Terashima Takeshi, Yamashita Tatsuya, Arai Kuniaki, Takata Noboru, Hayashi Tomoyuki, Seki Akihiro, Nakagawa Hidetoshi, Nio Kouki, Iida Noriho, Yamada Shinya, Shimakami Tetsuro, Takatori Hajime, Tsuji Kunihiro, Sunagozaka Hajime, Mizukoshi Eishiro, Honda Masao, Takeuchi Shinji, Yamashita Taro
Department of Gastroenterology, Kanazawa University Hospital, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.
Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan.
Hepatol Int. 2025 Feb;19(1):212-221. doi: 10.1007/s12072-024-10741-y. Epub 2024 Nov 14.
Although several therapeutic agents show efficacy in advanced hepatocellular carcinoma (HCC), biomarkers such as comprehensive genomic profiling (CGP) for the selection of second-line treatments after immunotherapy have not been established. We evaluated the value of CGP for the treatment decision in patients with HCC.
We retrospectively studied 52 patients with advanced HCC who received CGP tests at three tertiary hospitals between February 2022 and November 2023. Genomic profiles were obtained using one of three CGP tests; 49 and 3 patients were evaluated using tissue-based and blood-based assay, respectively. The impact of CGP results on subsequent treatment selection in clinical practice and correlations between representative gene alterations and patient characteristics or responses to immunotherapy were evaluated.
The most frequently observed variants were TERT mutations, followed by CTNNB1, TP53, ARID1A, and MYC mutations. Potentially druggable gene alterations were observed in 45 patients (87%), and 34 patients (65%) were recommended to receive treatments based on specific gene alterations by a molecular tumor board. Treatments were covered by health insurance in 13 patients (25%). Five patients (10%) received the recommended treatment by the date of data cut-off. There were no differences in the efficacy of immunotherapy with respect to mutation status in hTERT, CTNNB1, TP53, ARID1A, and MYC.
The results of the present study suggested that druggable gene alterations may provide useful information not only in proposing alternative treatment after standard of care but also in selecting second-line targeted treatments after immunotherapy for patients with advanced HCC.
尽管几种治疗药物在晚期肝细胞癌（HCC）中显示出疗效，但尚未建立用于免疫治疗后二线治疗选择的生物标志物，如综合基因组分析（CGP）。我们评估了CGP在HCC患者治疗决策中的价值。
我们回顾性研究了2022年2月至2023年11月期间在三家三级医院接受CGP检测的52例晚期HCC患者。使用三种CGP检测方法之一获得基因组图谱；分别使用基于组织和基于血液的检测方法对49例和3例患者进行评估。评估了CGP结果对临床实践中后续治疗选择的影响，以及代表性基因改变与患者特征或免疫治疗反应之间的相关性。
最常观察到的变异是TERT突变，其次是CTNNB1、TP53、ARID1A和MYC突变。45例患者（87%）观察到潜在可靶向治疗的基因改变，分子肿瘤委员会根据特定基因改变建议34例患者（65%）接受治疗。13例患者（25%）的治疗费用由医疗保险支付。截至数据截止日期，5例患者（10%）接受了推荐的治疗。在hTERT、CTNNB1、TP53、ARID1A和MYC的突变状态方面，免疫治疗的疗效没有差异。
本研究结果表明，可靶向治疗的基因改变不仅在提出标准治疗后的替代治疗方案方面，而且在为晚期HCC患者选择免疫治疗后的二线靶向治疗方面，可能提供有用的信息。
