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James H. Manfield and Kenny K. H. Yu

In the United Kingdom, ultrasound-guided external ventricular drain (EVD) insertion is becoming the standard of care to mitigate the morbidity associated with catheter malposition and multiple passes. Many neurosurgeons routinely use ultrasound to check the preinsertion trajectory, although real-time visualization of ventricular cannulation is preferable since minor deviations can be significant in patients with smaller ventricles, and live visualization further enables the catheter tip to be adjusted away from the choroid plexus. Such real-time ultrasound navigation has traditionally been limited by technical factors including the challenge of simultaneously manipulating the probe and inserting the catheter within the same image plane.

The authors here describe a simple technique for precise EVD placement using a readily available bur hole ultrasound transducer attached to a 10-gauge needle guide channel (principally used for biopsy procedures) to accommodate a ventriculostomy catheter. The anticipated trajectory line is then projected onto the display and followed into the ipsilateral lateral ventricle. This is illustrated with a representative case and video demonstrating this rapid, user-friendly, and reliable technique. The authors invite others to consider this useful technique to minimize the risks of catheter misplacement or multiple cannulation attempts, which can be of particular benefit to junior neurosurgeons performing difficult cases under pressured conditions.

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Teng-yu Li, Yu-lun Xu, Jun Yang, James Wang and Gui-Huai Wang

OBJECT

The aim of this study was to investigate the clinical characteristics, imaging features, differential diagnosis, treatment options, and prognosis for primary spinal epidural cavernous hemangiomas.

METHODS

Fourteen patients with pathologically diagnosed non–vertebral origin cavernous hemangiomas who had undergone surgery at Beijing Tiantan Hospital between 2003 and 2012 were identified in the hospital's database. The patients' clinical data, imaging characteristics, surgical treatment, and postoperative follow-up were analyzed retrospectively.

RESULTS

There were 9 males and 5 females with an average age of 51.64 years. The primary epidural cavernous hemangiomas were located in the cervical spine (2 cases), cervicothoracic junction (2 cases), thoracic spine (8 cases), thoracolumbar junction (1 case), and lumbar spine (1 case). Hemorrhage was confirmed in 4 cases during surgery. Preoperatively 5 lesions were misdiagnosed as schwannoma, 1 was misdiagnosed as a meningioma, and 1 was misdiagnosed as an arachnoid cyst. Preoperative hemorrhages were identified in 2 cases. Three patients had recurrent cavernous hemangiomas. The initial presenting symptoms were local pain in 5 cases, radiculopathy in 6 cases, and myelopathy in 3 cases. Upon admission, 1 patient had radicular symptoms and 13 had myelopathic symptoms. The average symptom duration was 18 months. All patients underwent surgery; complete resection was achieved in 8 cases, subtotal resection in 4 cases, and partial resection in 2 cases. Postoperative follow-up was completed in 10 cases (average follow-up 34 months); 1 patient died, 5 patients showed clinical improvement, and 4 patients remained neurologically unchanged.

CONCLUSIONS

Total surgical removal of spine epidural cavernous hemangiomas with a chronic course is the optimum treatment and carries a good prognosis. Secondary surgery for recurrent epidural cavernous hemangioma is technically more challenging. In patients with profound myelopathy from acute hemorrhage, even prompt surgical decompression can rarely reverse all symptoms.

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Charu Singh, Jack M. Qian, James B. Yu and Veronica L. Chiang

OBJECTIVE

Concurrent use of anti-PD-1 therapies with stereotactic radiosurgery (SRS) have been shown to be beneficial for survival and local lesional control in melanoma patients with brain metastases. It is not known, however, if immunotherapy (IT) confers the same outcome advantage in lung cancer patients with brain metastases treated with SRS.

METHODS

The authors retrospectively reviewed 85 non–small cell lung cancer (NSCLC) patients with brain metastases who were treated with SRS between January 2006 and December 2016. Thirty-nine PD-L1 antibody–positive patients received anti-PD-1 therapy with SRS (IT group) and 46 patients received chemotherapy (CT) with SRS (CT group). Results were obtained using chi-square, Kaplan-Meier, and Mann-Whitney U tests and Cox regression analyses.

RESULTS

Median survival following first radiosurgical treatment in the whole study group was 11.6 months (95% CI 8–15.5 months). Median survival times in the IT group and CT group were 10 months (95% CI 8.3–13.2 months) and 11.6 months (95% CI 7.7–15.6 months), respectively (p = 0.23). A Karnofsky Performance Status (KPS) score < 80 (p = 0.001) and lung-specific molecular marker Graded Prognostic Assessment (lungmol GPA) score < 1.5 (p = 0.02) were found to be predictive of worse survival.

