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Open Access 01-12-2017 | Review

Biology of high single doses of IORT: RBE, 5 R’s, and other biological aspects

Authors: Carsten Herskind, Lin Ma, Qi Liu, Bo Zhang, Frank Schneider, Marlon R. Veldwijk, Frederik Wenz

Published in: Radiation Oncology | Issue 1/2017

Abstract

Intraoperative radiotherapy differs from conventional, fractionated radiotherapy in several aspects that may influence its biological effect. The radiation quality influences the relative biologic effectiveness (RBE), and the role of the five R’s of radiotherapy (reassortment, repair, reoxygenation, repopulation, radiosensitivity) is different. Furthermore, putative special biological effects and the small volume receiving a high single dose may be important. The present review focuses on RBE, repair, and repopulation, and gives an overview of the other factors that potentially contribute to the efficacy. The increased RBE should be taken into account for low-energy X-rays while evidence of RBE < 1 for high-energy electrons at higher doses is presented. Various evidence supports a hypothesis that saturation of the primary DNA double-strand break (DSB) repair mechanisms leads to increasing use of an error-prone backup repair system leading to genomic instability that may contribute to inactivate tumour cells at high single doses. Furthermore, the elimination of repopulation of residual tumour cells in the tumour bed implies that some patients are likely to have very few residual tumour cells which may be cured even by low doses to the tumour bed. The highly localised dose distribution of IORT has the potential to inactivate tumour cells while sparing normal tissue by minimising the volume exposed to high doses. Whether special effects of high single doses also contribute to the efficacy will require further experimental and clinical studies.

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After acceptance of the present manuscript, an analysis of the effect of overall treatment time has been published by the START Trial Management Group [150]. Based on the combined cohorts of all three START trials (START pilot, START A, and START B), the effect of overall treatment time on loco-regional control was estimated at 0.60 Gy/day. Although independent validation of this observation is needed, the time effect is higher than the rough estimate made here suggesting that the potential benefit of IORT in eliminating the repopulation associated with fractionated WBRT might be even larger than 28 Gy.

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Title: Biology of high single doses of IORT: RBE, 5 R’s, and other biological aspects
Authors: Carsten Herskind
Lin Ma
Qi Liu
Bo Zhang
Frank Schneider
Marlon R. Veldwijk
Frederik Wenz
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Radiation Oncology / Issue 1/2017
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/s13014-016-0750-3

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Biology of high single doses of IORT: RBE, 5 R’s, and other biological aspects

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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