Use of Contrast-Enhanced Ultrasound with Sonazoid for Evaluating the Radiotherapy Efficacy for Hepatocellular Carcinoma

: Radiotherapy is one of the available curative therapies for hepatocellular carcinoma (HCC). We investigate the use of contrast-enhanced ultrasound using Sonazoid (SCEUS) in evaluating the efficacy of radiotherapy for HCC. We enrolled 59 patients with 59 HCCs in this retrospective study. Tumor size and tumor vascularity were evaluated using SCEUS before and 1, 3, 7, 10, and 13 months after radiotherapy. The median follow-up period was 44.5 months (range: 16–82 months). Of the HCCs, 95% (56/59) had no local recurrence, while 5% (3/59) did. At 13 months after radiotherapy, in cases with no local recurrence, SCEUS showed a reduction in tumor vascularity in all cases, while tumor size reduction (>30% reduction, compared with pre-radiotherapy) was observed in 82.1% (46/56). In all three cases of local recurrence, vascularity and tumor size reduction were not observed during the follow-up period and residual HCCs were demonstrated pathologically. Compared with cases with local recurrence, tumor size reduction and reduction in tumor vascularity ( p < 0.001) were significantly greater in cases with no local recurrence at 13 months after radiotherapy. SCEUS may be useful in evaluating radiotherapy efficacy for HCC.

[1]  M. Okada,et al.  Diagnostic Value of Imaging Methods in the Histological Four Grading of Hepatocellular Carcinoma , 2020, Diagnostics.

[2]  A. Takeda,et al.  Local control by salvage stereotactic body radiotherapy for recurrent/residual hepatocellular carcinoma after other local therapies , 2020, Acta oncologica.

[3]  T. Kimura,et al.  Stereotactic body radiation therapy vs. radiofrequency ablation in Asian patients with hepatocellular carcinoma. , 2020, Journal of hepatology.

[4]  Masahiro Okada,et al.  Application of new ultrasound techniques for focal liver lesions , 2020, Journal of Medical Ultrasonics.

[5]  A. Jemal,et al.  Cancer statistics, 2020 , 2020, CA: a cancer journal for clinicians.

[6]  Katsuaki Tanaka,et al.  Radiotherapy for Hepatocellular Carcinoma Results in Comparable Survival to Radiofrequency Ablation: A Propensity Score Analysis , 2019, Hepatology.

[7]  H. Fukuda,et al.  Comparison Between Low Mechanical Index and High Mechanical Index Contrast Modes of Contrast‐Enhanced Ultrasonography: Evaluation of Perfusion Defects of Hypervascular Hepatocellular Carcinomas During the Post–Vascular Phase , 2019, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[8]  Prasad R. Shankar,et al.  Magnetic Resonance Imaging Evaluation of Hepatocellular Carcinoma Treated With Stereotactic Body Radiation Therapy: Long Term Imaging Follow-Up. , 2019, International journal of radiation oncology, biology, physics.

[9]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[10]  J. Bruix,et al.  Diagnosis and staging of hepatocellular carcinoma (HCC): current guidelines. , 2018, European journal of radiology.

[11]  O. Matsui,et al.  Pathology and images of radiation-induced hepatitis: a review article , 2018, Japanese Journal of Radiology.

[12]  H. Fukuda,et al.  Fusion imaging with contrast-enhanced ultrasonography for evaluating the early therapeutic efficacy of radiofrequency ablation for small hypervascular hepatocellular carcinomas with iso-echoic or unclear margins on conventional ultrasonography , 2018, Journal of Medical Ultrasonics.

[13]  M. Abecassis,et al.  AASLD guidelines for the treatment of hepatocellular carcinoma , 2018, Hepatology.

[14]  A. Allen,et al.  Stereotactic body radiation therapy (SBRT) for definitive treatment and as a bridge to liver transplantation in early stage inoperable Hepatocellular carcinoma , 2017, Radiation oncology.

[15]  P. Nahon,et al.  Percutaneous treatment of hepatocellular carcinoma: State of the art and innovations. , 2017, Journal of hepatology.

[16]  E. Jung,et al.  Percutaneous Treatment of Malignant Liver Lesions: Evaluation of Success Using Contrast- Enhanced Ultrasound (CEUS) and Perfusion Software , 2017, Ultraschall in der Medizin - European Journal of Ultrasound.

