The radiosensitivity index predicts benefit from HDR brachytherapy in high-risk prostate cancer
Thiruthaneeswaran, Niluja Bibby, Becky A Pereira, R. More, E. Denley, H. Henry , A. Wylie, James P Hoskin, Peter J Bristow, Robert G Choudhury, Ananya
Thiruthaneeswaran, Niluja
Bibby, Becky A
Pereira, R.
More, E.
Denley, H.
Henry , A.
Wylie, James P
Hoskin, Peter J
Bristow, Robert G
Choudhury, Ananya
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Abstract
Purpose or Objective
There is a decline in the use of brachytherapy boost for
high-risk prostate cancer patients despite an accumulation of clinical data supporting improved outcomes. HDR boost
may be a convenient means of overcoming radioresistance
that needs further investigation. A clinically validated
multigene expression model of tumour radiosensitivity
(RSI) was developed by Torres-Roca and colleagues and
validated in multiple cohorts and disease types. In this
study, the RSI gene signature was validated in two prostate
cancer radiotherapy cohorts.
Material and Methods
A total of 386 D’Amico classified high-risk patients treated
from 2008-2014 were identified for this analysis: 218
patients received intensity modulated radiotherapy (IMRT)
to the prostate only (60 Gy in 20# or 74 Gy in 37# ) and 168
patients received IMRT (37.5 Gy in 15#) and a high dose
rate (HDR) brachytherapy boost (15 Gy). This equates to a
BEDα/β 1.5-3Gy of 120 – 180 Gy for IMRT only and 159 – 265 Gy
for IMRT and HDR boost. Androgen deprivation was given
to all patients with duration ranging from 3-36 months.
Biochemical failure was defined as prostate-specific
antigen (PSA) rise of ≥2 ng/ml above nadir post
radiotherapy. The clinical end-point was progression-free
survival (PFS). Gene expression data were generated from
diagnostic needle core biopsies using Affymetrix Clariom S
arrays. RSI scores were calculated using a published rankbased
linear regression algorithm. The RSI score cut-off
was the upper quartile to dichotomise patients into
radioresistant (RSI-R) and radiosensitive (RSI-S). Kaplan-
Meier statistics were used for survival outcomes.
Results
The mean follow-up for the entire cohort was 55 months
(95% CI 56 – 61 months). The upper quartile cut-off for the
RSI-R score was 0.41 (range 0.14 – 0.56). The 5-year PFS
for radioresistant (RSI-R) vs radiosensitive (RSI-S) patients
in the IMRT cohort was 54.9 % vs. 74.9% (p = 0.024). The 5-
year PFS for RSI-R vs RSI-S in the HDR boost cohort was 76.2
% vs 71.4% (p = 0.71).
Conclusion Our study validates for the first time use of the RSI in
prostate cancer patients undergoing definitive (without
surgery) radiotherapy. The RSI signature should be
explored further to select patients with high-risk prostate
cancer who should benefit from dose escalation with a HDR
brachytherapy boost.
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Thiruthaneeswaran N, Bibby BAS, Pereira R, More E, Denley H, Henry A, et al. OC-1031: The radiosensitivity index predicts benefit from HDR brachytherapy in high-risk prostate cancer. Radiotherapy and Oncology . 2020 Nov;152:S1086–7.