Observed Immune Response Following Histotripsy in Metastatic Hepatocellular Carcinoma

Background: Histotripsy is a novel, noninvasive, nonthermal tumor ablation therapy that uses focused ultrasound to mechanically disrupt tissue. Emerging evidence suggests that histotripsy may stimulate antitumor immune responses. To our knowledge, this is one of the first reported cases of histotripsy used in conjunction with systemic immunotherapy in a patient with hepatocellular carcinoma (HCC), resulting in an observed systemic immune response in nontarget lesions. Case Presentation: A 63-year-old male with noncirrhotic, nonviral multifocal metastatic HCC was treated with combination systemic immunotherapy (atezolizumab plus bevacizumab), followed by targeted histotripsy ablation of hepatic Segment II lesions. Given the presence of extrahepatic metastatic disease, liver transplantation was not a viable option. Posthistotripsy imaging demonstrated a partial response in the targeted lesion but partial responses in multiple nontarget lesions. This radiographic response occurred after discontinuation of systemic therapy due to toxicity. The patient maintained excellent functional status and continues to undergo histotripsy treatment. Conclusion: This case highlights the potential for histotripsy to elicit an abscopal-like immune response in metastatic HCC when combined with immunotherapy. Histotripsy may serve as a valuable adjunct to systemic therapy, particularly in patients unable to tolerate prolonged immunotherapy. Further studies are warranted to explore this potential synergy in controlled clinical trials.