Case Report: Tumor regression and neurological recovery in paraplegia from POLD1-mutated hepatocellular carcinoma treated with targeted immunotherapy and electroacupuncture.

Background: Hepatocellular carcinoma (HCC) patients with bone metastasis-induced paraplegia have an extremely poor prognosis. The potential for neurological recovery following immunotherapy and subsequent rehabilitation in this population remains unclear. Case: A 58-year-old male with Barcelona Clinic Liver Cancer stage C (BCLC) HCC and T11 vertebral metastasis causing American Spinal Injury Association (ASIA) grade C paraplegia carried a rare POLD1 c.1745C>T (p.T582M) germline mutation with low tumor mutational burden (TMB) and microsatellite instability-low status (MSI-L, blood-based MSI-L (bMSI-L) 7.76%). Immunotherapy with atezolizumab (1200 mg every 3 weeks [Q3W]) combined with targeted therapy with bevacizumab (600 mg Q3W) was initiated in July 2021.A substantial temporal gap of approximately 21 months followed, after which electroacupuncture-based rehabilitation (5-Hz continuous-wave, stimulating Jiaji acupoints, Zusanli, etc) was started in May 2023. Results: Following three months of targeted immunotherapy, the tumor exhibited complete response (CR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). At the 28-month follow-up assessment, the patient was eventually able to walk independently with a walker. Serial cytokine measurements revealed two distinct peaks in IL-1β, TNF-α, and IFN-γ relative to baseline (2021-06-25): an initial rise after immunotherapy initiation (IL-1β up 13.7-fold; TNF-α up 2.5-fold; IFN-γ up 33.3-fold) and a second, larger increase during electroacupuncture rehabilitation coinciding with neurological recovery (IL-1β up 31.8-fold; TNF-α up 7.2-fold; IFN-γ up 96.1-fold). These observations suggest temporal associations between immune activation and clinical milestones, but causality cannot be established from a single case. Conclusion: This case suggests that POLD1 mutation, despite low TMB and MSI-L, may be associated with enhanced sensitivity to immunotherapy in HCC, though the underlying mechanisms require further investigation. Targeted immunotherapy combined with electroacupuncture may influence neural remodeling by modulating a pro-reparative inflammatory microenvironment, which could potentially support functional reconstruction in patients with spinal metastases. However, there is no direct evidence that immunotherapy accelerates neural recovery, and these observations should be interpreted as hypothesis-generating findings requiring rigorous testing in prospective studies.