Impact of intrahepatic lesions on lesion-specific response rates in patients with hepatocellular carcinoma treated with lenvatinib or immune checkpoint inhibitors.

[BACKGROUND] This study evaluated how lesion location affects treatment response and prognosis in hepatocellular carcinoma (HCC) patients treated with lenvatinib (LEN) or immune checkpoint inhibitors (ICIs; atezolizumab/bevacizumab or durvalumab/tremelimumab). Considering tumor microenvironment and heterogeneity, we analyzed lesion-specific responses to optimize therapy.

[METHODS] In this retrospective study, lesion-specific responses were assessed for intrahepatic lesions (IHLs), lung, lymph node, intra-abdominal, and other lesions; bone metastases were excluded due to evaluation limitations. Responses were measured using a modified size-based RECIST 1.1 method. Lesion-specific objective response rate (ORR) and disease control rate (DCR) were compared between LEN and ICI groups.

[RESULTS] ORR for IHLs was higher with ICIs than LEN (16.3 % vs. 3.5 %, P = 0.002). No significant differences were observed for lung, lymph node, or intra-abdominal lesions; adrenal metastases showed no response in either group. Subgroup analysis indicated better ORR and DCR for lung lesions treated with ICIs and lymph node lesions treated with LEN in patients without IHLs versus those with IHLs.

[CONCLUSIONS] ICIs achieved higher ORR in IHLs than LEN, with no significant differences for metastatic lesions. The presence of IHLs may influence distant lesion response, and therapeutic efficacy varies with treatment regimen.