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Conference Paper: CSF-derived circulating tumor DNA as a biomarker for disease progression and tumor evolution in medulloblastoma

TitleCSF-derived circulating tumor DNA as a biomarker for disease progression and tumor evolution in medulloblastoma
Authors
Keywordscancer
chemotherapy regimen
aneuploidy
biological markers
chromosomes
Issue Date2020
PublisherOxford University Press. The Journal's web site is located at https://academic.oup.com/neuro-oncology
Citation
The 19th International Symposium on Pediatric Neuro-Oncology (ISPNO) 2020, Karuizawa, Japan, 13-16 December 2020. In Neuro-Oncology, 2020, v. 22 n. Suppl. 3, p. iii401-iii402 How to Cite?
AbstractBACKGROUND: Cell-free DNA (cfDNA) profiling has been shown to carry utility as a clinically relevant biomarker in a variety of cancers, but studies in pediatric brain tumors, including medulloblastoma, are scarce. We hereby evaluated the actionability of profiling cfDNA from cerebrospinal fluid (CSF) based on a multi-institutional cohort of children with medulloblastoma. METHODS: 103 children aged ≥ 3 years with medulloblastoma harboring chromosomal aneuploidy enrolled on two prospective therapeutic trials were included. cfDNA was extracted from CSF obtained longitudinally, and profiled by low-coverage wholegenome sequencing (lcWGS) for annotating copy-number variants (CNVs). cfDNA-derived CNVs were compared against patient-matched primary tumor-derived CNVs and correlated with outcome. cfDNA profiles at diagnosis and relapse were compared to evaluate tumor evolution. RESULTS: Tumor-derived somatic CNVs were detected in 72% of baseline cfDNA samples, with higher detection rate in samples from patients with metastatic disease than those without (90% versus 50%, chi-square p=0.001). Longitudinal profiling of cfDNA revealed correlation between CNV detectability and clinical course, with detection of tumorderived CNVs in cfDNA samples predating radiographic progression for ≥ 3 months in 62% of relapsing patients. Presence of cfDNA-derived CNVs in CSF collected during chemotherapy and at the end of therapy was significantly associated with inferior PFS (log-rank p<0.0001 for both time-points). Comparison of CNV profiles from cfDNA at baseline and relapse revealed molecular divergence in a subset of patients. CONCLUSION: These results carry major implications and supports the incorporation of cfDNA profiling in upcoming medulloblastoma protocols for more sensitive and accurate disease monitoring and personalization of treatment.
DescriptionPoster presentation - no. MBRS-20
Persistent Identifierhttp://hdl.handle.net/10722/288268
ISSN
2019 Impact Factor: 10.247
2015 SCImago Journal Rankings: 3.196
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, APY-
dc.contributor.authorKumar, R-
dc.contributor.authorKyle, S-
dc.contributor.authorPaul, L-
dc.contributor.authorChintagumpala, M-
dc.contributor.authorBouffet, E-
dc.contributor.authorFisher, MJ-
dc.contributor.authorHassall, T-
dc.contributor.authorGururangan, S-
dc.contributor.authorHansford, J-
dc.contributor.authorCohn, R-
dc.contributor.authorEllison, DW-
dc.contributor.authorGilbertson, RJ-
dc.contributor.authorGajjar, A-
dc.contributor.authorRobinson, GW-
dc.contributor.authorNorthcott, PA-
dc.date.accessioned2020-10-05T12:10:22Z-
dc.date.available2020-10-05T12:10:22Z-
dc.date.issued2020-
dc.identifier.citationThe 19th International Symposium on Pediatric Neuro-Oncology (ISPNO) 2020, Karuizawa, Japan, 13-16 December 2020. In Neuro-Oncology, 2020, v. 22 n. Suppl. 3, p. iii401-iii402-
dc.identifier.issn1522-8517-
dc.identifier.urihttp://hdl.handle.net/10722/288268-
dc.descriptionPoster presentation - no. MBRS-20-
dc.description.abstractBACKGROUND: Cell-free DNA (cfDNA) profiling has been shown to carry utility as a clinically relevant biomarker in a variety of cancers, but studies in pediatric brain tumors, including medulloblastoma, are scarce. We hereby evaluated the actionability of profiling cfDNA from cerebrospinal fluid (CSF) based on a multi-institutional cohort of children with medulloblastoma. METHODS: 103 children aged ≥ 3 years with medulloblastoma harboring chromosomal aneuploidy enrolled on two prospective therapeutic trials were included. cfDNA was extracted from CSF obtained longitudinally, and profiled by low-coverage wholegenome sequencing (lcWGS) for annotating copy-number variants (CNVs). cfDNA-derived CNVs were compared against patient-matched primary tumor-derived CNVs and correlated with outcome. cfDNA profiles at diagnosis and relapse were compared to evaluate tumor evolution. RESULTS: Tumor-derived somatic CNVs were detected in 72% of baseline cfDNA samples, with higher detection rate in samples from patients with metastatic disease than those without (90% versus 50%, chi-square p=0.001). Longitudinal profiling of cfDNA revealed correlation between CNV detectability and clinical course, with detection of tumorderived CNVs in cfDNA samples predating radiographic progression for ≥ 3 months in 62% of relapsing patients. Presence of cfDNA-derived CNVs in CSF collected during chemotherapy and at the end of therapy was significantly associated with inferior PFS (log-rank p<0.0001 for both time-points). Comparison of CNV profiles from cfDNA at baseline and relapse revealed molecular divergence in a subset of patients. CONCLUSION: These results carry major implications and supports the incorporation of cfDNA profiling in upcoming medulloblastoma protocols for more sensitive and accurate disease monitoring and personalization of treatment.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at https://academic.oup.com/neuro-oncology-
dc.relation.ispartofNeuro-Oncology-
dc.relation.ispartofThe 19th International Symposium on Pediatric Neuro-Oncology (ISPNO) 2020-
dc.subjectcancer-
dc.subjectchemotherapy regimen-
dc.subjectaneuploidy-
dc.subjectbiological markers-
dc.subjectchromosomes-
dc.titleCSF-derived circulating tumor DNA as a biomarker for disease progression and tumor evolution in medulloblastoma-
dc.typeConference_Paper-
dc.identifier.emailLiu, APY: apyliu@hku.hk-
dc.identifier.authorityLiu, APY=rp01357-
dc.description.natureabstract-
dc.identifier.doi10.1093/neuonc/noaa222.536-
dc.identifier.pmcidPMC7715976-
dc.identifier.hkuros314984-
dc.identifier.volume22-
dc.identifier.issueSuppl. 3-
dc.identifier.spageiii401-
dc.identifier.epageiii402-
dc.publisher.placeUnited States-
dc.identifier.issnl1522-8517-

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