Maximal percent lesional shrinkage and time to maximal shrinkage were not significantly different between the CT and IT groups. Of the lesions for which a complete response occurred, 94.8% had pre-SRS volumes < 500 mm3. The amount of lesion shrinkage and time to maximal shrinkage were not different between the IT and CT groups for lesions with volumes < 500 mm3. However, in lesions with volume > 500 mm3, 90% of lesions shrank after radiosurgery in the IT group compared with 47.8% in the CT group (p = 0.001). Median times to initial response and times to maximal shrinkage were faster in the IT group than in the CT group: initial response 49 days (95% CI 33.7–64.3 days) versus 84 days (95% CI 28.1–140 days), p = 0.001; maximal response 105 days (95% CI 59–150 days) versus 182 days (95% CI 119.6–244 days), p = 0.12.

CONCLUSIONS

Unlike patients with melanoma, patients with NSCLC with brain metastases undergoing SRS showed no significant benefit—either in terms of survival or total amount of lesional response—when anti-PD-1 therapies were used. However, in lesions with volume > 500 mm3, combining SRS with IT may result in a faster and better volumetric response which may be particularly beneficial in lesions causing mass effect or located in neurologically critical locations.

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James W. Simpkins, Gopal Rajakumar, Yu-Qi Zhang, Christopher E. Simpkins, David Greenwald, Chun J. Yu, Nicholas Bodor and Arthur L. Day

✓ The present study was undertaken to determine if estrogens protect female rats from the neurodegenerative effects of middle cerebral artery (MCA) occlusion. The rats were ovariectomized and 7 or 8 days later various estrogen preparations were administered before or after MCA occlusion. Pretreatment with 17β-estradiol (17β-E2) or a brain-targeted 17β-E2 chemical delivery system (CDS) decreased mortality from 65% in ovariectomized rats to 22% in 17β-E2—treated and 16% in 17β-E2 CDS—treated rats. This marked reduction in mortality was accompanied by a reduction in the ischemic area of the brain from 25.6 ± 5.7% in the ovariectomized rats to 9.8 ± 4% and 9.1 ± 4.2% in the 17β-E2—implanted and the 17β-E2 CDS—treated rats, respectively. Similarly, pretreatment with the presumed inactive estrogen, 17α-estradiol, reduced mortality from 36 to 0% and reduced the ischemic area by 55 to 81%. When administered 40 or 90 minutes after MCA occlusion, 17β-E2 CDS reduced the area of ischemia by 45 to 90% or 31%, respectively. In summary, the present study provides the first evidence that estrogens exert neuroprotective effects in an animal model of ischemia and suggests that estrogens may be a useful therapy to protect neurons against the neurodegenerative effects of stroke.

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Rovel J. Colaco, Pierre Martin, Harriet M. Kluger, James B. Yu and Veronica L. Chiang

OBJECT

Radiation necrosis (RN), or its imaging equivalent, treatment-related imaging changes (TRIC), is an inflammatory reaction to high-dose radiation in the brain. The authors sought to investigate the hypothesis that immunotherapy increases the risk of developing RN/TRIC after stereotactic Gamma Knife (GK) radiosurgery for brain metastases.

METHODS

A total of 180 patients who underwent GK surgery for brain metastases between 2006 and 2012 were studied. The systemic therapy they received was classified as cytotoxic chemotherapy (CT), targeted therapy (TT), or immunotherapy (IT). The timing of systemic therapy in relation to GK treatment was also recorded. Logistic regression was used to calculate the odds of developing RN according to type of systemic therapy received.

RESULTS

The median follow-up time was 11.7 months. Of 180 patients, 39 (21.7%) developed RN/TRIC. RN/TRIC rates were 37.5% (12 of 32) in patients who received IT alone, 16.9% (14 of 83) in those who received CT only, and 25.0% (5 of 20) in those who received TT only. Median overall survival was significantly longer in patients who developed RN/TRIC (23.7 vs 9.9 months, respectively). The RN/TRIC rate was increased significantly in patients who received IT alone (OR 2.40 [95% CI 1.06–5.44]; p = 0.03), whereas receipt of any CT was associated with a lower risk of RN/TRIC (OR 0.38 [95% CI 0.18–0.78]; p = 0.01). The timing of development of RN/TRIC was not different between patients who received IT and those who received CT.

CONCLUSIONS

Patients who receive IT alone may have an increased rate of RN/TRIC compared with those who receive CT or TT alone after stereotactic radiosurgery, whereas receiving any CT may in fact be protective against RN/TRIC. As the use of immunotherapies increases, the rate of RN/TRIC may be expected to increase compared with rates in the chemotherapy era.

