Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Liver Int. 2018 Feb;38(2):321-330. doi: 10.1111/liv.13527. Epub 2017 Aug 9.
BACKGROUND & AIMS: Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) but is challenging after treatment failure. Appropriate criteria for enrolling patients into second-line trials are still limited. In this study, we aimed to establish more objective criteria based on Albumin-Bilirubin (ALBI) grade to select patients with better post-progression survival (PPS) for second-line treatment.
Consecutive 404 advanced HCC patients receiving sorafenib were retrospectively enrolled. All patients were in Child-Pugh class A and BCLC stage C with either portal vein invasion or extrahepatic metastasis at the beginning of sorafenib treatment. Radiological evaluation based on mRECIST criteria and clinical assessments with compliance were performed on schedule.
During the median follow-up period of 5.8 months, 310 patients developed progressive disease (PD) and 350 deaths occurred. The PD patients were randomized into derivation and validation cohorts by a 1:1 ratio. The independent predictors of poor PPS in derivation cohort were ALBI grade 3 at PD (hazard ratio [HR]=3.24, P = .002), new extrahepatic lesions (NEH) (HR=1.75, P = .011), and early PD within 4 months (HR=1.88, P = .037). ALBI-PD criteria were proposed by incorporating these three risk factors. In the validation cohort, PPS could be independently predicted by presence of early PD, NEH as well as ALBI grade 3 at PD. Patients within ALBI-PD criteria had significant longer median PPS than those beyond it even in Child-Pugh A (9.7 vs 4.9 months, P = .005) subpopulations.
The ALBI-PD criteria can differentiate PPS and stratify the patients with advanced HCC for the second-line trials or salvage therapy.
索拉非尼是治疗晚期肝细胞癌（HCC）的标准治疗药物，但在治疗失败后，该药的应用极具挑战性。目前，纳入二线临床试验的患者仍缺乏适当的标准。本研究旨在根据白蛋白-胆红素（ALBI）分级建立更客观的标准，以选择具有更好进展后生存（PPS）的患者进行二线治疗。
回顾性纳入连续 404 例接受索拉非尼治疗的晚期 HCC 患者。所有患者在开始索拉非尼治疗时均为 Child-Pugh 分级 A 级和 BCLC 分期 C 期，且存在门静脉侵犯或肝外转移。根据 mRECIST 标准进行影像学评估，并按计划进行符合条件的临床评估。
在中位随访 5.8 个月期间，310 例患者发生疾病进展（PD），350 例患者死亡。PD 患者按 1:1 比例随机分为推导队列和验证队列。推导队列中，PD 时 ALBI 分级 3 （风险比 [HR]=3.24，P=.002）、新发肝外病灶（NEH）（HR=1.75，P=.011）和 4 个月内早期 PD（HR=1.88，P=.037）是 PPS 较差的独立预测因素。通过纳入这三个危险因素，提出了 ALBI-PD 标准。在验证队列中，早期 PD、NEH 以及 PD 时 ALBI 分级 3 均可独立预测 PPS。符合 ALBI-PD 标准的患者的中位 PPS 明显长于不符合该标准的患者，即使在 Child-Pugh A 亚组（9.7 个月比 4.9 个月，P=.005）也是如此。
ALBI-PD 标准可区分 PPS，并对晚期 HCC 患者进行分层，以进行二线试验或挽救性治疗。
