在肝细胞癌免疫治疗时代,肿瘤标志物作为生物标志物的现状:单靠甲胎蛋白是不够的。

IF 1.8 3区 医学 Q3 ONCOLOGY
Oncology Pub Date : 2025-02-03 DOI:10.1159/000543405
Atsushi Hiraoka, Masatoshi Kudo, Toshifumi Tada, Takeshi Hatanaka, Satoru Kakizaki, Kazuya Kariyama, Hideko Ohama, Kunihiko Tsuji, Toru Ishikawa, Koichi Takaguchi, Ei Itobayashi, Hidenori Toyoda, Tomomitsu Matono, Yutaka Yata, Chikara Ogawa, Atsushi Naganuma, Joji Tani, Masanori Atsukawa, Takashi Nishimura, Kazuto Tajiri, Kazuhito Kawata, Hisashi Kosaka, Hidekatsu Kuroda, Masashi Hirooka, Hiroki Nishikawa, Fujimasa Tada, Shinichiro Nakamura, Yuki Kanayama, Kazuhiro Nouso, Hironori Tanaka, Kazunari Tanaka, Michitaka Imai, Akemi Tsutsui, Takuya Nagano, Tomoko Aoki, Yuichi Koshiyama, Asahiro Morishita, Norio Itokawa, Tomomi Okubo, Taeang Arai, Shinya Fukunishi, Hidenao Noritake, Yoshiko Nakamura, Osamu Yoshida, Hirayuki Enomoto, Masaki Kaibori, Yoichi Hiasa, Takashi Kumada
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引用次数: 0

摘要

背景/目的:全身治疗的快速发展改善了不可切除的肝细胞癌(uHCC)患者的预后。由于免疫治疗显示出良好的治疗效果,使用肿瘤标志物作为监测治疗反应的生物标志物是必要的。本研究旨在阐明日本3种可用肿瘤标志物的阳性率变化,包括甲胎蛋白(AFP)、去γ -羧基凝血酶原(DCP)和鸡眼凝集素反应性AFP (AFP- l3)在接受全身治疗的uHCC患者中随时间的变化。材料/方法:2009 - 2023年,纳入1470例开始治疗前有肿瘤标志物数据的uHCC患者。AFP阳性临界值为20 ng/mL, AFP- l3阳性临界值为10%,DCP阳性临界值为40 mAU/mL。将研究的15年分为3个阶段,每个阶段5年(阶段1、阶段2、阶段3),回顾性评估入组患者的临床特征。结果:巴塞罗那诊所B期肝癌患者接受全身治疗的比例从I期到III期分别增加了27.7%、38.5%和46.6%。结论:基于早期全身治疗的引入和非病毒病因HCC病例的增加,AFP水平的阳性率呈下降趋势。因此,在联合免疫治疗作为一种强有力的治疗手段的时代,除AFP外,DCP和AFP- l3的测定应更积极地应用于临床实践,以及临床试验中监测和评估治疗反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Current Status of Tumor Markers as Biomarkers in the Era of Immunotherapy for Hepatocellular Carcinoma: Alpha-Fetoprotein Alone Is Not Sufficient.

Introduction: Rapid development of systemic treatments has resulted in improved prognosis for unresectable hepatocellular carcinoma (uHCC) patients. Since immune therapy shows a favorable therapeutic efficacy, use of tumor markers as biomarkers for monitoring treatment response is necessary. This study aimed to elucidate changes in positive rates of 3 available tumor markers in Japan, including alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive AFP (AFP-L3) in uHCC patients treated with systemic therapies over time.

Methods: From 2009 to 2023, 1,470 uHCC patients with data of tumor markers before starting treatment were enrolled. The positivity cutoff value for AFP was 20 ng/mL, for AFP-L3 was 10%, and for DCP was 40 mAU/mL. After dividing the 15 years examined into three periods of 5 years each (period I, II, and III), clinical features of the enrolled patients were evaluated, retrospectively.

Results: The percentage of Barcelona Clinic Liver Cancer stage B patients who received systemic therapy increased from period I to III (27.7%, 38.5%, 46.6%, respectively, p < 0.001), which was also seen for HCC patients with a nonviral etiology (alcohol and others) (29.9%, 39.7%, 49.6%, respectively p < 0.001). Positive rates for AFP (67.8%, 62.1%, 50.8%, respectively) and DCP (84.1%, 80.5%, 72.7%, respectively) were decreased (each p < 0.001), while the AFP-L3 rate did not show a significant change (54.4%, 57.7%, 51.9%, respectively, p = 0.390). Among the AFP-negative patients, the rate of positive for DCP or AFP-L3 was increased (24.4%, 28.1%, 35.4%, respectively, p = 0.002).

Conclusion: Based on introduction of systemic treatment in an early stage and increasing numbers of HCC cases with a nonviral etiology, the positive rate of AFP level has been declining. Thus, determination of DCP and AFP-L3 in addition to AFP as markers should be more actively utilized in clinical practice, as well as clinical trials for monitoring and evaluating treatment response in this era of combination immunotherapy as a powerful treatment.

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来源期刊
Oncology
Oncology 医学-肿瘤学
CiteScore
6.00
自引率
2.90%
发文量
76
审稿时长
6-12 weeks
期刊介绍: Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.
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