TY - JOUR
T1 - High weekly integral dose and larger fraction size increase risk of fatigue and worsening of functional outcomes following radiotherapy for localized prostate cancer
AU - Joseph, Nuradh
AU - Cicchetti, Alessandro
AU - McWilliam, Alan
AU - Webb, Adam
AU - Seibold, Petra
AU - Fiorino, Claudio
AU - Cozzarini, Cesare
AU - Veldeman, Liv
AU - Bultijnck, Renée
AU - Fonteyne, Valérie
AU - Talbot, Christopher J.
AU - Symonds, Paul R.
AU - Johnson, Kerstie
AU - Rattay, Tim
AU - Lambrecht, Maarten
AU - Haustermans, Karin
AU - De Meerleer, Gert
AU - Elliott, Rebecca M.
AU - Sperk, Elena
AU - Herskind, Carsten
AU - Veldwijk, Marlon
AU - Avuzzi, Barbara
AU - Giandini, Tommaso
AU - Valdagni, Riccardo
AU - Azria, David
AU - Jacquet, Marie Pierre Farcy
AU - Charissoux, Marie
AU - Vega, Ana
AU - Aguado-Barrera, Miguel E.
AU - Gómez-Caamaño, Antonio
AU - Franco, Pierfrancesco
AU - Garibaldi, Elisabetta
AU - Girelli, Giuseppe
AU - Iotti, Cinzia
AU - Vavassori, Vittotorio
AU - Chang-Claude, Jenny
AU - West, Catharine M.L.
AU - Rancati, Tiziana
AU - Choudhury, Ananya
AU - REQUITE Consortium, Consortium
N1 - Publisher Copyright:
Copyright © 2022 Joseph, Cicchetti, McWilliam, Webb, Seibold, Fiorino, Cozzarini, Veldeman, Bultijnck, Fonteyne, Talbot, Symonds, Johnson, Rattay, Lambrecht, Haustermans, De Meerleer, Elliott, Sperk, Herskind, Veldwijk, Avuzzi, Giandini, Valdagni, Azria, Jacquet, Charissoux, Vega, Aguado-Barrera, Gómez-Caamaño, Franco, Garibaldi, Girelli, Iotti, Vavassori, Chang-Claude, West, Rancati and Choudhury.
PY - 2022/10/26
Y1 - 2022/10/26
N2 - Introduction: 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). Methods: 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. Results: 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, Conclusion: 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.
AB - Introduction: 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). Methods: 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. Results: 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, Conclusion: 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.
KW - fatigue
KW - functional loss
KW - integral dose
KW - prostate cancer
KW - radiotherapy - adverse effects
UR - http://www.scopus.com/inward/record.url?scp=85141666278&partnerID=8YFLogxK
U2 - 10.3389/fonc.2022.937934
DO - 10.3389/fonc.2022.937934
M3 - Article
SN - 2234-943X
VL - 12
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 937934
ER -
