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

Abstract

BackgroundLow-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.MethodsTwelve 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.ResultsThe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-017-0792-1) contains supplementary material, which is available to authorized users.

Prostate Cancer Survivors Present Long-Term, Residual Systemic Immune Alterations

“…The majority of patients received hormone therapy, none were treated by surgery and all patients were treated with LDR brachytherapy. Therapy-related side effects were mild, most probably due to the applied RT protocol and in agreement with previous reports on LDR brachytherapy-induced late toxicities in prostate cancer patients [37][38][39][40]. Patient selection criteria allowed for the regular follow-up of the patients up to 36 months after the initiation of radiotherapy in order to investigate long-term phenotypical changes in several lymphocyte subpopulations known to be important players in the anti-tumor innate and adaptive immune response.…”

A Randomized Feasibility Trial of Stereotactic Prostate Radiation Therapy With or Without Elective Nodal Irradiation in High-Risk Localized Prostate Cancer (SPORT Trial)

“…Levels in lymphocytes peak 30-60 min after irradiation with subsequent rapid decay in an exponential fashion (23). γH2AX foci in circulating lymphocytes following radiotherapy have been studied in lung cancer (24,25) and prostate cancer (26,27) and are associated with radiation dose but correlation with toxicity is less well established.…”