接受阿替利珠单抗和贝伐单抗治疗的肝细胞癌患者改良白蛋白-胆红素分级和甲胎蛋白评分（mALF评分）的开发与验证

Development and validation of a modified albumin-bilirubin grade and α-fetoprotein score (mALF score) for hepatocellular carcinoma patients receiving atezolizumab and bevacizumab.

作者信息

Hatanaka Takeshi, Kakizaki Satoru, Hiraoka Atsushi, Tada Toshifumi, Hirooka Masashi, Kariyama Kazuya, Tani Joji, Atsukawa Masanori, Takaguchi Koichi, Itobayashi Ei, Fukunishi Shinya, Tsuji Kunihiko, Ishikawa Toru, Tajiri Kazuto, Ochi Hironori, Yasuda Satoshi, Toyoda Hidenori, Ogawa Chikara, Nishimura Takashi, Shimada Noritomo, Kawata Kazuhito, Kosaka Hisashi, Tanaka Takaaki, Ohama Hideko, Nouso Kazuhiro, Morishita Asahiro, Tsutsui Akemi, Nagano Takuya, Itokawa Norio, Okubo Tomomi, Arai Taeang, Imai Michitaka, Naganuma Atsushi, Koizumi Yohei, Nakamura Shinichiro, Kaibori Masaki, Iijima Hiroko, Hiasa Yoichi, Kumada Takashi

机构信息

Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Kamishindenmachi, Maebashi, Gunma, 564-1, Japan.

Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.

出版信息

Hepatol Int. 2023 Feb;17(1):86-96. doi: 10.1007/s12072-022-10406-8. Epub 2022 Sep 9.

DOI:10.1007/s12072-022-10406-8

PMID:36076009

Abstract

AIM

Predicting the survival of hepatocellular carcinoma (HCC) patients receiving atezolizumab and bevacizumab (Atez/bev) remains a challenge. This study aims to validate the modified albumin-bilirubin grade and α-fetoprotein score (mALF score).

METHODS

This retrospective, multicenter study included 426 HCC patients receiving Atez/Bev. Each patient was randomized 3:2 to a training set (n = 255) and a validation set (n = 171). We investigated prognostic factors in the training set and developed an easily applicable mALF score, which was evaluated in the validation set.

RESULTS

We built the mALF score using baseline mALBI grade 2b or 3 (HR 2.36, 95% CI 1.37-4.05, p = 0.002) and α-fetoprotein ≥ 100 ng/ml (HR 2.61, 95% CI 1.49-4.55, p < 0.001), which were identified as unfavorable prognostic factors in a multivariate analysis. The 1-year OS rates were 82.7% (95% CI 68.9-90.8) in patients who meet neither of the criteria (mALF 0 points, n = 101), 61.7% (95% CI 44.5-74.9) in patients who meet either of the two criteria (mALF 1 point, n = 109), and 24.6% (95% CI 9.0-44.3) in patients who meet both criteria (mALF 2 points, n = 45); the difference was statistically significant (p < 0.001). The median PFS in patients with mALF 0, 1, and 2 points was 9.5 months (95% CI 4.3-NA), 6.6 months (95% CI 6.0-8.0), and 3.8 months (95% CI 3.0-5.2), respectively, which amounted to a significant difference (p < 0.001). These results were confirmed in the validation set (1-year OS rates, 0/1/2 points = 94.2%/62.1%/46.3%, p < 0.001; median PFS, 0/1/2 points = 9.3/6.7/4.7 months, p = 0.018).

CONCLUSION

The mALF score can reliably predict the prognosis of HCC patients receiving Atez/Bev.

摘要

目的

预测接受阿替利珠单抗和贝伐珠单抗（阿替利珠单抗/贝伐珠单抗）治疗的肝细胞癌（HCC）患者的生存期仍然是一项挑战。本研究旨在验证改良的白蛋白-胆红素分级和甲胎蛋白评分（mALF评分）。

方法

这项回顾性多中心研究纳入了426例接受阿替利珠单抗/贝伐珠单抗治疗的HCC患者。每位患者按3:2随机分为训练集（n = 255）和验证集（n = 171）。我们在训练集中研究了预后因素，并开发了一种易于应用的mALF评分，并在验证集中进行了评估。

结果

我们使用基线mALBI 2b或3级（HR 2.36，95%CI 1.37 - 4.05，p = 0.002）和甲胎蛋白≥100 ng/ml（HR 2.61，95%CI 1.49 - 4.55，p < 0.001）构建了mALF评分，这两个因素在多变量分析中被确定为不良预后因素。不符合任何一项标准的患者（mALF 0分，n = 101）的1年总生存率为82.7%（95%CI 68.9 - 90.8），符合两项标准之一的患者（mALF 1分，n = 109）为61.7%（95%CI 44.5 - 74.9），符合两项标准的患者（mALF 2分，n = 45）为24.6%（95%CI 9.0 - 44.3）；差异具有统计学意义（p < 0.001）。mALF 0分、1分和2分患者的中位无进展生存期分别为9.5个月（95%CI 4.3 - NA）、6.6个月（95%CI 6.0 - 8.0）和3.8个月（95%CI 3.0 - 5.2），差异显著（p < 0.001）。这些结果在验证集中得到了证实（1年总生存率，0/1/2分 = 94.2%/62.1%/46.3%，p < 0.001；中位无进展生存期，0/1/2分 = 9.3/6.7/4.个月，p = 0.018）。