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

• Published in: Radiation oncology (London, England) Vol. 12; no. 1; p. 53
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central 14.03.2017
• Subjects: Acute toxicity; Aged; Antibodies; Biomarkers; Biomarkers - blood; Brachytherapy; DNA damage; Dosimetry; Follow-Up Studies; Health risks; Histones - blood; Humans; Immunofluorescence; Intestine; Lymphocytes; Male; Middle Aged; Neoplasm Grading; Prognosis; Prospective Studies; Prostate cancer; Prostatic Neoplasms - blood; Prostatic Neoplasms - pathology; Prostatic Neoplasms - radiotherapy; Quality of Life; Radiation therapy; Radiotherapy Dosage; Rectum; Survival Rate; Toxicity; Tumor Suppressor p53-Binding Protein 1 - blood; Urinary bladder; United Kingdom > UK; Permanent prostate brachytherapy; Sector analysis; EPIC; DNA damage biomarkers (γH2AX and 53BP1)
• DOI: 10.1186/s13014-017-0792-1
• ISSN: 1748-717X

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.