Salvage surgery after combination immunotherapy for initially unresectable or metastastic hepatocellular carcinoma: A retrospective clinical study

Jun-Shuai Xue, Hui Liu, Rui-Zhe Li, Si-Yu Tan, Yu-Chuan Yan, Zhao-Ru Dong, Jian-Guo Hong, En-Yu Liu, Qiang-Bo Zhang, Zhi-Qiang Chen, Dong-Xu Wang, Tao Li
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Abstract

Background

Combination immunotherapy has gradually become the mainstay of systematic therapy for advanced hepatocellular carcinoma (HCC), however, whether preoperative immunotherapy has the potential to reduce tumor activity, increase the resection rate and improve prognosis remains unclear. This study aimed to investigate the efficacy and safety of preoperative combined immunotherapies for patients with initially unresectable HCC.

Methods

This retrospective, real-world study involved patients with initially unresectable HCC receiving combined immunotherapies based on PD-1/L1 blockade before surgery. Tumor treatment responses, pathological manifestations in postoperative specimens and overall survival (OS) were evaluated. Treatment related adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0).

Results

The study consecutively included 54 initially unresectable HCC patients and 34 patients were evaluated for the safety, efficacy, and possibility of subsequent radical surgery. Among these patients with surgical resection, 57.1% (n=8) receiving combination immunotherapy before surgery achieved a partial response (PR). Pathological evaluation of postoperative specimens confirmed that 21.4% (n=3) achieved complete responses, and 78.6% (n=11) achieved PR. 28.6% (4/14) patients encountered grade 3 or 4 AEs. The main AEs included fatigue (n=11; 78.6%), leukocytopenia (n=8; 57.1%) and aspartate aminotransferase (AST) elevation (n=6; 42.9%).

Conclusions

After combination immunotherapy, patients should be comprehensively evaluated whether they meet the criteria for surgical resection. Surgical resection following combination immunotherapy might effectively and safely control tumor progression and could improve the prognosis at least for some patients with initially unresectable HCC.

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最初不可切除或转移性肝癌联合免疫治疗后的挽救性手术:回顾性临床研究
背景联合免疫疗法已逐渐成为晚期肝细胞癌(HCC)系统治疗的支柱,但术前免疫疗法是否有降低肿瘤活性、提高切除率和改善预后的潜力尚不清楚。本研究旨在研究术前联合免疫疗法对最初不可切除HCC患者的疗效和安全性。评估肿瘤治疗反应、术后标本的病理表现和总生存率(OS)。根据美国癌症研究所不良事件通用术语标准(NCI CTCAE,4.0版)评估治疗相关不良事件(AE)。在这些接受手术切除的患者中,57.1%(n=8)在手术前接受联合免疫治疗的患者获得了部分缓解(PR)。术后标本的病理学评估证实,21.4%(n=3)获得完全缓解,78.6%(n=11)获得PR。28.6%(4/14)的患者出现3或4级AE。主要不良事件包括疲劳(n=11;78.6%)、白细胞减少(n=8;57.1%)和天冬氨酸转氨酶(AST)升高(n=6;42.9%)。联合免疫治疗后的手术切除可能有效、安全地控制肿瘤进展,并至少可以改善一些最初无法切除的HCC患者的预后。
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