未切除胶质母细胞瘤患者循环短片段DNA的预后价值

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

作者信息

Daban Arthur, Beaussire-Trouvay Ludivine, Lévêque Émilie, Alexandru Cristina, Tennevet Isabelle, Langlois Olivier, Veresezan Ovidiu, Marguet Florent, Clatot Florian, Di Fiore Frédéric, Sarafan-Vasseur Nasrin, Fontanilles Maxime

机构信息

Department 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.

出版信息

Transl Oncol. 2024 Apr;42:101897. doi: 10.1016/j.tranon.2024.101897. Epub 2024 Feb 9.

DOI:10.1016/j.tranon.2024.101897

PMID:38340682

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10867437/

Abstract

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.

摘要

背景

液体活检在胶质母细胞瘤患者中的应用仍具有挑战性，短片段DNA（slDNA）的作用尚未明确。本研究旨在探讨slDNA浓度作为未切除胶质母细胞瘤患者预后标志物的价值。

方法

纳入接受放化疗（RT/TMZ）治疗的未切除胶质母细胞瘤患者。前瞻性收集患者在放疗前（pre-）、放疗后（post-）及疾病进展时三个时间点的血浆。主要目的是研究RT/TMZ期间slDNA浓度（[slDNA]）变化对生存的影响。次要目的是探讨肿瘤体积、皮质类固醇暴露与[slDNA]之间的关联，以及放疗前slDNA检测对生存的影响。

结果

共分析36例患者：11例患者（30.6%）在RT/TMZ期间[slDNA]下降，22例患者（61.1%）上升，3例患者（8.3%）稳定。与[slDNA]上升或稳定相比，RT/TMZ期间[slDNA]下降与更好的预后相关：放疗结束后的中位总生存期分别为13.2个月[11.4 - 未达到（NA）]、10.1个月[7.8 - 12.6]和6.8个月[4.5 - NA]，p = 0.015。放疗前检测到slDNA与总生存期改善相关：slDNA（+）组为11.7个月，slDNA（-）组为8.8个月，p = 0.004。[slDNA]与皮质类固醇暴露或肿瘤体积无关。全游离DNA浓度或slDNA峰值大小对生存均无影响。