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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Radiation Oncology 1/2017

Prostate cancer treated with brachytherapy; an exploratory study of dose-dependent biomarkers and quality of life

Zeitschrift:
Radiation Oncology > Ausgabe 1/2017
Autoren:
Sarah O. S. Osman, Simon Horn, Darren Brady, Stephen J. McMahon, Ahamed B. Mohamed Yoosuf, Darren Mitchell, Karen Crowther, Ciara A. Lyons, Alan R. Hounsell, Kevin M. Prise, Conor K. McGarry, Suneil Jain, Joe M. O’Sullivan
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13014-017-0792-1) contains supplementary material, which is available to authorized users.

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 125I PPB monotherapy (145Gy) for prostate cancer were included in this prospective study. Post-implant CT based dosimetry assessed the minimum dose encompassing 90% (D90%) of the whole prostate volume (global), sub-regions of the prostate (12 sectors) and the near maximum doses (D0.1cc, D2cc) 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.

Results

The minimum follow up was 2 years. Population mean prostate D90% was 144.6 ± 12.1 Gy and rectal near maximum dose D0.1cc = 153.0 ± 30.8 Gy and D2cc = 62.7 ± 12.1 Gy and for the bladder D0.1cc = 123.1 ± 27.0 Gy and D2cc = 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.

Conclusions

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.
Zusatzmaterial
Additional file 1: Figure S1. Twelve-sector analysis created by dividing the prostate into three equal lengths along the cranio-caudal axis to form the base, mid-gland, and apex and then subdivide with vertical and horizontal plans generating right/left posterior sectors (reused from (21) with permission from AB Mohamed Yoosuf). (PDF 61 kb)
13014_2017_792_MOESM1_ESM.pdf
Additional file 2: Figure S2. Top; dose rate (cGy/h) as a function of time since implant for 125I monotherapy plotted using the equation, \( Dose\ rate\ (t)= m P D\left(\frac{ \ln 2}{t_{\raisebox{1ex}{$1$}\!\left/ \!\raisebox{-1ex}{$2$}\right.}}\right){.2}^{\left(\frac{t}{t_{\raisebox{1ex}{$1$}\!\left/ \!\raisebox{-1ex}{$2$}\right.}}\right)} \), where t is the elapsed time, mPD is the minimum peripheral dose (=145 Gy for 125I) and \( {t}_{\raisebox{1ex}{$1$}\!\left/ \!\raisebox{-1ex}{$2$}\right.} \) is the half-life (=59.43 days for 125I). Bottom; the time required to deliver relative fraction of the prescribed dose, \( Fractional\ dose(t)=1-{e}^{-\left(\frac{t. \ln 2}{t_{\raisebox{1ex}{$1$}\!\left/ \!\raisebox{-1ex}{$2$}\right.}}\right)} \). Reference: Dale RG. The applications of the linear-quadratic dose effect equation to fractionated and protracted therapy. Br J Radiol 1985; 58: 515–28. (PDF 178 kb)
13014_2017_792_MOESM2_ESM.pdf
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