Summary

...

...

Research trials that incorporate imaging present unique challenges due to nonstandard use of terminologies, absence of uniform data collection and validation. These obstacles traditionally limit the impact of imaging as an effective biomarker in oncology. The purpose of this project was to assess reliability of tools and terminology developed by the Cancer Bioinformatics Grid (caBIG) initiative when performing a multireader simultaneous assessments of glioblastoma MR imaging features.

A controlled terminology for describing the MR features of human gliomas was devised based upon prior work (VASARI / REMBRANDT project). This comprehensive featureset consists of 24 observations familiar to neuroradiologists to describe the morphology of brain tumors on routine contrast-enhanced MRI. The National Biomedical Imaging Archive (NBIA) was used to store the de-identified baseline MRI studies for 78 glioblastomas collected for The Cancer Genome Atlas (TCGA) initiative. Six neuroradiologists in three disparate geographic locations were recruited and trained in the use of the featureset using a visual guidebook. Training cases were employed to assess competency and to ensure agreement. A open-source PACS workstation (Clear Canvas) was customized for clinical imaging research evaluation and deployed at each of the three centers. Networking tools built into the workstation were used to securely download studies from NBIA (caGRID). As studies were evaluated, scores were simultaneously uplinked to a single remote AIM (Annotation and Image Markup) repository for QC checks and interim analysis. Case assignments were deliberately staged in a staggered fashion to ensure that a minimum of three evaluations were efficiently obtained. Administrative tools were employed by coordinators in a fourth location. Qualitative assessments included: (1) effectiveness of training, (2) ease of deployment & functionality of the informatics solutions and (3) efficiency of the process. Inter-observer variation for each feature was assessed with the generalized kappa statistic of Berry&Miekle.

Training, deployment of resources and completion of three evaluations per case were accomplished in 30 days. Functionality of the IT solutions was rated superior in qualitative assessment. The results indicated strong overall average inter-observer agreement among all six readers. Agreement was highest for tumor side (generalized kappa statistic k=0.943, 95% CI 0.915-0.982) and tumor location (k=0.837, 95% CI 0.807-0.902). Other features with high agreement included proportion enhancing tumor (k=0.656, 95% CI 0.596-0.757), presence of satellites (k=0.663, 95% CI 0.591-0.780), and diffusion (k=0.730, 95% CI 0.664-0.828). Of the remaining, only three features (12.5%) showed low agreement (k<0.4): presence of calvarial remodeling (k=0.366, 95% CI 0.124-0.626), cortical involvement (k=0.167, 95% CI 0.157-0.335), and definition of non-enhancing margin (k=0.374, 95% CI 0.347-0.514).

Inclusion of vetted, tested and validated controlled terminologies into imaging arms of clinical trials is essential in adding value of imaging as a biomarker in cross-cutting correlative studies. Controlled terminologies such as the one described herein for assessment of gliomas can be effectively used by domain experts following a relatively short training period. Technologies developed through the caBIG initiative provide an effective and efficient framework for federated imaging assessments that can expedite cross-correlative analysis with other data repositories (e.g. genomics / proteomics / pathology).

Updates to the TCGA-GBM imaging data set are being stored within TCIA and the research group is continuing to expand on their work. Please contact the CIP Informatics Team if your research group would like to be kept in the loop as this effort moves forward. You can reach us by emailing John Freymann or Justin Kirby at:

• freymanj (at) mail (dot) nih (dot) gov
• kirbyju (at) mail (dot) nih (dot) gov

Accepted Abstracts

RSNA 2011 (Nov 27-Dec 2, 2011, Chicago, IL)

ASNR 2011 (June 4-9, 2011, Seattle, WA)

caBIG Tools for TCGA-GBM Analysis

Imaging Source Site (ISS) Groups are being formed and governed by participants from institutions that have provided imaging data to the archive for a given cancer type. Modeled after TCGA analysis groups, ISS groups are given the opportunity to publish a marker paper for a given cancer type per the guidelines in the table above. This opportunity will generate increased participation in building these multi-institutional data sets as they become an open community resource. Current The Cancer Genome Atlas Glioblastoma Multiforme Collection (TCGA-GBM) (glioblastoma) and The Cancer Genome Atlas Low Grade Glioma Collection (TCGA-LGG) (low grade glioma) source sites include:

