Sheng Zhiyuan, Bu Chaojie, Mei Jie, Xu Sensen, Zhang Ziyue, Guo Guangzhong, Gao Yushuai, Xing Liyuan, Chen Zhongcan, Hernesniemi Juha, Zemmar Ajmal, Bu Xingyao
Department of Neurosurgery, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China.
Juha International Center for Neurosurgery, Henan Provincial People's Hospital, Zhengzhou, China.
Front Oncol. 2023 Oct 17;13:1238607. doi: 10.3389/fonc.2023.1238607. eCollection 2023.
Tumor fluid (TISF) refers to the fluid within surgical cavities of glioma. Several studies preliminarily proved the value of cell-free tumor DNA (cf-tDNA) from TISF in the dynamic characterization of the glioma genome. Here, we assessed the potential utility of TISF cf-tDNA in broad aspects of tumor evolution under therapeutic pressure.
This study was conducted under an Institutional Review Board-approved protocol at Henan Provincial People's Hospital (China). Cf-tDNA samples were sequenced with a designed 68-gene panel. A total of 205 cf-tDNA samples from 107 patients were studied. The clinical relevance of serial cf-tDNA profiling during the postoperative course was analyzed.
At least one tumor mutations were detected in 179/205 (87.3%) TISF cf-tDNA samples. Serial cf-tDNA was complementary to molecular residual disease and to initial tumors. Serial cf-tDNA revealed the selection of pre-existing mismatch repair-deficient cells by temozolomide as a resistant mechanism. Cf-tDNA parameters during treatment were predictive of recurrence, and serial cf-tDNA monitoring had diagnostic value for early recurrence. A total of 223 potentially actionable genomic alterations were assessed in cf-tDNA samples, wherein 78% were not found in any tumor tissue.
In conclusion, serial TISF cf-tDNA profiling is valuable in tracking the tumor evolution of glioma during treatment and may be a feasible non-invasive option for monitoring glioma in future prospective studies and clinical practice.
肿瘤组织间液（TISF）是指胶质瘤手术腔隙内的液体。多项研究初步证实了TISF中游离肿瘤DNA（cf-tDNA）在胶质瘤基因组动态特征分析中的价值。在此，我们评估了TISF cf-tDNA在治疗压力下肿瘤演变广泛方面的潜在效用。
本研究在河南省人民医院（中国）经机构审查委员会批准的方案下进行。cf-tDNA样本采用设计的68基因检测板进行测序。共研究了来自107例患者的205份cf-tDNA样本。分析了术后过程中连续cf-tDNA分析的临床相关性。
在179/205（87.3%）的TISF cf-tDNA样本中检测到至少一种肿瘤突变。连续cf-tDNA与分子残留疾病和初始肿瘤具有互补性。连续cf-tDNA揭示了替莫唑胺对预先存在的错配修复缺陷细胞的选择是一种耐药机制。治疗期间的cf-tDNA参数可预测复发，连续cf-tDNA监测对早期复发具有诊断价值。在cf-tDNA样本中评估了总共223种潜在可操作的基因组改变，其中78%在任何肿瘤组织中均未发现。
总之，连续的TISF cf-tDNA分析在追踪胶质瘤治疗期间的肿瘤演变方面具有价值，并且在未来的前瞻性研究和临床实践中可能是监测胶质瘤的一种可行的非侵入性选择。
