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@ARTICLE{Joseph:182686,
      author       = {N. Joseph and A. Cicchetti and A. McWilliam and A. Webb and
                      P. Seibold$^*$ and C. Fiorino and C. Cozzarini and L.
                      Veldeman and R. Bultijnck and V. Fonteyne and C. J. Talbot
                      and P. R. Symonds and K. Johnson and T. Rattay and M.
                      Lambrecht and K. Haustermans and G. De Meerleer and R. M.
                      Elliott and E. Sperk and C. Herskind and M. Veldwijk and B.
                      Avuzzi and T. Giandini and R. Valdagni and D. Azria and M.
                      F. Jacquet and M. Charissoux and A. Vega and M. E.
                      Aguado-Barrera and A. Gómez-Caamaño and P. Franco and E.
                      Garibaldi and G. Girelli and C. Iotti and V. Vavassori and
                      J. Chang-Claude$^*$ and C. M. L. West and T. Rancati and A.
                      Choudhury},
      title        = {{H}igh weekly integral dose and larger fraction size
                      increase risk of fatigue and worsening of functional
                      outcomes following radiotherapy for localized prostate
                      cancer.},
      journal      = {Frontiers in oncology},
      volume       = {12},
      issn         = {2234-943X},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2022-02854},
      pages        = {937934},
      year         = {2022},
      abstract     = {We hypothesized that increasing the pelvic integral dose
                      (ID) and a higher dose per fraction correlate with worsening
                      fatigue and functional outcomes in localized prostate cancer
                      (PCa) patients treated with external beam radiotherapy
                      (EBRT).The study design was a retrospective analysis of two
                      prospective observational cohorts, REQUITE (development,
                      n=543) and DUE-01 (validation, n=228). Data were available
                      for comorbidities, medication, androgen deprivation therapy,
                      previous surgeries, smoking, age, and body mass index. The
                      ID was calculated as the product of the mean body dose and
                      body volume. The weekly ID accounted for differences in
                      fractionation. The worsening (end of radiotherapy versus
                      baseline) of European Organisation for Research and
                      Treatment of Cancer EORTC) Quality of Life Questionnaire
                      (QLQ)-C30 scores in physical/role/social functioning and
                      fatigue symptom scales were evaluated, and two outcome
                      measures were defined as worsening in ≥2 (WS2) or ≥3
                      (WS3) scales, respectively. The weekly ID and clinical risk
                      factors were tested in multivariable logistic regression
                      analysis.In REQUITE, WS2 was seen in $28\%$ and WS3 in
                      $16\%$ of patients. The median weekly ID was 13.1 L·Gy/week
                      [interquartile (IQ) range 10.2-19.3]. The weekly ID,
                      diabetes, the use of intensity-modulated radiotherapy, and
                      the dose per fraction were significantly associated with WS2
                      [AUC (area under the receiver operating characteristics
                      curve) =0.59; $95\%$ CI 0.55-0.63] and WS3 (AUC=0.60; $95\%$
                      CI 0.55-0.64). The prevalence of WS2 $(15.3\%)$ and WS3
                      $(6.1\%)$ was lower in DUE-01, but the median weekly ID was
                      higher (15.8 L·Gy/week; IQ range 13.2-19.3). The model for
                      WS2 was validated with reduced discrimination (AUC=0.52
                      $95\%$ CI 0.47-0.61), The AUC for WS3 was 0.58.Increasing
                      the weekly ID and the dose per fraction lead to the
                      worsening of fatigue and functional outcomes in patients
                      with localized PCa treated with EBRT.},
      keywords     = {fatigue (Other) / functional loss (Other) / integral dose
                      (Other) / prostate cancer (Other) / radiotherapy - adverse
                      effects (Other)},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36387203},
      pmc          = {pmc:PMC9645430},
      doi          = {10.3389/fonc.2022.937934},
      url          = {https://inrepo02.dkfz.de/record/182686},
}