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

TITLE=High 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=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.937934

DOI=10.3389/fonc.2022.937934

ISSN=2234-943X

ABSTRACT=Introduction

We hypothesized that increasing pelvic integral dose and 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. Integral dose (ID) was calculated as the product of mean body dose and body volume. Weekly ID accounted for differences in fractionation. Worsening (end of radiotherapy versus baseline) of EORTC QLQ-C30 scores in physical/role/social functioning and fatigue symptom scales were evaluated and two outcome measures defined as worsening in ≥2 (WS2) or ≥3 (WS3) scales, respectively. Weekly ID and clinical risk factors were tested in a 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 range 10.2-19.3). Weekly ID, diabetes, use of intensity modulated radiotherapy and dose per fraction were significantly associated with WS2 (AUC=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%) were lower in DUE-01, but the median weekly ID was higher (15.8 L∙Gy/week; interquartile range 13.2-19.3). The model for WS2 validated with reduced discrimination (AUC=0.52 95% CI 0.47-0.61), AUC for WS3 was 0.58,

Conclusion

Increasing weekly ID and dose per fraction lead to worsening of fatigue and functional outcomes in patients with localized PCa treated with EBRT.