Advances in Brain Tumor Surgery for Glioblastoma in Adults

Abstract

Glioblastoma (GBM) is the most common primary intracranial neoplasia, and is characterized by its extremely poor prognosis. Despite maximum surgery, chemotherapy, and radiation, the histological heterogeneity of GBM makes total eradication impossible, due to residual cancer cells invading the parenchyma, which is not otherwise seen in radiographic images. Even with gross total resection, the heterogeneity and the dormant nature of brain tumor initiating cells allow for therapeutic evasion, contributing to its recurrence and malignant progression, and severely impacting survival. Visual delimitation of the tumor's margins with common surgical techniques is a challenge faced by many surgeons. In an attempt to achieve optimal safe resection, advances in approaches allowing intraoperative analysis of cancer and non-cancer tissue have been developed and applied in humans resulting in improved outcomes. In addition, functional paradigms based on stimulation techniques to map the brain's electrical activity have optimized glioma resection in eloquent areas such as the Broca's, Wernike's and perirolandic areas. In this review, we will elaborate on the current standard therapy for newly diagnosed and recurrent glioblastoma with a focus on surgical approaches. We will describe current technologies used for glioma resection, such as awake craniotomy, fluorescence guided surgery, laser interstitial thermal therapy and intraoperative mass spectrometry. Additionally, we will describe a newly developed tool that has shown promising results in preclinical experiments for brain cancer: optical coherence tomography.

Keywords: awake craniotomy; brain tumor surgery; laser therapy; novel treatments for glioma; optical coherence tomography.

Figure 1

Kaplan Meyer curves of extent of resection in high grade gliomas (HGG). (A) The median survival for patients with >70% tumor resection was 14.4 months compared with 10.5 months for patients with ≤70% resection (p = 0.0003); (B) The median percent free survival for patients with >70% tumor resection was 9.0 months compared with 7.1 months for patients with ≤70% resection (p = 0.01). (Reproduced from Chaichana et al. [7]).

Figure 2

Awake craniotomy for cortical mapping and tumor resection. Electrode placement for monitoring and localization of eloquent areas. (Original image).

Figure 3

Intraoperative mass spectrometry of an onco-metabolite to guide brain tumor resection. (a) H & E-stained smear (Left), frozen tissue section (Center), and immunohistochemistry using an IDH1 R132H point mutation-specific antibody in an oligoastrocytoma grade III samples; (b) 3D tumor volume representation showing normalized 2-hydroxyglutarate (2-HG) signal represented with a warm color scale (lowest (yellow) to highest (red)); (c) Negative ion mode DESI mass spectra obtained from a smear (Left) and a section from an oligoastrocytoma grade III (Right). Used with permission from Santagata et al. [82].

Figure 4

OCT for tumor tissue identification in ex vivo samples. (A) Sensitivity and specificity rates for cancer core and infiltrated zone in tissues obtained from a set of 16 samples; (B) OCT attenuation map results in cancer core and infiltrated zones, and its correlation with histology. Used with permission from Kut et al. [85].

Figure 4

OCT for tumor tissue identification in ex vivo samples. (A) Sensitivity and specificity rates for cancer core and infiltrated zone in tissues obtained from a set of 16 samples; (B) OCT attenuation map results in cancer core and infiltrated zones, and its correlation with histology. Used with permission from Kut et al. [85].