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Article Open Access

Efficacy and safety of the immune checkpoint inhibitor‑radiotherapy combination in advanced/unresectable hepatocellular carcinoma: A systematic review and meta‑analysis

  • Authors:
    • Ran Cui
    • Xinlin Yu
    • Yan Jiang
    • Xingming Li
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, The First People's Hospital of Neijiang, Neijiang, Sichuan 641000, P.R. China
    Copyright: © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 460
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    Published online on: July 28, 2025
       https://doi.org/10.3892/ol.2025.15206
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Abstract

Limited treatment options are available for patients with advanced stages of hepatocellular carcinoma (HCC), which is a major global health challenge. The present systematic review and meta‑analysis examined the therapeutic potential of the combination of immune checkpoint inhibitors (ICIs) and radiotherapy (RT) for advanced (a)HCC or unresectable HCC. The PubMed, Embase, Cochrane Library and Web of Science databases were searched to identify studies examining the therapeutic efficacy of the ICI‑RT combination for aHCC published until August 31, 2024. The following clinical outcomes were analyzed: Objective response rate (ORR), median progression‑free survival (mPFS) and median overall survival (mOS). Additionally, targeted subgroup analyses were performed based on tumor thrombus presence and the use of transarterial chemoembolization (TACE) and stereotactic body RT. The present single‑arm meta‑analysis, encompassing 16 studies involving 633 patients with aHCC or unresectable HCC, revealed that the ICI‑RT combination exhibits potent therapeutic efficacy. The pooled ORR of patients in the ICI‑RT combination group was 54.4% [95% confidence interval (CI), 46.8‑62.0%]. The mPFS and mOS of patients treated with the ICI‑RT combination were 10.1 (95% CI, 7.2‑12.9) and 18.3 months (95% CI, 14.6‑21.9), respectively. The ORR of patients in the TACE combination subgroup was 53.8% (95% CI, 44.6‑62.9%). Meanwhile, the ORR and mOS of patients with Barcelona Clinic Liver Cancer stage C tumors were 55.6% (95% CI, 44.3‑66.9%) and 21.2 months (95% CI, 13.5‑29.0), respectively. These findings suggest that ICI and RT exert synergistic effects. The ICI‑RT combination, a promising therapeutic regime for aHCC, is associated with potent efficacy and favorable ORR and survival outcomes. Further studies are needed to optimize treatment strategies and identify patient subgroups who can benefit from this approach. The findings of the present study contribute to advances in aHCC treatment. The protocol for the present systematic review was registered at PROSPERO (registration no. CRD42024583148) and is available in full on the Health Technology Assessment website of the National Institutes of Health (http://www.hta.ac.uk/2283).
View Figures

Figure 1

Flow diagram for the
inclusion/exclusion of studies in the present meta-analysis.

Figure 2

Forest plot of the pooled objective
response rate. ES, effect size; CI, confidence interval.

Figure 3

Forest plots of the pooled mPFS and
mOS. (A) mPFS and (B) mOS of treatment regimen. ES, effect size;
CI, confidence interval; mPFS, median progression-free survival;
mOS, median overall survival.

Figure 4

Forest plots of the pooled ORR. (A)
ORR of the subgroup with tumor thrombus. (B) ORR of the subgroup
treated with transarterial chemoembolization. ES, effect size; CI,
confidence interval; ORR, objective response rate.

Figure 5

Forest plots of the pooled ORR. (A)
ORR of the subgroup treated with stereotactic body radiotherapy.
(B) ORR of the subgroup treated with Barcelona Clinic Liver Cancer
stage C. ES, effect size; CI, confidence interval; ORR, objective
response rate.

Figure 6

Forest plots of the pooled ORR. (A)
ORR of the subgroup of RT metrology (groups >5 Gy and groups
<5 Gy). (B) ORR of the subgroup of treatment sequence
(synchronous treatment; RT sequential ICIs therapy; ICIs sequential
RT therapy). ES, effect size; CI, confidence interval; ORR,
objective response rate; RT, radiotherapy; ICIs, immune checkpoint
inhibitors.

