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Monthly CBTTC Advisory Council Report-Out
July 2020

To our CBTTC partners,

We hope this finds you all safe and healthy. Thank you for your time and dedication towards developing the revised structure of the council. We are thrilled with the outcome and look forward to the improved partnership we hope this will bring. 

As a reminder we encourage you to share the newsletter subscription link with your personal networks so we can continue to inform the community of the work being done by investigators and patient advocates on behalf of children with brain tumors.

Please find the report for June below. 

 

-CBTTC Executive Committee
CBTTC Research Core Updates:

CBTTC Site Status:

Goal: is to increase membership to create the largest pediatric brain tumor resource, with representation across all histologies.

CBTTC now has 21 member sites with the US, Australia, Italy, and China represented globally! As previously reported, CBTTC/PNOC Leadership sent invitations to PNOC sites that aren’t CBTTC sites already. This will facilitate and accelerate the transfer of data and specimens through our Master agreements, decreasing timelines and increasing efficiency. We will provide additional updates as soon as final applications are received. 

If you identify a hospital that would like to join CBTTC, please contact us. We can reach out, provide a background of the consortium and then steps to apply. Please note additional primary sites receive annual funding so we are precluded from bringing on new primary sites currently, unless the site fund’s their participation they are sponsored.


Total Number of Sites (internationally): 21 
listing of all sites can be found at: https://cbttc.org/about-cbttc/member-institutions/
New Site Applications in Progress (not yet submitted): 2
New Site Applications: 2

  • Sydney Children’s
  • University Children's Zürich

New Sites Recently Approved and Onboarding: 3

  • NYU/Langone Children’s Hospital - Core Member
  • Arnold Palmer Children’s Hospital - Data Satellite
  • University of Michigan/CS Mott Children’s Hospital - Data Satellite

If you have interest in assisting one of our already existing sites or those now on-boarding, please let us know! Many sites have informed us of what they expect to be upcoming shortfalls for research funding due to COVID-19. We thank all that have donated to CBTTC COVID relief needs to ensure all of the CBTTC sites continue to move forward full steam this year.

CBTTC Enrollment:
Goal: is to increase membership to create the largest pediatric brain tumor resource, with representation across all histologies.

CBTTC consents children and biological parents for participation. For patients, medical information about their brain tumor is collected, as well as biospecimens. For biological parents, only a biospecimen is collected; normally saliva. This is a sample collection that can be done at home and mailed in. Having the family participate is extremely important for research efforts.

 

  • Total Enrolled: 4,648
    • Children: 3,546 
    • Mothers: 620
    • Fathers: 482 
CBTTC Research Resources:

The CBTTC collects, manages, and distributes longitudinal clinical data, biospecimens, pre-clinical models, genomic, proteomic, and other data generated from the collected biospecimens. These resources are available for any investigator to request. 

The following is a breakdown of some of the major histological groups (however, more is available). As you all talk with researchers, please let them know these resources are available for their research. All of these have longitudinal clinical data, and as funds become available we generate genomic data, proteomic data, and pre-clinical models. If you have an interest in supporting data generation or pre-clinical model development and drug testing for a specific histology, please let us know. Generation of data and pre-clinical models are critical as they are non-consumptive (unlike biospecimens) and can be used by anyone as many times as needed.

You can query the available data here https://portal.kidsfirstdrc.org/dashboard.

Numbers remain stable during COVID-19 lab shut downs.


Histology    |   Number of Subjects Enrolled with this Diagnosis
  • ATRT - 97
  • DMG - 133
  • Medulloblastoma - 431
  • Low Grade Glioma - 976
  • High Grade Glioma - 372
  • Ependymoma - 313
  • Craniopharyngioma - 128
  • Dysembryoplastic Neuroeithelial Tumor (DNET) - 71
  • Ganglioglioma - 171

Financial Updates:
As expected philanthropic donations are still down due in part to the current pandemic. We want to thank the many of you that responded to this critical situation and provided funds to keep CBTTC moving forward. As we continue to work with the PIs, their institutions, and donors, we will keep you updated on the emergent needs. Jena Lilly (lillyj@email.chop.edu) will continue to act as the point of contact for questions, recommendations and updates. 


