Guideline for the use of Radiomics in NRG Oncology Clinical Trial Involving Brain Tumors

Guidelines for the Use of Radiomics in NRG Oncology Clinical

Trials Involving Brain Tumors

Authors:
Yunfeng Cui, Duke University; Mimi Huang, Duke University; Mihaela Rosu-Bulular, Virginia
Commonwealth University; John Kang, University of Rochester; Michael Boss, American
College of Radiology; Ke Nie, Rutgers University; Christina Tsien, Washington University in St.
Louis; James Monroe, Mercy Hospital South; Jason Sohn, Allegheny Health Network; Olivier
Morin, University of California, San Francisco; Andrew Sloan, Case Western Reserve
University; Kevin Teo, University of Pennsylvania; Zuofeng Li, University of Florida; Carrie
Glide-Hurst, Henry Ford Health System; Yuxiang Zhou, Mayo Clinic; Ying Xiao, University of
Pennsylvania; Fang-Fang Yin, Duke University

Reviewers:
Tony J. C. Wang, Columbia University
Charles Simone, New York Proton Center

Maintained By: NRG Oncology Medical Physics Subcommittee

Last Updated: 03-02-2020

Original: 12-02-2019

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 Guideline for the use of Radiomics in NRG Oncology Clinical Trial Involving Brain Tumors

I. Introduction
Radiomics is an emerging science of mining medical imaging data sets for new information
in non-traditional ways that can be used for clinical decision making. Radiomics features are
extracted from medical images and then are typically modeled using some machine learning
techniques to draw clinical decisions. The applications of radiomics in the treatment of brain
tumors include but are not limited to correlating radiomics with genomic findings, grading brain
tumors, discriminating tissue and tumor types, determining tumor margins, predicting treatment
outcomes and prognoses, etc. A number of uncertainties, including image acquisition, image
quality, image processing, segmentation, feature extraction, mathematical modeling, and
validation may confound the clinical efficacy of applying radiomics. Thus, it is critical that these
uncertainties are taken into account for contributing factors that may affect the outcomes when
applying radiomics for brain cancer clinical trials. The reproducibility of any radiomics study
must be maintained, and that relies on a clear chain of evidence any researcher can follow and
replicate – from detailed notes of imaging sources and techniques to the analysis steps employed.

This document provides recommendations for brain clinical trial development in the
following two aspects: 1) protocol development and 2) credentialing of participating institutions.
Radiomics can be applied in clinical trials at different levels based on its impact to the clinical
trials. Level 1, the result of radiomics analysis is directly used to determine the treatment method
in the clinical trial; Level 2, the result of radiomics analysis from the current clinical trial will
influence future treatment decision or future clinical trial design; Level 3, the secondary analysis
of radiomics is performed to explore the potential application of new biomarkers. The
recommendations listed in the following two sections are considering the application of
radiomics with the highest impact (Level 1) on the brain clinical trial. The physics principal
investigator (PI) should work with the protocol development team (including radiation oncology
PI, radiology PI, surgical PI, etc.) to carefully review the level of involvement using radiomics
and adopt the entire or a portion of the recommendations in this document based on the specific
use of radiomics in the proposed trial, available resources, and practical considerations, etc.

II. Protocol development

When radiomics is applied in NRG Oncology clinical trials involving brain tumors, the
following information should be included in the protocol in order to ensure the quality of the
trial:

 Justification of applying radiomics to the clinical trial with supporting evidence.

 Trial design, raw data and patient population selection related to radiomics analyses.
 Define the workflow to include

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 Guideline for the use of Radiomics in NRG Oncology Clinical Trial Involving Brain Tumors

 Imaging protocol specifications (to make sure all images follow same technical
standard) - imaging modality (CT; MRI T1, T2, Flair, DCE-MRI, diffusion weighted
MRI; PET), contrast agents, acquisition protocols (scan parameters, vendors, models).
 Specifications of input images and types of ROIs if applicable for radiomics
calculations
 Clarification of image pre-processing and post processing for input images such as
normalization, enhancement, standardization, etc. Specific descriptions are important
here since software processing can vary widely between vendors.
 Particular radiomics feature calculation formulas: either listing the calculation
formula explicitly or specifying what software and function is to be used for
calculations (version, vendors, etc.).
 Specifications of machine learning or mathematical modeling algorithms to be used
(criteria, model, etc.).
 Discussion about the reproducibility and robustness of radiomics features should be
addressed.
 Methods for cross validation and external validation approaches should be presented.

III. Credentialing
In order to secure the appropriate materials are available and a thorough evaluation is
performed, both a pre-trial credentialing process and an on-going quality assurance process will
be carried out by NRG Oncology staff for institutions participating in clinical trials involving
radiomics:
 Imaging devices credentialing including quality assurance (QA) procedures for
quantitative imaging analysis. (Needs to be coordinated with Imaging CoreLab of IROC
QA center). It may include credentialing of imaging devices, imaging protocols, quality
assurance programs, etc.
 Phantom calculation and workflow: Development/identification of digital or physical
phantoms for institutional benchmark testing. Digital or physical phantom credentialing
is needed to assure standardization of imaging method, segmentation/contouring method,
radiomics feature extraction, feature selection, modeling methodology, etc. The protocol
development team should determine appropriate phantom credentialing method based on
the specific use of radiomics in the trial.
 Standard operating procedure (SOP) for applications of radiomics software.
 Benchmarks from multi-institutions.
 SOP and methodologies for archiving and transfer of raw and/or processed images.
 On-going quality assurance of submitted data will also be arranged. For each step in the
workflow, a detailed quality control procedure is required.