% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @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}, }