Nancy A. Melville

May 07, 2015

Washington, DC — The total resection of glioblastoma multiforme (GBM) brain tumors in addition to surrounding abnormal regions, when safe, is associated with prolonged survival without increased morbidity, a new study shows.

GBM is the most common but least survivable of primary brain tumors, and while previous studies have also linked increased survival with the extent of tumor resection, the new study (by Yan Michael Li, MD, PhD, and colleagues at the University of Texas MD Anderson Cancer Center, Houston) is the largest single-center series of patients with extensive tumor resections.

"What this really shows us is if [a patient] gets a gross total resection of a glioblastoma multiforme tumor, they are 40% more likely to be alive at 1 year than if they undergo anything less," said Michael Glantz, MD, a neurologist with the Penn State Milton S. Hersey Medical Center, in Hershey, Pennsylvania, in commenting on the study.

In addition to looking at the effects of total resection of tumor identified by MRI T1 contrast-enhancing volume, the authors looked at even further resection of abnormal surrounding areas identified with fluid-attenuated inversion recovery (FLAIR).

The results were presented here at the American Association of Neurological Surgeons (AANS) 83rd Annual Meeting.

The researchers evaluated 1229 patients with glioblastoma multiforme who had at least 78% resection of their tumors at the cancer center between June 1993 and December 2012.

Patients with more than one tumor or those older than age 80 years were excluded.

Among the patients, 876 (71%) had complete resection of MRI T1 contrast-enhancing tumor volume and 353 (29%) had less than 100% resection.

Patients with the complete resection showed a significantly longer median survival time (15.2 months) than those who had a less than complete resection of (8.8 months; P < .007).

Risk for overall or neurologic postoperative deficits did not increase after adjustment for prognostic factors, such as age, score on Karnofsky Performance Scale, preoperative contrast-enhancing tumor volume, presence of necrosis and cyst, and prior treatment status.

The overall complication rate was 21% in the group with 100% resection, compared with 28% in the less-than-total resection group (P = .02); the rate of neurologic complications was also lower in the 100% resection group (16.6%) than in the subtotal resection group (P = .02).

In addition, prolonged survival was also seen with resection of less than 53.21% of the surrounding FLAIR abnormality that exceeded the 100% contrast-enhancing resection, compared with less extensive resection (median survival times, 20.7 vs 15.2 months; P < .001).

In those two groups, overall complications were also lower in the group with the greater FLAIR resection (18%) vs the lesser resection (26%; P = .04), as were neurologic complications (14% vs 20%, respectively; P = .12).

With the study adding to numerous previous studies also linking the extent of resection with longer survival, the line of research needs to advance to the next stage, Dr Glantz asserted.

"In looking at the last 30 years of clinical trials of this, interestingly, the same result is seen, and I think what this tells us we need a randomized controlled trial, but we're probably not going to be able to do that, so what we desperately need is a prospective registry on this that is well designed and maybe multinational."

"I would meanwhile urge editors not to accept any more studies of this type — we have the definitive study and we need to move on."

Specific Tumors

Andrew H. Kaye, MD, a professor of surgery at the University of Melbourne's Royal Melbourne Hospital, Australia, and a discussant of the study, cautioned that the findings relate only to the specific GBM tumors that were evaluated.

"The manuscript provides further evidence that there is an appropriate time to take a maximal safe resection, but it does not give license to undertake a resection that would produce a significant neurological deficit," he said.

"The ability to perform a total resection could be, at least in part, a surrogate marker for the biology of the tumor, and as such, these results cannot be extrapolated to tumors involving deep regions."

Clark C. Chen, MD, PhD, an associate professor of neurosurgery and vice chair of research and academic development at the University of California, San Diego, expressed strong reservations regarding resection into areas such as FLAIR regions, which may in fact have more normal cells than tumor cells.

While the notion of radical cancer removal is attractive — particularly to neurosurgeons — it is important to keep in mind that each millimeter of brain removed contained more neural connections than people in the world. Dr. Clark Chen

"While the notion of radical cancer removal is attractive — particularly to neurosurgeons — it is important to keep in mind that each millimeter of brain removed contained more neural connections than people in the world," he told Medscape Medical News.

"The aggregate of these connections contributes to the definition of who we are. As such, consideration for extended resection into regions where the number of normal neurons significantly outnumbers the number of cancer should be undertaken with judicious caution — particularly when survival benefits are on the order of weeks rather than years."  

A musician who loses the ability to play an instrument, for instance, or a patient who loses the ability to speak, or countless other scenarios of potential deficits, should be considered, he said.

"The quality of life for our patients is every bit as, if not more, important as the length of life," he asserted.

"While the work represents a major effort in pushing the limit of what surgeons can potentially do for our brain cancer patients, it falls short in addressing this critical issue."

Drs Li and Kaye have disclosed no relevant financial relationships. Dr Glantz's disclosures include consulting for AbbVie Pharmaceuticals and receipt of an honorarium from SigmaTau Pharmaceuticals. Dr Chen has consulted for Monteris and Clearpoint and received an honorarium from Varian.

American Association of Neurological Surgeons (AANS) 83rd Annual Meeting. Abstract 600. Presented May 4, 2015.


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