Circulating miR-21 as a prognostic biomarker in HCC treated by CT-guided high-dose rate brachytherapy.


Journal

Radiation oncology (London, England)
ISSN: 1748-717X
Titre abrégé: Radiat Oncol
Pays: England
ID NLM: 101265111

Informations de publication

Date de publication:
28 Jul 2023
Historique:
received: 18 02 2023
accepted: 05 07 2023
medline: 31 7 2023
pubmed: 29 7 2023
entrez: 28 7 2023
Statut: epublish

Résumé

Prognostic biomarkers identifying patients with early tumor progression after local ablative therapy remain an unmet clinical need. The aim of this study was to investigate circulating miR-21 and miR-210 levels as prognostic biomarkers of HCC treated by CT-guided high-dose rate brachytherapy (HDR-BT). 24 consecutive HCC patients (BCLC A and B) treated with CT-guided HDR-BT (1 × 15 Gy) were included in this prospective IRB-approved study. RT-PCR was performed to quantify miR-21 and miR-210 levels in blood samples acquired prior to and 2 d after HDR-BT. Follow-up imaging (contrast-enhanced liver MRI and whole-body CT) was performed in 3 months follow-up intervals. Therapy response was assessed with patients classified as either responders or non-responders (12 each). Responders were defined as having no local or diffuse systemic progression within 6 months and no diffuse systemic progression exceeding 3 nodules/nodule diameter > 3 cm from 6 months to 2 years. Non-responders had recurrence within 6 months and/or tumor progression with > 3 nodules or individual lesion diameter > 3 cm or extrahepatic disease within two years, respectively. Biostatistics included parametric and non-parametric testing (Mann-Whitney-U-test), as well as Kaplan-Meier curve construction. The responder group demonstrated significantly decreasing miR-21 values 2 d post therapy compared to non-responders (median miR-21 2 Increasing circulating miR-21 levels are associated with poor response and shorter time to systemic progression in HDR-BT-treated HCC. This proof-of-concept study provides a basis for further investigation of miR-21 as a prognostic biomarker and potential stratifier in future clinical trials of interventional oncology therapies. In this monocentric clinical study, we analyzed prospectively acquired data of 24 patients from the "ESTIMATE" patient cohort (Studiennummer: DRKS00010587, Deutsches Register Klinischer Studien). Ethical approval was provided by the ethics committee "Ethikkommission bei der LMU München" (reference number "17-346") on June 20, 2017 and August 26, 2020.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
Prognostic biomarkers identifying patients with early tumor progression after local ablative therapy remain an unmet clinical need. The aim of this study was to investigate circulating miR-21 and miR-210 levels as prognostic biomarkers of HCC treated by CT-guided high-dose rate brachytherapy (HDR-BT).
MATERIALS AND METHODS METHODS
24 consecutive HCC patients (BCLC A and B) treated with CT-guided HDR-BT (1 × 15 Gy) were included in this prospective IRB-approved study. RT-PCR was performed to quantify miR-21 and miR-210 levels in blood samples acquired prior to and 2 d after HDR-BT. Follow-up imaging (contrast-enhanced liver MRI and whole-body CT) was performed in 3 months follow-up intervals. Therapy response was assessed with patients classified as either responders or non-responders (12 each). Responders were defined as having no local or diffuse systemic progression within 6 months and no diffuse systemic progression exceeding 3 nodules/nodule diameter > 3 cm from 6 months to 2 years. Non-responders had recurrence within 6 months and/or tumor progression with > 3 nodules or individual lesion diameter > 3 cm or extrahepatic disease within two years, respectively. Biostatistics included parametric and non-parametric testing (Mann-Whitney-U-test), as well as Kaplan-Meier curve construction.
RESULTS RESULTS
The responder group demonstrated significantly decreasing miR-21 values 2 d post therapy compared to non-responders (median miR-21 2
CONCLUSION CONCLUSIONS
Increasing circulating miR-21 levels are associated with poor response and shorter time to systemic progression in HDR-BT-treated HCC. This proof-of-concept study provides a basis for further investigation of miR-21 as a prognostic biomarker and potential stratifier in future clinical trials of interventional oncology therapies.
TRIAL REGISTRATION BACKGROUND
In this monocentric clinical study, we analyzed prospectively acquired data of 24 patients from the "ESTIMATE" patient cohort (Studiennummer: DRKS00010587, Deutsches Register Klinischer Studien). Ethical approval was provided by the ethics committee "Ethikkommission bei der LMU München" (reference number "17-346") on June 20, 2017 and August 26, 2020.

Identifiants

pubmed: 37507808
doi: 10.1186/s13014-023-02316-2
pii: 10.1186/s13014-023-02316-2
pmc: PMC10375621
doi:

Substances chimiques

Biomarkers 0
MicroRNAs 0
MIRN21 microRNA, human 0
MIRN210 microRNA, human 0

Banques de données

DRKS
['DRKS00010587']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

125

Subventions

Organisme : Deutsche Forschungsgemeinschaft
ID : SFB841
Organisme : ERC advance - GA
ID : No. 786575 - RxmiRcanceR
Organisme : Israeli Science Foundation
ID : 904/2020

Informations de copyright

© 2023. The Author(s).

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Auteurs

Matthias Stechele (M)

Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. matthias.stechele@med.uni-muenchen.de.

Henrike Link (H)

Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

Heidrun Hirner-Eppeneder (H)

Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

Marianna Alunni-Fabbroni (M)

Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

Moritz Wildgruber (M)

Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

Lukas Salvermoser (L)

Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

Stefanie Corradini (S)

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Regina Schinner (R)

Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

Najib Ben Khaled (N)

Department of Medicine II, University Hospital, LMU Munich, Munich, Germany.

Daniel Rössler (D)

Department of Medicine II, University Hospital, LMU Munich, Munich, Germany.

Eithan Galun (E)

Goldyne Savad Institute of Gene Therapy and Division of Image-Guided Therapy and Interventional Oncology, Department of Radiology, Hadassah Hebrew University Hospital, Jerusalem, Israel.

Shraga Nahum Goldberg (SN)

Goldyne Savad Institute of Gene Therapy and Division of Image-Guided Therapy and Interventional Oncology, Department of Radiology, Hadassah Hebrew University Hospital, Jerusalem, Israel.

Jens Ricke (J)

Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

Philipp Maximilian Kazmierczak (PM)

Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

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Classifications MeSH