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For Immediate Release
June 10, 2015
New England Journal study with Dr. Andrew Sloan from Case Comprehensive Cancer Center
and UH Case Medical Center discovers new method of classifying low-grade brain tumors
New approach should improve diagnosis and treatment, and identifies biological targets for
future therapies
CLEVELAND – A Case Comprehensive Cancer Center (CCCC) brain surgeon and neurosurgery
professor is among the primary authors of a new approach to classifying tumors that could lead
to significant improvements in their diagnosis and treatment. The research and
recommendations appear online June 10 in The New England Journal of Medicine.
Andrew Sloan, MD, Director of the Brain Tumor and Neuro-Oncology Center at University
Hospitals Case Medical Center, said the new classification system has the potential to provide
far more accurate assessments of brain tumors known as low and intermediate grade gliomas
(LGGs) – which in turn could enhance patients’ outcomes.
Scientists and physicians from Cleveland and 43 other federally designated cancer centers used
molecular and genetic analysis to develop an approach that reduces the role of individual
observers’ assessments of the tumors’ appearance.
“This genome-wide analysis will be much more objective and likely will be practice changing,”
said Sloan, Professor of Neurosurgery and Vice Chair of Neurosurgery at Case Western Reserve
School of Medicine. “It can be easily implemented and will markedly improve diagnosis, patient
care and treatment planning.”
Sloan said that the findings would need to be validated by other groups before they could be
implemented in practice.
In the past, pathologists classified LGGs based on two primary factors: their presumed cell of
origin (or lineage) and the degree of severity (graded I through IV, least to most severe) based
on how the glia looked when viewed through a microscope. This classification, in turn, drove
oncologists’ decisions regarding treatment.
“Choice of therapy takes into account lineage and grade based on the microscopic
appearance,” explained Sloan, “which is necessarily subjective with variability between
observers.”
The new system decreases the number of categories from six to three and also correlates more
closely with patient outcomes. Under the existing model, some patients with low- or
intermediate-grade gliomas suffered symptoms as quick and lethal as those with glioblastomas,
considered the most severe form of brain tumor. Others with LGGs, meanwhile, had far better
prognoses – even though they all look quite similar under the microscope.
To develop the new system, the study’s authors performed genome-wide analysis of 293 adult
LGGs from cancer centers that are part of the National Institutes of Health’s Cancer Genome
Atlas Research Network. A genome contains the complete set of DNA for each cell – in other
words, its genetic information and instructions. Cancers emerge from errors in DNA, and the
Atlas provides a national, coordinated effort to understand more about which of those errors
contribute to the more than 200 kinds of cancer known to exist today.
For this project, the researchers applied next-generation gene sequencing and then correlated
the findings with data regarding patients’ clinical outcomes.
The researchers found that the characteristics of one group of LGGs had significant scientific
similarities to those of glioblastomas, the most serious form of brain cancer. Patients with this
kind of LGG had median survival rates of about 1.7 years – only slightly longer than
glioblastomas which have median survival rates of 1.1 years.
Patients with the other two kinds of LGG – identified by other genetic markers - had median
survival rates of 6.3 and 8 years, respectively.
Sloan’s team analyzed tissue samples and outcomes of patients from the UH Seidman Cancer
Center. Patients consented for the samples to be used for research and their names were not
attached to the data.
One of the markers - the IDH-1 mutation - previously has been linked to low- and intermediate
gliomas and the U.S. Food and Drug Administration already has approved testing for its
presence. Some brain tumor centers have used it – as well as the other two markers (P53 and
LOH at 1p and 19q) for years.
“The findings demonstrate that these three groups of LGGs can be identified objectively by
three different markers,” Sloan said. “While various centers have been using some of these
markers for years, this study helps validate these three markers.”
The study’s lead author is Daniel J. Brat, MD, PhD, Professor of Pathology at Emory University
and member of its Winship Cancer Institute. Other Case Comprehensive Cancer Center
members of the involved with the study are Jill S. Barnholtz-Sloan, PhD, Marc Cohen, MD,
Wendi Barrett, Karen Devine, BS, RN, CCRN, and Jordonna Fulop, ASN, RN. (Barrett, Devine and
Fulop are also with UH). The study was funded by multiple grants from the National Institutes
of Health in support of the Cancer Genome Atlas, including one to the Case Western Reserve
School of Medicine.
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About Case Comprehensive Cancer Center
Case Comprehensive Cancer Center is an NCI-designated Comprehensive Cancer Center located at Case Western
Reserve University. The center, which has been continuously funded since 1987, integrates the cancer research
activities of the largest biomedical research and health care institutions in Ohio – Case Western Reserve, University
Hospitals (UH) Case Medical Center and the Cleveland Clinic. NCI-designated cancer centers are characterized by
scientific excellence and the capability to integrate a diversity of research approaches to focus on the problem of
cancer. It is led by Stanton Gerson, MD, Asa and Patricia Shiverick-Jane Shiverick (Tripp) Professor of Hematological
Oncology, director of the National Center for Regenerative Medicine, Case Western Reserve, and director of the
Seidman Cancer Center at UH Case Medical Center.
About Case Western Reserve University School of Medicine
Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in
Ohio and is among the nation’s top medical schools for research funding from the National Institutes of Health. The
School of Medicine is recognized throughout the international medical community for outstanding achievements in
teaching. The School’s innovative and pioneering Western Reserve2 curriculum interweaves four themes--research
and scholarship, clinical mastery, leadership, and civic professionalism—to prepare students for the practice of
evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates
have been affiliated with the School of Medicine.
Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S.
research-oriented medical schools as designated by U.S. News & World Report’s “Guide to Graduate Education.”
The School of Medicine’s primary affiliate is University Hospitals Case Medical Center and is additionally affiliated
with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and
the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western
Reserve University in 2002. http://case.edu/medicine
About University Hospitals
University Hospitals, the second largest employer in Northeast Ohio with 25,000 employees, serves the needs of
patients through an integrated network of 15 hospitals, 28 outpatient health centers and primary care physician
offices in 15 counties. At the core of our $3.5 billion health system is University Hospitals Case Medical Center,
ranked among America’s 50 best hospitals by U.S. News & World Report in all 12 methodology-ranked specialties.
The primary affiliate of Case Western Reserve University School of Medicine, UH Case Medical Center is home to
some of the most prestigious clinical and research centers of excellence in the nation, including cancer, pediatrics,
women's health, orthopaedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health,
transplantation and genetics. Its main campus includes UH Rainbow Babies & Children's Hospital, ranked among the
top children’s hospitals in the nation; UH MacDonald Women's Hospital, Ohio's only hospital for women; and UH
Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center at Case Western Reserve
University. For more information, go to www.uhhospitals.org