Genetic Signatures May Lead To Precision Treatments For Childhood Brain Tumors

Roger Packer MD Senior Vice President Center for Neuroscience & Behavioral Health Children's National Medical Center Washington, D.C. Interview with:
Roger Packer MD
Senior Vice President
Center for Neuroscience & Behavioral Health
Children’s National Medical Center
Washington, D.C.


MedicalResearch: What is the background for this study? What are the main findings?

Dr. Packer: The background is that medulloblastoma is the most common childhood malignant brain tumor. It carries with it a variable prognosis. For some subsets of patients, with current available treatment which includes surgery, radiation and chemotherapy, we see survival rates as high as 90% (and often cures) 5 years following diagnosis and treatment. However, for some subsets of patients, survival rates are much poorer, in those with higher risk characteristics as low as 40% at 5 years. Current treatment also carries with it a significant risk for long term sequelae, including intellectual loss secondary to radiation therapy and persistent, at times devastating neurologic complications such as unsteadiness.

To try to improve our understanding and ultimately our therapy for medulloblastoma, an international working group has shared patient specimens and patient information to attempt to determine what the molecular predictors of outcome are for children with medulloblastoma and if such molecular genetic findings can be used to develop better, safer therapies. Children’s National is part of this international collective of institutions, which published this and other studies.

The main findings of this study are that complex, integrated genetic analysis of tumor specimens can be used to better understand and set the scene for better treatment of medulloblastoma.  Medulloblastoma can be broken into relatively distinct, molecular subtypes each with its own prognosis and potential therapy. A major finding of this study was that within a given tumor, different areas showed the same molecular genetic pattern. The importance of this is that since the tumors are relatively the same in different areas, molecularly-targeted therapies have an excellent chance of working on the entire tumor, resulting in better tumor control and safer treatments.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Packer: There are a couple of important takeaways.

  • There first is that institutions are now banding together, like ours, to try to share resources and make discoveries that have critical impact on patient outcomes and make those discovers in the shortest time possible.
  • Second that for medulloblastoma and for that matter for other childhood brain tumors, the era of personalized or precise therapies already is upon us and the next few years will be critical in developing these new therapies and getting them to patients in a safe, but expeditious manner.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Packer: I think the directions for future research are to define, as soon as possible what the key molecular targets (or what people call the driver mutations) are for these tumors. The tools are already in place to make these kinds of judgments, as our international groups strive to work together to make these discoveries fasters. Based on these discoveries, working with industry and other partners, the critical next step is to identify agents which can reverse the molecular genetic aberrations (and some have already been identified and are in early clinical testing). These novel therapies have to be carefully but expeditiously used in children with this life-threatening disease. This will require well-designed clinic trials, however, because of the changing landscape of our understanding of this disease these trials must be relatively short in duration and will give us answers quickly.


Integrated genomics elucidates relative spatial homogeneity of embryonal brain tumors

Marc Remke1,2*, Florence Cavalli1 , A Sorana Morrissy1 , Vijay Ramaswamy1 , David Jones3 , Roger Packer4 , Eric Bouffet1 , Gary Bader5 , Arndt Borkhardt2 , Stefan Pfister3 , Nada Jabado6 , Marco Marra7 , Michael D Taylor1 From 51st Workshop for Pediatric Research Göttingen, Germany. 16-17 April 2015

Remke et al. Molecular and Cellular Pediatrics 2015, 2(Suppl 1):A10 Interview with:, & Roger Packer MD (2015). Genetic Signatures May Lead To Precision Treatments For Childhood Brain Tumors