Clinical Trials Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2023; 29(24): 3871-3882
Published online Jun 28, 2023. doi: 10.3748/wjg.v29.i24.3871
Stereotactic body radiotherapy combined with sintilimab in patients with recurrent or oligometastatic hepatocellular carcinoma: A phase II clinical trial
Yi-Xing Chen, Ping Yang, Shi-Suo Du, Yuan Zhuang, Cheng Huang, Yong Hu, Wen-Chao Zhu, Yi-Yi Yu, Tian-Shu Liu, Zhao-Chong Zeng
Yi-Xing Chen, Ping Yang, Shi-Suo Du, Yuan Zhuang, Yong Hu, Wen-Chao Zhu, Zhao-Chong Zeng, Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Cheng Huang, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Yi-Yi Yu, Tian-Shu Liu, Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Author contributions: Zeng ZC, Liu TS, Chen YX, Du SS, and Yu YY contributed to the conception and study design; Chen YX, Yang P, Zhuang Y, Huang C, Hu Y, and Zhu WC contributed to the investigation and data curation; Chen YX, Zeng ZC, and Liu TS performed the data analysis and interpretation; Chen YX wrote the original draft; Zeng ZC, Liu TS, Chen YX, and Du SS wrote the review and editing; Liu TS and Zeng ZC contributed equally to this work. All authors reviewed and approved the final draft of the manuscript.
Supported by The Ministry of Science and Technology of The People's Republic of China, No. 2022YFC2503700, and No. 2022YFC2503704.
Institutional review board statement: The Medical Ethics Committee of Zhongshan Hospital, Fudan University, approved this study (B2019-010R), which was conducted in accordance with the standards of Good Clinical Practice and the Declaration of Helsinki. All patients consented to participate after being informed of the study’s purpose.
Clinical trial registration statement: This was a single-arm, open-label, single-center, phase II trial registered with ClinicalTrials.gov (NCT03857815).
Informed consent statement: All patients consented to participate after being informed of the study’s purpose.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhao-Chong Zeng, PhD, Professor, Department of Radiation Oncology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, China. zeng.zhaochong@zs-hospital.sh.cn
Received: March 26, 2023
Peer-review started: March 26, 2023
First decision: April 26, 2023
Revised: May 6, 2023
Accepted: May 30, 2023
Article in press: May 30, 2023
Published online: June 28, 2023
Abstract
BACKGROUND

Stereotactic body radiotherapy (SBRT) and programmed cell death 1 inhibitors have shown potential in treating hepatocellular carcinoma (HCC) in retrospective studies.

AIM

To evaluate the efficacy of combining SBRT with sintilimab for patients with recurrent or oligometastatic HCC.

METHODS

This trial involved patients with recurrent or oligometastatic HCC intravenously treated with SBRT plus sintilimab every 3 wk for 12 mo or until disease progression. The primary endpoint was progression-free survival (PFS).

RESULTS

Twenty-five patients were enrolled from August 14, 2019, to August 23, 2021. The median treatment duration was 10.2 (range, 0.7-14.6) months. SBRT was delivered at a median dose of 54 (range, 48-60) Gy in 6 (range, 6-10) fractions. The median follow-up time was 21.9 (range, 10.3-39.7) mo, and 32 targeted lesions among 25 patients were evaluated for treatment response according to the Response Evaluation Criteria in Solid Tumors version 1.1. The median PFS was 19.7 mo [95% confidence interval (CI): 16.9-NA], with PFS rates of 68% (95%CI: 52-89) and 45.3% (95%CI: 28-73.4) at 12 and 24 mo, respectively. The median overall survival (OS) was not reached, with OS rates of 91.5% (95%CI: 80.8-100.0) and 83.2% (95%CI: 66.5-100.0) at 12 and 24 mo, respectively. The 1- and 2-year local control rate were 100% and 90.9% (95%CI: 75.4%-100.0%), respectively. The confirmed objective response rate and disease control rate was 96%, and 96%, respectively. Most adverse events were graded as 1 or 2, and grade 3 adverse events were observed in three patients.

CONCLUSION

SBRT plus sintilimab is an effective, well-tolerated treatment regimen for patients with recurrent or oligometastatic HCC.

Keywords: Stereotactic body radiotherapy, Programmed cell death 1, Sintilimab, Hepatocellular carcinoma, Efficacy and safety

Core Tip: In this single-arm phase II trial, stereotactic body radiotherapy (SBRT) plus sintilimab showed outstanding progression-free survival and objective response rate in the treatment of recurrent or oligometastatic hepatocellular carcinoma. Moreover, the combined use of SBRT and sintilimab is safe and tolerable. Patients can recover rapidly from radiotherapy-induced decreases in lymphocyte counts. This result suggests that SBRT combined with sintilimab may be a new treatment option for patients with recurrent or oligometastatic hepatocellular carcinoma.