• Thomas Jefferson University
• Henry Ford Hospital
• University of California, San Francisco
• MD Anderson Cancer Center
• Emory University
• Mayo Clinic
• Case Western Reserve University School of Medicine

A number of other collaborators have also been invited to join the group by its members.  Please contact Adam Flanders (adam.flanders@jefferson.edu) if you have scientific questions for TCGA-GBM/LGG ISS or if you are interested in collaborating with their group.

Publications

TCGA Glioma Phenotype Research Group Publications

1. Wangaryattawanich, P., M. Hatami, et al.  "Multicenter imaging outcomes study of The Cancer Genome Atlas glioblastoma patient cohort: imaging predictors of overall and progression-free survival." Neuro-oncology, (2015): nov117 .

2. Colen RR, Wang J, Singh SK, Gutman DA, Zinn PO. Glioblastoma: Imaging Genomic Mapping Reveals Sex-specific Oncogenic Associations of Cell Death. Radiology. 2014.

3. Colen RR, Vangel M, Wang J, Gutman DA, Hwang SN, Wintermark M, Rajan J, Jilwan-Nicola M, Chen JY, Raghavan P, Holder CA, Rubin D, Huang E, Kirby J, Freymann J, Jaffee CC, Flanders A, Zinn PO. Imaging genomic mapping of an invasive MRI phenotype predicts patient outcome and metabolic dysfunction: a TCGA glioma phenotype research group project.BMC Medical Genomics, 2014. 7(1):30. doi:10.1186/1755-8794-7-30 (link)
4. Gevaert O, Mitchell LA, Achrol AS, Xu J, Echegaray S, Steinberg GK, Chesier SH, Napel S, Zaharchuk G, Plevritis SK. Glioblastoma Multiforme: Exploratory Radiogenomic Analysis by Using Quantitative Image Features. Radiology, 2014. doi: 10.1148/radiol.14131731 (link)
5. Jain R, Poisson L, Gutman D, Scarpace L, Hwang SN, Holder C, Wintermark M, Colen RR, Kirby J, Freymann J, Jaffe C, Mikkelsen T, Flanders A. Outcome Prediction in Patients with Glioblastoma by Using Imaging, Clinical, and Genomic Biomarkers: Focus on the Nonenhancing Component of the Tumor. Radiology. 2014 Aug;272(2):484-93. doi: 10.1148/radiol.14131691. Epub 2014 Mar 19. 2014 (link)
6. Nicolasjilwan M, Hu Y, Yan C, Meerzaman D, Holder CA, Gutman D, et al. Addition of MR imaging features and genetic biomarkers strengthens glioblastoma survival prediction in TCGA patients. Journal of Neuroradiology, July 2014. doi: 10.1016/j.neurad.2014.02.006
7. Wassal E, Zinn P, Colen R. DIFFUSION AND CONVENTIONAL MR IMAGING GENOMIC BIOMARKER SIGNATURE FOR EGFR MUTATION IDENTIFICATION IN GLIOBLASTOMA. Neuro-Oncology. 2014;16(suppl 5):v156-v7.

8. Wassal E, Zinn P, Colen R. DIFFUSION AND CONVENTIONAL MR IMAGING GENOMIC BIOMARKER SIGNATURE PREDICTS IDH-1 MUTATION IN GLIOBLASTOMA PATIENTS. Neuro-Oncology. 2014;16(suppl 5):v157-v.

9. Amer A, Zinn P, Colen R. IMMEDIATE POST OPERATIVE VOLUME OF ABNORMAL FLAIR SIGNAL PREDICTS PATIENT SURVIVAL IN GLIOBLASTOMA PATIENTS. Neuro-Oncology. 2014;16(suppl 5):v138-v.

