Systemic antitumor responses to hypofractionated radiotherapy plus Poly(I:C) in advanced hepatocellular carcinoma: A phase 2 trial
In brief
Distant tumor responses occurred in 45% with radiotherapy plus Poly(I:C)
In this phase 2 trial, 45% of evaluable patients receiving radiotherapy plus Poly(I:C) had responses in tumors outside the radiation field, compared with 10.5% of matched patients receiving radiotherapy alone. The combination was also associated with higher overall response and longer progression-free survival, but the comparison was not randomized and needs confirmation in a randomized trial.
- Journal
- Med (New York, N.Y.) (Q1)
- Published
- 20 October 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Liman Qiu, Qizhen Huang, Xinting Pan, Geng Chen, Wenhui Liu, Kai Wang, et al.
- PMID
- 42901168
- DOI
- 10.1016/j.medj.2026.101331
Why clinicians should know about it
- Picked for Radiation Oncology (paper of the day, 21 October 2026): Phase II trial directly evaluates hypofractionated radiotherapy and immune combination
Abstract
BACKGROUND: The abscopal effect, regression of unirradiated tumors after localized radiotherapy, is rare. Whether hypofractionated radiotherapy (HFRT) plus the innate immune agonist polyinosinic-polycytidylic acid [Poly(I:C)] amplifies systemic antitumor immunity in advanced hepatocellular carcinoma is unclear. METHODS: In this single-arm, phase 2 trial (ChiCTR2100053441), 37 patients received HFRT plus subcutaneous Poly(I:C); 33 were response evaluable. Outcomes were compared with 33 propensity score-matched patients treated with HFRT alone. The primary endpoint was the objective response rate per RECIST v.1.1; secondary endpoints included progression-free survival, overall survival, and safety; and abscopal response was prespecified. Mechanisms were explored by single-cell RNA sequencing and flow cytometry in patients and by CD8 depletion and CD28 blockade in mice. FINDINGS: HFRT plus Poly(I:C) was well tolerated; it was associated with a higher objective response rate (54.5% vs. 21.2%; p = 0.011) and abscopal response rate (45.0% vs. 10.5%; p = 0.042) as well as longer progression-free survival (8.4 vs. 4.6 months; adjusted hazard ratio = 0.542; p = 0.042) and overall survival (not reached vs. 13.6 months; adjusted hazard ratio = 0.386; p = 0.011) vs. HFRT alone. The progression-free survival benefit was also higher in patients concurrently receiving tyrosine kinase inhibitors (p for interaction = 0.013). Peripheral CD8+CD28+ T cell expansion correlated with abscopal tumor control; in mice, CD8+ T cells and CD28 co-stimulation were required for this effect. CONCLUSIONS: HFRT plus Poly(I:C) showed promising systemic antitumor activity with manageable safety in advanced hepatocellular carcinoma, with CD8+CD28+ T cells as an immune correlate of response. These exploratory findings warrant confirmation in randomized trials. FUNDING: The National Natural Science Foundation of China.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.