Prospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2019; 25(19): 2365-2372
Published online May 21, 2019. doi: 10.3748/wjg.v25.i19.2365
Change in arterial tumor perfusion is an early biomarker of lenvatinib efficacy in patients with unresectable hepatocellular carcinoma
Hidekatsu Kuorda, Tamami Abe, Yudai Fujiwara, Takuya Okamoto, Miki Yonezawa, Hiroki Sato, Kei Endo, Takayoshi Oikawa, Kei Sawara, Yasuhiro Takikawa
Hidekatsu Kuorda, Tamami Abe, Yudai Fujiwara, Takuya Okamoto, Miki Yonezawa, Hiroki Sato, Kei Endo, Takayoshi Oikawa, Kei Sawara, Yasuhiro Takikawa, Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Iwate 020-8505, Japan
Author contributions: Kuroda H drafted the manuscript, and assisted with data analysis; Abe T participated in design and oversight of the study, and was involved with data collection; Fujiwara Y participated in design of the study, and was involved with data collection; Okamoto T was involved with data collection, and assisted with data analysis; Yonezawa M was involved with data collection, and assisted with data analysis; Sato H was involved with data collection, and assisted with data analysis; Endo K drafted the manuscript, and assisted with data analysis; Oikawa T participated in study design and performed statistical analysis; Sawara K participated in design of the study, was involved with data collection; Takikawa Y drafted the manuscript, and assisted with data analysis; all authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the local Ethics Committee of the Iwate Medical University (MH2018-533).
Clinical trial registration statement: The clinical trial is registered at clinical hospital center Iwate medical trial registry. The registration identification number is MH2018-533.
Informed consent statement: All study participants, or their legal guardian, provided written consent prior to study enrollment.
Conflict-of-interest statement: The authors of this manuscript having no conflicts of interest to disclose.
Data sharing statement: There is no additional data available.
CONSORT 2010 statement: The manuscript was prepared according to CONSORT 2010 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Hidekatsu Kuroda, MD, PhD, Doctor, Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Uchimaru 19-1, Morioka, Iwate 020-8505, Japan. hikuro@iwate-med.ac.jp
Telephone: +81-19-6515111 Fax: +81-19-6526664
Received: February 10, 2019
Peer-review started: February 12, 2019
First decision: March 20, 2019
Revised: April 12, 2019
Accepted: April 29, 2019
Article in press: April 29, 2019
Published online: May 21, 2019
Processing time: 101 Days and 19.8 Hours
ARTICLE HIGHLIGHTS
Research background

Lenvatinib is one of the first-line tyrosine kinase inhibitors used for unresectable hepatocellular carcinoma (HCC).

Research motivation

The overall prognosis for patients with HCC is poor, and more than half of the patients are diagnosed at a stage when the tumor is unresectable. The treatment options for unresectable HCC are limited, and oral administration of sorafenib, a receptor tyrosine kinase inhibitor, has been the only treatment that substantially prolongs survival.

Research objectives

To evaluate the potential of the early changes in the time-intensity curve (TIC) of contrast-enhanced ultrasound (CEUS) as early imaging biomarkers of lenvatinib efficacy in patients with unresectable HCC.

Research methods

We analyzed 20 consecutive patients with unresectable HCC treated with lenvatinib from March to November 2018. Tumor response at 8 wk was assessed by computed tomography using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). CEUS was performed at baseline before treatment (Day 0) and on day 7 (Day 7), and the images were analyzed in the arterial phase for 20 seconds after the contrast agent arrived at the target tumor. Three perfusion parameters were extracted from the TICs: the slope of wash-in (Slope), time to peak (TTP) intensity, and the total area under the curve (AUC) during wash-in. The rate of change in the TIC parameters between Day 0 and Day 7 was compared between treatment responders and non-responders based on mRECIST.

Research results

The rate of change for all TIC parameters showed significant differences between the responders (n = 9) and non-responders (n = 11) (Slope, P = 0.025; TTP, P = 0.004; and AUC, P = 0.0003). The area under the receiver operating curve values for slope, TTP, and AUC for the prediction of responders were 0.805, 0.869, and 0.939, respectively.

Research conclusions

To the best of our knowledge, this is the first prospective study to assess the potential of CEUS for making early predictions of outcomes following lenvatinib therapy, which makes it a significant contribution to the literature.

Research perspectives

Further, we believe that this paper will be of interest to the readership especially hepatologists and oncologists because we demonstrate that CEUS may be useful for the early prediction of tumor response in patients with unresectable HCC treated with lenvatinib.