Department of Oncology and Hematology, Division of Oncology, University of Modena and Reggio Emilia, Modena, Italy.
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Higashi-osaka, Japan.
ESMO Open. 2021 Dec;6(6):100330. doi: 10.1016/j.esmoop.2021.100330. Epub 2021 Nov 27.
BACKGROUND: Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. PATIENTS AND METHODS: We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. RESULTS: Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin-bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). CONCLUSION: NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients.
背景：肝细胞癌（HCC）的治疗仍然是肿瘤学领域的一大挑战。导致 HCC 的肝脏疾病（病毒性或非病毒性）对于确定肿瘤的生物学行为，包括其对治疗的反应，起着至关重要的作用。本分析的目的是研究潜在肝脏疾病病因在生存结果中的作用。
患者和方法：我们对来自东方和西方机构的接受乐伐替尼作为一线治疗晚期 HCC 的大量患者进行了多中心回顾性研究。进行了单变量和多变量分析。
结果：在 1232 名接受乐伐替尼治疗的 HCC 患者中，453 名（36.8%）为丙型肝炎病毒阳性，268 名乙型肝炎病毒阳性（21.8%），236 名为非酒精性脂肪性肝炎（NASH）相关性（19.2%），275 名有其他病因（22.3%）。无进展生存期（mPFS）的中位数为 6.2 个月[95%置信区间（CI）为 5.9-6.7 个月]，总生存期（mOS）的中位数为 15.8 个月（95%CI 为 14.9-17.2 个月）。在 OS 的单变量分析中，NASH-HCC 与更长的 mOS 相关[22.2 与 15.1 个月；风险比（HR）0.69；95%CI 0.56-0.85；P=0.0006]。在 PFS 的单变量分析中，NASH-HCC 与更长的 mPFS 相关（7.5 与 6.5 个月；HR 0.84；95%CI 0.71-0.99；P=0.0436）。多变量分析证实，NASH-HCC（HR 0.64；95%CI 0.48-0.86；P=0.0028）是 OS 的独立预后因素，此外还有白蛋白-胆红素（ALBI）分级、肝外扩散、中性粒细胞与淋巴细胞比值、门静脉血栓形成、东部肿瘤协作组（ECOG）表现状态和甲胎蛋白。对索拉非尼和乐伐替尼队列进行了交互检验，结果突出了 NASH 在有利于乐伐替尼组的阳性预测作用（P=0.0047）。
结论：在接受乐伐替尼治疗的晚期 HCC 患者的大队列中，NASH 已被确定为独立的预后因素，这表明病因在选择酪氨酸激酶治疗患者方面的作用。如果得到验证，这一结果可以为改善这些患者的治疗管理提供新的见解。
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