Abstract：
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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 (PRFS=0.016, POS=0.011) and C (PRFS<0.001, POS<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.
UNASSIGNED: 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.
Key findingsHigh 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.
UNASSIGNED: 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.
UNASSIGNED: 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 (PRFS=0.016, POS=0.011) and C (PRFS<0.001, POS<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.
UNASSIGNED: 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.
Key findingsHigh 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.
摘要：
■本研究旨在探讨泛免疫炎症值（PIV）的预后作用，并开发一种新的风险模型，以指导射频消融（RFA）治疗早期肝细胞癌（HCC）。
■接受RFA治疗的早期HCC患者随机分为训练队列A（n=65）和测试队列B（n=68）。在队列A中筛选各种免疫炎症生物标志物(IIB)。在队列B和C中评估和验证了PIV的预后作用。分别。在队列C中建立列线图风险模型，并在合并队列D中进行验证。在低和高风险组中评估RFA后辅助抗血管生成疗法加免疫检查点抑制剂（AA-ICI）的临床益处。
■PIV的截止点是120。高PIV是不利的无复发生存率（RFS）和总生存率（OS）的独立预测因子。在队列B（PRFS=0.016，POS=0.011）和C（PRFS<0.001，POS<0.001）中，高PIV患者的RFS和OS率均明显低于低PIV患者。基于PIV的列线图模型，在外部验证队列C中,肿瘤数量和BCLC分期在风险分层中表现良好。AA-ICI辅助治疗对高危患者的OS有额外益处(p=0.011).
■PIV是接受治愈性RFA的早期HCC患者RFS和OS的可行独立预后因素。提出的基于PIV的列线图风险模型可以帮助临床医生识别高危患者，并制定辅助系统治疗和疾病随访方案。
关键发现高泛免疫炎症值（PIV）是接受根治性射频消融（RFA）的早期肝细胞癌（HCC）患者的不良无复发生存期（RFS）和总生存期（OS）的独立指标。佐剂抗血管生成靶向治疗加免疫检查点抑制剂（AA-ICI）治疗显示，对于基于PIV的列线图风险模型定义的高危患者，OS有额外的益处。肿瘤数量和BCLC分期。什么是已知的，什么是新的？炎症和宿主免疫力受损与肝癌的发生和进展有关。越来越多的证据表明，免疫炎症生物标志物（IIB）在接受RFA的早期HCC患者中具有预后作用。然而,在这种情况下，尚未确定PIV的预后潜力。在这里，首次报道,在接受根治性RFA治疗的早期HCC患者中,高PIV是导致RFS和OS不良的独立危险因素,并有助于区分低危和高危患者.RFA后辅助AA-ICI治疗有利于高危患者的OS。这意味着什么，现在应该改变什么？对于具有高风险因素的早期肝癌(高PIV，多个肿瘤病灶和更晚期的BCLC分期），有必要在治愈性RFA后进行强化随访和系统辅助治疗.
■接受RFA治疗的早期HCC患者随机分为训练队列A（n=65）和测试队列B（n=68）。在队列A中筛选各种免疫炎症生物标志物(IIB)。在队列B和C中评估和验证了PIV的预后作用。分别。在队列C中建立列线图风险模型，并在合并队列D中进行验证。在低和高风险组中评估RFA后辅助抗血管生成疗法加免疫检查点抑制剂（AA-ICI）的临床益处。
■PIV的截止点是120。高PIV是不利的无复发生存率（RFS）和总生存率（OS）的独立预测因子。在队列B（PRFS=0.016，POS=0.011）和C（PRFS<0.001，POS<0.001）中，高PIV患者的RFS和OS率均明显低于低PIV患者。基于PIV的列线图模型，在外部验证队列C中,肿瘤数量和BCLC分期在风险分层中表现良好。AA-ICI辅助治疗对高危患者的OS有额外益处(p=0.011).
■PIV是接受治愈性RFA的早期HCC患者RFS和OS的可行独立预后因素。提出的基于PIV的列线图风险模型可以帮助临床医生识别高危患者，并制定辅助系统治疗和疾病随访方案。
关键发现高泛免疫炎症值（PIV）是接受根治性射频消融（RFA）的早期肝细胞癌（HCC）患者的不良无复发生存期（RFS）和总生存期（OS）的独立指标。佐剂抗血管生成靶向治疗加免疫检查点抑制剂（AA-ICI）治疗显示，对于基于PIV的列线图风险模型定义的高危患者，OS有额外的益处。肿瘤数量和BCLC分期。什么是已知的，什么是新的？炎症和宿主免疫力受损与肝癌的发生和进展有关。越来越多的证据表明，免疫炎症生物标志物（IIB）在接受RFA的早期HCC患者中具有预后作用。然而,在这种情况下，尚未确定PIV的预后潜力。在这里，首次报道,在接受根治性RFA治疗的早期HCC患者中,高PIV是导致RFS和OS不良的独立危险因素,并有助于区分低危和高危患者.RFA后辅助AA-ICI治疗有利于高危患者的OS。这意味着什么，现在应该改变什么？对于具有高风险因素的早期肝癌(高PIV，多个肿瘤病灶和更晚期的BCLC分期），有必要在治愈性RFA后进行强化随访和系统辅助治疗.
