2023 World Conference on Lung Cancer (Posters)-P1.23. Cerebrospinal Fluid ctDNA Based Therapy Associated with Survival of CNS Metastases in Advanced NSCLC: A Large Scale, Comprehensive Study

P1.23. Cerebrospinal Fluid ctDNA Based Therapy Associated with Survival of CNS Metastases in Advanced NSCLC: A Large Scale, Comprehensive Study - PDF(Slides)

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A comprehensive study conducted in China explored the use of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) in the risk stratification and treatment guidance for patients with central nervous system (CNS) metastases of non-small cell lung cancer (NSCLC). The study included 584 NSCLC patients with CNS metastases who underwent CSF ctDNA sequencing, along with matched tissue and plasma ctDNA sequencing. The results showed that CSF ctDNA was a superior liquid biopsy source for CNS metastases compared to plasma, and it was associated with survival outcomes. The study also identified unique genetic profiles of CNS metastases and their clinical significance.<br /><br />The study cohort consisted of patients with brain metastases (BM), leptomeningeal metastases (LM), and patients without CNS metastases. CSF samples, as well as tumor tissue and plasma samples, were evaluated using targeted panel next-generation sequencing. The study found that CSF ctDNA positivity was associated with shorter survival in the overall population, both treated and untreated patients, and in both BM and LM cases. CSF ctDNA was also shown to be an independent prognostic factor for CNS metastases. It outperformed existing risk stratification models in LM and BM cases.<br /><br />Additionally, the study demonstrated that CSF ctDNA could reflect tumor burden and shed light on the proteomic correlates of ctDNA in BM. It also revealed CSF-unique genomic alterations and resistant mechanisms in CNS metastases that were not present in matched tissue samples. These CSF-specific alterations could potentially be targeted for treatment.<br /><br />Overall, the study highlights the clinical implications of CSF ctDNA in the risk stratification, treatment guidance, and understanding of the molecular features of CNS metastases in NSCLC patients. It provides valuable insights into the use of liquid biopsies for CNS metastases and the potential for personalized therapy based on CSF ctDNA profiling.

Asset Subtitle

Mei-Mei Zheng

Meta Tag

Speaker Mei-Mei Zheng

Topic Pathology & Biomarkers: Liquid Based Biomarkers

Keywords

China

cerebrospinal fluid

CSF

circulating tumor DNA

ctDNA

NSCLC

liquid biopsy

survival outcomes

prognostic factor

personalized therapy