371MO - Usefulness of circulating tumour DNA detection from cerebrospinal fluid in recurrent high-grade glioma

Background

Molecular characterization of high-grade glioma (HGG) at recurrence is promising for disease monitoring and therapeutic decision. We aimed to analyze the mutational profile between primary tumor and circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) obtained at recurrence in patients treated for a HGG.

Methods

This prospective pilot trial included patients suffering from HGG at the time of recurrence, defined by RANO criteria, after standard radiotherapy and temozolomide treatment. CSF (2mL) was collected by lumbar puncture within 3 weeks after recurrence MRI. ctDNA from CSF and DNA from primary tumor (tDNA) were both sequenced using next-generation sequencing (NGS) Illumina Miseq® with custom targeted panel dedicated to HGG hotspot mutations.

Results

Eighteen patients were included (16 IDH-wild type glioblastoma, 1 gliosarcoma and 1 anaplastic astrocytoma). Two-thirds (10/15) of patients had somatic mutations in CSF (ctDNA+) at recurrence (3 pts had insufficient ctDNA amount). Mutational profile differed between tDNA at baseline versus ctDNA at recurrence, especially regarding altered genes frequencies: PTEN 37.5% vs 26.7%, TERT 43.8% vs 20%, TP53 13.3% vs 20% and ATRX 31.3% vs 13.3%. Interestingly, two patients harbored de novo driver mutations (IDH2 and MSH6) in ctDNA at recurrence. Regarding factors associated with ctDNA+: 7/10 had CSF protein level >.55g/L with a mean of 1.17 g/L for ctDNA+ vs .65 g/L for ctDNA-, p=.06. Whole circulating cell-free DNA concentration also correlated to CSF protein content (Rsquared 0.4, p=.003). The 1-year overall survival was 90% in ctDNA+ group and 40% in ctDNA- group.

Conclusions

ctDNA from CSF is a promising and minimally-invasive tool to characterize molecular evolution of HGG after RT-TMZ treatment in a subset of patients. Meningeal inflammation likely influences ctDNA detection in CSF.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

GIRCI Nord-Ouest.

Disclosure

M. Fontanilles: Travel/Accommodation/Expenses: La Roche-Hoffman; Travel/Accommodation/Expenses: GSK. All other authors have declared no conflicts of interest.