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Aggressive Surgery for Low-grade Brain Tumor May Lengthen Life
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Rooting out cancer. Real-time imaging during brain surgery shows changes that occur during the operation. This sequence, taken by intraoperative MRI, shows (from top to bottom) a low-grade glioma before surgery, the compressed tumor bulging out after the craniotomy, and the resection before the bone is replaced and the incision closed. |
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 Images courtesy of Peter Black |
Surgery falls short of a cure, but it is the cornerstone of treatment. Removing as much of a tumor as is safely possible will extend and improve the lives of afflicted people for years or even decades, doctors believe. Yet that plausible idea has turned out to be remarkably difficult to prove.
A new study of neurosurgery patients at Brigham and Women’s Hospital bolsters the case for aggressive surgery to excise low-grade gliomas, said first author Elizabeth Claus, an associate neurosurgeon at BWH and an associate professor of biostatistics at the Yale University School of Medicine.
Claus and her colleagues followed the outcomes of 156 patients for an average of three years after surgery. People whose tumors could be only partially removed were 1.4 times more likely to relapse and 4.9 times more likely to die than people whose postoperative brain scans showed no traces of remaining tumor, they report in the March 15 issue of Cancer.
“If we can safely take all the imaged tumor out, patients will be better off,” said senior author Peter Black, chair of neurosurgery at BWH and Children’s Hospital Boston and the Franc D. Ingraham professor of neurosurgery at HMS, whose patients were studied. “The trick is knowing where the tumor is, exactly; that taking it out won’t hurt valuable brain tissue; and knowing when it’s gone,” he said.
| “The trick is knowing where the tumor is, exactly; that taking it out won’t hurt valuable brain tissue; and knowing when it’s gone.” |
More recently, studies have suggested people will live longer if more of their tumors are removed, but they are far from conclusive. Some retrospective analyses have shown that total removal of a low-grade glioma can delay or prevent it from growing into a malignant cancer and can extend life, but others have suggested that radiation therapy may make full resection less important, according to the guidelines of the National Comprehensive Cancer Network, an alliance of 19 of the leading U.S. cancer centers.
“The vast majority of clinicians in the field believe in their hearts that it is important to resect the tumor when the majority of it can be safely removed,” said John Henson, HMS associate professor of neurology and radiology at Massachusetts General Hospital, who studies the tumors.
Low-grade gliomas start in the glial cells that support and surround the neurons. They usually grow slowly, but most of them eventually turn malignant. In fact, about one third of Black’s patients who appear to have a low-grade tumor have one that has begun to transform into a malignant cancer extending invisible arms into the brain.
“Part of why this is so important is that it affects young people in the prime of life,” Claus said. In their study, the mean age was about 42. Slightly less than half were women. Followup ranged from one to six years after surgery.
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Peter Black helped design one of the first operating rooms in the country that allows for real-time brain imaging, a tool that enables neurosurgeons to safely remove more tumor tissue in people with low-grade gliomas. |
The attraction is an operating suite that allows real-time imaging during surgery to confirm the presence or absence of residual tumor. The facility was developed 15 years ago by Black and his colleagues, especially Ferenc Jolesz, the B. Leonard Holman professor of radiology at BWH, in collaboration with General Electric. It was one of the first such operating rooms in the country. The operating table lies within specially designed magnetic resonance imaging (MRI) equipment. To date, more than 700 people have undergone a craniotomy for biopsy or surgery in the unit.
Refining the Target
The definitive diagnosis of a low-grade glioma is a biopsy. After
confirmation, Black and Claus generally aim to remove as much
of the tumor as possible.
If the tumor threatens areas of the brain involved in speech
or movement, called “eloquent” regions, the patient
will be awake during surgery to test the functional impact
of ablating these areas of the cancer. In these
cases, surgeons may have to leave some of it to avoid paralyzing
the other side of the patient’s body.
Studies by Black and others have shown that intraoperative MRI allows surgeons to safely remove a greater portion of the malignancy. Typically, MRI is most commonly used outside of the operating room before surgery for a preliminary diagnosis and to precisely locate the tumor for operative planning. It is also used postoperatively to detect response to treatment and tumor progression over time.
According to Claus, the new study aimed to address the role of surgery with more statistical precision. “It is not known with certainty if surgical resection is the ultimate therapy for people with low-grade gliomas in terms of long-term survival,” she said.
Ultimately, the study does not provide the long-sought authoritative answer to the question, said Henson. “I do think that intraoperative MRI is the wave of the future and that it leads to better resections. It just is difficult to formally prove that better resections lead to better survival,” he added.
The current analysis falls short of definitive evidence, Claus agrees, because it is subject to the biases inherent in a retrospective, hospital-based study. “The next step is to examine this question within the setting of a clinical trial or population-based study,” said Claus, who hopes to look at more data from other centers that treat low-grade gliomas. Further analyses will include data on genetic variants to better define the effect of such information on neurosurgical outcomes.