Shawn L. Hervey-Jumper, Jing Li, Joseph A. Osorio, Darryl Lau, Annette M. Molinaro, Arnau Benet and Mitchel S. Berger
Though challenging, maximal safe resection of insular gliomas enhances overall and progression-free survival and deters malignant transformation. Previously published reports have shown that surgery can be performed with low morbidity. The authors previously described a Berger-Sanai zone classification system for insular gliomas. Using a subsequent dataset, they undertook this study to validate this zone classification system for predictability of extent of resection (EOR) in patients with insular gliomas.
The study population included adults who had undergone resection of WHO Grade II, III, or IV insular gliomas. In accordance with our prior published report, tumor location was classified according to the Berger-Sanai quadrant-style classification system into Zones I through IV. Interobserver variability was analyzed using a cohort of newly diagnosed insular gliomas and independent classification scores given by 3 neurosurgeons at various career stages. Glioma volumes were analyzed using FLAIR and T1-weighted contrast-enhanced MR images.
One hundred twenty-nine procedures involving 114 consecutive patients were identified. The study population from the authors’ previously published experience included 115 procedures involving 104 patients. Thus, the total experience included 244 procedures involving 218 patients with insular gliomas treated at the authors’ institution. The most common presenting symptoms were seizure (68.2%) and asymptomatic recurrence (17.8%). WHO Grade II glioma histology was the most common (54.3%), followed by Grades III (34.1%) and IV (11.6%). The median tumor volume was 48.5 cm3. The majority of insular gliomas were located in the anterior portion of the insula with 31.0% in Zone I, 10.9% in Zone IV, and 16.3% in Zones I+IV. The Berger-Sanai zone classification system was highly reliable, with a kappa coefficient of 0.857. The median EOR for all zones was 85%. Comparison of EOR between the current and prior series showed no change and Zone I gliomas continue to have the highest median EOR. Short- and long-term neurological complications remain low, and zone classification correlated with short-term complications, which were highest in Zone I and in Giant insular gliomas.
The previously proposed Berger-Sanai classification system is highly reliable and predictive of insular glioma EOR and morbidity.
Shawn L. Hervey-Jumper, Jing Li, Darryl Lau, Annette M. Molinaro, David W. Perry, Lingzhong Meng and Mitchel S. Berger
Awake craniotomy is currently a useful surgical approach to help identify and preserve functional areas during cortical and subcortical tumor resections. Methodologies have evolved over time to maximize patient safety and minimize morbidity using this technique. The goal of this study is to analyze a single surgeon's experience and the evolving methodology of awake language and sensorimotor mapping for glioma surgery.
The authors retrospectively studied patients undergoing awake brain tumor surgery between 1986 and 2014. Operations for the initial 248 patients (1986–1997) were completed at the University of Washington, and the subsequent surgeries in 611 patients (1997–2014) were completed at the University of California, San Francisco. Perioperative risk factors and complications were assessed using the latter 611 cases.
The median patient age was 42 years (range 13–84 years). Sixty percent of patients had Karnofsky Performance Status (KPS) scores of 90–100, and 40% had KPS scores less than 80. Fifty-five percent of patients underwent surgery for high-grade gliomas, 42% for low-grade gliomas, 1% for metastatic lesions, and 2% for other lesions (cortical dysplasia, encephalitis, necrosis, abscess, and hemangioma). The majority of patients were in American Society of Anesthesiologists (ASA) Class 1 or 2 (mild systemic disease); however, patients with severe systemic disease were not excluded from awake brain tumor surgery and represented 15% of study participants. Laryngeal mask airway was used in 8 patients (1%) and was most commonly used for large vascular tumors with more than 2 cm of mass effect. The most common sedation regimen was propofol plus remifentanil (54%); however, 42% of patients required an adjustment to the initial sedation regimen before skin incision due to patient intolerance. Mannitol was used in 54% of cases. Twelve percent of patients were active smokers at the time of surgery, which did not impact completion of the intraoperative mapping procedure. Stimulation-induced seizures occurred in 3% of patients and were rapidly terminated with ice-cold Ringer's solution. Preoperative seizure history and tumor location were associated with an increased incidence of stimulation-induced seizures. Mapping was aborted in 3 cases (0.5%) due to intraoperative seizures (2 cases) and patient emotional intolerance (1 case). The overall perioperative complication rate was 10%.
Based on the current best practice described here and developed from multiple regimens used over a 27-year period, it is concluded that awake brain tumor surgery can be safely performed with extremely low complication and failure rates regardless of ASA classification; body mass index; smoking status; psychiatric or emotional history; seizure frequency and duration; and tumor site, size, and pathology.
Darryl Lau, Shawn L. Hervey-Jumper, Susan Chang, Annette M. Molinaro, Michael W. McDermott, Joanna J. Phillips and Mitchel S. Berger
There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity.
A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4-point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated.
A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating with cellularity Grade 3 ranged from 95% to 100% and 86% to 100%, respectively. In biopsies without tumor (cellularity Grade 0), 35.4% still demonstrated ALA fluorescence. Of those biopsies, 90.9% contained abnormal brain tissue, characterized by reactive astrocytes, scattered atypical cells, or inflammation, and 8.1% had normal brain. In nonfluorescent (ALA intensity 0) biopsies, 62.3% had tumor cells present. The ALA-associated complication rate among the study cohort was 3.4%.
The PPV of utilizing the most robust ALA fluorescence intensity (lava-like orange) as a predictor of tumor presence is high. However, the NPV of utilizing the absence of fluorescence as an indicator of no tumor is poor. ALA intensity is a strong predictor for degree of tumor cellularity for the most fluorescent areas but less so for lower ALA intensities. Even in the absence of tumor cells, reactive changes may lead to ALA fluorescence.