In this two-center retrospective study, the complete pretreatment LIPI was firstly used to stratify our HCC population under ICIs into 3 groups (good LIPI, intermediate LIPI, and poor LIPI). In our overall population of 224 patients treated with ICI, median OS and PFS were 12.7 and 8.0 months, respectively, consistent with prior reports in patients with HCC treated with PD-1 inhibitors in second or later lines. The poor LIPI group was more likely to have progress under ICI and had both shorter PFS (median, 4.0 months) and OS (median, 9.5 months) than those with an intermediate or good LIPI (P < 0.001). Additionally, a significant association was both identified between LIPI and survival outcomes for patients treated with PD-1 inhibitor monotherapy and PD-1 inhibitor combined with target treatment in subgroup analysis. Based on the results reported here, LIPI was shown to be a prognostic marker for survival/response outcomes in advanced HCC using ICI.
Systemic inflammatory status has been closely correlated with worse prognosis in various solid tumors[16, 17]. However, the effect of inflammatory status on the benefits of immunotherapy is unclear. Previous studies had demonstrated that some routine blood parameters such as elevated neutrophils, platelets, hypoalbuminemia, LDH, and dNLR were associated with poor outcomes in cancer[18, 19]. LDH, with the potential to evaluate tumor burden, is a well-established, independent prognostic factor for survival[20, 21]. S Diem et al demonstrated that LDH could be prognostic factor in patients with cancer under immunotherapy[22]. dNLR also had been evaluated by Proctor et al as the prognostic factor on cancer outcome in various solid tumors and the study demonstrated that the dNLR had a similar prognostic value to the established NLR[14]. LIPI, synthesized LDH and dNLR, has been used as a new indicator to predict the efficacy and prognosis of immunotherapy in patients with different cancer types[23]. Recently, Shixue Chen et al had firstly demonstrated the association of LIPI and the survival/response treatment outcomes of HCC patients under PD-1 inhibitor[24]. However, subject to small sample, they stratified all patients into two groups (good and intermediate/poor LIPI) instead of three groups (good, intermediate, and poor LIPI) to perform analyses, which cannot fully demonstrate the role of LIPI. Our study assigned HCC patients under PD-1 inhibitor into three groups (good LIPI, intermediate LIPI, and poor LIPI). Benefiting from the above grouping methods, our study not only found that the population of good LIPI had better survival/response outcomes but also found the significant difference in survival/response outcomes between intermediate LIPI group and poor LIPI group.
Notably, the 50% of the population were treated with PD-1 inhibitor combined with targeted treatment. Our subgroup analysis revealed the population of poor LIPI had worse survival outcomes than those with intermediate or good LIPI in both PD-1 inhibitor monotherapy and combination treatment groups. We know that HCC patients were encouraged to receive immunotherapy combined with targeted therapy based on the results of IMbrave 150 [25]. Therefore, our study based on real-world data could provide information for patients with similar conditions for PD-1 inhibitor in clinical practice.
Due to the nature of retrospective study, our study has several potential limitations. First, some HCC patients who met the inclusion criteria were unable to be included because of missing pretreatment clinical data. Second, there may be selection bias in the patient population due to the prevalence of HBV infection in China. Third, although the study included patients from both institutions, the study sample was small. Therefore, further investigations such as large-scale prospective study are needed to confirm the present results.