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

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.

Frontiers in oncology. 2022 Oct 26*** epublish ***

Nuradh Joseph, Alessandro Cicchetti, Alan McWilliam, Adam Webb, Petra Seibold, Claudio Fiorino, Cesare Cozzarini, Liv Veldeman, Renée Bultijnck, 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, David Azria, Marie-Pierre Farcy Jacquet, Marie Charissoux, Ana Vega, Miguel E Aguado-Barrera, Antonio Gómez-Caamaño, Pierfrancesco Franco, Elisabetta Garibaldi, Giuseppe Girelli, Cinzia Iotti, Vittotorio Vavassori, Jenny Chang-Claude, Catharine M L West, Tiziana Rancati, Ananya Choudhury

Department of Clinical Oncology, District General Hambantota, Hambantota, Sri Lanka., Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Hambantota, Italy., Department of Medical Physics, University of Manchester, Manchester, United Kingdom., Leicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom., Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Department of Medical Physics, San Raffaele Scientific Institute - IRCCS, Milan, Italy., Department of Radiation Oncology, San Raffaele Scientific Institute - IRCCS, Milan, Italy., Department of Human Structure and Repair, Ghent University, Ghent, Belgium., Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium., Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, and The Christie NHS Foundation Trust, Manchester, United Kingdom., Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Department of Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Department of Medical Physics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Department of Radiation Oncology, University Federation of Radiation Oncology, Montpellier Cancer Institute, Univ Montpellier MUSE, Grant INCa_Inserm_DGOS_12553, Inserm U1194, Montpellier, France., University Federation of Radiation Oncology of Mediterranean Occitanie, ICG CHU Caremaux, Nîmes, France., University Federation of Radiation Oncology of Mediterranean Occitanie, ICM Montpellier, Univ Montpellier, Montpellier, France., Fundación Pública Galega de Medicina Xenómica, Grupo de Medicina Xenómica (USC), Santiago de Compostela, Spain., Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain., Department of Radiation Oncology, Ospedale Regionale U. Parini-AUSL Valle d'Aosta, Aosta, Italy., Department of Radiation Oncology, Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia IRCCS, Candiolo, Italy., Department of Radiation Oncology, Ospedale ASL9, Ivrea, Italy., Department of Radiation Oncology, Azienda USL - IRCCS di Reggio Emilia, Emilia-Romagna, Italy., Department of Radiation Oncology, Cliniche Gavazzeni-Humanitas, Bergamo, Italy.

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