Novel strategies in glioblastoma surgery aim at safe, supra-maximum resection in conjunction with local therapies

Abstract

The biggest challenge in neuro-oncology is the treatment of glioblastoma, which exhibits poor prognosis and is increasing in incidence in an increasing aging population. Diverse treatment strategies aim at maximum cytoreduction and ensuring good quality of life. We discuss multimodal neuronavigation, supra-maximum tumor resection, and the postoperative treatment gap. Multimodal neuronavigation allows the integration of preoperative anatomic and functional data with intraoperative information. This approach includes functional magnetic resonance imaging (MRI) and diffusion tensor imaging in preplanning and ultrasound, computed tomography (CT), MRI and direct (sub)cortical stimulation during surgery. The practice of awake craniotomy decreases postoperative neurologic deficits, and an extensive supra-maximum resection appears to be feasible, even in eloquent areas of the brain. Intraoperative MRI- and fluorescence-guided surgery assist in achieving this goal of supra-maximum resection and have been the subject of an increasing number of reports. Photodynamic therapy and local chemotherapy are properly positioned to bridge the gap between surgery and chemoradiotherapy. The photosensitizer used in fluorescence-guided surgery persists in the remaining peripheral tumor extensions. Additionally, blinded randomized clinical trials showed firm evidence of extra cytoreduction by local chemotherapy in the tumor cavity. The cutting-edge promise is gene therapy although both the delivery and efficacy of the numerous transgenes remain under investigation. Issues such as the choice of (cell) vector, the choice of therapeutic transgene, the optimal route of administration, and biosafety need to be addressed in a systematic way. In this selective review, we present various evidence and promises to improve survival of glioblastoma patients by supra-maximum cytoreduction via local procedures while minimizing the risk of new neurologic deficit.

Genetic, epigenetic, and molecular landscapes of multifocal and multicentric glioblastoma

“…Currently, surgical resection and radiotherapy, combined with adjuvant temozolomide (TMZ) chemotherapy, are standard treatment strategies for this disease [30]. However, despite our increased understanding of the oncological mechanisms that underlie the pathophysiological characteristics of GBM and despite the use of TMZ, the prognosis of the disease remains very poor, with a median patient survival duration of 15 to 17 months [17].…”

Surgical management of periventricular glioma: decision-making and preoperative assessment of resectability

“…At the same time, surgery remains a key link in the treatment of patients with PVG that could clarify the histological diagnosis, contributes to clinical improvement and provides additional time for adjuvant therapy application. The improvement of the prognosis for the deep-seated gliomas is associated with the technologies of intraoperative visualization of brain tumors such as the multimodal neuronavigation, intraoperative MRI, intraoperative fluorescence and endoscopic assistance as well as the introduction of the newest methods of adjuvant treatment, in particular, photodynamic therapy, brachytherapy, and radiosurgery [9][10][11][12][13][14][15][16].…”

Current Standards of Care in Glioblastoma Therapy

“…A more extensive surgical resection is associated with longer life expectancy, achieving the longest survival in those patients who undergo gross total resection followed by RT and TMZ (13)(14)(15). An important issue is the fine balance between the aggressive removal and the preservation of function; so the goal is to achieve maximal safe surgical resection.…”

“…While strong predictors of good outcome are essentially patient related, the most important treatment-related predictor is extent of resection (EOR) (13). A more extensive surgical resection is associated with longer life expectancy, achieving the longest survival in those patients who undergo gross total resection followed by RT and TMZ (13)(14)(15).…”