Novel Imaging for Treatment Planning
An Automated Multiparametric MRI Quantitative Imaging Prostate Habitat Risk Scoring System for Defining External Beam Radiation Therapy Boost Volumes

https://doi.org/10.1016/j.ijrobp.2018.06.003Get rights and content

Purpose

To develop a prostate tumor habitat risk scoring (HRS) system based on multiparametric magnetic resonance imaging (mpMRI) referenced to prostatectomy Gleason score (GS) for automatic delineation of gross tumor volumes. A workflow for integration of HRS into radiation therapy boost volume dose escalation was developed in the framework of a phase 2 randomized clinical trial (BLaStM).

Methods and Materials

An automated quantitative mpMRI–based 10-point pixel-by-pixel method was optimized to prostatectomy GSs and volumes using referenced dynamic contrast–enhanced and apparent diffusion coefficient sequences. The HRS contours were migrated to the planning computed tomography scan for boost volume generation.

Results

There were 51 regions of interest in 12 patients who underwent radical prostatectomy (26 with GS ≥7 and 25 with GS 6). The resultant heat maps showed inter- and intratumoral heterogeneity. The HRS6 level was significantly associated with radical prostatectomy regions of interest (slope 1.09, r = 0.767; P < .0001). For predicting the likelihood of cancer, GS ≥7 and GS ≥8 HRS6 area under the curve was 0.718, 0.802, and 0.897, respectively. HRS was superior to the Prostate Imaging, Reporting and Diagnosis System 4/5 classification, wherein the area under the curve was 0.62, 0.64, and 0.617, respectively (difference with HR6, P < .0001). HRS maps were created for the first 37 assessable patients on the BLaStM trial. There were an average of 1.38 habitat boost volumes per patient at a total boost volume average of 3.6 cm3.

Conclusions

An automated quantitative mpMRI-based method was developed to objectively guide dose escalation to high-risk habitat volumes based on prostatectomy GS.

Introduction

Radiation dose escalation improves control of intermediate- to high-risk prostate cancer, with doses above 80 Gy improving outcomes (1). Limiting the highest radiation doses to the gross tumor volume (GTV), as opposed to whole prostate, is hypothesized to result in equivalent tumor control without increasing side effects 2, 3, 4. A major obstacle is defining the GTV in a systematic and reproducible way. Although the use of multiparametric (mp) magnetic resonance imaging (MRI) for GTV identification is gaining momentum because of its diagnostic reliability for distinguishing intraprostatic tumors with a Gleason score (GS) of 7 or greater 5, 6, there is considerable variability in how boost volumes are defined. Currently, the Prostate Imaging, Reporting and Diagnosis System (PIRADS) is the standard of care for region of interest (ROI) identification and risk classification 7, 8. However, there is subjectivity in PIRADS; the system was not designed for 3-dimensional (3D) volume assessment, a wealth of quantitative information in mpMRI is ignored, and PIRADS does not accurately and reproducibly elucidate inter- and intralesional spatial heterogeneity.

In this report, a quantitative mpMRI analysis technique that combines perfusion (dynamic contrast enhanced [DCE]) and diffusion mpMRI sequences to identify distinct pathophysiologic regions, or Habitats (9), is described. In 2 prior reports, we described (1) DCE-Score (10) and (2) apparent diffusion coefficient (ADC) thresholds and volumes to describe risk based on GS. We describe herein a pixel-by-pixel habitat risk scoring (HRS) system that combines the quantitative DCE and ADC information by referencing a prostatectomy data set. The automatically generated heat maps were used prospectively to guide radiation therapy (RT) boost volumes in a randomized phase 2 clinical trial, BLaStM, comparing 2 methods of increasing dose to the mpMRI-defined tumor habitat region(s).

Section snippets

Patients

For the development of the prostate mpMRI analysis techniques, the institutional review board approved a protocol for retrospective review of patients who have undergone prostate mpMRI. Patients who underwent radical prostatectomy (RP) during 2016 and had an mpMRI done using the 3T Discovery MR750 magnet (GE, Waukesha, WI) were identified. The institutional review board waived the need for informed consent for the prostatectomy cohort. The BLaStM clinical trial was open for accrual in February

HRS

HRS was calculated in 12 prostatectomy patients with available mpMRI preoperatively, using η1 = 0.8 and η2 = 0.2 for TZ and η1 = 0.5 and η2 = 0.5 for PZ; ε = 0.01 cm3. The ability of HRS to discriminate between cancer versus no cancer, GS ≥7 versus no cancer, and GS = 6 and GS ≥8 versus no cancer or GS = 6 or 7 was compared with PIRADS4/5 in 51 tumor nodules (26 GS ≥7 and 25 GS = 6) (Table E1; available online at https://doi.org/10.1016/j.ijrobp.2018.06.003). The HRS algorithm had a higher

Discussion

Prostate cancer radiation dose escalation improves clinical outcomes, and there is evidence that doses beyond 80 Gy result in substantive improvements 1, 21. However, when the whole prostate is dose escalated, there is an increase in the risk of grade 3 complications (22). An alternative approach is to dose escalate beyond 80 Gy only to determinate tumor areas in the prostate. Although multiple groups 2, 3, 4 have sought to direct radiation dose to such high-risk tumor regions in lieu of

Conclusions

An automated quantitative method was developed to identify habitats in the prostate determinate with the potential to be determinate of outcome. The HRS system assigns risk pixel by pixel in mpMRI sequences and was referenced to prostatectomy. The HRS6 contour was associated with GS risk and was then used to guide RT boost volumes.

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    This work was supported by National Institutes of Health (grant numbers R01CA189295 and R01CA190105).

    Conflict of interest: none

    Supplementary material for this article can be found at https://doi.org/10.1016/j.ijrobp.2018.06.003.

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