Prognostic significance of pan-immune-inflammation value in hepatocellular carcinoma treated by curative radiofrequency ablation: potential role for individualized adjuvant systemic treatment

Abstract

Background

This study aimed to explore the prognostic role of pan-immune-inflammation value (PIV) and develop a new risk model to guide individualized adjuvant systemic treatment following radiofrequency ablation (RFA) for early-stage hepatocellular carcinoma (HCC).

Materials and methods

Patients with early-stage HCC treated by RFA were randomly divided into training cohort A (n = 65) and testing cohort B (n = 68). Another 265 counterparts were enrolled into external validating cohort C. Various immune-inflammatory biomarkers (IIBs) were screened in cohort A. Prognostic role of PIV was evaluated and validated in cohort B and C, respectively. A nomogram risk model was built in cohort C and validated in pooled cohort D. Clinical benefits of adjuvant anti-angiogenesis therapy plus immune checkpoint inhibitor (AA-ICI) following RFA was assessed in low- and high-risk groups.

Results

The cutoff point of PIV was 120. High PIV was an independent predictor of unfavorable recurrence-free survival (RFS) and overall survival (OS). RFS and OS rates of patients with high PIV were significantly lower than those with low PIV both in cohort B (P_RFS=0.016, P_OS=0.011) and C (P_RFS<0.001, P_OS<0.001). The nomogram model based on PIV, tumor number and BCLC staging performed well in risk stratification in external validating cohort C. Adjuvant AA-ICI treatment showed an added benefit in OS (p = 0.011) for high-risk patients.

Conclusions

PIV is a feasible independent prognostic factor for RFS and OS in early-stage HCC patients who received curative RFA. The proposed PIV-based nomogram risk model could help clinicians identify high-risk patients and tailor adjuvant systemic treatment and disease follow-up scheme.

HIGHLIGHTS

Key findings

• High pan-immune-inflammation value (PIV) is an independent indicator of unfavorable recurrence-free survival (RFS) and overall survival (OS) for early-stage hepatocellular carcinoma (HCC) patients who received curative radiofrequency ablation (RFA).

• Adjuvant anti-angiogenesis target therapy plus immune checkpoint inhibitor (AA-ICI) treatment showed added benefit in OS for the high-risk patients defined by a nomogram risk model based on PIV, tumor number and BCLC staging.

What is known and what is new?

• Inflammation and impaired host immunity are associated with carcinogenesis and progression of HCC. Increasing evidences showed that immune-inflammatory biomarkers (IIBs) had prognostic roles in early-stage HCC patients who received RFA. However, prognostic potential of PIV has not been determined in this setting.

• Herein, high PIV was first reported to be an independent risk factor of poor RFS and OS in early-stage HCC patients treated by curative RFA and helped to discriminate patients between low- and high-risk groups. Adjuvant AA-ICI treatment following RFA was beneficial to OS of patients in the high-risk group.

What is the implication, and what should change now?

• For early-stage HCC with high-risk factors (high PIV, multiple tumor foci and more advanced BCLC stage), intensive follow-up and adjuvant systemic therapy following curative RFA were warranted.

Keywords:

• Hepatocellular carcinoma
• radiofrequency ablation
• pan-immune-inflammation value
• prognosis predictor
• adjuvant systemic treatment

Acknowledgement

We thanked Miss Yanna Ma for her selfless help in checking and revising the writing language.

Authors’ contributions

Xuexia Liang designed this research. Xuexia Liang, Juyuan Bu, Yanhui Jiang, Shuqin Zhu, Qing Ye and Yun Deng collected and analyzed the data. Xuexia Liang drafted the manuscript. Wuzhu Lu provided imaging resources and contributed substantially to the review & editing of this manuscript. Qiaodan Liu made substantial contribution to the design of the work and revised the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by all authors.

Data availability statement

Data can not be shared publicly because the data from this study contain potentially sensitive private information. Data would be available from the corresponding authors upon reasonable request or on the research data deposit (RDD) platform of Sun Yat-sen University after the manuscript was published.

Additional information

Funding

This work was supported by a grant from the Guangdong Province Medical Science and Technology Research Fund Project (Grant No. A2021295).