The need for new approaches to treating brain cancer in children is
urgent. Precision medicine - in which diagnosis and treatments are keyed to
the genetic susceptibilities of individual cancers - has advanced to the
point where it can now impact the care of a majority of children with
brain tumors, a new study by investigators at Dana-Farber/Boston
Children's Cancer and Blood Disorders Center suggests.
In the largest clinical study to date of genetic abnormalities in
pediatric brain tumors, researchers performed clinical testing on more
than 200 tumor samples and found that a majority had genetic
irregularities that could influence how the disease was diagnosed and/or
treated with approved drugs or agents being evaluated in clinical
‘Precision medicine has advanced to the point where it can now impact the care of a majority of children with brain tumors.’
The findings, reported online today by the journal Neuro-Oncology
demonstrate that testing pediatric brain tumor tissue for genetic
abnormalities is clinically feasible and that in many cases the results
can guide patients' treatment.
"Although there has been a great deal of
progress over the past 30 years in improving survival rates for children
with cancer, advances in pediatric brain cancer haven't been as
dramatic," says co-lead author Pratiti Bandopadhayay of
Dana-Farber/Boston Children's. "In a recent study, brain tumors
accounted for 25% of all pediatric deaths attributed to cancer.
In addition, many of the current therapies can result in long-term
difficulties in cognitive or physical functioning."
Since emerging from research labs more than a decade ago, targeted
therapies for cancer have significantly improved the treatment of
certain types of leukemia, digestive system tumors, and breast cancer,
among other malignancies. The new study is unique in that it reports on
the largest collection of pediatric brain tumors to be genetically
profiled as patients came to clinic.
Pathologists and cytogeneticists
performed the testing in a federally approved clinical
laboratory - certified under Clinical Laboratory Improvement Amendments
(CLIA) as the only type of labs in the United States whose findings can
guide patient treatment. Dana-Farber/Boston Children's, the researchers
noted, is one of the few centers in the country to regularly analyze the
genetics of patients' pediatric brain tumors.
The researchers plumbed the genomes of 203 pediatric brain tumor
samples, representing all major subtypes of the disease. They analyzed
117 of the samples with OncoPanel testing, a technology that sequences
the exomes - the sections of DNA that hold the blueprints for making
specific cell proteins - for irregularities in 300 cancer-related
They also studied 146 samples tested with OncoCopy, which
examines how many copies of genes are missing or overabundant within the
tumor cells. Sixty samples underwent both forms of testing ,which
allowed researchers to explore whether combining the two tests was more
powerful than each alone.
Of the samples tested by OncoPanel, 56% harbored genetic
abnormalities that were clinically relevant - that could impact a
patient's diagnosis or be targeted by drugs already in clinical use or
under study in clinical trials. (Many of these drugs cross the
blood-brain barrier, the dense web of cells that can prevent medicines
from exiting the bloodstream to reach the brain.) Among the findings:
- Alterations were found in the gene BRAF, one of the
most commonly mutated genes in pediatric brain tumors, and one for which
several targeted drugs are being tested.
- The two-pronged testing approach revealed clinically
relevant abnormalities in 89% of medulloblastomas, which account
for nearly a fifth of all brain tumors in children. Combining the two
tests was found to be particularly useful for these patients.
"The importance of genomic profiling in the diagnosis and treatment
of pediatric brain cancers is reflected in the World Health
Organization's recent decision to classify such tumors by the genetic
alterations within them, rather than by broad tumor type" says study
co-senior author Susan Chi of Dana-Farber/Boston Children's.
"Targeted therapies are likely to be most effective when they're matched
to specific abnormalities within tumor cells. Our findings show that
precision medicine for pediatric brain tumors can now be a reality."