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John S. Yu, M. Priscilla Short, James Schumacher, Paul H. Chapman and Griffith R. Harsh IV

✓ The authors describe two cases of intramedullary hemorrhage caused by thoracic hemangioblastoma. Both patients presented with acute paraplegia. The lesion in the first case was diagnosed by myelography and in the second by magnetic resonance imaging. Emergency surgical evacuation of the intramedullary hematoma and tumor was performed in these patients. Hemangioblastoma was confirmed by histopathological examination in both cases. Both patients remain paraplegic after 7 and 1 years, respectively. Intramedullary hemorrhage is a rare and devastating effect of spinal hemangioblastoma.

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Teng-yu Li, Jun-sheng Chu, Yu-lun Xu, Jun Yang, James Wang, Yu-Hua Huang, Aij-Lie Kwan and Gui-Huai Wang

Object

The aim of this study was to investigate the surgical strategies and outcomes for spinal ependymomas of different lengths.

Methods

The authors used data from 210 patients with spinal ependymomas (WHO Grades II and III) in this 10-year retrospective study (January 1999 to December 2008), dividing them into 3 different groups according to length (spinal ependymomas < 5 cm, 5–10 cm, and > 10 cm). All patients underwent tumor resection. The basic characteristics of the patients were reviewed and the functional status was assessed using the McCormick classification.

Results

There were 89, 81, and 40 patients, respectively, in the 3 groups (< 5 cm, 5–10 cm, and > 10 cm). Grosstotal resections (GTRs) were performed in 172 patients (81.9% overall, or 86.5%, 79.0%, and 77.5% in the 3 groups, respectively). Subtotal and partial resections were achieved in 38 patients (18.1%). Eight patients with medulla oblongata or upper cervical cord tumors received a tracheotomy postoperatively. The follow-up period ranged from 56 to 176 months. One hundred thirty-five patients (76.7%) experienced improvement, (88.2%, 83.8%, and 34.4% in the < 5 cm, 5–10 cm, and > 10 cm groups, respectively). Thirty-three patients (18.8%) maintained their pretreatment status, and 8 patients (4.5%) showed deterioration following tumor resection at 6 months. Tumor recurrence or progression was observed in 6 (2.9%) of the 210 patients. Among the 6 patients, recurrent tumors were located in the conus (n = 3), thoracic (n = 1), and medullocervical cord (n = 2).

Conclusions

Radical resection of spinal ependymomas could be performed in most patients, and the rate of GTR was significantly different in the different-length groups (< 10 cm vs > 10 cm, p = 0.032). Patients with longer tumors had worse surgical results compared with those with small tumors (p < 0.001), and more postoperative neuropathic pain and proprioceptive deficits could usually be observed in patients harboring larger tumors. Early diagnosis and timely operation are critical to achieving better neurological outcomes. For tumors with dense adhesions, complete removal should be performed cautiously because of the significant incidence of neurological deterioration.

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Henry S. Park, Elyn H. Wang, Charles E. Rutter, Christopher D. Corso, Veronica L. Chiang and James B. Yu

OBJECT

Single-fraction stereotactic radiosurgery (SRS) is a crucial component in the management of limited brain metastases from non-small cell lung cancer (NSCLC). Intracranial SRS has traditionally been delivered using a frame-based Gamma Knife (GK) platform, but stereotactic modifications to the linear accelerator (LINAC) have made an alternative approach possible. In the absence of definitive prospective trials comparing the efficacy and toxicities of treatment between the 2 techniques, nonclinical factors (such as technology accessibility, costs, and efficiency) may play a larger role in determining which radiosurgery system a facility may choose to install. To the authors’ knowledge, this study is the first to investigate national patterns of GK SRS versus LINAC SRS use and to determine which factors may be associated with the adoption of these radiosurgery systems.

METHODS

The National Cancer Data Base was used to identify patients > 18 years old with NSCLC who were treated with single-fraction SRS to the brain between 2003 and 2011. Patients who received “SRS not otherwise specified” or who did not receive a radiotherapy dose within the range of 12–24 Gy were excluded to reduce the potential for misclassification. The chi-square test, t-test, and multivariable logistic regression analysis were used to compare potential demographic, clinicopathologic, and health care system predictors of GK versus LINAC SRS use, when appropriate.

RESULTS

This study included 1780 patients, among whom 1371 (77.0%) received GK SRS and 409 (23.0%) underwent LINAC SRS. Over time, the proportion of patients undergoing LINAC SRS steadily increased, from 3.2% in 2003 to 30.8% in 2011 (p < 0.001). LINAC SRS was adopted more rapidly by community versus academic facilities (overall 29.2% vs 17.2%, p < 0.001). On multivariable analysis, 4 independent predictors of increased LINAC SRS use emerged, including year of diagnosis in 2008–2011 versus 2003–2007 (adjusted OR [AOR] 2.04, 95% CI 1.52–2.73, p < 0.001), community versus academic facility type (AOR 2.04, 95% CI 1.60–2.60, p < 0.001), non-West versus West geographic location (AOR 4.50, 95% CI 2.87–7.09, p < 0.001), and distance from cancer reporting facility of < 20 versus ≥ 20 miles (AOR 1.57, 95% CI 1.21–2.04, p = 0.001).

