanematsu M, Kondo H, et al. Evaluating local hepatocellular carcinoma recurrence post-transcatheter arterial chemoembolization: is diffusion-weighted MRI reliable as an indicator? J Magn Reson Imaging 2008;27:834-9. [PubMed]
  41. Yuan Z, Ye XD, Dong S, et al. Role of magnetic resonance diffusion-weighted imaging in evaluating response after chemoembolization of hepatocellular carcinoma. Eur J Radiol 2010;75:e9-14. [PubMed]
  42. Mannelli L, Kim S, Hajdu CH, et al. Serial diffusion-weighted MRI in patients with hepatocellular carcinoma: prediction and assessment of response to transarterial chemoembolization-preliminary experience. Eur J Radiol 2013;82:577-82. [PubMed]
  43. Kim SY, Lee SS, Byun JH, et al. Malignant hepatic tumors: short-term reproducibility of apparent diffusion coefficients with breath-hold and respiratory-triggered diffusion-weighted MR imaging. Radiology 2010;255:815-23. [PubMed]
  44. Kim SY, Lee SS, Park B, et al. Reproducibility of measurement of apparent diffusion coefficients of malignant hepatic tumors: effect of DWI techniques and calculation methods. J Magn Reson Imaging 2012;36:1131-8. [PubMed]
  45. Chilla GS, Tan CH, Xu C, et al. Diffusion weighted magnetic resonance imaging and its recent trend-a survey. Quant Imaging Med Surg 2015;5:407-22. [PubMed]
  46. Padhani AR. Dynamic contrast-enhanced MRI in clinical oncology: current status and future directions. J Magn Reson Imaging 2002;16:407-22. [PubMed]
  47. Petralia G, Summers P, Viotti S, et al. Quantification of variability in breath-hold perfusion CT of hepatocellular carcinoma: a step toward clinical use. Radiology 2012;265:448-56. [PubMed]
  48. Jarnagin WR, Schwartz LH, Gultekin DH, et al. Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival. Ann Oncol 2009;20:1589-95. [PubMed]
  49. Yopp AC, Schwartz LH, Kemeny N, et al. Antiangiogenic therapy for primary liver cancer: correlation of changes in dynamic contrast-enhanced magnetic resonance imaging with tissue hypoxia markers and clinical response. Ann Surg Oncol 2011;18:2192-9. [PubMed]
  50. Wang D, Gaba RC, Jin B, et al. Intraprocedural transcatheter intra-arterial perfusion MRI as a predictor of tumor response to chemoembolization for hepatocellular carcinoma. Acad Radiol 2011;18:828-36. [PubMed]
  51. Ippolito D, Sironi S, Pozzi M, et al. Perfusion CT in cirrhotic patients with early stage hepatocellular carcinoma: assessment of tumor-related vascularization. Eur J Radiol 2010;73:148-52. [PubMed]
  52. Thng CH, Koh TS, Collins DJ, et al. Perfusion magnetic resonance imaging of the liver. World J Gastroenterol 2010;16:1598-609. [PubMed]
  53. Iwazawa J, Ohue S, Hashimoto N, et al. Survival after C-arm CT-assisted chemoembolization of unresectable hepatocellular carcinoma. Eur J Radiol 2012;81:3985-92. [PubMed]
  54. Miyayama S, Yamashiro M, Hashimoto M, et al. Identification of small hepatocellular carcinoma and tumor-feeding branches with cone-beam CT guidance technology during transcatheter arterial chemoembolization. J Vasc Interv Radiol 2013;24:501-8. [PubMed]
  55. Jeon UB, Lee JW, Choo KS, et al. Iodized oil uptake assessment with cone-beam CT in chemoembolization of small hepatocellular carcinomas. World J Gastroenterol 2009;15:5833-7. [PubMed]
  56. Iwazawa J, Ohue S, Kitayama T, et al. C-arm CT for assessing initial failure of iodized oil accumulation in chemoembolization of hepatocellular carcinoma. AJR Am J Roentgenol 2011;197:W337-42. [PubMed]
  57. Chen R, Geschwind JF, Wang Z, et al. Quantitative assessment of lipiodol deposition after chemoembolization: comparison between cone-beam CT and multidetector CT. J Vasc Interv Radiol 2013;24:1837-44. [PubMed]
  58. Wang Z, Lin M, Lesage D, et al. Three-dimensional evaluation of lipiodol retention in HCC after chemoembolization: a quantitative comparison between CBCT and MDCT. Acad Radiol 2014;21:393-9. [PubMed]
  59. Lencioni R, de Baere T, Burrel M, et al. Transcatheter treatment of hepatocellular carcinoma with Doxorubicin-loaded DC Bead (DEBDOX): technical recommendations. Cardiovasc Intervent Radiol 2012;35:980-5. [PubMed]
  60. Suk Oh J, Jong Chun H, Gil Choi B, et al. Transarterial chemoembolization with drug-eluting beads in hepatocellular carcinoma: usefulness of contrast saturation features on cone-beam computed tomography imaging for predicting short-term tumor response. J Vasc Interv Radiol 2013;24:483-9. [PubMed]
  61. Tacher V, Radaelli A, Lin M, et al. How I do it: Cone-beam CT during transarterial chemoembolization for liver cancer. Radiology 2015;274:320-34. [PubMed]
  62. Monsky WL, Jin B, Molloy C, et al. Semi-automated volumetric quantification of tumor necrosis in soft tissue sarcoma using contrast-enhanced MRI. Anticancer Res 2012;32:4951-61. [PubMed]
Cite this article as: Favelier S, Estivalet L, Pottecher P, Loffroy R. Novel imaging biomarkers of response to transcatheter arterial chemoembolization in hepatocellular carcinoma patients. Chin J Cancer Res 2015;27(6):611-616. doi: 10.3978/j.issn.1000-9604.2015.07.02