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@ARTICLE{Isebia:299826,
author = {K. T. Isebia and A. C. de Jong and L. F. van Dessel and V.
de Weerd and C. Beaufort and J. Helmijr and J. A.
Nakauma-González and J. van Riet$^*$ and P. Hamberg and D.
Vis and M. S. van der Heijden and N. Beije and M. P. Lolkema
and T. Deger and S. M. Wilting and R. de Wit and M. P. H. M.
Jansen and J. W. M. Martens},
title = {{C}ell-free {DNA} aneuploidy score as a dynamic early
response marker in prostate cancer.},
journal = {Molecular oncology},
volume = {nn},
issn = {1574-7891},
address = {Hoboken, NJ},
publisher = {John Wiley $\&$ Sons, Inc.},
reportid = {DKFZ-2025-00563},
pages = {nn},
year = {2025},
note = {epub},
abstract = {Cell-free circulating tumor DNA (ctDNA) has emerged as a
promising biomarker for response evaluation in metastatic
castration-resistant prostate cancer (mCRPC). The current
study evaluated the modified fast aneuploidy screening
test-sequencing system (mFast-SeqS), a quick, tumor-agnostic
and affordable ctDNA assay that requires a small input of
DNA, to generate a genome-wide aneuploidy (GWA) score in
mCRPC patients, and correlated this to matched metastatic
tumor biopsies. In this prospective multicenter study, GWA
scores were evaluated from blood samples of 196 mCRPC
patients prior to treatment (baseline) with taxanes
(docetaxel and cabazitaxel) and androgen receptor signaling
inhibitors (ARSI; abiraterone and enzalutamide), and from 74
mCRPC patients at an early timepoint during treatment (early
timepoint; median 21 days). Z-scores per chromosome arm were
tested for their association with tumor tissue genomic
alterations. We found that a high tumor load in blood
(GWAhigh) at baseline was associated with poor response to
ARSI [HR: 2.63 $(95\%$ CI: 1.86-3.72) P < 0.001] but not to
taxanes. Interestingly, GWAhigh score at the early timepoint
was associated with poor response to both ARSIs [HR: 6.73
$(95\%$ CI: 2.60-17.42) P < 0.001] and taxanes [2.79 $(95\%$
CI: 1.34-5.78) P = 0.006]. A significant interaction in Cox
proportional hazards analyses was seen when combining GWA
status and type of treatment (at baseline P = 0.008; early
timepoint P = 0.018). In summary, detection of ctDNA in
blood by mFast-SeqS is cheap, fast and feasible, and could
be used at different timepoints as a potential predictor for
outcome to ARSI and taxane treatment in mCRPC.},
keywords = {abiraterone (Other) / cabazitaxel (Other) / ctDNA (Other) /
docetaxel (Other) / enzalutamide (Other) / prostate cancer
(Other)},
cin = {B450},
ddc = {610},
cid = {I:(DE-He78)B450-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40084488},
doi = {10.1002/1878-0261.13797},
url = {https://inrepo02.dkfz.de/record/299826},
}