1. Sarah Leary, MD MS CBTTC 5/25/2016
A CBTTC Project: Genomic Evaluation of Malignant Pediatric Cortical Tumors
Sarah Leary, MD MS
CBTTC 5/25/2016

2. Mountain climbing is a good metaphor for cancer research -Peter Phillips (paraphrasing)

3. What do cancer biology and cancer medicine have in common?
COMPUTER SCIENCE AND BIOINFORMATICS
BIOLOGY Oncogenes Tumor suppressors Gene expression Whole genome analysis Epigenetic changes
MEDICINE
Surgery
Radiation
Chemotherapy
High dose therapy
Survival
Scientific method
Aim to cure cancer
$$$$?

4. Malignant brain tumor in a child

5. Survival is poor for children diagnosed with sPNET
50% survival on toxic treatment which cures 85% of medulloblasoma
No medical progress in the past 20 years
No current international strategy

6. Molecular approach to CNS-PNET
Li Cancer Cell 2009
Picard Lancet 2012

7. Classification of glioblastoma by DNA methylation

8. Classification of CNS PNET by DNA methylation

9. Extent of resection is the best predictor of survival in children with brain tumors

10. Pilot study of sequencing panel in malignant pediatric supratentorial tumors
Original
Original

11. Pilot study of sequencing panel in malignant pediatric supratentorial tumors

12. Patient 3
MSH2

13. Pilot study of sequencing panel in malignant pediatric supratentorial tumors
Original
Original

14. Evaluation of potential therapeutics in a laboratory model of CNS PNET model
Original
Original

15. CBTTC Project: Malignant Cortical Tumors
RATIONALE
Clinical need
Children without standard of care or study options
50% survival
Potential for rapid impact
Molecular subtyping promising
Lack of connection with clinically relevant factors

16. CBTTC Project: Malignant Cortical Tumors
AIMS
Unbiased approach to molecularly characterize malignant pediatric supratentorial tumors
Evaluate relationship between molecular subgroup, treatment and survival
Craniospinal versus focal radiation
Combination chemotherapy
New agents

17. CBTTC Project: Malignant Cortical Tumors
Biology in the context of the patient
Risk Stratification
Therapy selection
International consensus and collaboration
MEDICINE
>70 children
Treatment
Survival
BIOLOGY RNA seq Methylation Sequencing
DATA SHARING – In 2 weeks 6/12/2016 at pre-ISPNO PNET group!!!

18. What can the CBTTC do for children with brain tumors?
Molecular diagnosis, Targeted therapy, Precision medicine
MEDICINE
INFORMATICS
BIOLOGY

19. Thanks and Questions? Funding: Children’s Brain Tumor Foundation
Co-Investigators:
Pathology: Bonnie Cole
Seattle site CRA: Jeff Stevens
CHOP/CBTTC: Angela Waanders, Adam Resnick
CBTTC founding sites: CHOP, Lurie Children’s, Pittsburgh