Circulating miR-21 as a prognostic biomarker in HCC treated by CT-guided high-dose rate brachytherapy
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Published:2023-07-28
Issue:1
Volume:18
Page:
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ISSN:1748-717X
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Container-title:Radiation Oncology
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language:en
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Short-container-title:Radiat Oncol
Author:
Stechele Matthias,Link Henrike,Hirner-Eppeneder Heidrun,Alunni-Fabbroni Marianna,Wildgruber Moritz,Salvermoser Lukas,Corradini Stefanie,Schinner Regina,Ben Khaled Najib,Rössler Daniel,Galun Eithan,Goldberg Shraga Nahum,Ricke Jens,Kazmierczak Philipp Maximilian
Abstract
Abstract
Background and aims
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
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
The responder group demonstrated significantly decreasing miR-21 values 2 d post therapy compared to non-responders (median miR-21 2−ΔΔCт: responders 0.73 [IQR 0.34], non-responders 1.53 [IQR 1.48]; p = 0.0102). miR-210 did not show any significant difference between responders and non-responders (median miR-210 2−ΔΔCт: responders 0.74 [IQR 0.45], non-responders 0.99 [IQR 1.13]; p = 0.8399). Kaplan–Meier curves demonstrated significantly shorter time to systemic progression for increased miR-21 (p = 0.0095) but not miR-210 (p = 0.7412), with events accumulating > 1 year post therapy in non-responders (median time to systemic progression 397 days).
Conclusion
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: 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.
Funder
Bayer Science & Education Foundation
MOST - DKFZ
ISF collaboration with Canada
the personalised medicine ISF grant
Deutsche Forschungsgemeinschaft
ERC advance - GA
Israeli Science Foundation
Universitätsklinik München
Publisher
Springer Science and Business Media LLC
Subject
Radiology, Nuclear Medicine and imaging,Oncology
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