Surgery for Diffuse Low-Grade Gliomas (DLGG) Functional Ouctomes

Abstract

Early and maximal surgical resection is currently the first treatment in DLGG. Beyond oncological considerations, preservation of the quality of life (QoL) is a priority in DLGG patients with long survivals. For a long time, it was claimed that these patients had a no functional deficits. In fact, extensive neuropsychological assessments performed before any oncological therapy have found a high rate of cognitive disorders, even in DLGG incidentally discovered. This is due to the tumor progression that disrupts functional connectivity and/or epilepsy as well as anticonvulsants. Thus, these findings plead against a wait-and-see attitude, also for functional reasons. Moreover, because this chronic and diffuse tumoral disease often involves critical neural networks, it was thought that the chances to perform an extensive glioma removal were low, whereas the risks to induce permanent neurological deficits were high. To adapt the surgical procedure to the individual cerebral anatomo-functional organization, that can be highly variable from patient to patient—or even in the same patient over time due to brain reorganization induced by the slow growth of DLGG—neurosurgeons should see first the brain, and not the tumor. The use of the data provided by functional neuroimaging for surgical selection and planning has been proposed. However, this technique is not reliable enough to guide surgery, especially because it can not distinguish neural pathways crucial for brain functions from those which can be compensated after removal. Therefore, to talk about “radical safe resection” based upon neuroimaging is a non-sense. Here, the goal is to introduce an original concept in neuro-oncological surgery, that is, to achieve early resection of DLGG up to the individual functional limits, with no margin left around the critical structures, thanks to intraoperative electrical mapping and on-line neurocognitive monitoring achieved in awake patients. To this end, in addition to cortical mapping, it is crucial to map the subcortical connectivity, with the aim of preserving the networks underlying the “minimal common core” of the brain. This “hodotopical” workframe considering both cortical hubs and axonal pathways, opens the door to a paradigmatic shift in surgery, switching from anatomic/oncological-guided resection to functional mapping-guided resection—based upon an accurate study of brain connectomics and neuroplasticity in each patient. These conceptual advances have permitted an optimization of the benefit-to-risk ratio of surgery in DLGG patients, including in “eloquent areas” traditionally thought to be “unresectable”, by improving significantly not only survival but also QoL—thanks to a preservation or even an increase of the neurocognitive scores as demonstrated by postoperative neuropsychological evaluation, and thanks to epilepsy control, related to the quality of resection. Thus, early maximal surgical resection should be performed not only for oncological but also for functional/epileptological purposes in DLGG—knowing that QoL is also a predictor of overall survival. With this in mind, stronger interactions between cognitive/behavioral neurosciences and oncological neurosurgery must be built. In other words, brain surgeons should also be neuroscientists, to open the door to “precision neuro-oncological surgery”.