CONCLUSIONS

GK remains the most commonly used single-fraction SRS modality for NSCLC brain metastases in the US. However, LINAC-based SRS has been rapidly disseminating in the past decade, especially in the community setting. Wide geographic variation persists in the distribution of GK and LINAC SRS cases. Further comparative effectiveness research will be needed to evaluate the impact of these shifts on SRS-related toxicities, local control, and survival, as well as treatment costs and efficiency.

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Jonathan P. S. Knisely, James B. Yu, Jaclyn Flanigan, Mario Sznol, Harriet M. Kluger and Veronica L. S. Chiang

Object

A prospectively collected cohort of 77 patients who underwent definitive radiosurgery between 2002 and 2010 for melanoma brain metastases was retrospectively reviewed to assess the impact of ipilimumab use and other clinical variables on survival.

Methods

The authors conducted an institutional review board–approved chart review to assess patient age at the time of brain metastasis diagnosis, sex, primary disease location, initial radiosurgery date, number of metastases treated, performance status, systemic therapy and ipilimumab history, whole-brain radiation therapy (WBRT) use, follow-up duration, and survival at the last follow-up. The Diagnosis-Specific Graded Prognostic Assessment (DSGPA) score was calculated for each patient based on performance status and the number of brain metastases treated.

Results

Thirty-five percent of the patients received ipilimumab. The median survival in this group was 21.3 months, as compared with 4.9 months in patients who did not receive ipilimumab. The 2-year survival rate was 47.2% in the ipilimumab group compared with 19.7% in the nonipilimumab group. The DS-GPA score was the most significant predictor of overall survival, and ipilimumab therapy was also independently associated with an improvement in the hazard for death (p = 0.03).

Conclusions

The survival of patients with melanoma brain metastases managed with ipilimumab and definitive radiosurgery can exceed the commonly anticipated 4–6 months. Using ipilimumab in a supportive treatment paradigm of radiosurgery for brain oligometastases was associated with an increased median survival from 4.9 to 21.3 months, with a 2-year survival rate of 19.7% versus 47.2%. This association between ipilimumab and prolonged survival remains significant even after adjustment for performance status without an increased need for salvage WBRT.

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Nataniel H. Lester-Coll, Arie P. Dosoretz, William J. Magnuson, Maxwell S. Laurans, Veronica L. Chiang and James B. Yu

OBJECTIVE

The JLGK0901 study found that stereotactic radiosurgery (SRS) is a safe and effective treatment option for treating up to 10 brain metastases. The purpose of this study is to determine the cost-effectiveness of treating up to 10 brain metastases with SRS, whole-brain radiation therapy (WBRT), or SRS and immediate WBRT (SRS+WBRT).

METHODS

A Markov model was developed to evaluate the cost effectiveness of SRS, WBRT, and SRS+WBRT in patients with 1 or 2–10 brain metastases. Transition probabilities were derived from the JLGK0901 study and modified according to the recurrence rates observed in the Radiation Therapy Oncology Group (RTOG) 9508 and European Organization for Research and Treatment of Cancer (EORTC) 22952–26001 studies to simulate the outcomes for patients who receive WBRT. Costs are based on 2015 Medicare reimbursements. Health state utilities were prospectively collected using the Standard Gamble method. End points included cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The willingness-to-pay (WTP) threshold was $100,000 per QALY. One-way and probabilistic sensitivity analyses explored uncertainty with regard to the model assumptions.

RESULTS

In patients with 1 brain metastasis, the ICERs for SRS versus WBRT, SRS versus SRS+WBRT, and SRS+WBRT versus WBRT were $117,418, $51,348, and $746,997 per QALY gained, respectively. In patients with 2–10 brain metastases, the ICERs were $123,256, $58,903, and $821,042 per QALY gained, respectively. On the sensitivity analyses, the model was sensitive to the cost of SRS and the utilities associated with stable post-SRS and post-WBRT states. In patients with 2–10 brain metastases, SRS versus WBRT becomes cost-effective if the cost of SRS is reduced by $3512. SRS versus WBRT was also cost effective at a WTP of $200,000 per QALY on the probabilistic sensitivity analysis.

CONCLUSIONS

The most cost-effective strategy for patients with up to 10 brain metastases is SRS alone relative to SRS+WBRT. SRS alone may also be cost-effective relative to WBRT alone, but this depends on WTP, the cost of SRS, and patient preferences.