A higher whole pelvic integral dose is associated with worsening fatigue and functional outcome in prostate cancer patients treated with intensity modulated radiotherapy


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Nuradh Joseph1,Tiziana Rancati2,Alessandro Cicchetti2,Riccardo Valdagni2,Jenny Chang-Claude3,Susan Davidson4,Kerstie Johnson5,Chris Talbot6,Adam Webb6,Alan McWilliam4,Catharine West7,Ananya Choudhury4
1Ministry of Health, Sri Lanka,2Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.,3German Cancer Research Center (DKFZ), Heidelberg, Germany.,4The Christie NHS Foundation Trust,5Universtiy of Leicester, United Kingdom,6University of Leicester, United Kingdom,7Institute of Cancer Sciences, University of Manchester, UK.

Abstract

Background

Although intensity modulated radiotherapy (IMRT) permits the delivery of a highly conformal dose to target volumes while sparing dose to identified organs at risk, it results in a higher body integral dose due to irradiation of a larger volume of tissue at lower doses. We hypothesized that a higher integral pelvic dose is associated with worsening fatigue and an adverse functional outcome in patients with localized prostate cancer treated with intensity modulated external beam radiotherapy.

Method

142 patients with localized adenocarcinoma of prostate treated with intensity modulated external beam radiotherapy were included in this analysis. The whole pelvic integral dose was calculated as the product of mean body dose and body volume. To account for differences in fractionation weekly integral dose was used in the analysis. The fatigue, physical functioning and role functioning domains of the EORTC QLQ-C30 questionnaire prior to radiotherapy and upon completion of radiotherapy were assessed. The outcome measure was defined as worsening in any of these three domains. The association with whole pelvic integral dose was analysed as a continuous variable as well as a binary variable dichotomized at median.

Results

The median weekly integral dose was 22.2 litre-Gy (range 8.9 – 48.9). In the whole population 68/142 (48%) had worsening of fatigue, physical or role functioning. A higher whole pelvic integral dose was significantly associated with worsening fatigue when analysed in both the binary variable (p=0.000005) and continuous variable (p=0.000001, Area Under Curve = 0.7322) models.

Conclusion

To our knowledge this is the first study to demonstrate a robust association between whole pelvic integral dose and worsening fatigue and functional outcome. These results need validation in a larger cohort and the relationship between integral dose and acute toxicity merits further investigation.