Current CBTTC Grant Submissions & Awards

NIH Funding Awarded

NCI Childhood Cancer Data Initiative: The Childhood Cancer Data Initiative (CCDI) focuses on the critical need to collect, analyze, and share data to address the burden of cancer in children, adolescents, and young adults (AYAs). The initiative supports maximizing the use and benefit of data from childhood and AYA cancer research for patients and survivors and aims to make it easier for researchers to learn from each of the approximately 16,000 children and adolescents diagnosed with cancer in the United States each year. CBTTC data will be supported as part of CCDI and additionally we received personnel support.

Office of Data Science ODSS:  The Office of Data Science Strategy (ODSS) leads implementation of the NIH Strategic Plan for Data Science through scientific, technical, and operational collaboration with the institutes, centers, and offices that comprise NIH. The office was formed in 2018 within the Division of Program Coordination, Planning, and Strategic Initiatives, which plans and coordinates trans-NIH initiatives and research supported by the NIH Common Fund.Funding from ODSS was awarded due to the success of Kids First DRC to build out and integrate the Kids First platform with the other NIH cloud portals. This will connect and make available the CBTTC across the NIH.

Common Fund Data Ecosystem CFDETo address this challenge, the Common Fund is supporting the Common Fund Data Ecosystem (CFDE), an ongoing investment in data management infrastructure that will support past, current, and future Common Fund data sets. The goals of the CFDE are: Enhance the ability to ask scientific questions across data sets. Funding from this grant will allow CBTTC data by additional investigators and with new features allow us to do more research with the data.
 

NIH Grant Submissions

Pediatric Brain Tumor SPORE: Mike Prados and Adam Resnick presented to the NCI SPORE program on May 27 and received approval to move forward with the submission in September 2020 as all requirements were met.
  • This would provide funding for four preclinical research projects, CBTTC operations, and PNOC operations if awarded in late 2021 or early 2022. 
  • The grant does not provide funding for the clinical trials that will result from these efforts. If you are interested in support a clinical trial for the SPORE grant please let us know.
  • 123 letters of support (LOS) received to date.
Four translational research projects were selected to participate:
Mechanism, Function, and Expression of ERVs Across H3K27me3 Depleted Brain Tumors
  • Co-lead: Stephen C. Mack, PhD; Texas Children’s Hospital
  • Co-lead: Donald W. Parsons, MD, PhD; Texas Children’s Hospital
A multipronged approach for targeting tumor cell energy metabolism and activation of the integrative stress response pathway
  • Co-lead: Sabine Muller MD, PhD; UCSF Benioff Children’s Hospital, University Children’s Hospital of Zurich
  • Co-lead: Javad Nazarian, PhD; University Children’s Hospital of Zurich
  • Co-lead: Eric Raabe, MD, PhD; Johns Hopkins School of Medicine.
Proteogenomically determined neoantigen-specific T cell therapy for infant embryonal tumors
  • Co-lead: Brian R. Rood, MD; Children's National Health System
  • Co-lead: Eugene I. Hwang, MD; Children's National Health System
  • Co-lead: Catherine M. Bollard, MBChB, MD; Children's National Health System
Optimization of CAR T cell therapy for DIPG
  • Project lead: Nick Vitanza, MD; Seattle Children’s Hospital
  • Co-lead: Jessica Foster, MD; Children’s Hospital of Philadelphia
  • Genomic lead: Mike Berens, PhD; Translational Genomics Research Institute 
  • CSF lead: Jeffrey Iliff, PhD; UW Medicine
  • Clinical oversight: Julie Park, MD; Seattle Children’s Hospital
  • Scientific oversight: Rimas Orentas, PhD; Seattle Children’s Hospital
CBTTC Research
 

Key Highlights: CBTTC has collaborated on 160 research projects with over 100 investigators across 9 countries. 55 are CBTTC investigators and 66 are non-CBTTC investigators. This includes three collaborations with the PNOC disease working groups for the pre-clinical work required for the development of a new clinical trial.



