Patients With Newly Diagnosed Glioblastoma Benefit Even From Less Than Total Resection

Daniel M. Keller, PhD

May 13, 2010

May 13, 2010 (Philadelphia, Pennsylvania) — The extent of resection (EOR) of glioblastomas necessary to improve patient survival has remained controversial. Now, in a study of 500 patients with newly diagnosed glioblastomas, researchers have found a significant survival advantage with as little as 78% EOR, and a stepwise greater advantage was observed even in the 95% to 100% range. Previous studies have suggested that a 98% resection was necessary to have an effect on survival.

Senior study author Mitchel Berger, MD, chairman of the Department of Neurosurgery at the University of California, San Francisco, said his study used a volumetric analysis to gauge presenting and residual tumor burden, rather than the multidimensional, cross-sectional analyses that have been used in most other studies.

Obtaining accurate measures of the tumors is important "to really get a sense of graded effectiveness of extent of resection — percent by percent — so that we not only know what the most significant level is, but we also get a sense of the threshold for efficacy for the subtotal resection," Dr. Berger said. "In other words, when do you stop? When do you make a difference?"

Graded Degree of Benefit

The study involved consecutive patients newly diagnosed as having supratentorial glioblastomas between 1997 and 2009. Median age was 60.0 years, and the median Karnofsky Performance Score (KPS) at presentation was 80.

Volumetric tumor analysis was derived from T1-weighted, contrast-enhanced magnetic resonance imaging. The median preoperative tumor volume was 57.0 cm3, and the median postoperative volume was 2.3 cm3, for an EOR of 96%.

Most tumors (n = 206) occupied eloquent brain areas. All patients received chemotherapy and radiation therapy after resection. Mean follow-up was 12.8 months, all patients were accounted for, and median survival was 12.2 months. Most patients had resections of 70% or more, and in this group, the overall survival was 15.3 months.

Age, KPS, and EOR were predictive of survival (P < .0001) by Cox proportional hazards analysis.

"What we found was that there was a graded degree of benefit in extent of resection in that newly diagnosed patient [at] the 78th percentile; in other words, that was the threshold," Dr. Berger concluded. "Once we got underneath that level...there was no benefit. If you have a patient that's under 35 [years], regardless of tumor size, volume, location, if you had more than a 95% extent of resection, you could give them a 2-year overall survival of 55%."

Dr. Berger said 1 implication of his findings is that clinicians need to approach glioblastomas in a new way for patients with newly diagnosed conditions.

"We can't think any more about the 98% level...That's what we should strive for, and if we can't get there and the patient is symptomatic with mass effect, we should think about doing more than a biopsy," he advised. "We have to think about an 'all or most' paradigm in which we're going to strive to achieve a very aggressive resection...but if we can't do that and we fall short...we can still make an impact on that patient's life," he added. "Above 78%, the extent of resection, continuously percent by percent, correlates with improved survival."

A second implication of this study is that Dr. Berger said he is going do his future studies thinking more about the volume of residual disease than purely the extent of resection.

New Compelling Data

Philip Gutin, MD, chairman of the Department of Neurosurgery at Memorial Sloan-Kettering Cancer Center in New York City, presented a discussion of Dr. Berger's study.

He reanalyzed the data for the attendees and said that if one removes the data from the analysis for the group of patients with an 80% to 90% resection, "which is the first group that is a sort of less than near total resection, [it] contributes no survivors beyond about 15 months."

Nonetheless, he said that point is a "niggling criticism for what is really an excellent paper."

The researchers "provide new compelling data from a careful retrospective study supporting the idea that aggressive resection when possible is an important aspect in the surgical treatment of glioblastoma," he said.

He questioned whether the investigators have shown conclusively that less or near-complete resection benefits survival. Still, "there is no question about the palliative value of a resection whatever extent is possible," he advised.

Dr. Berger and Dr. Gutin have disclosed no relevant financial relationships.

American Association of Neurological Surgeons (AANS) 2010 Annual Meeting: Abstract 807. Presented May 5, 2010.

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