[17]  H. Hussain,et al.  Imaging Findings Within the First 12 Months of Hepatocellular Carcinoma Treated With Stereotactic Body Radiation Therapy. , 2017, International journal of radiation oncology, biology, physics.

[18]  Jieun Kim,et al.  Radiation-induced liver disease: current understanding and future perspectives , 2017, Experimental &Molecular Medicine.

[19]  J. Salleron,et al.  Tumor response assessment by MRI following stereotactic body radiation therapy for hepatocellular carcinoma , 2017, PloS one.

[20]  E. Kunieda,et al.  Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation , 2016, Cancer.

[21]  Manabu Watanabe,et al.  Evaluation of contrast-enhanced ultrasonography for hepatocellular carcinoma prior to and following stereotactic body radiation therapy using the CyberKnife® system: A preliminary report , 2015, Oncology letters.

[22]  K. Chayama,et al.  The Time Course of Dynamic Computed Tomographic Appearance of Radiation Injury to the Cirrhotic Liver Following Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma , 2015, PloS one.

[23]  Y. Imai,et al.  JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan , 2014, Liver Cancer.

[24]  Zahra Kassam,et al.  Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  B. Goldberg,et al.  Radiological Clinical Practice Guidelines Published in the Last Decade: A Bibliometric Analysis , 2019, Journal of the Belgian Society of Radiology.

[26]  Dong Han Lee,et al.  Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization , 2012, Cancer.

[27]  M. Okada,et al.  Use of fusion imaging combining contrast-enhanced ultrasonography with a perflubutane-based contrast agent and contrast-enhanced computed tomography for the evaluation of percutaneous radiofrequency ablation of hypervascular hepatocellular carcinoma. , 2012, European journal of radiology.

[28]  Junji Shiraishi,et al.  Comparison of Kupffer‐Phase Sonazoid‐Enhanced Sonography and Hepatobiliary‐Phase Gadoxetic Acid‐Enhanced Magnetic Resonance Imaging of Hepatocellular Carcinoma and Correlation With Histologic Grading , 2012, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[29]  M. Choi,et al.  Salvage treatment with hypofractionated radiotherapy in patients with recurrent small hepatocellular carcinoma. , 2012, International journal of radiation oncology, biology, physics.

[30]  E. Kunieda,et al.  CT evaluations of focal liver reactions following stereotactic body radiotherapy for small hepatocellular carcinoma with cirrhosis: relationship between imaging appearance and baseline liver function. , 2010, The British journal of radiology.

[31]  Kinuyo Hatanaka,et al.  Newly Developed Novel Ultrasound Technique, Defect Reperfusion Ultrasound Imaging, Using Sonazoid in the Management of Hepatocellular Carcinoma , 2010, Oncology.

[32]  J. Bruix,et al.  Current Strategy for Staging and Treatment: The BCLC Update and Future Prospects , 2010, Seminars in liver disease.

[33]  Riccardo Lencioni,et al.  Modified RECIST (mRECIST) Assessment for Hepatocellular Carcinoma , 2010, Seminars in liver disease.

[34]  M. Okada,et al.  Ablation Therapy Guided by Contrast‐Enhanced Sonography with Sonazoid for Hepatocellular Carcinoma Lesions Not Detected by Conventional Sonography , 2008, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[35]  G. van Kaick,et al.  Assessment of focal liver reaction by multiphasic CT after stereotactic single-dose radiotherapy of liver tumors. , 2003, International journal of radiation oncology, biology, physics.

[36]  G. McDonald,et al.  Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). , 2002, Seminars in liver disease.

[37]  M. Dumont,et al.  European Association for the Study of the Liver , 1971 .

[38]  M. Okada,et al.  Central vascular structures as a characteristic finding of regenerative nodules using hepatobiliary phase gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid-enhanced MRI and arterial dominant phase contrast-enhanced US , 2016, Journal of Medical Ultrasonics.

[39]  Akiko Hayakawa,et al.  The safety and the efficacy of ultrasound contrast media Perflubutane microbubbles in clinical practice , 2011 .

[40]  D. Woodfield Hepatocellular carcinoma. , 1986, The New Zealand medical journal.