Maximizing extent of resection while minimizing the risk of neurological morbidity in glioma patients: a novel grading scale to translate these surgical goals into a merged onco-functional clinical outcome

We read with great interest the recent article by Wen et al. reviewing the joint consensus by the SNO (Society for Neuro-Oncology) and EANO (European Society of Neuro-Oncology) on the current management and future directions for adult glioblastoma patients.¹

Dr. Wen and colleagues state in their chapter “Surgical Management” that “the goal for glioblastoma surgery should be gross total resection of the enhancing solid tumor mass whenever feasible.” They rightly stress that in order to achieve this:

current standard surgical adjuncts include stereotactic navigation systems using anatomical and functional MRI datasets, intraoperative MRI, ultrasound, intraoperative functional monitoring and the fluorescent dye 5-aminolevulinic acid (5-ALA) to visualize vital tumor tissue, all of which are increasingly used to improve and maximize the extent of resection while reducing the risk of new neurological deficits.

They conclude that “preventing new permanent neurological deficits is more important than maximizing the extent of resection because glioblastomas are not cured by surgery alone, while recognizing and taking into consideration the benefits of maximal safe resection.”

Neurosurgeons operating on glioblastomas in- or near-eloquent areas face a well-known dilemma: maximizing extent of resection and -cytoreduction (to optimize progression-free and overall survival) while simultaneously minimizing the risk of postoperative neurological complications (to preserve clinical performance and -quality of life [QoL]). These two goals do not exclude one another, but even reinforce each other though this may seem paradoxical at first.² As elaborately explained by Dr. Sanai and Prof. Berger,³ the answer lies mainly in the application of intraoperative stimulation mapping techniques—such as awake craniotomy, asleep mapping techniques (motor evoked potentials, somatosensory evoked potentials, continuous dynamic mapping)—or even diffusion tensor imaging tractography or navigated transcranial magnetic stimulation, for that matter.

Both the surgical-oncological objective (maximizing cytoreduction) and the goal to preserve neurological function (minimizing postoperative neurological morbidity) can be assessed and compared in both an objective and quantitative manner. The former usually as extent of resection (EoR)—defined as the percentage of (non)-contrast–enhancing tumor resected—the latter in terms of (a) QoL (using questionnaires such as the EQ-5D, QNQ-BN20, or QNQ-C30); (b) clinical performance (KPS—Karnofsky Performance Scale); or (c) neurological functioning (eg, NIHSS—National Institute of Health Stroke Scale). All aforementioned outcome measures are very valid and useful, with the major advantage of being able to compare these outcomes between, for example, surgical modalities or centers.

However, there is currently no tool to assess these two goals simultaneously, consequently running the real risk of forgetting the actual intent of a (monitored) resection, which is optimizing the individual “onco-functional” outcome. We deem the development of such a novel, integrated grading scale in regard to this vital outcome a necessary addition to the current arsenal of outcome measures in these patients. For example, the extent of resection can be combined with one of the “functional” outcomes (eg, KPS, NIHSS), thereby creating an individual 2-fold coordinate which represents a unique position of each single patient in a 2-dimensional (x,y) graph. Alternatively, one can choose to incorporate both QoL and neurological morbidity in the model, subsequently creating a 3-fold coordinate with its associated representation in a corresponding 3-dimensional (x,y,z) graph. Different subgroups of glioblastoma patients will consequently yield a cluster of coordinates, thereby enabling researchers to compare subgroups more effectively and in better alignment with the original aim of the resection. We believe that by reflecting the existing surgical dilemma in a novel clinical outcome measurement, this “onco-functional” outcome-coordinate has the potential to be of great additional value as it really captures the relevant outcome parameters to assess the maximal, safe resection for each individual, single patient. This will ultimately allow the comparison of outcome-coordinates for different surgical strategies in comparable subgroups of glioma patients.

Conflict of interest statement. None declared.