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.
Bryan D. Choi, William T. Curry, Bob S. Carter and Marcela V. Maus
Roukoz B. Chamoun, William E. Whitehead, Daniel J. Curry, Thomas G. Luerssen and Andrew Jea
The use of C-1 lateral mass screws provides an alternative to C1–2 transarticular screws in the pediatric population. However, the confined space of the local anatomy and unfamiliarity with the technique may make the placement of a C-1 lateral mass screw more challenging, especially in the juvenile or growing spine.
A CT morphometric analysis was performed in 76 pediatric atlases imaged at Texas Children's Hospital from October 1, 2007 until April 30, 2008. Critical measurements were determined for potential screw entry points, trajectories, and lengths, with the goal of replicating the operative technique described by Harms and Melcher for adult patients.
The mean height and width for screw entry on the posterior surface of the lateral mass were 2.6 and 8.5 mm, respectively. The mean medially angled screw trajectory from an idealized entry point on the lateral mass was 16° (range 4 to 27°). The mean maximal screw depth from this same ideal entry point was 20.3 mm. The overhang of the posterior arch averaged 6.3 mm (range 2.1–12.4 mm). The measurement between the left- and right-side lateral masses was significantly different for the maximum medially angled screw trajectory (p = 0.003) and the maximum inferiorly directed angle (p = 0.045). Those measurements in children < 8 years of age were statistically significant for the entry point height (p = 0.038) and maximum laterally angled screw trajectory (p = 0.025) compared with older children. The differences between boys and girls were statistically significant for the minimum screw length (p = 0.04) and the anterior lateral mass height (p < 0.001).
A significant variation in the morphological features of C-1 exists, especially between the left and right sides and in younger children. The differences between boys and girls are clinically insignificant. The critical measurement of whether the C-1 lateral mass in a child could accommodate a 3.5-mm-diameter screw is the width of the lateral mass and its proximity to the vertebral artery. Only 1 of 152 lateral masses studied would not have been able to accommodate a lateral mass screw. This study reemphasizes the importance of a preoperative CT scan of the upper cervical spine to assure safe and effective placement of the instrumentation at this level.
Ashwin Viswanathan, Katherine Relyea, William E. Whitehead, Daniel J. Curry, Thomas G. Luerssen and Andrew Jea
The authors describe a rare case of pneumothorax as a complication of thoracic pedicle screw placement in an 11-year-old girl undergoing posterior segmental instrumentation for a kyphotic deformity. Spontaneous pneumothorax after posterior fusion for adolescent idiopathic scoliosis has been reported in the orthopedic literature; however, to the best of the authors' knowledge, pneumothorax directly related to pedicle screw placement for spinal deformity has not been previously described. The authors discuss the anatomical and technical aspects leading to this complication and the lessons learned from it.
Pamela S. Jones, Daniel P. Cahill, Priscilla K. Brastianos, Keith T. Flaherty and William T. Curry
In patients with large or symptomatic brain lesions from metastatic melanoma, the value of resection of metastases to facilitate administration of systemic ipilimumab therapy has not yet been described. The authors undertook this study to investigate whether craniotomy creates the opportunity for patients to receive and benefit from ipilimumab who would otherwise succumb to brain metastasis prior to the onset of regression.
All patients with metastatic melanoma who received ipilimumab and underwent craniotomy for metastasis resection between 2008 and 2014 at the Massachusetts General Hospital were identified through retrospective chart review. The final analysis included cases involving patients who underwent craniotomy within 3 months prior to initiation of therapy or up to 6 months after cessation of ipilimumab administration.
Twelve patients met the inclusion criteria based on timing of therapy (median age 59.2). The median number of metastases at the time of craniotomy was 2. The median number of ipilimumab doses received was 4. Eleven of 12 courses of ipilimumab were stopped for disease progression, and 1 was stopped for treatment-induced colitis. Eight of 12 patients had improvement in their performance status following craniotomy. Of the 6 patients requiring corticosteroids prior to craniotomy, 3 tolerated corticosteroid dose reduction after surgery. Ten of 12 patients had died by the time of data collection, with 1 patient lost to follow-up. The median survival after the start of ipilimumab treatment was 7 months.
