BRAIN metastases from hepatocellular carcinoma (HCC) may remain rare, but new findings suggest carefully selected patients could gain meaningful survival benefits from local therapy alongside modern systemic treatment.
In a retrospective cohort study, patients with HCC brain metastases who underwent surgery and/or radiotherapy survived markedly longer than those receiving supportive care alone.
Researchers analysed 55 patients with HCC and radiologically confirmed brain metastases treated at a single institution. The primary endpoint was overall survival from the time of brain metastasis diagnosis.
Local Therapy Linked to Longer Survival
Among the cohort, 34 patients received local interventions, mainly radiotherapy, while 21 received supportive care alone. Median overall survival following brain metastasis diagnosis was 3.3 months across the full cohort.
However, outcomes differed substantially by treatment approach. Patients managed with surgery and/or radiotherapy achieved a median overall survival of 8.8 months, compared with 1.0 month in those receiving symptomatic treatment alone.
At 24 months, 33.5% of patients in the intervention group remained alive, whereas no patients in the supportive care group survived beyond 15 months.
Radiotherapy approaches included conventional linear accelerator techniques, helical tomotherapy, and CyberKnife stereotactic radiosurgery. Seven patients also underwent surgical resection.
Performance Status Remained Central to Prognosis
Poor functional status emerged as one of the clearest predictors of worse outcomes. Patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) above 2 had a markedly higher risk of mortality, alongside those with brain metastases larger than 3 cm and those managed with symptomatic treatment alone.
ECOG PS is a standard clinical scale used to assess how well patients can carry out daily activities, with higher scores reflecting greater disability and reduced ability to tolerate treatment.
By contrast, patients aged 60 years or older had a lower risk of death in the adjusted analyses.
Machine learning analysis identified local intervention and ECOG PS as the strongest prognostic factors. However, patients receiving local therapy also tended to have lower metastatic burden and better baseline functional status, raising the possibility that some survival differences reflected patient selection rather than treatment effect alone.
Modern Systemic Therapy Reshapes the Treatment Landscape
Outcomes among patients receiving local therapy appeared improved compared with historical cohorts treated before the introduction of targeted therapies and immune checkpoint inhibitors.
Current systemic therapies for advanced HCC include tyrosine kinase inhibitors alongside immune checkpoint inhibitor combinations. However, the blood-brain barrier may limit intracranial activity, leaving surgery and radiotherapy important for local disease control and relief of neurological symptoms.
Several limitations temper interpretation of the findings. The retrospective, single-centre design and relatively small sample size limit generalisability, while treatment heterogeneity made comparisons between different radiotherapy approaches difficult. Selection bias also remains a major consideration, as patients receiving local interventions generally had better performance status and lower metastatic burden at baseline.
Still, the results support considering local intervention in selected patients with preserved performance status and limited intracranial disease burden.
Reference
Zhao Q et al. Local interventions improve survival of hepatocellular carcinoma patients with brain metastases in the era of targeted and immune‑based therapies: a single‑center retrospective cohort study. Hepatobiliary Surg Nutr. 2026;DOI:10.21037/hbsn-2025-aw-803.
Featured image: Photographee.eu at Adobe Stock
