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

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

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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 (125)I 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.

Original languageEnglish
Pages (from-to)53
JournalRadiation oncology (London, England)
Volume12
Issue number1
DOIs
Publication statusPublished - 14 Mar 2017

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Brachytherapy
Prostate
Prostatic Neoplasms
Biomarkers
Quality of Life
Urinary Bladder
Double-Stranded DNA Breaks
Therapeutics
Rectum
DNA Damage
Fluorescent Antibody Technique
Prospective Studies
Radiation
Staining and Labeling
Tumor Suppressor p53-Binding Protein 1
Antibodies
Population

Keywords

  • Journal Article

Cite this

@article{072e974be2b7424593fc74c8b30afd98,
title = "Prostate cancer treated with brachytherapy; an exploratory study of dose-dependent biomarkers and quality of life",
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 (125)I 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.",
keywords = "Journal Article",
author = "Osman, {Sarah O S} and Simon Horn and Darren Brady and McMahon, {Stephen J} and Yoosuf, {Ahamed B Mohamed} and Darren Mitchell and Karen Crowther and Lyons, {Ciara A} and Hounsell, {Alan R} and Prise, {Kevin M} and McGarry, {Conor K} and Suneil Jain and O'Sullivan, {Joe M}",
year = "2017",
month = "3",
day = "14",
doi = "10.1186/s13014-017-0792-1",
language = "English",
volume = "12",
pages = "53",
journal = "Radiation Oncology",
issn = "1748-717X",
publisher = "BioMed Central",
number = "1",

}

Prostate cancer treated with brachytherapy; an exploratory study of dose-dependent biomarkers and quality of life. / Osman, Sarah O S; Horn, Simon; Brady, Darren; McMahon, Stephen J; Yoosuf, Ahamed B Mohamed; Mitchell, Darren; Crowther, Karen; Lyons, Ciara A; Hounsell, Alan R; Prise, Kevin M; McGarry, Conor K; Jain, Suneil; O'Sullivan, Joe M.

In: Radiation oncology (London, England), Vol. 12, No. 1, 14.03.2017, p. 53.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prostate cancer treated with brachytherapy; an exploratory study of dose-dependent biomarkers and quality of life

AU - Osman, Sarah O S

AU - Horn, Simon

AU - Brady, Darren

AU - McMahon, Stephen J

AU - Yoosuf, Ahamed B Mohamed

AU - Mitchell, Darren

AU - Crowther, Karen

AU - Lyons, Ciara A

AU - Hounsell, Alan R

AU - Prise, Kevin M

AU - McGarry, Conor K

AU - Jain, Suneil

AU - O'Sullivan, Joe M

PY - 2017/3/14

Y1 - 2017/3/14

N2 - 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 (125)I 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.

AB - 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 (125)I 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.

KW - Journal Article

U2 - 10.1186/s13014-017-0792-1

DO - 10.1186/s13014-017-0792-1

M3 - Article

C2 - 28288658

VL - 12

SP - 53

JO - Radiation Oncology

JF - Radiation Oncology

SN - 1748-717X

IS - 1

ER -