Prognostic value of circulating short-length DNA fragments in unresected glioblastoma patients

Background: Liquid biopsy application is still challenging in glioblastoma patients and the usefulness of short-length DNA (slDNA) fragments is not established. The aim was to investigate slDNA concentration as a prognostic marker in unresected glioblastoma patients. Methods: Patients with unresecte...

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Main Authors: Arthur Daban, Ludivine Beaussire-Trouvay, Émilie Lévêque, Cristina Alexandru, Isabelle Tennevet, Olivier Langlois, Ovidiu Veresezan, Florent Marguet, Florian Clatot, Frédéric Di Fiore, Nasrin Sarafan-Vasseur, Maxime Fontanilles
Format: Article
Language:English
Published: Elsevier 2024-04-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523324000238
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author Arthur Daban
Ludivine Beaussire-Trouvay
Émilie Lévêque
Cristina Alexandru
Isabelle Tennevet
Olivier Langlois
Ovidiu Veresezan
Florent Marguet
Florian Clatot
Frédéric Di Fiore
Nasrin Sarafan-Vasseur
Maxime Fontanilles
author_facet Arthur Daban
Ludivine Beaussire-Trouvay
Émilie Lévêque
Cristina Alexandru
Isabelle Tennevet
Olivier Langlois
Ovidiu Veresezan
Florent Marguet
Florian Clatot
Frédéric Di Fiore
Nasrin Sarafan-Vasseur
Maxime Fontanilles
author_sort Arthur Daban
collection DOAJ
description Background: Liquid biopsy application is still challenging in glioblastoma patients and the usefulness of short-length DNA (slDNA) fragments is not established. The aim was to investigate slDNA concentration as a prognostic marker in unresected glioblastoma patients. Methods: Patients with unresected glioblastoma and treated by radiochemotherapy (RT/TMZ) were included. Plasmas were prospectively collected at three times: before (pre-) RT, after (post-) RT and at the time of progression. Primary objective was to investigate the impact on survival of slDNA concentration [slDNA] variation during RT/TMZ. Secondary objectives were to explore the association between tumor volume, corticosteroid exposition and [slDNA]; and the impact of slDNA detection at pre-RT on survival. Results: Thirty-six patients were analyzed: 11 patients (30.6 %) experienced [slDNA] decrease during RT/TMZ, 22 patients (61.1 %) experienced increase and 3 patients (8.3 %) had stability. Decrease of [slDNA] during RT/TMZ was associated with better outcome compared to increase or stability: median OS, since end of RT, of 13.2 months [11.4 - NA] vs 10.1 months [7.8 - 12.6] and 6.8 months [4.5 - NA], p = 0.015, respectively. slDNA detection at pre-RT time was associated with improved OS: 11.7 months in the slDNA(+) group versus 8.8 months in the slDNA(-) group, p = 0.004. [slDNA] was not associated with corticosteroids exposition or tumor volume. No influence on survival was observed for both whole cfDNA concentration or slDNA peak size. Conclusion: [slDNA] decrease during radiochemotherapy phase is a favorable prognostic marker on OS for unresected glioblastoma patients. Larger and independent cohorts are now required. Trial registration: ClinicalTrial, NCT02617745. Registered 1 December 2015, https://clinicaltrials.gov/ct2/show/NCT02617745?term=glioplak&draw=2&rank=1
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spelling doaj.art-f41d5629bae3487789a40aed28f0e2742024-02-11T05:09:08ZengElsevierTranslational Oncology1936-52332024-04-0142101897Prognostic value of circulating short-length DNA fragments in unresected glioblastoma patientsArthur Daban0Ludivine Beaussire-Trouvay1Émilie Lévêque2Cristina Alexandru3Isabelle Tennevet4Olivier Langlois5Ovidiu Veresezan6Florent Marguet7Florian Clatot8Frédéric Di Fiore9Nasrin Sarafan-Vasseur10Maxime Fontanilles11Department of Medical Oncology, Cancer Centre Henri Becquerel, Rue d'Amiens, 76038, Rouen, FranceUniv Rouen Normandy, INSERM unit U1245 Brain and Cancer Genomics, Rouen, 76000 FranceClinical Research Unit, Cancer Centre Henri Becquerel, Rue d'Amiens, 76038, Rouen, FranceDepartment of Medical Oncology, Cancer Centre Henri Becquerel, Rue d'Amiens, 76038, Rouen, FranceDepartment of Medical Oncology, Cancer Centre Henri Becquerel, Rue d'Amiens, 76038, Rouen, FranceDepartment of Neurosurgery, Rouen University Hospital, F-76031, 1 Rue de Germont, Rouen, CEDEX 76031, FranceDepartment