Takahashi Toshiaki, Shigeyasu Kunitoshi, Kondo Yoshitaka, Takeda Sho, Umeda Hibiki, Moriwake Kazuya, Kayano Masashi, Sakurai Yuya, Nakamura Shunsuke, Takahashi Masafumi, Nitta Kaori, Yoshida Kazuhiro, Matsumi Yuki, Michiue Hiroyuki, Yamamoto Hideki, Kishimoto Hiroyuki, Teraishi Fuminori, Shoji Ryohei, Kanaya Nobuhiko, Kashima Hajime, Kakiuchi Yoshihiko, Kuroda Shinji, Kagawa Shunsuke, Fujiwara Toshiyoshi
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-Cho, Kita-Ku, Okayama, 700-8558, Japan.
Neutron Therapy Research Center, Okayama University, Okayama, Japan.
BMC Cancer. 2025 Jan 2;25(1):1. doi: 10.1186/s12885-024-13370-8.
Trifluridine/tipiracil (FTD/TPI) is one of the options for late-line treatment of colorectal cancer (CRC). However, the specific patient populations that would particularly benefit from it remain unclear. This study attempted to identify predictive markers of chemotherapy efficacy with trifluridine/tipiracil (FTD/TPI), focusing on the RNA-editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) expression and neutrophil-lymphocyte ratio (NLR).
To assess the effectiveness of FTD/TPI in CRC patients, we retrospectively analyzed 72 CRC patients at Okayama University Hospital from 2014 to 2022.
Adding bevacizumab to FTD/TPI resulted in a more prolonged progression-free survival (PFS), consistent with the SUNLIGHT study findings (p = 0.0028). Among the participants, those with a high NLR had a shorter PFS (p = 0.0395). Moreover, high ADAR1 expression was associated with longer PFS (p = 0.0151). In multivariate analysis, low ADAR1 (HR = 3.43, p = 0.01) and absence of bevacizumab (HR = 4.25, p = 0.01) were identified as factors shortening PFS. The high ADAR1 group demonstrated fewer cases of progressive disease and a higher proportion of stable disease than the low ADAR1 group (p = 0.0288). Low NLR and high ADAR1 were predictive markers of prolonged PFS in the bevacizumab-treated group (p = 0.0036).
Low NLR and high ADAR1 were predictive markers for a positive response to the FTD/TPI plus bevacizumab regimen associated with prolonged PFS. The FTD/TPI plus bevacizumab regimen should be proactively implemented in the low NLR and high ADAR1 subgroups.
曲氟尿苷/替匹嘧啶（FTD/TPI）是晚期结直肠癌（CRC）治疗的选择之一。然而，能从该治疗中特别获益的具体患者群体仍不明确。本研究试图确定曲氟尿苷/替匹嘧啶（FTD/TPI）化疗疗效的预测标志物，重点关注作用于RNA 1的RNA编辑酶腺苷脱氨酶（ADAR1）表达和中性粒细胞与淋巴细胞比值（NLR）。
为评估FTD/TPI在CRC患者中的有效性，我们回顾性分析了2014年至2022年在冈山大学医院的72例CRC患者。
FTD/TPI联合贝伐单抗可使无进展生存期（PFS）延长，这与SUNLIGHT研究结果一致（p = 0.0028）。在参与者中，NLR高的患者PFS较短（p = 0.0395）。此外，ADAR1高表达与较长的PFS相关（p = 0.0151）。多因素分析显示，低ADAR1（HR = 3.43，p = 0.01）和未使用贝伐单抗（HR = 4.25，p = 0.01）是缩短PFS的因素。与低ADAR1组相比，高ADAR1组疾病进展病例更少，疾病稳定比例更高（p = 0.0288）。在贝伐单抗治疗组中，低NLR和高ADAR1是PFS延长的预测标志物（p = 0.0036）。
低NLR和高ADAR1是FTD/TPI联合贝伐单抗方案获得阳性反应并伴有PFS延长的预测标志物。FTD/TPI联合贝伐单抗方案应在低NLR和高ADAR1亚组中积极应用。
