‘Maximising’ Extent of Resection Matters a lot in Glioblastoma Management

Glioblastoma is the most common malignant primary brain tumor in adults and is known for its invasiveness, aggressive behavior and high relapse rates. Dating back to Dandy’s era, investigations on the best surgical procedures to maximize treatment outcome in gliomas have been spanning for almost 100 years. Based on the concept of obtaining tissue sample for definitive diagnosis and reducing intracranial pressure, biopsy remained the main purpose of surgery in the middle to late twentieth century which was performed by either burr-hole or craniotomy. As more evidence surfaced supporting the positive correlation between resection and survival, gross total resection came to the scientific community attention. Now, maximal safe resection of glioblastoma as the first step of standard therapy is an accepted treatment strategy in malignant glioma surgery, and more evidence has elucidated a positive relationship between surgical resection and survival.

With the advent of computed tomography (CT) and magnetic resonance imaging (MRI), neurosurgeons have been able to localize the tumor preoperatively, dramatically improving surgical accuracy and lowering morbidity and mortality. Moreover, the amount of tumor mass removed is no longer an approximate estimate of the neurosurgeons. In addition to this, evolution of advanced MRI techniques and algorithms like functional MRI, perfusion imaging, diffusion tensor imaging / tractography, treatment response assessment maps (TRAMs) etc. (Fig. 1) have really made a difference in assessment and resection of glioblastoma.

Initially, Lacroix et al. introduced the novel concept of a maximum extent of resection (EOR) and reported that resection of 89% or more of the tumor volume was necessary to obtain significant survival improvement after surgery, while resection of 98% or more of the tumor volume is a significant independent predictor of survival. In another study, Sanai et al. demonstrated in their study that as little as 78% EOR resulted in a significant survival advantage. In another paper, Orringer et al. showed that EOR is significantly affected by tumor location, size, and neurosurgeon’s expertise.

The concept of maximum EOR has stimulated active research and lead to several other publications on the relationship among gross total resection (GTR), residual volume (RV), and survival. In a large meta-analysis, it has been found that patients with newly diagnosed glioblastoma undergoing gross total resection (GTR) are 61% more likely to survive 1 year ,19% more likely to survive 2 years, and 51% more likely to be progression free at 12 months compared with patients receiving only an subtotal resection(STR).

In recent years, some new tools and techniques have been implemented to safely achieve GTR and to improve surgical results, such as fluorescein-guided techniques, awake craniotomy, intraoperative ultrasonography, intraoperative MRI (iMRI), intraoperative cortical stimulation/ mapping and neuronavigation with functional MRI (fMRI). In the past few years, fluorescein sodium- and 5-ALA-guided techniques have been reported in many institutions to be effective for maximal safe resection of GBM and for prolonging the patients’ progression-free survival.

Of particular interest is the fact that the use of preoperative fMRI and neuro-navigation (Fig. 2) has improved maximal safe resection of glioblastoma and prolonged median survival time to 20.7 months in literature. However, brain shift is an intrinsic difficulty in the use of neuronavigation, which result from patient’s positioning, dural opening, cerebrospinal fluid (CSF) loss, residual tumor volume decreasing, and peritumoral edema. It can be overcome by intraoperative MRI and intraoperative ultrasound. Intraoperative ultrasound is relatively inexpensive tool compared to iMRI and is convenient to account for brain shift, predict residual tumor, and visualize vascular relationships to tumor. Intraoperative ultrasound is an operator-dependent technique, so the learning curve for the technique can be steep and the level of experience in its use can affect image quality, orientation, and interpretation.

In conclusion, maximal safe resection (Fig. 3, 4 & 5) should be the aim of glioblastoma surgery to pass on the survival benefit to the patients. Experience has proven that such surgeries should be performed at dedicated neuro-oncology centres where most neurosurgical gadgets/adjuncts and necessary expertise is available so that required balance between maximal resection and safety is maintained.

Dr. Ramandeep Singh Jaggi
Sr. Consultant and Unit Head
Neurosurgical Oncology (Brain and Spine)