Bryan D. Choi, William T. Curry, Bob S. Carter, and Marcela V. Maus
The prognosis for glioblastoma (GBM) remains exceedingly poor despite state-of-the-art multimodal therapy. Immunotherapy, particularly with cytotoxic T cells, represents a promising alternative. Perhaps the most prominent T-cell technology is the chimeric antigen receptor (CAR), which in 2017 received accelerated approval from the Food and Drug Administration for the treatment of hematological malignancies. Several CARs for GBM have been recently tested in clinical trials with exciting results. The authors review these clinical data and discuss areas of ongoing research.
Nelson M. Oyesiku
Tiffany R. Hodges, Bryan D. Choi, Darell D. Bigner, Hai Yan, and John H. Sampson
Isocitrate dehydrogenase 1 (IDH1) mutations have been discovered to be frequent and highly conserved in secondary glioblastoma multiforme and lower-grade gliomas. Although IDH1 mutations confer a unique genotype that has been associated with a favorable prognosis, the role of the mutated IDH1 enzyme and its metabolites in tumor initiation and maintenance remains unresolved. However, given that IDH1 mutations are homogeneously expressed and are limited solely to tumor tissue, targeting this mutation could potentially yield novel treatment strategies for patients with glioblastoma multiforme.
Bryan D. Choi, Michael R. DeLong, David M. DeLong, Allan H. Friedman, and John H. Sampson
The purpose of this study was to report the prevalence of neurosurgeons with both medical degrees (MDs) and doctorates (PhDs) at top-ranked US academic institutions and to assess whether the additional doctorate education is associated with substantive career involvement in academia as well as greater success in procuring National Institutes of Health (NIH) research funding compared with an MD-only degree.
The authors reviewed the training of neurosurgeons across the top 10 neurosurgery departments chosen according to academic impact (h index) to examine whether MD-PhD training correlated significantly with career outcomes in academia.
Six hundred thirteen neurosurgery graduates and residents between the years 1990 and 2012 were identified for inclusion in this analysis. Both MD and PhD degrees were held by 121 neurosurgeons (19.7%), and an MD alone was held by 492. Over the past 2 decades, MD-PhD trainees represented a gradually increasing percentage of neurosurgeons, from 10.2% to 25.7% (p < 0.01). Of the neurosurgeons with MD-PhD training, a greater proportion had appointments in academic medicine compared with their MD-only peers (73.7% vs 52.3%, p < 0.001). Academic neurosurgeons with both degrees were also more likely to have received NIH funding (51.9% vs 31.8%, p < 0.05) than their single-degree counterparts in academia. In a national analysis of all active NIH R01 grants awarded in neurosurgery, MD-PhD investigators held a disproportionate number, more than 4-fold greater than their representation in the field.
Dual MD-PhD training is a significant factor that may predict active participation in and funding for research careers among neurological surgeons at top-ranked academic institutions. These findings and their implications are of increasing relevance as the population of neurosurgeons with dual-degree training continues to rise.
Bryan D. Choi, Peter E. Fecci, and John H. Sampson
Bryan D. Choi, Daniel K. Lee, Jimmy C. Yang, Caroline M. Ayinon, Christine K. Lee, Douglas Maus, Bob S. Carter, Fred G. Barker II, Pamela S. Jones, Brian V. Nahed, Daniel P. Cahill, Reiner B. See, Mirela V. Simon, and William T. Curry
Intraoperative seizures during craniotomy with functional mapping is a common complication that impedes optimal tumor resection and results in significant morbidity. The relationship between genetic mutations in gliomas and the incidence of intraoperative seizures has not been well characterized. Here, the authors performed a retrospective study of patients treated at their institution over the last 12 years to determine whether molecular data can be used to predict the incidence of this complication.
The authors queried their institutional database for patients with brain tumors who underwent resection with intraoperative functional mapping between 2005 and 2017. Basic clinicopathological characteristics, including the status of the following genes, were recorded: IDH1/2, PIK3CA, BRAF, KRAS, AKT1, EGFR, PDGFRA, MET, MGMT, and 1p/19q. Relationships between gene alterations and intraoperative seizures were evaluated using chi-square and two-sample t-test univariate analysis. When considering multiple predictive factors, a logistic multivariate approach was taken.
Overall, 416 patients met criteria for inclusion; of these patients, 98 (24%) experienced an intraoperative seizure. Patients with a history of preoperative seizure and those treated with antiepileptic drugs prior to surgery were less likely to have intraoperative seizures (history: OR 0.61 [95% CI 0.38–0.96], chi-square = 4.65, p = 0.03; AED load: OR 0.46 [95% CI 0.26–0.80], chi-square = 7.64, p = 0.01). In a univariate analysis of genetic markers, amplification of genes encoding receptor tyrosine kinases (RTKs) was specifically identified as a positive predictor of seizures (OR 5.47 [95% CI 1.22–24.47], chi-square = 5.98, p = 0.01). In multivariate analyses considering RTK status, AED use, and either 2007 WHO tumor grade or modern 2016 WHO tumor groups, the authors found that amplification of the RTK proto-oncogene, MET, was most predictive of intraoperative seizure (p < 0.05).
This study describes a previously unreported association between genetic alterations in RTKs and the occurrence of intraoperative seizures during glioma resection with functional mapping. Future models estimating intraoperative seizure risk may be enhanced by inclusion of genetic criteria.