Specific genomic biomarkers can be used to identify glioma patients most likely to benefit from post-radiation chemotherapy and serve as a significant predictor of overall and progression-free survival, according to new data published by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

These new findings, says principal investigator Arnab Chakravarti, MD, provide practice-changing data to guide treatment of brain tumor patients diagnosed with gliomas based on their underlying genomic characteristics.

Previous studies of molecular-based prognostic classification for low-grade gliomas led to the WHO’s 2016 reclassification of central nervous system tumor grades, a system that categorizes tumor risk groups based on both anatomical and molecular features. However, follow-up research on the prognostic value of this grading system in clinical outcomes has been limited by the relative rarity of the disease and by having limited access to significant patient populations.

For this new retrospective study, OSUCCC – James researchers sought to determine the prognostic and predictive impact of the WHO-defined molecular subgroups and corresponding molecular alterations of 106 patients who received treatment as part of the NRG Oncology/RTOG 9802 phase III clinical trial. These patients had both comprehensive molecular profiling data based on the WHO-defined molecular groups and information about clinical outcomes available for review.

“Our study is the first prospective, randomized international phase III clinical study to demonstrate that the World Health Organization (WHO) molecular glioma subgroups that are inclusive of the mutant version of the Isocitrate dehydrogenase (IDH 1/2) gene appear to derive greatest benefit from the addition of PCV-based chemotherapy to radiation versus radiation alone,” says Chakravarti, principal investigator of the study and chair of the Department of Radiation Oncology at Ohio State. “PCV-based chemotherapy regimens can be highly effective but can at the same time harbor significant risk for the occurrence of serious toxicities for high-risk, low-grade glioma patients. Hence, it is absolutely critical to identify upfront which of these patients would normally serve to derive greatest survival benefit from a PCV-based chemotherapy regimen while sparing others, who do not derive such survival benefits, from its potentially harmful side-effects.”

Researchers reported their findings in the June 23 issue of the Journal of Clinical Oncology.

Researchers specifically investigated the presence IDH1/2 gene mutations by themselves in the tumors and their association with progression-free survival and overall survival among patients. They determined that IDH 1/2 gene mutations were significant predictors of both overall and progression-free survival after adjustment for clinical variables and treatment.

“Treatment with post-radiation chemotherapy was associated with longer overall and progression-free survival among low-grade glioma patients with WHO groups inclusive of IDH gene mutations,” says Chakravarti, who serves as the Klotz Family Chair of Cancer Research and Professor and Director of the Brain Tumor Program at The Ohio State University College of Medicine. “This new data removes at least some of the controversy about management of low-grade gliomas, primarily related to accurate predictive biomarker classification and treatment selection. We can now definitively use molecular biomarkers to identify people who are likely to reap the greatest benefit from post-radiation chemotherapy and spare those who are unlikely to garner any additional benefit from unnecessary treatment.”

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 51 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only a few centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs sponsored by the NCI.

As the cancer program’s 356-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet® designation, the highest honor an organization can receive for quality patient care and professional nursing practice. With 21 floors and more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care.