Journal
PHYSICS IN MEDICINE AND BIOLOGY
Volume 61, Issue 2, Pages 515-526Publisher
IOP Publishing Ltd
DOI: 10.1088/0031-9155/61/2/515
Keywords
out-of-field effects; dose fractionation; cell survival; DNA damage
Funding
- Breast Cancer Campaign [2009MayPR03]
- Cancer Research UK [C1513/A7047]
- EU Marie Curie Fellowship [FP7-MC IOF-623630]
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To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions.
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