Clinical application of a programmed death ligand-1 inhibitor combined with low-dose pulsed radiotherapy in recurrent metastatic hepatocellular carcinoma

doi:10.4251/wjgo.121184

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Oct 15, 2026; 18(10): 121184
Published online Oct 15, 2026. doi: 10.4251/wjgo.121184

Clinical application of a programmed death ligand-1 inhibitor combined with low-dose pulsed radiotherapy in recurrent metastatic hepatocellular carcinoma

Xin-An Wan, Ming-Xing Fang, Le Yuan, Hang Zhang, Dan Wang, Zhao-Di Liu

Xin-An Wan, Le Yuan, Hang Zhang, Dan Wang, Zhao-Di Liu, Department of Oncology, The Second People’s Hospital, Wuhu, Wuhu 241000, Anhui Province, China

Ming-Xing Fang, Department of Anesthesiology, The Second People’s Hospital, Wuhu, Wuhu 241000, Anhui Province, China

Author contributions: Wan XA designed the study, supervised the study and revised the manuscript; Fang MX collected data and drafted the manuscript; Yuan L, Zhang H, Wang D, and Liu ZD contributed to patient recruitment, follow-up and acquisition of data; all authors have read and approve the final manuscript.

AI contribution statement: AI tools were used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.

Supported by Clinical Medical Research Transformation Project of Anhui Province of China, No. 202204295107020064.

Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Second People’s Hospital, Wuhu (approval No. 2024-KY-41).

Clinical trial registration statement: This trial was not registered. The local institutional review board was aware of the trial and approved study.

Informed consent statement: All participants provided informed consent.

Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.

CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.

Data sharing statement: Technical appendix and dataset available from the corresponding author.

Corresponding author: Xin-An Wan, MD, PhD, Chief Physician, Department of Oncology, The Second People’s Hospital, Wuhu, No. 6 Duchun Road, Wuhu 241000, Anhui Province, China. 2263853630@qq.com

Received: March 18, 2026
Revised: June 16, 2026
Accepted: July 9, 2026
Published online: October 15, 2026
Processing time: 182 Days and 19.8 Hours

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is among the malignancies with the poorest prognosis. The first-line standard treatment for recurrent metastatic HCC achieves an objective response rate of only approximately 30%, with a median progression-free survival (PFS) of approximately 6 months. The efficacy of second-line and subsequent therapies is even more limited.

AIM

To investigate the efficacy and safety of a programmed death ligand-1 inhibitor combined with low-dose pulsed radiotherapy in patients with recurrent metastatic HCC.

METHODS

Patients with confirmed advanced primary HCC who experienced disease progression following at least one prior line of therapy were enrolled. A low-dose pulsed radiotherapy regimen was administered, consisting of 0.2 Gy per pulse delivered at 3-minute intervals, with 10 fractions per day over 5 consecutive days per week. One week after the initiation of radiotherapy, intravenous atezolizumab (1200 mg every 3 weeks) was added. Efficacy was evaluated after 2 cycles of atezolizumab according to the response evaluation criteria in solid tumors 1.1 criteria. Peripheral blood T-lymphocyte subsets were analyzed before treatment and after the completion of pulsed radiotherapy plus 2 cycles of atezolizumab.

RESULTS

Patient A eventually had a PFS of 4.7 months and an overall survival (OS) of 7.7 months. Patients B and C are still under follow-up (March 2026) and remain well controlled without progression. The PFS and OS of patient B exceeded 15 months, and the PFS and OS of patient C exceeded 8 months. Patient D was the only progressive case, with an OS of only 2.2 months. According to peripheral blood T lymphocyte subset analysis, the percentage of programmed death 1-positive T lymphocytes in patients A, B, and C remained low or even decreased, whereas the percentage of programmed death 1-positive T lymphocytes in patient D significantly increased after treatment. Conversely, the ratio of CD8⁺ terminally differentiated effector T cells/cytotoxic T lymphocytes in patients A, B, and C was greater than the ratio of CD8⁺ effector memory T cells/cytotoxic T lymphocytes, whereas the opposite was true for patient D.

CONCLUSION

A programmed death ligand-1 inhibitor combined with low-dose pulsed radiotherapy achieved clear efficacy in some patients, with good safety and tolerability.

Keywords: Programmed death ligand-1 inhibitor; Pulsed radiotherapy; Hepatocellular carcinoma; Clinical application; T lymphocyte subsets

Core Tip: The combination of a programmed death ligand-1 inhibitor (atezolizumab) and low-dose pulsed radiation therapy has shown good efficacy and safety in some patients with recurrent metastatic hepatocellular carcinoma.