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  • br Introduction br Despite technical


    1. Introduction
    Despite technical improvements to external beam radiation therapy (EBRT), 15–30% of patients with intermediate to high risk localized prostate cancer develop disease recurrence [1]. Targeting subprostatic regions of higher tumor burden for dose intensification to an imaging defined gross tumor volume (GTV) could improve tumor control probability and reduce dose to organs-at-risk [2]. PIRADS version-2 (v-2) criteria provide standardized diagnostic guidelines for GTV identification and scoring from MR images [3], primarily based on signal features in T2-weighted (T2w) images and apparent diffusion coefficient (ADC) maps derived from diffusion-
    weighted images (DWI). Compared to PIRADS v-2 criteria, radiomics applied to multi-parametric MR images can improve the automated detection, localization, and grading of prostate tumor [4–6]. Applied to radiotherapy, radiomics analysis of pretreatment multi-parametric MR images can predict for biochemical recurrence [7], and rectal wall toxicity [8], and have been used to generate focal treatment plans when combined with MRI-to-CT deformable co-registration [9]. r> Radiomics may also improve on current use of first-order ADC metrics as early radiation response biomarkers which may then guide dose Ferrostatin-1 [10,11]. Response assessment has historically tracked changes in mean GTV ADC post-EBRT, based on a consensus position that prostate tumor ADC is inversely related to tumor cellularity
    Corresponding author at: Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, 101 College Street, 7th Floor, Toronto, Ontario M5G 1L7, Canada. E-mail address: [email protected] (W.D. Foltz).
    2405-6316/ © 2018 The Authors. Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology. This is an open access article under the CC BY-NC-ND license (
    [12–14]. Our own data identified week six as the time of peak change in prostate tumor ADC [11]. This study also noted a trend towards homogenization of ADC across the tumor and zonal regions post-EBRT, which may be reflected in textural features and variance metrics in whole prostate regions-of-interest. Potentially, whole prostate radio-mics metrics could provide a surrogate of GTV response, without need for computationally-intensive deformable registration in post-EBRT cases when the GTV is no longer apparent.
    This study is a proof-of-principle investigation of early changes in ADC radiomics features for patients undergoing radiotherapy. Methodology is presented to assess prostate gland and gross tumor volume (GTV) features in PIRADS v-2 compliant T2-weighted images and ADC maps between baseline and week six. This methodology in-cludes deformable registration between time-points of T2-weighted image sets and GTVs applied to ADC maps, to account for image con-trast homogenization post-EBRT. Features presenting significant dif-ferences post-EBRT were extracted, plus prostate and GTV features were correlated to test for inter-predictive value.
    2. Materials and methods
    Between November 2012 and August 2016, patients with localized prostate cancer were enrolled on an institutionally-approved pro-spective tumor dose-escalation trial, based on either simultaneous in-tegrated boost (SIB) or high dose rate brachytherapy boost (HDRB) at the discretion of the patient and their treating physician. All patients received 76 Gy in 38 fractions delivered to the prostate gland using volume modulated arc therapy (VMAT). SIB arm patients received an additional 19 Gy to the GTV. HDRB arm patients received 10 Gy in a single fraction to the GTV the week prior to EBRT initiation.
    Image-guided confirmatory biopsy and fiducial marker placement was performed at baseline prior to EBRT, and follow-up scanning was performed during week six of EBRT. MR images were acquired using a 3T Verio (Siemens Medical Systems, Erlangen, DE) with VQ gradients (40 mT/m peak amplitude; 200 T/m/s peak slew rate), with a four-channel phased-array surface coil placed anterior to the pelvis in combination with a two channel endorectal coil (Hologic Inc. Bedford, MA). Pulse sequence details are provided as Supplementary Material.
    2.2. Gradient non-linearity bias
    The superior/inferior (S/I) offset of the central slice through the dominant lesion from MRI system isocenter was tracked at each time-point, because ADC bias from gradient non-linearity approaches 5% at 9 cm S/I offsets from isocenter [15]. Across all patients, the absolute offset of the central slice through the dominant tumor from magnet isocenter was 35 ± 28 mm at baseline (136 mm max), and 31 ± 24 mm at week six (83 mm max). The mean and standard de-viation difference in slice offset between time-points was 33 ± 23 mm (93 mm max).