Last November, Dell
announced it was donating an initial $4 million including
cloud-computing technology to speed up development of personalized
medicine trials for children with neuroblastoma and other pediatric
cancers. According to the American Cancer Society, about 650
children under the age of 15 are diagnosed with neuroblastoma each
year. It is the second most common tumor in children and the most
common cancer in babies less than 1 year old. Although 
5-year survival
rates for children with low- and intermediate-risk neuroblastoma is
higher than 95%, only between 40% and 50% of children with
high-risk neuroblastoma survive long-term. The disease is
responsible for one in seven pediatric cancer deaths.
To increase survival
rates, researchers need the ability to analyze a patient's genomic
profile quickly and then determine highly targeted, effective
therapies for that patient's tumor type, saidGiselle Sholler, MD,
Chair of the Neuroblastoma and Medulloblastoma Translational
Research Consortium (NMTRC); Co-director of the Van Andel Research
Institute (VARI) Pediatric Cancer Translational Research Program;
and Director of the Haworth Family Pediatric Oncology Innovative
Therapeutics Clinic at the Helen DeVos Children's Hospital in Grand
Rapids, Michigan.
Pilot Study
To accomplish that goal,
last spring, Dr. Sholler launched the first genomic-based
personalized medicine pediatric cancer trial in neuroblastoma. "The
program developed over the past 5 years while we were profiling all
of our neuroblastoma patients by isolating the neruoblastoma cells
from their bone marrow and noticing that they had very different
tumor profiles," says Dr. Sholler.
Dr. Sholler worked
withCraig Webb, PhD, Co-director of VARI's Pediatric Cancer
Translational Research Program, who developed the computer
algorithms to analyze the RNA expression of the tumors of each of
the five patients in a pilot study, completed in 2010, and then
found drugs that targeted each tumor type. All of the children had
relapsed from front-line therapy and had no other therapeutic
options.
"The Institutional Review
Board wanted us to be able to get the data back in real time
because neuroblastoma tumors grow so quickly. Our goal was to be
able to do a biopsy of each patient's tumor, analyze the data from
the gene-expression profile, generate a report, and then bring
together members of our molecular tumor board, which includes
researchers, oncologists, pharmacists, bioinformaticians,
pathologists, and radiologists. The board would discuss each
patient's clinical care so far, the status of the patient, and,
based on the report, the list of drugs that target the patient's
tumor, so that we could create an individual treatment plan. All of
this would be done in less than 2 weeks," said Dr. Sholler.
Larger Trial
A larger 14-patient trial
opened last summer at five centers by the NMTRC in collaboration
with Intervention Insights-there are 11 clinical trial sites
nationwide and 7 more are expected to open this year-and three
neuroblastoma patients have enrolled so far. Implementation of
Dell's cloud supercomputer, which is 1,200% faster than the current
technology in use at the Translational Genomics Research Institute
(TGen), where the data is stored, will allow Dr. Sholler to not
only sequence each patient's RNA expression profile, but his DNA
expression profile as well, in less time.
"Sequencing itself takes
about 2 weeks, but the analysis that takes time too. Right now,
2 months is the quickest we can get good data to make clinical
decisions. The supercomputer will shorten that time to about 2
weeks for RNA sequencing and 1 month for DNA sequencing. We will
make clinical decisions based on the RNA sequencing and expression
and go through a cycle or two of therapy and then have our second
molecular tumor board meeting, when we will have the DNA
information as well and we can reassess treatment options," said
Dr. Sholler.
Future of
Personalized Medicine
"We choose to fund the
personalized medicine trials of the NMTRC because neuroblastoma is
such a deadly cancer and we wanted to take the cancer and use it as
the first model for how we will do this kind of pediatric research
going forward," saidJames M. Coffin, PhD, Vice President and
General Manager of Dell Healthcare and Life Sciences. "This model
of personalized medicine is transferable to every kind of cancer,
and we expect to build one of the largest supercomputing platforms
in the genomic field."
Analysis of the genomic
profiling will be done using software developed by VARI's Pediatric
Cancer Translational Research Program and TGen, which Dr. Sholler
can then use to create a treatment plan for each patient, using
FDA-approved drugs with known pediatric dosing for the specific
tumor type. For this study, the FDA has approved the use of a
combination of up to four drugs from any drug classification.
"Our goal is to offer
these children a good quality of life, and we are not leaning
toward the use of high-dose chemotherapies. Instead, we're looking
at lower-dose targeted therapies in combination with maybe one or
two chemotherapies," said Dr. Sholler.
Although Dr. Sholler's
trials are the first attempt in personalized medicine for children
with relapsed disease, if successful, genomic-based medicine for
pediatric patients with cancer may eventually be used in the
front-line setting, where the greatest chance for cure may be
possible.
Improving Cure
Rates
"Once a child with
neuroblastoma has relapsed, there is no curative therapy. We have
been able with lower-dose therapies to extend the lives of these
children over the past 5 years. If we can understand what's
driving the tumors, stop them from growing, and ultimately kill
them, that's a cure," Dr. Sholler said.
"I'm hoping that as we
validate this type of methodology and bring this to upfront
therapy, that's when we're going to see the cure rates change.
Right now we treat all the kids with the same high-dose therapy,
but only 50% are responding. We're not serving the other 50% very
well," she concluded. ■