Biospecimen Requests:
In an attempt to increase the utilization of biospecimens, CBTTC has recruited additional scientific experts to review proposals and formed two committees. You can find information on these projects here https://cbttc.org/research/scientific-projects-biospecimen/

All-time total number of requests: 74

  • 60 total requests approved
    • 44 sample requests approved
    • 17 cell line requests approved
  • 4 requests changed to data access requests (data was already generated)
  • 3 requests were withdrawn from consideration by the investigator
  • 1 request is now under review by the Scientific Committee for approval
  • 4 requests are in primary review
  • 1 request is with the investigator for revisions


Data Requests for raw genomic data:Our goal is to increase the number of requests and utilization of data. Our goal was to double request from last year 14, to 28 and as of April we have exceeded this goal with 49. Additionally, “processed data” is available anytime without request has been utilized thousands of times. You can find more information on the data projects here https://cbttc.org/scientific-projects-data/

  • 103 total requests approved


Map of current CBTTC Data Users


OPEN PBTA landscape analysis phase one is complete and the goal is to finalize a paper in 2020. All data are available and a request was sent out for anyone to contribute to the manuscript and analysis.

Research Opportunities:
We are looking for opportunities to empower and accelerate brain tumor research. Please let us know if there any other researchers you’ve connected with that you would like us to reach out to?



Research Publications:

CBTTC has several key publications occurring now, with new submission to 8 different scientific journals.

Accepted: 10

  1. Bobyn, A., Zarrei, M., Zhu, Y., Hoffman, M., Brenner, D., Resnick, A. C., Scherer, S. W., & Gallo, M. (2020). Ancestry and frequency of genetic variants in the general population are confounders in the characterization of germline variants linked to cancer. BMC medical genetics, 21(1), 92.

  2. Connors, M., W. Paden, P. B. Storm, A. J. Waanders, and S. S. Lang. 2019. 'Low-grade astrocytoma in the setting of a developmental venous anomaly', Childs Nerv Syst.
     
  3. Dang, Mai T, Michael Gonzalez, Krutika S Gaonkar, Komal S Rathi, Patricia Young, Sherjeel Arif, Li Zhai, Md Zahidul Alam, Samir Devalaraja, and Tsun Ki To. 2020. 'Single-cell transcriptomic profile reveals macrophage heterogeneity in medulloblastoma and their treatment-dependent recruitment', BioRxiv.
     
  4. Gaonkar, Krutika S., Komal S. Rathi, Payal Jain, Yuankun Zhu, Miguel A. Brown, Bo Zhang, Pichai Raman, Phillip B. Storm, John M. Maris, Adam C. Resnick, Jaclyn N. Taroni, and Jo Lynne Rokita. 2019. 'annoFuse: an R Package to annotate and prioritize putative oncogenic RNA fusions', BioRxiv: 839738
     
  5. Hoffman, M., A. H. Gillmor, D. J. Kunz, M. J. Johnston, A. Nikolic, K. Narta, M. Zarrei, J. King, K. Ellestad, N. H. Dang, F. M. G. Cavalli, M. M. Kushida, F. J. Coutinho, Y. Zhu, B. Luu, Y. Ma, A. J. Mungall, R. Moore, M. A. Marra, M. D. Taylor, T. J. Pugh, P. B. Dirks, D. Strother, L. Lafay-Cousin, A. C. Resnick, S. Scherer, D. L. Senger, B. D. Simons, J. A. Chan, A. S. Morrissy, and M. Gallo. 2019. 'Intratumoral Genetic and Functional Heterogeneity in Pediatric Glioblastoma', Cancer Res, 79: 2111-23.
     
  6. Ijaz, H., M. Koptyra, K. S. Gaonkar, J. L. Rokita, V. P. Baubet, L. Tauhid, Y. Zhu, M. Brown, G. Lopez, B. Zhang, S. J. Diskin, Z. Vaksman, J. L. Mason, E. Appert, J. Lilly, R. Lulla, T. De Raedt, A. P. Heath, A. Felmeister, P. Raman, J. Nazarian, M. R. Santi, P. B. Storm, A. Resnick, A. J. Waanders, and K. A. Cole. 2020. ‘Pediatric High Grade Glioma Resources From the Children’s Brain Tumor Tissue Consortium (CBTTC) and Pediatric Brain Tumor Atlas (PBTA)’ , Neuro Oncol, 22: 163-65.
     
