Low Grade Glioma: from technology to molecular neurosurgery
Introduction: Several volumetric retrospective studies have shown that the extent of surgical resection (EOR) is the strongest independent risk factor for overall survival (OS), progression free survival (PFS) and malignant transformation (MPFS) in Low Grade Gliomas (LGGs) patients.
Objective: Beyond conventional neurosurgical principles, several technological tools (i.e. intraoperative contrast-enhanced ultrasound (CEUS), functional MRI e DTI tractography overlapped on the neuronavigation system) allow the surgeon to increase EOR. Moreover, awake surgery in combination with complex real-time neuropsychological testing (RTNT) enables continuous intraoperative feedback, allowing the surgeon to increase EOR for LGGs in eloquent areas.
Methods: Considering that gliomas tend to infiltrate functional areas, both at cortical and subcortical levels, radical surgery is unfortunately limited to only a few selected cases and tumor recurrence is inevitable. The aim of this study was to evaluate the impact of the technological enhancements and integration of multidisciplinary surgical protocols on EOR.
Results: We also analyzed the limited role of EOR on overall survival, even for cases of radical resection (EOR 100%) at first surgery, underling the emerging need to develop targeted therapies that specifically bind to surface markers of glioma cells.
Between 2000 and 2018, 290 patients underwent surgery for LGGs. Three different technical intraoperative protocols were used: Protocol 1, intraoperative electrical stimulation alone; Protocol 2, intraoperative stimulation in addition to overlap of functional MRI/fiber tracking diffusion tensor imaging data on a Neuronavigation system; Protocol 3, Series 2 plus intraoperative RTNT. All surgical procedures were conducted under cortico-subcortical stimulation. The role of each protocol on OS was evaluated. Overall survival and progression free survival results were stratified by the EOR achieved.
Overall, the EOR obtained was 77%, 86% and 92% by using the intraoperative Protocol 1, Protocol 2 and Protocol 3, respectively (p = 0.001).
Amongst these patients, a radical resection (EOR=100%) was achieved in 77 cases (27%).
Specifically, an EOR of 100% was obtained in 14%, 25% and 38% of patients belonging to Protocol 1, Protocol 2 and Protocol 3, respectively (p = 0.0003).
In the subgroup of patients with an EOR of 100%, the median OS was 92 months (range 12-239), while the median PFS was 65 months (range 12-185).
In the subgroup with a tumor resection less than 100%, the median OS was 72 months (range 12-173), while the median PFS was 46 months (range 12-118).
Conclusions: Combined awake craniotomy, intraoperative brain mapping and functional imaging analysis is advantageous in developing a multidisciplinary, safe and efficient technique allowing maximal safe resection of eloquent area gliomas with possible subsequent OS benefits.
Technological tools are clinically useful to improve the extent of resection, but LGGs have the tendency to recur even in case of radical resection. A better understanding of the natural history of LGG, provided by volumetric studies, opens the pathway to molecular neurosurgery.