In this series, patients who underwent resection of brain metastases in temporal proximity to receiving ipilimumab had qualitatively improved performance status following surgery in most cases. Surgery facilitated corticosteroid reduction in select patients. Larger analyses are required to better understand possible synergies between craniotomy for melanoma metastases and ipilimumab treatment.
William T. Curry Jr., G. Rees Cosgrove, Bradley R. Buchbinder and Robert G. Ojemann
Intraventricular meningiomas of the lateral ventricle occur relatively rarely, but they are often large at the time of detection and present more commonly on the left side. Although the ability to resect these tumors safely has greatly improved over time, standard surgical approaches often traverse cortex close to areas of specific cortical function. Precise cortical mapping of language and sensorimotor cortices can be accomplished noninvasively by using functional magnetic resonance (fMR) imaging. The authors used fMR imaging in planning the cortical incision for resection of a large intraventricular trigone meningioma in the dominant hemisphere of a patient who, postoperatively, suffered no aphasia or hemiparesis. The authors discuss the advantages of mapping cortical function preoperatively with fMR imaging when approaching intraventricular lesions.
William T. Curry Jr., Garth Rees Cosgrove, Fred H. Hochberg, Jay Loeffler and Nicholas T. Zervas
Object. The Photon Radiosurgery System (PRS) is a miniature x-ray generator that can stereotactically irradiate intracranial tumors by using low-energy photons. Treatment with the PRS typically occurs in conjunction with stereotactic biopsy, thereby providing diagnosis and treatment in one procedure. The authors review the treatment of patients with brain metastases with the aid of the PRS and discuss the indications, advantages, and limitations of this technique.
Methods. Clinical characteristics, treatment parameters, neuroimaging-confirmed outcome, and survival were reviewed in all patients with histologically verified brain metastases who were treated with the PRS at the Massachusetts General Hospital between December 1992 and November 2000. Local control of lesions was defined as either stabilization or diminution in the size of the treated tumor as confirmed by Gd-enhanced magnetic resonance imaging.
Between December 1992 and November 2000, 72 intracranial metastatic lesions in 60 patients were treated with the PRS. Primary tumors included lung (33 patients), melanoma (15 patients), renal cell (five patients), breast (two patients), esophageal (two patients), colon (one patient), and Merkle cell (one patient) cancers, and malignant fibrous histiocytoma (one patient). Supratentorial metastases were distributed throughout the cerebrum, with only one cerebellar metastasis. The lesions ranged in diameter from 6 to 40 mm and were treated with a minimal peripheral dose of 16 Gy (range 10–20 Gy). At the last follow-up examination (median 6 months), local disease control had been achieved in 48 (81%) of 59 tumors. An actuarial analysis demonstrated that the survival rates at 6 and 12 months were 63 and 34%, respectively. Patients with a single brain metastasis survived a mean of 11 months. Complications included four patients with postoperative seizures, three with symptomatic cerebral edema, two with hemorrhagic events, and three with symptomatic radiation necrosis requiring surgery.
Conclusions. Stereotactic interstitial radiosurgery performed using the PRS can obtain local control of cerebral metastases at rates that are comparable to those achieved through open resection and external stereotactic radiosurgery. The major advantage of using the PRS is that effective treatment can be accomplished at the time of stereotactic biopsy.
William T. Curry, Michael W. McDermott, Bob S. Carter and Fred G. Barker II
Object. The goal of this study was to determine the risk of adverse outcomes after contemporary surgical treatment of meningiomas in the US and trends in patient outcomes and patterns of care.