  7. Ijaz, Heba, Mateusz Koptyra, Krutika S. Gaonkar, Jo Lynne Rokita, Valerie P. Baubet, Lamiya Tauhid, Yankun Zhu, Miguel Brown, Gonzalo Lopez, Bo Zhang, Sharon J. Diskin, Zalman Vaksman, Jennifer L. Mason, Elizabeth Appert, Jena Lilly, Rishi Lulla, Thomas De Raedt, Allison P. Heath, Alex Felmeister, Pichai Raman, Javad Nazarian, Maria Rita Santi, Phillip B. Storm, Adam Resnick, Angela J. Waanders, and Kristina A. Cole. 2019. 'Pediatric High Grade Glioma Resources From the Children’s Brain Tumor Tissue Consortium (CBTTC) and Pediatric Brain Tumor Atlas (PBTA)', BioRxiv: 656587.
     
  8. Rivero-Hinojosa S, Kinney N, Garner HR, Rood BR. ‘Germline microsatellite genotypes differentiate children with medulloblastoma’, Neuro-Oncology. 2020 Jan 11;22(1):152-62.
     
  9. Steidle, E. A., V. A. Morrissette, K. Fujimaki, L. Chong, A. C. Resnick, A. P. Capaldi, and R. J. Rolfes. 2020. 'The InsP7 phosphatase Siw14 regulates inositol pyrophosphate levels to control localization of the general stress response transcription factor Msn2', J Biol Chem, 295: 2043-56.
     
  10. Surrey, L. F., P. Jain, B. Zhang, J. Straka, X. Zhao, B. N. Harding, A. C. Resnick, P. B. Storm, A. M. Buccoliero, L. Genitori, M. M. Li, A. J. Waanders, and M. Santi. 2019. 'Genomic Analysis of Dysembryoplastic Neuroepithelial Tumor Spectrum Reveals a Diversity of Molecular Alterations Dysregulating the MAPK and PI3K/mTOR Pathways', J Neuropathol Exp Neurol, 78: 1100-11.
Submitted: 3
  1. Francesca Petralia, Nicole Tignor, Boris Reva, Mateusz Koptyra, Shrabanti Chowdhury, Dmitry Rykunov, Azra Krek, Weiping Ma, Jiayi Ji, Xiaoyu Song,  Pichai Raman, Yuankun Zhu, Jeffrey R. Whiteaker, Antonio Colaprico, Anna Calinawan, Selim Kalayci, Zeynep H. Gümüş, Yiran Guo, Miguel A. Brown, Richard G. Ivey, Gonzalo Lopez, Seungyeul Yoo, Lizabeth Katsnelson, Ying Wang,  Jacob J. Kennedy, Uliana J. Voytovich, Lei Zhao, Felipe da Veiga Leprevost, Hui-Yin Chang, Krutika Satish Gaonkar, Brian M. Ennis, Bo Zhang, Valerie Baubet, Lamiya Tauhib, Jena V. Lilly, Jennifer L. Mason, Bailey Farrow, Nathan Young, John Spytz, Sanjukta Thakurta, Javad Nazarian, Nithin D. Addapa, James N. Palmer,  Robert M. Lober, Samuel Rivero-Hinojosa, Liang-bo Wang, Joshua Wang, Matilda Broberg, Xi Steven Chen, Jun Zhu, Eric E. Schadt, Mehdi Mesri, Emily Boja, Tara Hiltke, Henry Rodriguez, Bing Zhang, Li Ding, Antonio Iavarone, Maciej Wiznerowicz, Allison P. Heath, Jo Lynne Rokita,  Alexey I. Nesvizhskii, David Fenyo, Steven Gygi, Amanda G. Paulovich, Adam C Resnick, Phillip B. Storm, Brian R. Rood, Pei Wang, Children’s Brain Tumor Tissue Consortium and Clinical Proteomic Tumor Analysis Consortium. Integrated Proteogenomic Characterization across Major Histological types of Pediatric Brain Cancer. (Submitted to Cell, December 2019).
     
