Prostate cancer treated with brachytherapy; an exploratory study of dose-dependent biomarkers and quality of life
Low-dose-rate permanent prostate brachytherapy (PPB) is an attractive treatment option for patients with localised prostate cancer with excellent outcomes. As standard CT-based post-implant dosimetry often correlates poorly with late treatment-related toxicity, this exploratory (proof of concept) st...
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Published in | Radiation oncology (London, England) Vol. 12; no. 1; p. 53 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
BioMed Central
14.03.2017
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Subjects | |
Online Access | Get full text |
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Summary: | Low-dose-rate permanent prostate brachytherapy (PPB) is an attractive treatment option for patients with localised prostate cancer with excellent outcomes. As standard CT-based post-implant dosimetry often correlates poorly with late treatment-related toxicity, this exploratory (proof of concept) study was conducted to investigate correlations between radiation - induced DNA damage biomarker levels, and acute and late bowel, urinary, and sexual toxicity.
Twelve patients treated with
I PPB monotherapy (145Gy) for prostate cancer were included in this prospective study. Post-implant CT based dosimetry assessed the minimum dose encompassing 90% (D
) of the whole prostate volume (global), sub-regions of the prostate (12 sectors) and the near maximum doses (D
, D
) for the rectum and bladder. Six blood samples were collected from each patient; pre-treatment, 1 h (h), 4 h, 24 h post-implant, at 4 weeks (w) and at 3 months (m). DNA double strand breaks were investigated by staining the blood samples with immunofluorescence antibodies to γH2AX and 53BP1 proteins (γH2AX/53BP1). Patient self-scored quality of life from the Expanded Prostate Cancer Index Composite (EPIC) were obtained at baseline, 1 m, 3 m, 6 m, 9 m, 1 year (y), 2y and 3y post-treatment. Spearman's correlation coefficients were used to evaluate correlations between temporal changes in γH2AX/53BP1, dose and toxicity.
The minimum follow up was 2 years. Population mean prostate D
was 144.6 ± 12.1 Gy and rectal near maximum dose D
= 153.0 ± 30.8 Gy and D
= 62.7 ± 12.1 Gy and for the bladder D
= 123.1 ± 27.0 Gy and D
= 70.9 ± 11.9 Gy. Changes in EPIC scores from baseline showed high positive correlation between acute toxicity and late toxicity for both urinary and bowel symptoms. Increased production of γH2AX/53BP1 at 24 h relative to baseline positively correlated with late bowel symptoms. Overall, no correlations were observed between dose metrics (prostate global or sector doses) and γH2AX/53BP1 foci counts.
Our results show that a prompt increase in γH2AX/53BP1foci at 24 h post-implant relative to baseline may be a useful measure to assess elevated risk of late RT - related toxicities for PPB patients. A subsequent investigation recruiting a larger cohort of patients is warranted to verify our findings. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1748-717X 1748-717X |
DOI: | 10.1186/s13014-017-0792-1 |