Methods. The authors performed a retrospective cohort study by using the Nationwide Inpatient Sample covering the period of 1988 to 2000. Multivariate regression models with disposition end points of death and hospital discharge were used to test patient, surgeon, and hospital characteristics, including volume of care, as outcome predictors.
Multivariate analyses revealed that larger-volume centers had lower mortality rates for patients who underwent craniotomy for meningioma (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.59–0.93, p = 0.01). Adverse discharge disposition was also less likely at high-volume hospitals (OR 0.71, 95% CI 0.62–0.80, p < 0.001). With respect to the surgeon caseload, there was a trend toward a lower rate of mortality after surgery when higher-caseload providers were involved, and a significantly less frequent adverse discharge disposition (OR 0.71, 95% CI 0.62–0.80, p <, 0.001).
The annual meningioma caseload in the US increased 83% between 1988 and 2000, from 3900 patients/year to 7200 patients/year. In-hospital mortality rates decreased 61%, from 4.5% in 1988 to 1.8% in 2000. Reductions in the mortality rates were largest at high-volume centers (a 72% reduction in the relative mortality rate at largest-volume-quintile centers, compared with a 6% increase in the relative mortality rate at lowest-volume-quintile centers). The number of US hospitals where craniotomies were performed for meningiomas increased slightly. Fewer centers hosted one meningioma resection annually, whereas the largest centers had disproportionate increases in their caseloads, indicating a modest centralization of meningioma surgery in the US during this interval.
Conclusions. The mortality and adverse hospital discharge disposition rates were lower when meningioma surgery was performed by high-volume providers. The annual US caseload increased, whereas the mortality rates decreased, especially at high-volume centers.
Roberto C. Heros
Pamela S. Jones, Gavin P. Dunn, Fred G. Barker II, William T. Curry, Fred H. Hochberg and Daniel P. Cahill
The authors' goal was to review the current understanding of the underlying molecular and genetic mechanisms involved in low-grade glioma development and how these mechanisms can be targets for detection and treatment of the disease and its recurrence.
On October 4, 2012, the authors convened a meeting of researchers and clinicians across a variety of pertinent medical specialties to review the state of current knowledge on molecular genetic mechanisms of low-grade gliomas and to identify areas for further research and drug development.
The meeting consisted of 3 scientific sessions ranging from neuropathology of IDH1 mutations; CIC, ATRX, and FUBP1 mutations in oligodendrogliomas and astrocytomas; and IDH1 mutations as therapeutic targets. Sessions consisted of a total of 10 talks by international leaders in low-grade glioma research, mutant IDH1 biology and its application in glioma research, and treatment.
The recent discovery of recurrent gene mutations in low-grade glioma has increased the understanding of the molecular mechanisms involved in a host of biological activities related to low-grade gliomas. Understanding the role these genetic alterations play in brain cancer initiation and progression will help lead to the development of novel treatment modalities than can be personalized to each patient, thereby helping transform this now often-fatal malignancy into a chronic or even curable disease.
Steven W. Hwang, George Al-Shamy, William E. Whitehead, Daniel J. Curry, Robert Dauser, Thomas G. Luerssen and Andrew Jea
Endoscopic third ventriculostomy (ETV) is an accepted option in the treatment of obstructive hydrocephalus in children and is considered by many pediatric neurosurgeons to be the treatment of choice in this population. The procedure involves perforation of the floor of the third ventricle, specifically, the tuber cinereum, which is part of the hypothalamic-pituitary axis of cerebral endocrine regulation. Endocrine dysfunction, such as amenorrhea, weight gain, and precocious puberty, which are recognized only months to years after the procedure, may be underreported because patients and physicians may not relate the endocrine sequelae to the ETV. Few detailed reports of endocrinerelated complications following ETV exist to better understand these issues. In this study, the authors add to the literature with case descriptions of and correlative laboratory findings in 2 adolescent girls who underwent ETV for obstructive hydrocephalus and in whom amenorrhea subsequently developed.