Gene mutation defines brain tumors that benefit from aggressive surgery

Patients with malignant astrocytoma whose tumors carry the gene mutation isocitrate dehydrogenase 1 (IDH1) may benefit greatly from surgical removal of the largest possible amount of tumor, according to a newly published study.

Astrocytomas are the most common type of malignant brain tumor, and are a type of glioma that includes the highly aggressive glioblastoma and the less aggressive but still dangerous anaplastic astrocytoma. Although the tumors in most patients prove to be quite aggressive, outcomes overall can vary widely, and some patients survive for many years.

"We found that the benefit of surgery and how aggressively the surgery should be done depend, in large part, on whether or not patients' tumors have the mutated form of the IDH1 gene," said corresponding author Daniel Cahill, MD, PhD, of Massachusetts General Hospital (MGH) Cancer Center in Boston, Massachusetts. The study, which took place at the University of Texas MD Anderson Cancer Center in Houston, was published in Neuro-Oncology (2014;16[1]:81-91). "Under the prior system of categorization, these tumors were considered the same diagnosis and were treated the same way; but we have found that this mutation identifies a completely different subclass of glioma that probably should be treated differently."

In 2008, a comprehensive genetic analysis of glioblastomas found IDH1 mutations in more than 10% of patient tumors, and subsequent studies have found similar mutations in from 50% to 70% of anaplastic astrocytomas. Significant clinical differences between IDH1-mutant tumors and those without that mutation have been identified previously; patients with mutant tumors tend to be younger and survive longer, and the tumors are more likely to be located in the frontal lobe.

The current study was designed to investigate whether the presence or absence of the IDH1 mutation might help determine the optimal treatment strategy—in particular, how extensive surgery should be. Traditionally, how much of a brain tumor is removed depends on its location and whether that tissue can be safely removed. A key question has been whether to take out only the most actively growing part of the tumor—what is called enhancing disease—or also to remove the nonenhancing edge of the tumor that infiltrates adjacent tissue.

To determine whether IDH1 status made a difference, the research team examined data on 335 patients—128 with anaplastic astrocytoma, 67% of which were IDH1-mutated; and 207 with glioblastoma, 13% of which had the mutation—treated from June 1993 to April 2009. The analysis revealed that more than 90% of tumors with the IDH1 mutation had been completely removed compared with 67% of the nonmutant tumors.

More importantly, whereas removal beyond the enhancing disease of nonmutated tumors did not substantially improve patient survival, more complete removal of IDH1-mutant tumors had a remarkable association with survival. The average survival of all patients with mutant tumors was 13.5 years, compared with less than 1.5 years for those with nonmutant tumors, but almost all of those with mutant tumors who received aggressive surgery are still alive, some nearly 20 years after surgery.

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