Abstract

The use of different scoring systems for radiation-induced toxicity limits comparability between studies. We examined dose-dependent tissue alterations following hypofractionated X-ray irradiation and evaluated their use as scoring criteria. Four dose fractions (0, 5, 10, 20, 30 Gy/fraction) were applied daily to ear pinnae. Acute effects (ear thickness, erythema, desquamation) were monitored for 92 days after fraction 1. Late effects (chronic inflammation, fibrosis) and the presence of transforming growth factor beta 1 (TGFβ1)-expressing cells were quantified on day 92. The maximum ear thickness displayed a significant positive correlation with fractional dose. Increased ear thickness and erythema occurred simultaneously, followed by desquamation from day 10 onwards. A significant dose-dependency was observed for the severity of erythema, but not for desquamation. After 4 × 20 and 4 × 30 Gy, inflammation was significantly increased on day 92, whereas fibrosis and the abundance of TGFβ1-expressing cells were only marginally increased after 4 × 30 Gy. Ear thickness significantly correlated with the severity of inflammation and fibrosis on day 92, but not with the number of TGFβ1-expressing cells. Fibrosis correlated significantly with inflammation and fractional dose. In conclusion, the parameter of ear thickness can be used as an objective, numerical and dose-dependent quantification criterion to characterize the severity of acute toxicity and allow for the prediction of late effects.

Highlights

  • At least half of all cancer patients receive ionizing radiation as part of their treatment [1,2,3]

  • Our study demonstrates that the severity of the acute side effects, erythema and ear thickness, are significantly dose-dependent

  • Our study showed that quantitatively determined ear swelling as an acute side effect is significantly correlated with the fibrotic area and inflammation on day 92 after radiation exposure

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Summary

Introduction

At least half of all cancer patients receive ionizing radiation as part of their treatment [1,2,3]. Despite the effective tumor control of radiation therapy, the risk of acute and late side effects remains a main problem [4]. Acute side effects develop within a few weeks of treatment [1] and usually last four to six weeks [4]. Side effects of radiation therapy typically manifest in tissues with a high proliferative activity, such as the skin or the mucosae of the gastro-intestinal tract [6]. Cells of the basal layer of the epidermis of the skin are rapidly dividing and are very prone to cell death upon radiation therapy [6,7]

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