The largest transcriptomic resource for radiotherapy-treated high-risk prostate cancer?
Thiruthaneeswaran, Niluja Bibby, Becky A Pereira, Ronnie R Bristow, Robert G Choudhury, Ananya
Thiruthaneeswaran, Niluja
Bibby, Becky A
Pereira, Ronnie R
Bristow, Robert G
Choudhury, Ananya
Citations
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Abstract
Purpose/Objective(s): The Cancer Genome Atlas (TCGA) is a valuable
resource for developing and validating gene signatures for personalizing
treatments. TCGA samples came from patients who received heterogeneous
treatments e dominated by surgery. Improving the biological precision
of radiotherapy is hampered by the lack of well annotated cohorts
that reflect patient populations relevant for radiation oncologists.We aimed
to generate transcriptomic data from needle core biopsies for a large
multicenter cohort of high-risk prostate cancer patients and use the data to
validate published gene signatures.
Materials/Methods: A total of 478 NCCN classified high-risk patients
treated from 2008-2016 were identified: 244 patients received intensity modulated radiotherapy (IMRT) to the prostate only (BEDa/b 1.5-3Gy of 120
e 180 Gy) and 234 patients received IMRT to the prostate and a high dose
rate (HDR) brachytherapy boost (BEDa/b 1.5-3Gy 159 e 265 Gy). Androgen
deprivation was given to all patients for 3-36 months. Biochemical failure
was defined as prostate-specific antigen (PSA) rise of 2 ng/ml above
nadir post radiotherapy. The primary clinical end-point was 7-year
biochemical-relapse free survival (bRFS). Gene expression data were
generated from diagnostic needle core biopsies using arrays. Two (28-gene
and 32 gene) published hypoxia gene signatures were tested for prognostic
significance. Additional non-prostate gene expression signatures were also
validated.
Results: The median follow-up for the entire cohort was 6.3 years. Both
the 28 gene (pZ0.021) and 32-gene (pZ0.033) hypoxia signatures were
prognostic for 7-year bRFS. Non-prostate hypoxia signatures were not
prognostic.
Conclusion: We generated the largest high-risk prostate radiotherapy
cohort with full gene expression data and showed its value in validating
published gene signatures. Our resource will be a valuable asset for future
research generating and validating signatures for personalizing radiotherapy
in men with prostate cancer.
Affiliation
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Thiruthaneeswaran N, Bibby BA, Pereira RR, Bristow RG, Choudhury A, West CML. The largest transcriptomic resource for radiotherapy-treated high-risk prostate cancer? International Journal of Radiation Oncology Biology Physics. 2020;108(3):S25-S