Hamada Kazuki, Nagumo Yoshiyuki, Kandori Shuya, Tanuma Kozaburo, Shiga Masanobu, Hoshi Akio, Negoro Hiromitsu, Kojima Takahiro, Mathis Bryan J, Nishiyama Hiroyuki
Department of Urology, Faculty of Medicine and Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Department of Urology, Aichi Cancer Center Hospital, Nagoya, Aichi 464-8681, Japan.
Oncol Lett. 2023 Jul 24;26(3):389. doi: 10.3892/ol.2023.13975. eCollection 2023 Sep.
Prognoses for patients with metastatic urothelial carcinoma (mUC) have improved with pembrolizumab treatment, an immune checkpoint inhibitor, but clinical benefits are limited to a subset of patients. Therefore, a non-invasive biomarker to predict pembrolizumab response is required. The present study retrospectively examined genomic alterations in 25 plasma circulating tumor DNA (ctDNA) samples using targeted sequencing of 77 genes from 16 patients with mUC during pembrolizumab treatment. A total of 11 (68.8%) patients demonstrated ≥2 genomic alterations, including mutations (as defined by ctDNA-positive status). The proportion of responders to pembrolizumab in the ctDNA-positive group was higher compared with that in the ctDNA-negative group (72.7 vs. 20.0%). Furthermore, among all detected genomic alterations, variant allele frequency decreases in during pembrolizumab treatment were mainly associated with therapeutic response. Collectively, these data suggest that profiling of ctDNA in plasma, particularly , may be useful for predicting and monitoring therapeutic responses to pembrolizumab in patients with mUC.
使用免疫检查点抑制剂派姆单抗治疗转移性尿路上皮癌（mUC）患者的预后有所改善，但临床益处仅限于一部分患者。因此，需要一种非侵入性生物标志物来预测派姆单抗的反应。本研究回顾性分析了16例接受派姆单抗治疗的mUC患者的25份血浆循环肿瘤DNA（ctDNA）样本中的基因组改变，采用靶向测序77个基因的方法。共有11例（68.8%）患者表现出≥2种基因组改变，包括 突变（由ctDNA阳性状态定义）。ctDNA阳性组中对派姆单抗有反应者的比例高于ctDNA阴性组（72.7%对20.0%）。此外，在所有检测到的基因组改变中，派姆单抗治疗期间 中变异等位基因频率的降低主要与治疗反应相关。总体而言，这些数据表明，血浆中ctDNA的分析，尤其是 ，可能有助于预测和监测mUC患者对派姆单抗的治疗反应。
