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Acute Skin Damage and Late Radiation-Induced Fibrosis and Inflammation in Murine Ears after High-Dose Irradiation

1
Institute for Radiation Medicine, Helmholtz Zentrum München GmbH, 85764 Neuherberg, Germany
2
Department of Radiation Oncology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, 81675 Munich, Germany
3
Institute for Applied Physics and Metrology, Universität der Bundeswehr München, 85577 Neubiberg, Germany
4
Research Unit Analytical Pathology, Helmholtz Zentrum München GmbH, 85764 Neuherberg, Germany
5
German Cancer Consortium, 69120 Heidelberg, Germany
6
Clinical Cooperation Unit Translational Radiation Oncology, Heidelberg Ion Therapy Center (HIT), Heidelberg Institute of Radiation Oncology Heidelberg University Medical School and National Center for Tumor Diseases, German Cancer Research Center, 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
These authors share equal contribution.
Cancers 2019, 11(5), 727; https://doi.org/10.3390/cancers11050727
Received: 27 April 2019 / Revised: 17 May 2019 / Accepted: 21 May 2019 / Published: 25 May 2019
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. View Full-Text
Keywords: hypofractionation; side effects; acute; late; high-dose; fractionated radiotherapy; skin hypofractionation; side effects; acute; late; high-dose; fractionated radiotherapy; skin
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Dombrowsky, A.C.; Schauer, J.; Sammer, M.; Blutke, A.; Walsh, D.W.M.; Schwarz, B.; Bartzsch, S.; Feuchtinger, A.; Reindl, J.; Combs, S.E.; Dollinger, G.; Schmid, T.E. Acute Skin Damage and Late Radiation-Induced Fibrosis and Inflammation in Murine Ears after High-Dose Irradiation. Cancers 2019, 11, 727.

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