New Low-Grade Brain Tumor Classification Uses Molecular and Genetic Analysis
New approach should improve diagnosis and treatment, and identifies biological targets for future therapies
Newswise — 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, less 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 LGGs – 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 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.
“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 as the accepted standards.”
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.