  2. The Immunogenomic Landscape of Primary Pediatric Solid Tumours- (Submitted to Cancer Cell)
     
  3. Payal Jain, Lea F. Surrey, Joshua Straka, Pierre Russo, Richard Womer, Marilyn M. Li, Phillip B. Storm, Angela Waanders, Michael D. Hogarty, Adam Resnick, Jennifer Picarsic. ‘Novel BRAF fusions in pediatric histiocytic neoplasms define distinct therapeutic responsiveness to RAF paradox breakers’. (Submitted to Cancer Research, May 2020)

Pending Submission: 5

  1. High-grade glioma cell line models for pediatric cancer. Mateusz Koptyra, Komal S. Rathi, Valerie Baubet, Jo Lynne Rokita
     
  2. OPEN PBTA Manuscript is on track, goal pre-print Sept 2020
     
  3. CBTTC Resource Paper being reviewed submission to J Neuro-Oncology and Neurosurgery goal Sept 2020
     
  4. A Transcriptome-based Classifier to Determine Molecular Subtypes in Medulloblastoma.
     
  5. Ammar S. Naqvi, Brian Ennis, Krutika S. Gaonkar, Michael Koldobskiy, Yuankun Zhu, Miguel A. Brown, Bo Zhang, Phillip B. Storm, Adam C. Resnick, Jo Lynne Rokita (2020). “Molecular mechanisms and functional impact of aberrant splicing in diffuse intrinsic pontine gliomas”.


Research Presentations at Conferences:

2 Abstracts accepted
  1. Ammar S. Naqvi, Brian Ennis, Krutika S. Gaonkar, Michael Koldobskiy, Yuankun Zhu, Miguel A. Brown, Bo Zhang, Phillip B. Storm, Adam C. Resnick, Jo Lynne Rokita (2020). “Molecular mechanisms and functional impact of aberrant splicing in diffuse intrinsic pontine gliomas”. ABSTRACT #446. RNA 2020 on-line meeting.
     
  2. Payal Jain will be presenting to the AACR meeting (June 22-24). Her abstract is #6746: Novel BRAF gene fusions in pediatric histiocytic neoplasms respond differently to RAF targeted therapies based on dimerization profiles.

Cell line Data Generation Efforts
Currently the CBTTC has 70+ cell lines that are available for pre-clinical testing. To enhance these pre-clinical models researchers perform genomic testing WGS and RNA Seq on the cell lines in addition to the tumor samples. Currently, this genomic characterization has begun for specific brain tumor types but is funding-dependent to continue. Please reach out to Jena Lilly (lillyj@gmail.com) if you would like to sponsor.



 

CBTTC/PNOC Working Groups:
There are seven CBTTC/PNOC working groups - Medulloblastoma, DMG, ATRT, LGG, Ependymoma, Craniopharyngioma and Imaging. Each working group has their own goals and they convene once every month and collaborate on preclinical and clinical research. The groups are facilitated with CBTTC by allowing for sharing of resources, clinical data, biospecimens, preclinical models and genomic and proteomic data that can be used to develop new data-driven clinical trials. If you would like to participate or learn more please contact Kamnaa Arya (ARYAK@EMAIL.CHOP.EDU

Medulloblastoma Leads: 

  • Robert Wechsler-Reya, PhD; Sanford Burnham Prebys
  • Tabitha Cooney, MD; UCSF Benioff Children’s Hospital

Craniopharyngioma  Leads: 

  • Cassie Kline, MD; UCSF Brain Tumor Center
  • Fatema Malbari, MD; Texas Children’s Hospital

LGG leads: 

  • Angela Waanders, MD, MPH; Ann & Robert H. Lurie Children’s Hospital of Chicago
  • Daphne Adele Haas-Kogan, MD; Dana-Farber Cancer Institute
  • Pratiti Bandopadhayay, MBBS, PhD; Dana-Farber Cancer Institute
  • Joanna Phillips, MD, PhD; UCSF Helen Diller Family Comprehensive Cancer Center

ATRT leads: 

  • Ashley Margol, MD, MS; Children’s Hospital Los Angeles
  • Annie Huang, MD, PhD, FRCP(C); The Hospital for Sick Kids
  • Eric Raabe, MD, PhD; Johns Hopkins School of Medicine.

