Serial assessment of measurable residual disease in medulloblastoma liquid biopsies.

in Cancer cell by Anthony P Y Liu, Kyle S Smith, Rahul Kumar, Leena Paul, Laure Bihannic, Tong Lin, Kendra K Maass, Kristian W Pajtler, Murali Chintagumpala, Jack M Su, Eric Bouffet, Michael J Fisher, Sridharan Gururangan, Richard Cohn, Tim Hassall, Jordan R Hansford, Paul Klimo, Frederick A Boop, Clinton F Stewart, Julie H Harreld, Thomas E Merchant, Ruth G Tatevossian, Geoffrey Neale, Matthew Lear, Jeffery M Klco, Brent A Orr, David W Ellison, Richard J Gilbertson, Arzu Onar-Thomas, Amar Gajjar, Giles W Robinson, Paul A Northcott

TLDR

  • The study investigates whether a type of DNA found in the cerebrospinal fluid (CSF) of children with a type of brain tumor called medulloblastoma can be used to predict whether the tumor will come back after treatment. The study used a type of DNA called cell-free DNA (cfDNA) that is found in the CSF. The study used a type of technology called whole-genome sequencing to look at the DNA in the CSF and see if there were any changes that could be used to predict whether the tumor would come back. The study found that the DNA in the CSF could be used to predict whether the tumor would come back in half of the children who relapsed (meaning their tumor came back). The study also found that the number of children who had the DNA in the CSF decreased with treatment, but those who still had it had a higher risk of the tumor coming back. The study suggests that using the DNA in the CSF to predict whether the tumor will come back could be helpful in the future for treating children with medulloblastoma.

Abstract

Nearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease. Conventional response monitoring by imaging and cerebrospinal fluid (CSF) cytology remains challenging, and a marker for measurable residual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of MRD in serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial. Using low-coverage whole-genome sequencing, tumor-associated copy-number variations in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients declines with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse. Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma.

Overview

  • The study aims to investigate the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of measurable residual disease (MRD) in serial samples collected from children with medulloblastoma enrolled on a prospective trial. The study uses low-coverage whole-genome sequencing to investigate tumor-associated copy-number variations in CSF-derived cfDNA as an MRD surrogate. The primary objective of the study is to determine the clinical utility of CSF-derived liquid biopsies in future trials for medulloblastoma.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions detailed in the study. The study identifies that MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients declines with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse.

Implications and Future Directions

  • The study's findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma. The study identifies that CSF-derived cfDNA can be used as a biomarker of MRD in serial samples collected from children with medulloblastoma. The study also identifies that MRD detection precedes radiographic progression in half who relapse. The study suggests that CSF-derived liquid biopsies could be used to monitor response to therapy and predict progression in children with medulloblastoma.
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