Figure 7

Forest plot of the objective response
rate of the subgroup of biomarkers (PD-1 or PD-L1). ES, effect
size; CI, confidence interval; PD-1, programmed cell death protein
1; PD-L1, programmed death-ligand 1.

Figure 8

Forest plots of the pooled mPFS and
mOS. (A) mPFS of the subgroup with tumor thrombus. (B) mOS of the
subgroup with tumor thrombus. ES, effect size; CI, confidence
interval; mPFS, median progression-free survival; mOS, median
overall survival.

Figure 9

Forest plots of the pooled mPFS and
mOS. (A) mPFS of the subgroup undergoing SBRT. (B) mOS of the
subgroup undergoing SBRT. ES, effect size; CI, confidence interval;
mPFS, median progression-free survival; mOS, median overall
survival; SBRT, stereotactic body radiation therapy.

Figure 10

Forest plots of the pooled mPFS and
mOS. (A) mPFS with Barcelona Clinic Liver Cancer stage C subgroup.
(B) mOS with stage C subgroup. ES, effect size; CI, confidence
interval; mPFS, median progression-free survival; mOS, median
overall survival.

Figure 11

Forest plots of the pooled AEs. (A)
All grades of AEs. (B) AEs of grade ≥3. ES, effect size; CI,
confidence interval; AEs, adverse events.
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Copy and paste a formatted citation
Spandidos Publications style
Cui R, Yu X, Jiang Y and Li X: Efficacy and safety of the immune checkpoint inhibitor‑radiotherapy combination in advanced/unresectable hepatocellular carcinoma: A systematic review and meta‑analysis. Oncol Lett 30: 460, 2025.
APA
Cui, R., Yu, X., Jiang, Y., & Li, X. (2025). Efficacy and safety of the immune checkpoint inhibitor‑radiotherapy combination in advanced/unresectable hepatocellular carcinoma: A systematic review and meta‑analysis. Oncology Letters, 30, 460. https://doi.org/10.3892/ol.2025.15206
MLA
Cui, R., Yu, X., Jiang, Y., Li, X."Efficacy and safety of the immune checkpoint inhibitor‑radiotherapy combination in advanced/unresectable hepatocellular carcinoma: A systematic review and meta‑analysis". Oncology Letters 30.4 (2025): 460.
Chicago
Cui, R., Yu, X., Jiang, Y., Li, X."Efficacy and safety of the immune checkpoint inhibitor‑radiotherapy combination in advanced/unresectable hepatocellular carcinoma: A systematic review and meta‑analysis". Oncology Letters 30, no. 4 (2025): 460. https://doi.org/10.3892/ol.2025.15206
Copy and paste a formatted citation
x
Spandidos Publications style
Cui R, Yu X, Jiang Y and Li X: Efficacy and safety of the immune checkpoint inhibitor‑radiotherapy combination in advanced/unresectable hepatocellular carcinoma: A systematic review and meta‑analysis. Oncol Lett 30: 460, 2025.
APA
Cui, R., Yu, X., Jiang, Y., & Li, X. (2025). Efficacy and safety of the immune checkpoint inhibitor‑radiotherapy combination in advanced/unresectable hepatocellular carcinoma: A systematic review and meta‑analysis. Oncology Letters, 30, 460. https://doi.org/10.3892/ol.2025.15206
MLA
Cui, R., Yu, X., Jiang, Y., Li, X."Efficacy and safety of the immune checkpoint inhibitor‑radiotherapy combination in advanced/unresectable hepatocellular carcinoma: A systematic review and meta‑analysis". Oncology Letters 30.4 (2025): 460.
Chicago
Cui, R., Yu, X., Jiang, Y., Li, X."Efficacy and safety of the immune checkpoint inhibitor‑radiotherapy combination in advanced/unresectable hepatocellular carcinoma: A systematic review and meta‑analysis". Oncology Letters 30, no. 4 (2025): 460. https://doi.org/10.3892/ol.2025.15206
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