Assessing patient characteristics and radiation-induced non-targeted effects in vivo for high dose-rate (HDR) brachytherapy

Abstract

Purpose: To test whether blood, urine, and tissue based colony-forming assays are a useful clinical detection tool for assessing fractionated treatment responses and non-targeted radiation effects in bystander cells.

Materials and methods: To assess patients’ responses to radiation treatments, blood serum, urine, and an esophagus explant-based in vivo colony-forming assay were used from oesophageal carcinoma patients. These patients underwent three fractions of high dose rate (HDR) intraluminal brachytherapy (ILBT).

Results: Human keratinocyte reporters exposed to blood sera taken after the third fraction of brachytherapy had a significant increase in cloning efficiency compared to baseline samples (p < 0.001). Such results may suggest an induced radioresistance response in bystander cells. The data also revealed a clear inverse dose-rate effect during late treatment fractions for the blood sera data only. Patient characteristics such as gender had no statistically significant effect (p > 0.05). Large variability was observed among the patients’ tissue samples, these colony-forming assays showed no significant changes throughout fractionated brachytherapy (p > 0.05).

Conclusion: Large inter-patient variability was found in the urine and tissue based assays, so these techniques were discontinued. However, the simple blood-based assay had much less variability. This technique may have future applications as a biological dosimeter to predict treatment outcome and assess non-targeted radiation effects.

Keywords::

• Bystander effect
• high dose-rate (HDR) brachytherapy
• esophageal carcinoma
• urine
• blood
• esophageal explants

Acknowledgements

We wish to thank Varian International B.V. for supporting a portion of this work. We are grateful for the Hamilton Health Sciences JCC brachytherapy staff for assisting in sample collection. We acknowledge and thank all the patients who participated in this study. A special thanks to the Molecular Medicine laboratory at McMaster University and the JCC Clinical trials laboratory for centrifuge usage. All authors have read and approved this manuscript for submission, and have also read the journal's authorship agreement.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary material available online

Supplementary Tables 1 and 2 and Figure 1 available online at http://informahealthcare.com/abs/doi/10.3109/09553002.2015.1068458.