Ependymoma leads: 

  • Eugene Hwang, MD; Children’s National Health System
  • Mariella Filbin, MD, PhD; Dana-Farber Cancer Institute
  • Steven Mack, PhD; Texas Children's Hospital
  • Derek Hanson, MD; Hackensack Meridian Health

DMG leads:

  • Sabine Mueller, MD, PhD; UCSF Benioff Children’s Hospital
  • Javad Nazarian, PhD; University Children’s Hospital of Zurich]
Imaging Working Group leads:
  • Josh Rubin, MD, PhD; Washington University School of Medicine, St. Louis
  • Javier Villaneuva-Meyer, MD; University of California, San Francisco
  • S. Ali Nabavizadeh, MD; Hospital of the University of Pennsylvania 
CBTTC Communications:

Pinot for PNOC - Fundraising Event:
Saturday, July 25; 4pm - 5pm (PST)

Support clinical trial development at PNOC by joining this Virtual Wine Tasting Experience with Donum Estate and PNOC Foundation! Through the generosity of Donum Estate a portion of the PNOC wine sets sales will be donated to the Pacific Pediatric Neuro-Oncology Consortium (PNOC). Registration is complimentary but wine must be purchased to taste along. Click Here for more details.


Please consider making a donation - all donations will be matched up to $25,000! Support the much needed research and trials for underserved children diagnosed with brain cancer.


Events/Communications:

Do you need any resources, collateral materials, or participation from the CBTTC for any scheduled event or any other activity.




Brand Development Updates:


We are working to develop and design the new CBTN website which includes a space for scientific discovery projects modeled after experiment.com. The website will also feature more interactive searching and provide information about the CBTN in a simplified and easier-to-digest format. Website development is anticipated to be completed in August - opportunities for review and feedback will be circulated to members of the supporting CBTN foundations as well as members of the Executive and scientific committees. 

A new style guide is being developed to support internal and external agency design and marketing activities. This style guide is targeted for completion by Wednesday, July 15th. The guide will include branding standards for logo usage, font and typeface applications, templates for materials and other design recommendations to represent the CBTN. This will help maintain consistency across all CBTN materials and provide a colorful and bright brand standard to represent the CBTN’s overall mission and vision. 

If you have suggestions or feedback for website features to include, perhaps from other websites you’ve especially liked, please contact us at communications@cbttc.org.

 


 

Social Media Metrics - June 2020:

Facebook

  • Audience Reach: 5,737 users (6,555 impressions)
  • Users Directly Engaged: 1,552
  • Engagement Rate: 27.05% (1-3%: industry avg.)
  • Followers Gained: 29
Facebook Audience Growth Goal:
50% growth in followers through FY-20
(407 followers to 610 from July '19 to June '20)

Current Followers: 572 (40.5% increase from FY-19)

Twitter

  • Audience Reach: 11,937 users
  • Users Directly Engaged: 92
  • Engagement Rate: 0.77% (0.33% industry avg.)
  • Followers Gained: 8
Twitter Audience Growth Goal:
50% growth in followers through FY 2020
(420 followers to 630 from July '19 to June '20)

Current Followers: 593 (41.19% increase from FY-19)


CBTTC Website Traffic - June 2020:

  • 901 Unique Users (85.9% New Users)
  • 1,164 Sessions
  • 2,326 Pageviews
Past Reports
 
Did you miss one of our last CBTTC Advisory Council Reports? You can access them here!
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Copyright © 2020 Children's Hospital of Philadelphia/Center for Data-Driven Discovery in Biomedicine, All rights reserved.


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