In patients with newly diagnosed glioblastoma, maximal extent of surgical resection of contrast-enhancing tumor has consistently been associated with benefits to survival. However, in a practice-changing study published recently in JAMA Oncology, a team of investigators under the leadership of Mitchel Berger, MD, found that extending resection to include non–contrast-enhancing tumor as well as contrast-enhancing tumor is associated with increased survival, regardless of tumor genetic subtype. In this interview with i3 Health, Dr. Berger, Chair of Neurological Surgery and Director of the Brain Tumor Research Center at the University of California, San Francisco (UCSF), discusses how this finding should be applied in clinical practice.
What prompted you to investigate the impact of maximal extent of resection of contrast-enhancing and non–contrast-enhancing tumor on survival for patients with newly diagnosed glioblastoma?
Mitchel Berger, MD: Well, I've noticed for some time that patients who had a more aggressive resection beyond the contrast enhancement were doing better in terms of patterns of recurrence and ultimately survival. We decided to confirm whether this suspicion was correct and began that study, which resulted in this paper.
Can you comment on the significance of your findings?
Dr. Berger: So the reason that this study is so dramatic, in terms of what I would call a paradigm shift in our thinking, is that first of all, it makes us realize that we have to remove more tumor, meaning that we can't just remove the contrast-enhancing area anymore; we have to go beyond this. The other critically important aspect of this study is to realize that even in the molecular era that we're in, patients still do better, regardless of the molecular marker, if they have a more aggressive resection to begin with: extent of resection outweighs the potential negative effect of the wrong molecular marker. This is a very important advance in how we will have to treat glioblastoma in the future. The other important part of the study was the blinded validation of our findings using data from the Mayo Clinic and the Cleveland Clinic to confirm that we were correct.
In terms of how these results should impact clinical practice, what do neurosurgeons need to keep in mind when removing the non–contrast-enhancing tumor? Are there any concerns with this more aggressive approach?
Dr. Berger: Well, the other message, which we did not specifically look at in this paper, but we've examined in many others, is that in order to be aggressive, you have to do it safely, and the only way to do it safely is to use brain-mapping strategies in order to find functional tissue and leave it alone. So the reason why our morbidity is no higher with this approach—meaning that the morbidity of removing the tumor in the non-enhancing area is no greater than just taking out the enhancement—is because we use brain-mapping techniques to be able to remove tumors safely, spare function, and prevent injury.
So what neurosurgeons need to know is that first of all, they have to take out more than just contrast enhancement; they have to go beyond it into the non-enhancing area. Second, it really doesn't matter what the molecular markers are, because extent of removal trumps the molecular marker, so to speak. And finally, in order to do this, you have to have safe surgical techniques, and the only way to push the margin is to use brain-mapping techniques to identify function and prevent injury.
Are you doing any further research on this topic?
Dr. Berger: What we're trying to do now is determine whether the same data applies for the lower-grade gliomas. We're doing that study as we speak.
Do you have any final words of advice for neurosurgeons as they treat patients with glioblastoma?
Dr. Berger: Again, I think that the advice I would give to neurosurgeons is that you have to be aggressive in order to make a difference in the patient's outcome, and you have to be safe if you're going to be aggressive. And the only way to be safe is to use brain-mapping techniques.
About Dr. Berger
Mitchel S. Berger, MD, is the Chair of the Department of Neurological Surgery at UCSF, where he is also the Director of the Brain Tumor Research Center, Director of the Center for Neurological Injury and Repair, and Co-Director of the Adult Brain Tumor Surgery Program. Formerly, he served as President of the American Association of Neurological Surgeons and as Director of the American Board of Neurological Surgery. Dr. Berger's primary areas of expertise include the treatment of brain tumors, spinal cord tumors, and tumor-related epilepsy, as well as use of brain mapping techniques and the Gamma Knife, a precise, noninvasive tool that applies radiation beams for tumor treatment.
For More Information
Molinaro AM, Hervey-Jumper S, Morshed RA, et al (2020). Association of maximal extent of resection of contrast-enhanced and non–contrast-enhanced tumor with survival within molecular subgroups of patients with newly diagnosed glioblastoma. JAMA Oncol. [Epub ahead of print] DOI:10.1001/jamaoncol.2019.6143
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.