Predictive Value of the Hepatic Immune Predictive Index for Patients with Primary Liver Cancer Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved survival outcomes and resulted in long-term responses in primary liver cancer in some patients. Nevertheless, not all patients with PLC could benefit from immunotherapy. Therefore, it is necessary to identify patients suitable for such therapy. METHODS: 215 patients with primary liver cancer with immunotherapy from Nanfang Hospital were screened between August 2018 and October 2020 as a training set and our validation set included 71 patients of hepatocellular carcinoma from Jiangxi Cancer Hospital from May 2019 to July 2021. The primary endpoint was the disease control rate (DCR), and the secondary endpoints were overall survival (OS) and progression-free survival. RESULTS: In the training set, neutrophil-lymphocyte ratio (NLR) ≥3 and alpha-fetoprotein (AFP) level ≥20 ng/mL were independently associated with non-DCR in the training set after adjusting for distant metastasis at baseline and targeted therapy combination. Furthermore, a hepatic immune predictive index (HIPI) based on NLR and AFP level was developed and patients with poor HIPI associated with worse clinical outcomes. In validation set, high HIPI was associated with poor OS. CONCLUSION: HIPI, based on NLR and AFP level, is an effective indicator in ICI-treated patients with primary liver cancer. Our findings may help guide the selection and on-treatment strategies for immunotherapies for primary liver cancer patients.

Use of computed tomography-derived body composition to determine the prognosis of patients with primary liver cancer treated with immune checkpoint inhibitors: a retrospective cohort study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been used to successfully treat primary liver cancer (PLC); however, identifying modifiable patient factors associated with therapeutic benefits is challenging. Obesity is known to be associated with increased survival after ICI treatment; however, the relationship between body composition (muscle, fat) and outcomes is unclear. This study aimed to evaluate the association between sarcopenia and CT-derived fat content and the prognosis of ICIs for the treatment of PLC. METHODS: In this retrospective cohort study of 172 patients with PLC, we measured the skeletal muscle index (SMI), skeletal muscle density, visceral adipose tissue index, subcutaneous adipose tissue index, total adipose tissue index (TATI), and visceral-to-subcutaneous adipose tissue area ratio using CT. In addition, we analyzed the impact of body composition on the prognosis of the patients. Multivariate Cox regression analysis was used to screen for influencing factors. RESULTS: Among the seven body composition components, low SMI (sarcopenia) and low TATI were significantly associated with poor clinical outcomes. Multivariate analysis revealed that sarcopenia (hazard ratio [HR], 5.39; 95% confidence interval [CI], 1.74-16.74; p = 0.004) was a significant predictor of overall survival (OS). Kaplan-Meier curves showed that sarcopenia and TATI were significant predictors of OS. Body mass index was not associated with survival outcomes. CONCLUSIONS: Sarcopenia and fat tissue content appear to be independently associated with reduced survival rates in patients with PLC treated with ICIs.

Splenomegaly in predicting the survival of patients with advanced primary liver cancer treated with immune checkpoint inhibitors.

BACKGROUND & AIMS: Immune checkpoint inhibitors (ICIs) play an increasingly important role in the treatment of primary liver cancer (PLC). Some patients with PLC experience symptoms of splenomegaly. Splenomegaly may affect the efficacy of ICIs due to an imbalance of the immune microenvironment. Currently, there is a lack of evidence on the relationship between splenomegaly and prognosis in patients with PLC treated with ICIs. This study analyzed the relationship between splenomegaly and prognosis in patients with PLC treated with ICIs. METHODS: In this retrospective cohort study of 161 patients with PLC treated with ICIs, splenomegaly was diagnosed using computed tomography or magnetic resonance imaging and the impact of splenomegaly on patient survival was analyzed. RESULTS: Through univariate and multivariate Cox regression analyses, we determined that splenomegaly was associated with shortened overall survival (p = 0.002) and progression-free survival (p = 0.013) in patients with PLC treated with ICIs. Kaplan-Meier analysis further validated our results. The overall survival and progression-free survival of patients with splenomegaly were significantly shorter than those of patients without splenomegaly (p < 0.01 and p = 0.02, respectively). CONCLUSIONS: We concluded that splenomegaly was a predictor of prognosis in patients with PLC treated with ICIs. This is the first study to report this important finding.

Lung metastasis and lymph node metastasis are risk factors for hyperprogressive disease in primary liver cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: At present, some cancer patients experience hyperprogressive disease (HPD) after receiving immunotherapy. This study used the Response Evaluation Criteria in Solid Tumors 1.1 to evaluate the incidence of HPD in patients receiving immune checkpoint inhibitors (ICIs) for treating primary liver cancer (PLC) and to explore the risk factors for HPD. METHODS: This retrospective, single-center study included patients with PLC who were treated with ICIs. The RECIST 1.1 was used to determine patients with HPD. Univariate and multivariate regression analyses were performed to explore the risk factors for HPD, and clinical variables with prognostic significance for HPD were included to establish a risk model. RESULTS: Among 129 patients with PLC treated with ICIs, HPD occurred in 13 patients (10.1%). In the multivariate regression analysis, lymph node metastasis and lung metastasis were risk factors for HPD. The area under the curve of the risk model, established by including lymph node metastasis, lung metastasis, neutrophil-lymphocyte ratio, albumin, and performance status, was 0.801 (P<0.001). The progression-free survival of HPD patients was significantly worse than that of non-HPD patients (P<0.001). CONCLUSIONS: In this study, 10.1% of patients with PLC had HPD. Compared with the non-HPD patients, lung metastasis and lymph node metastasis were independent risk factors of HPD.