Frontiers in Oncology (Oct 2022)

High weekly integral dose and larger fraction size increase risk of fatigue and worsening of functional outcomes following radiotherapy for localized prostate cancer

  • Nuradh Joseph,
  • Nuradh Joseph,
  • Alessandro Cicchetti,
  • Alan McWilliam,
  • Adam Webb,
  • Petra Seibold,
  • Claudio Fiorino,
  • Cesare Cozzarini,
  • Liv Veldeman,
  • Liv Veldeman,
  • Renée Bultijnck,
  • Renée Bultijnck,
  • Valérie Fonteyne,
  • Valérie Fonteyne,
  • Christopher J. Talbot,
  • Paul R. Symonds,
  • Kerstie Johnson,
  • Tim Rattay,
  • Maarten Lambrecht,
  • Karin Haustermans,
  • Gert De Meerleer,
  • Rebecca M. Elliott,
  • Elena Sperk,
  • Carsten Herskind,
  • Marlon Veldwijk,
  • Barbara Avuzzi,
  • Tommaso Giandini,
  • Riccardo Valdagni,
  • Riccardo Valdagni,
  • Riccardo Valdagni,
  • David Azria,
  • Marie-Pierre Farcy Jacquet,
  • Marie Charissoux,
  • Ana Vega,
  • Ana Vega,
  • Ana Vega,
  • Miguel E. Aguado-Barrera,
  • Miguel E. Aguado-Barrera,
  • Antonio Gómez-Caamaño,
  • Antonio Gómez-Caamaño,
  • Pierfrancesco Franco,
  • Elisabetta Garibaldi,
  • Giuseppe Girelli,
  • Cinzia Iotti,
  • Vittotorio Vavassori,
  • Jenny Chang-Claude,
  • Jenny Chang-Claude,
  • Catharine M. L. West,
  • Tiziana Rancati,
  • Ananya Choudhury

DOI
https://doi.org/10.3389/fonc.2022.937934
Journal volume & issue
Vol. 12

Abstract

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IntroductionWe 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).MethodsThe 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.ResultsIn 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,ConclusionIncreasing 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.

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