Takada Hitomi, Kurosaki Masayuki, Tsuchiya Kaoru, Komiyama Yasuyuki, Itakura Jun, Takahashi Yuka, Nakanishi Hiroyuki, Yasui Yutaka, Tamaki Nobuharu, Maeyashiki Chiaki, Kaneko Shun, Takaura Kenta, Higuchi Mayu, Okada Mao, Wang Wan, Osawa Leona, Sekiguchi Shuhei, Hayakawa Yuka, Yamashita Koji, Enomoto Nobuyuki, Izumi Namiki
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo 180-8610, Japan.
First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
Cancers (Basel). 2019 Aug 27;11(9):1256. doi: 10.3390/cancers11091256.
Recent advances in the development of tyrosine kinase inhibitors (TKIs) have enabled patients with unresectable hepatocellular carcinoma (HCC) to receive multiple TKIs in sequence. The aim of this study was to identify predictors of good candidates for second-line treatment after disease progression during sorafenib treatment. This is a retrospective cohort study of 190 consecutive HCC patients who were treated with sorafenib in our hospital. Three criteria of good candidates for second-line TKI at the time of disease progression during sorafenib treatment were defined as follows: criterion 1 was the same as the inclusion criteria of the regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE) study, criterion 2 was the inclusion criteria of the RESORCE study plus Child-Pugh score 5, and criterion 3 was the inclusion criteria of the RESORCE study plus albumin-bilirubin (ALBI) grade 1. Factors at baseline and at week 4 during sorafenib treatment were used to predict patients fulfilling each of these three criteria. The distribution of patients was 29%, 13%, and 6% in criteria 1, 2, and 3, respectively. Significant factors for meeting criterion 1 was the combination of baseline albumin >3.7 g/dL (odds ratio (OR) 2.7) plus degree of decrease in albumin (Δalbumin) at week 4 <0.2 g/dL (OR 2.6), or the combination of baseline ALBI score <-2.33 (OR 2.5) and ΔALBI at week 4 <0.255 (OR 4.9). For criterion 2, the value of baseline albumin and ALBI score was identical to criterion 1; however, Δalbumin (<0.1 g/dL) and ΔALBI score (<0.19) became stricter. For criterion 3, the value of baseline albumin (>3.8 g/dL) and ALBI (<-2.55) became stricter, as did Δalbumin (<0.1 g/dL) and ΔALBI (<0.085). Furthermore, tumor burden (>11) was selected as an additional predictor (OR 5.4). Predictors to satisfy the RESORCE study inclusion criteria were as follows: preserved liver function at baseline, as reflected by albumin or ALBI score, and small deterioration of liver function early during sorafenib therapy, as reflected by Δalbumin or ΔALBI at week 4. Liver function at baseline and degree of change in liver function during sorafenib treatment need to be stricter for better outcomes of liver function with disease progression.
酪氨酸激酶抑制剂（TKIs）的最新进展使无法切除的肝细胞癌（HCC）患者能够依次接受多种TKIs治疗。本研究的目的是确定索拉非尼治疗期间疾病进展后二线治疗的良好候选者的预测因素。这是一项对我院190例连续接受索拉非尼治疗的HCC患者进行的回顾性队列研究。索拉非尼治疗期间疾病进展时二线TKI良好候选者的三个标准定义如下：标准1与瑞戈非尼用于索拉非尼治疗后进展的肝细胞癌患者（RESORCE）研究的纳入标准相同，标准2是RESORCE研究的纳入标准加上Child-Pugh评分5，标准3是RESORCE研究的纳入标准加上白蛋白-胆红素（ALBI）1级。使用索拉非尼治疗基线和第4周时的因素来预测符合这三个标准的患者。符合标准1、2和3的患者分布分别为29%、13%和6%。符合标准1的显著因素是基线白蛋白>3.7 g/dL（比值比（OR）2.7）加上第4周时白蛋白降低程度（Δ白蛋白）<0.2 g/dL（OR 2.6），或基线ALBI评分<-2.33（OR 2.5）和第4周时ΔALBI<0.255（OR 4.9）。对于标准2，基线白蛋白和ALBI评分的值与标准1相同；然而，Δ白蛋白（<0.1 g/dL）和ΔALBI评分（<0.19）变得更严格。对于标准3，基线白蛋白（>3.8 g/dL）和ALBI（<-2.55）变得更严格，Δ白蛋白（<0.1 g/dL）和ΔALBI（<0.085）也是如此。此外，肿瘤负荷（>11）被选为额外的预测因素（OR 5.4）。满足RESORCE研究纳入标准的预测因素如下：基线时肝功能良好，以白蛋白或ALBI评分反映，以及索拉非尼治疗早期肝功能轻度恶化，以第4周时的Δ白蛋白或ΔALBI反映。随着疾病进展，为了获得更好的肝功能结果，基线时的肝功能和索拉非尼治疗期间肝功能变化程度需要更严格。
