Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Mini Oral - CNS

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

Date

18 Sep 2020

Session

Mini Oral - CNS

Presenters

Maxime Fontanilles

Citation

Annals of Oncology (2020) 31 (suppl_4): S396-S408. 10.1016/annonc/annonc269

Authors

M. Fontanilles1, A. Deniel1, F. Marguet2, L. Beaussire3, N. Magne4, S. Derrey5, D. Richard6, C. Alexandru1, F. Clatot1, A. Laquerrière2, N. Sarafan Vasseur3, F. Di Fiore7

Author affiliations

  • 1 Department Of Medical Oncology, Cancer Centre Henri Becquerel, 76038 - Rouen/FR
  • 2 Service D'anatomopathologie, CHU Charles Nicolle, 76000 - Rouen/FR
  • 3 Normandie University, Inserm 1245, Rouen university Hospital, 76031 - Rouen/FR
  • 4 Service D'imagerie Médicale, CHU Charles Nicolle, 76000 - Rouen/FR
  • 5 Service De Neurochirurgie, CHU Charles Nicolle, 76000 - Rouen/FR
  • 6 Clinical Research, Cancer Centre Henri Becquerel, Rouen/FR
  • 7 Gastroentérologie, Hop. Charles Nicolle, 76000 - Rouen/FR
More

Resources

Login to access the resources on OncologyPRO.

Abstract 371MO

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.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings