Blood advances · 2025
Reflecting on 30 years of miRNA biology in malignant hematology: current challenges and future directions.
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Asaoka Yoshinari, Tateishi Ryosuke, Yamada Yasuhide, Kokudo Takashi, Saito Akiko, Hasegawa Kiyoshi, Iijima Hiroko, Kato Naoya, Shimada Mitsuo, Hatano Etsuro, Fukumoto Takumi, Murakami Takamichi, Yano Hirohisa, Yoshimitsu Kengo, Kurosaki Masayuki, Sakamoto Michiie, Matsuyama Yutaka, Kudo Masatoshi, Miyata Hiroaki, Kokudo Norihiro
Аннотация
BACKGROUND AND AIMS: As systemic therapy for hepatocellular carcinoma (HCC) rapidly advances, eight treatment regimens are currently approved in Japan. However, the limited settings of phase III clinical trials necessitate large-scale real-world data to evaluate effective treatment sequences. To address this, we established a nationwide registry called the Hepatoma Registry of Integrating and Aggregating Electronic Health Record (HERITAGE).
APPROACH AND RESULTS: HERITAGE, associated with a nationwide follow-up survey by the Japan Liver Cancer Association, included cases where first-line systemic therapy commenced between April 2015 and December 2022. We collected data on treatment regimens, patient demographics, effectiveness, and duration and assessed changes in regimens, trends in patient characteristics, efficacy per regimen, and cross-resistance in combinations of first- and second-line treatments. The study enrolled over 8,000 treatment lines from 5,525 cases. Chronological analysis revealed a progression in first-line treatments from sorafenib to lenvatinib and then to atezolizumab plus bevacizumab. These regimens were frequently reused in second and subsequent lines. There was an increase in older patients and those with nonviral etiologies and robust liver function. Treatments were generally initiated at earlier disease stages. Cross-resistance studies indicated that responses to second-line treatments were significantly influenced by the efficacy of first-line therapies, particularly in tyrosine kinase inhibitor sequences.
CONCLUSIONS: Through establishing a comprehensive registry, this study unveiled evolving patterns in treatment regimens and shifts in patient demographics for systemic HCC therapy in Japan.
APPROACH AND RESULTS: HERITAGE, associated with a nationwide follow-up survey by the Japan Liver Cancer Association, included cases where first-line systemic therapy commenced between April 2015 and December 2022. We collected data on treatment regimens, patient demographics, effectiveness, and duration and assessed changes in regimens, trends in patient characteristics, efficacy per regimen, and cross-resistance in combinations of first- and second-line treatments. The study enrolled over 8,000 treatment lines from 5,525 cases. Chronological analysis revealed a progression in first-line treatments from sorafenib to lenvatinib and then to atezolizumab plus bevacizumab. These regimens were frequently reused in second and subsequent lines. There was an increase in older patients and those with nonviral etiologies and robust liver function. Treatments were generally initiated at earlier disease stages. Cross-resistance studies indicated that responses to second-line treatments were significantly influenced by the efficacy of first-line therapies, particularly in tyrosine kinase inhibitor sequences.
CONCLUSIONS: Through establishing a comprehensive registry, this study unveiled evolving patterns in treatment regimens and shifts in patient demographics for systemic HCC therapy in Japan.