Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA.
Department of Biostatistics, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, USA.
Cancer Biomark. 2024;41(1):83-91. doi: 10.3233/CBM-230431.
Circulating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC).
This study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab.
We analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions.
Of 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04).
ctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.
循环肿瘤 DNA（ctDNA）是一种很有前途的非侵入性标志物，可用于检测、诊断、治疗选择和预测肝细胞癌（HCC）的预后。
本研究旨在探讨 ctDNA 作为预测 HCC 患者接受纳武利尤单抗治疗的预后和预测工具的效用。
我们使用商业上可用的平台对 44 例 HCC 患者的治疗前 ctDNA 进行了全面的基因组测试。我们利用对数秩检验和单变量 Cox 模型，将总生存期（OS）和无进展生存期（PFS）与 ctDNA 表达相关联。
44 例患者中，77.3%为男性，中位年龄为 67 岁。除 3 例患者外，所有患者均至少有一个改变，TP53 是最常改变的基因（52.3%）。中位 OS 为 17.5 个月（95%CI：12.7，NA）。PIK3CA、BRCA1 和 CCND1 扩增的突变与较短的 OS 相关（P 0.0001、0.0001 和 0.01）。中位 PFS 时间为 4.01 个月（95%CI：3.06，9.33）。KIT 和 PIK3CA 的突变与较短的 PFS 相关（P 0.0001 和 0.0004），而 CTNNB1 的突变与较长的 PFS 相关（p=0.04）。
ctDNA 分析可能为预测接受纳武利尤单抗治疗的 HCC 患者的生存和进展提供益处。需要进一步的研究来证实。
