Frontiers in Oncology (Oct 2023)

Tracking tumor evolution during the first-line treatment in brain glioma via serial profiling of cell-free tumor DNA from tumor in situ fluid

  • Zhiyuan Sheng,
  • Zhiyuan Sheng,
  • Chaojie Bu,
  • Chaojie Bu,
  • Jie Mei,
  • Jie Mei,
  • Sensen Xu,
  • Ziyue Zhang,
  • Guangzhong Guo,
  • Yushuai Gao,
  • Liyuan Xing,
  • Zhongcan Chen,
  • Zhongcan Chen,
  • Juha Hernesniemi,
  • Juha Hernesniemi,
  • Ajmal Zemmar,
  • Ajmal Zemmar,
  • Xingyao Bu,
  • Xingyao Bu

DOI
https://doi.org/10.3389/fonc.2023.1238607
Journal volume & issue
Vol. 13

Abstract

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ObjectiveTumor in situ 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.MethodsThis 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.ResultsAt 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.ConclusionsIn 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.

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