Abstract
Background: 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.
Methods: Twelve patients treated with I-125 PPB monotherapy (145Gy) for prostate cancer were included in this prospective study. Post-implant CT based dosimetry assessed the minimum dose encompassing 90% (D-90%) of the whole prostate volume (global), sub-regions of the prostate (12 sectors) and the near maximum doses (D-0.1cc, D-2cc) 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.H2AX and 53BP1 proteins (gamma H2AX/53BP1). Patient selfscored 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 gamma H2AX/53BP1, dose and toxicity.
Results: The minimum follow up was 2 years. Population mean prostate D-90% was 144.6 +/- 12.1 Gy and rectal near maximum dose D-0.1cc = 153.0 +/- 30.8 Gy and D-2cc = 62.7 +/- 12.1 Gy and for the bladder D-0.1cc = 123.1 +/- 27.0 Gy and D-2cc = 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.H2AX/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 gamma H2AX/53BP1 foci counts.
Conclusions: Our results show that a prompt increase in gamma H2AX/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.