10. Amer A, Zinn P, Colen R. IMMEDIATE POST-RESECTION PERICAVITARIAN DWI HYPERINTENSITY IN GLIOBLASTOMA PATIENTS IS PREDICTIVE OF PATIENT OUTCOME. Neuro-Oncology. 2014;16(suppl 5):v138-v9.
11. Gutman DA, Cooper LAD, Hwang SN, Holder CA, Gao J, Aurora TD, Dunn WD, Scarpace L, Mikkelsen T, Jain R, Wintermark M, Jilwan M, Raghavan P, Huang E, Clifford RJ, Monqkolwat P, Kleper V, Freymann J, Kirby J, Zinn PO, Moreno CS, Jaffe C, Colen R, Rubin DL, Saltz J, Flanders A, Brat DJ. MR Imaging Predictors of Molecular Profile and Survival: Multi-institutional Study of the TCGA Glioblastoma Data Set. Radiology. 2013 May:267(2):560-569,doi:10.1148/radiol.13120118 (link)
12. Jain R, Poisson L, Narang J, Gutman D, Scarpace L, Hwang SN, Holder C, Wintermark M, Colen RR, Kirby J, Freymann J, Brat DJ, Jaffe C, Mikkelsen T. Genomic Mapping and Survival Prediction in Glioblastoma: Molecular Subclassification Strengthened by Hemodynamic Imaging Biomarkers. Radiology, 2013 Apr:267(1):212 –220, doi:10.1148/radiol.12120846 (link)
13. Zinn PO, Colen RR. Imaging Genomic Mapping in Glioblastoma. Neurosurgery 60:126-130. Aug 2013 (link)
14. Jain R, Poisson L, Narang J, Scarpace L, Rosenblum ML, Rempel S, Mikkelson T. Correlation of Perfusion Parameters with Genes Related to Angiogenesis Regulation in Glioblastoma: A Feasibility Study. American Journal of Neuroradiology, 2012. 33(7):1343-1348 [Epub ahead of print] (link)
15. Zinn PO, Sathyan P, Mahajan B, Bruyere J, Hegi M, et al. (2012) A Novel Volume-Age-KPS (VAK) Glioblastoma Classification Identifies a Prognostic Cognate microRNA-Gene Signature. PLoS ONE, 2012 7(8): e41522. doi:10.1371/journal.pone.0041522 (link)
16. Zinn PO, Majadan B, Sathyan P, Singh SK, Majumder S, et al. 2011Radiogenomic Mapping of Edema/Cellular Invasion MRI-Phenotypes in Glioblastoma Multiforme. PLoS ONE, 2011 6(10): e25451. doi:10.1371/journal.pone.0025451 (link)

17. Zinn, P. O., M. Hatami, et al. (2015). "138 Diffusion MRI ADC Mapping of Glioblastoma Edema/Tumor Invasion and Associated Gene Signatures." Neurosurgery 62: 210.

Publications written by other members of the research community can be found on our TCIA Publications page.  Please contact us at help@cancerimagingarchive.net if you have a publication you would like us to add.

TCGA Genomics Publications

Read the 2008 Nature paper and 2013 Cell paper to learn more about the GBM genomic study.  Read the New England Journal of Medicine LGG paper to learn more about the LGG genomic study.  Additional TCGA publications can be found at: http://cancergenome.nih.gov/publications.

Publication Policies

Per TCGA and TCIA Guidelines, formal permission requests are no longer required to submit publications using TCGA-GBM or TCGA-LGG data.  Please see the following links for more information about the freedom-to-publish criteria for these data sets:

Please contact us at help@cancerimagingarchive.net if you have any questions about these policiesInformatics software for use with this data has also been developed as part of the caBIG TCGA Enterprise Use-Case project. This caBIG enterprise use-case enabled TCGA images stored in NBIA (the same software powering the Cancer Imaging Archive) to be displayed on three different free and/or open source DICOM viewer workstations that possess annotation and markup capabilities based on Annotation Imaging Markup (AIM).  These workstations were customized to allow retrieval of images from NBIA over the caGrid (from the NCI CBIIT deployed NBIA server only), markup by AIM standards, and storage back to an AIM-E Grid data service. Some of these tools have been leveraged as part of the CIP TCGA Radiology Initiative where possible.