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@ARTICLE{Wirsching:142206,
      author       = {H.-G. Wirsching and G. Tabatabai and U. Roelcke and A. F.
                      Hottinger and F. Jörger and A. Schmid and L. Plasswilm and
                      D. Schrimpf$^*$ and C. Mancao and D. Capper$^*$ and K. Conen
                      and T. Hundsberger and F. Caparrotti and R. von Moos and C.
                      Riklin and J. Felsberg and P. Roth and D. Jones$^*$ and S.
                      Pfister$^*$ and E. J. Rushing and L. Abrey and G.
                      Reifenberger and L. Held and A. von Deimling$^*$ and A.
                      Ochsenbein and M. Weller},
      title        = {{B}evacizumab plus hypofractionated radiotherapy versus
                      radiotherapy alone in elderly patients with glioblastoma:
                      the randomized, open-label, phase {II} {ARTE} trial.},
      journal      = {Annals of oncology},
      volume       = {29},
      number       = {6},
      issn         = {1569-8041},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2019-00020},
      pages        = {1423 - 1430},
      year         = {2018},
      abstract     = {The addition of bevacizumab to temozolomide-based
                      chemoradiotherapy (TMZ/RT → TMZ) did not prolong overall
                      survival (OS) in patients with newly diagnosed glioblastoma
                      in phase III trials. Elderly and frail patients are
                      underrepresented in clinical trials, but early reports
                      suggested preferential benefit in this population.ARTE was a
                      2 : 1 randomized, multi-center, open-label,
                      non-comparative phase II trial of hypofractionated RT
                      (40 Gy in 15 fractions) with bevacizumab
                      (10 mg/kg×14 days) (arm A, N = 50) or without
                      bevacizumab (arm B, N = 25) in patients with newly
                      diagnosed glioblastoma aged ≥65 years. The primary
                      objective was to obtain evidence for prolongation of median
                      OS by the addition of bevacizumab to RT. Response was
                      assessed by RANO criteria. Quality of life (QoL) was
                      monitored by the EORTC QLQ-C30/BN20 modules. Exploratory
                      studies included molecular subtyping by 450k whole methylome
                      and gene expression analyses.Median PFS was longer in arm A
                      than in arm B (7.6 and 4.8 months, P = 0.003), but OS
                      was similar (12.1 and 12.2 months, P = 0.77). Clinical
                      deterioration was delayed and more patients came off
                      steroids in arm A. Prolonged PFS in arm A was confined to
                      tumors with the receptor tyrosine kinase (RTK) I methylation
                      subtype (HR 0.25, P = 0.014) and proneural gene
                      expression (HR 0.29, P = 0.025). In a Cox model of OS
                      controlling for established prognostic factors, associations
                      with more favorable outcome were identified for
                      age <70 years (HR 0.52, P = 0.018) and Karnofsky
                      performance score $90\%-100\%$ (HR 0.51, P = 0.026).
                      Including molecular subtypes into that model identified an
                      association of the RTK II gene methylation subtype with
                      inferior OS (HR 1.73, P = 0.076).Efficacy outcomes and
                      exploratory analyses of ARTE do not support the hypothesis
                      that the addition of bevacizumab to RT generally prolongs
                      survival in elderly glioblastoma patients. Molecular
                      biomarkers may identify patients with preferential benefit
                      from bevacizumab.NCT01443676.},
      cin          = {G380 / B062},
      ddc          = {610},
      cid          = {I:(DE-He78)G380-20160331 / I:(DE-He78)B062-20160331},
      pnm          = {315 - Imaging and radiooncology (POF3-315)},
      pid          = {G:(DE-HGF)POF3-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29648580},
      doi          = {10.1093/annonc/mdy120},
      url          = {https://inrepo02.dkfz.de/record/142206},
}