ctDNA detection in cerebrospinal fluid and plasma and mutational concordance with the primary tumor in a multicenter prospective study of patients with glioma.

IF 56.7 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2025-02-18 DOI:10.1016/j.annonc.2025.02.005

S Cabezas-Camarero, R Pérez-Alfayate, V García-Barberán, M L Gandía-González, P García-Feijóo, I López-Cade, V Lorca, I Casado-Fariñas, M A Cerón, M Paz-Cabezas, M J Sotelo, M García Conde, H Roldán Delgado, Y Sánchez Medina, I Díaz-Millán, P Pérez-Segura

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引用次数: 0

Abstract

Background: Cerebrospinal fluid (CSF) stands as an easily accessible reservoir for circulating tumor DNA (ctDNA) analysis in patients with central nervous system (CNS) tumors, although evidence is still limited. Our aim was to prospectively evaluate the feasibility of detecting ctDNA for mutational analysis in CSF and plasma in patients with glioma.

Methods: This was a prospective study of patients with glioma diagnosed at four third-level hospitals in Spain. A customized next-generation sequencing (NGS) eight-gene panel (IDH1, IDH2, ATRX, TP53, PTEN, PIK3CA, EGFR, BRAF) was used in paired CSF, plasma and tumor samples. Mutation concordance occurred when the same pathogenic gene variant was detected in tumor and ctDNA. The prognostic value of ctDNA and that of its median variant allele frequency (mVAF) were analyzed.

Results: Between February 2017 and March 2020, 37 patients with glioma were enrolled. The 32 patients with analyzable CSF samples comprised patients with new diagnosis (n = 23) and relapse (n = 9); World Health Organization fifth Edition types: IDH-mutant astrocytoma (n = 10), IDH-mutant oligodendroglioma (n = 6) and IDH-wildtype glioblastoma (n = 16); CSF-ctDNA-positive: 19/32 (59%); and CSF-ctDNA-negative: 13/32 (41%). CSF mutation numbers were 1 (10/19), 2 (7/19) and 3 (2/19). Frequencies of CSF-ctDNA-mutated genes were EGFR (8/19, 42%), PTEN (7/19, 37%), TP53 (6/19, 32%), IDH1 (5/19, 26%) and PIK3CA (4/19, 21%). Tumor-CSF mutation concordance was found in 16/19 (84%). Progression-free and overall survival were significantly shorter in ctDNA-positive patients with VAF equal to or greater than the mVAF compared with ctDNA-positive patients with VAF lower than the mVAF. No association was found between ctDNA in CSF and distance to closest CSF reservoir, tumor size or IDH status. ctDNA was detected in 2 of 14 (14%) individual plasma samples, in both cases concordant with the primary tumor.

Conclusion: CSF is a reliable reservoir for ctDNA analyses in patients with glioma. ctDNA is detectable in plasma although at a lower rate. Larger, prospective studies should be conducted to refine the potential role of liquid biopsy in this disease.

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来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.