of Radiation Oncology, Henri Becquerel Cancer Center, 76038, Rouen, FranceUniv Rouen Normandy, INSERM unit U1245 Brain and Cancer Genomics, Rouen, 76000 France; Department of Pathology, Rouen University Hospital, 1 Rue de Germont, Rouen, CEDEX 76031, FranceDepartment of Medical Oncology, Cancer Centre Henri Becquerel, Rue d'Amiens, 76038, Rouen, France; Univ Rouen Normandy, INSERM unit U1245 Brain and Cancer Genomics, Rouen, 76000 FranceDepartment of Medical Oncology, Cancer Centre Henri Becquerel, Rue d'Amiens, 76038, Rouen, France; Univ Rouen Normandy, INSERM unit U1245 Brain and Cancer Genomics, Rouen, 76000 FranceUniv Rouen Normandy, INSERM unit U1245 Brain and Cancer Genomics, Rouen, 76000 FranceDepartment of Medical Oncology, Cancer Centre Henri Becquerel, Rue d'Amiens, 76038, Rouen, France; Univ Rouen Normandy, INSERM unit U1245 Brain and Cancer Genomics, Rouen, 76000 France; Corresponding author at: Univ Rouen Normandy, INSERM unit U1245 Brain and Cancer Genomics, Department of Medical Oncology, Cancer Centre Henri Becquerel, Rouen, 76000 France.Background: Liquid biopsy application is still challenging in glioblastoma patients and the usefulness of short-length DNA (slDNA) fragments is not established. The aim was to investigate slDNA concentration as a prognostic marker in unresected glioblastoma patients. Methods: Patients with unresected glioblastoma and treated by radiochemotherapy (RT/TMZ) were included. Plasmas were prospectively collected at three times: before (pre-) RT, after (post-) RT and at the time of progression. Primary objective was to investigate the impact on survival of slDNA concentration [slDNA] variation during RT/TMZ. Secondary objectives were to explore the association between tumor volume, corticosteroid exposition and [slDNA]; and the impact of slDNA detection at pre-RT on survival. Results: Thirty-six patients were analyzed: 11 patients (30.6 %) experienced [slDNA] decrease during RT/TMZ, 22 patients (61.1 %) experienced increase and 3 patients (8.3 %) had stability. Decrease of [slDNA] during RT/TMZ was associated with better outcome compared to increase or stability: median OS, since end of RT, of 13.2 months [11.4 - NA] vs 10.1 months [7.8 - 12.6] and 6.8 months [4.5 - NA], p = 0.015, respectively. slDNA detection at pre-RT time was associated with improved OS: 11.7 months in the slDNA(+) group versus 8.8 months in the slDNA(-) group, p = 0.004. [slDNA] was not associated with corticosteroids exposition or tumor volume. No influence on survival was observed for both whole cfDNA concentration or slDNA peak size. Conclusion: [slDNA] decrease during radiochemotherapy phase is a favorable prognostic marker on OS for unresected glioblastoma patients. Larger and independent cohorts are now required. Trial registration: ClinicalTrial, NCT02617745. Registered 1 December 2015, https://clinicaltrials.gov/ct2/show/NCT02617745?term=glioplak&draw=2&rank=1http://www.sciencedirect.com/science/article/pii/S1936523324000238GlioblastomaLiquid biopsyShort-length DNAPlasmaPrognostic
spellingShingle Arthur Daban
Ludivine Beaussire-Trouvay
Émilie Lévêque
Cristina Alexandru
Isabelle Tennevet
Olivier Langlois
Ovidiu Veresezan
Florent Marguet
Florian Clatot
Frédéric Di Fiore
Nasrin Sarafan-Vasseur
Maxime Fontanilles
Prognostic value of circulating short-length DNA fragments in unresected glioblastoma patients
Translational Oncology
Glioblastoma
Liquid biopsy
Short-length DNA
Plasma
Prognostic
title Prognostic value of circulating short-length DNA fragments in unresected glioblastoma patients
title_full Prognostic value of circulating short-length DNA fragments in unresected glioblastoma patients
title_fullStr Prognostic value of circulating short-length DNA fragments in unresected glioblastoma patients
title_full_unstemmed Prognostic value of circulating short-length DNA fragments in unresected glioblastoma patients
title_short Prognostic value of circulating short-length DNA fragments in unresected glioblastoma patients
title_sort prognostic value of circulating short length dna fragments in unresected glioblastoma patients
topic Glioblastoma
Liquid biopsy
Short-length DNA
Plasma
Prognostic
url http://www.sciencedirect.com/science/article/pii/S1936523324000238
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