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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},
}