Outcomes in the radiosurgical management of metastatic spine disease.

PURPOSE: Stereotactic body radiation therapy (SBRT) is a common treatment option for patients with metastatic tumors of the spine. The optimal treatment-, tumor-, and patient-specific characteristics necessary to achieve durable outcomes remain less well understood given the heterogeneous nature of the patient population this modality typically serves. The objective of this analysis was to better understand the determinants underlying SBRT spine treatment outcomes. METHODS AND MATERIALS: A total of 127 patients with 287 spine tumors were treated between March 2010 and May 2015. The median total doses for single-fraction and hypofractionated courses of treatment were 16 Gy (range, 16-20 Gy) and 24 Gy (range, 16-40 Gy), respectively. Radiologic local control and numeric pain score data were measured, and univariate and multivariate analyses were done to determine factors predictive of treatment response. RESULTS: Median follow-up was 5.9 months (range, 1-61 months). Radiologic local control was achieved in 84.7% of patients at 6 months and in 74.7% of patients at 1 year. Local control was found to be affected by the Spinal Instability Neoplastic Score, and was worse in patients with scores ≥7 (hazard ratio [HR]: 4.25; 95% confidence interval [CI], 1.57-11.51). Patients who required upfront surgical intervention to alleviate spinal cord compression, address mechanical spinal instability, or both had worse local control than those who did not require surgery (HR: 2.32; 95% CI, 1.04-5.17). Patients treated with a hypofractionated course compared with a single fraction had worse radiologic local control (HR: 2.63; 95% CI, 1.27-5.45). No patients developed radiation-induced myelitis after treatment, and the vertebral compression fracture rate was 9.1% after SBRT. CONCLUSIONS: Patients with potentially unstable spines or needing upfront spinal surgery before SBRT are less likely to achieve durable radiologic local control. Additionally, patients treated with single-fraction regimens have improved local control compared with those treated with hypofractionated radiation.

Supracerebellar Transtentorial Approach for Occipital Meningioma to Maximize Visual Preservation: Technical Note.

BACKGROUND AND IMPORTANCE: Surgery for resection of tentorial meningiomas compressing primary visual cortex carries a significant risk of worsening vision. This concern is especially acute in patients with a preexisting visual deficit. Approaches that involve mechanical retraction of the occipital lobe further threaten visual function. The supracerebellar transtentorial (SCTT) approach, which does not carry a risk of occipital retraction injury, should be considered for patients with occipital tentorial meningiomas to maximize functional visual outcomes. CLINICAL PRESENTATION: A 54-yr-old woman underwent 2 resections and radiation therapy for a right occipital oligodendroglioma as a teenager. She was left with a complete left homonymous hemianopsia. The patient now presented with progressive vision loss in her remaining right visual field. Imaging revealed a left occipital superiorly projecting tentorial meningioma. To preserve her remaining visual function the SCTT approach was chosen for resection. A Simpson grade 1 removal was achieved without disrupting the occipital lobe pia or requiring mechanical cerebellar retraction. A diagnosis of a WHO grade II meningioma (presumably radiation induced) was made. The patient's vision returned to premorbid baseline 1 wk after surgery. CONCLUSION: The SCTT approach should be considered for the surgical management of patients with occipital tentorial meningiomas when visual preservation is at risk. This approach avoids transgression of visual cortex and minimizes the risk of venous infarction or contusions from retraction injury.

Intraoperative MRI for resection of intracranial meningiomas.

OBJECTIVE: To examine whether intraoperative MRI can enhance safety and extent of resection of complex intracranial meningiomas, given its positive role in the resection of malignant brain tumors and pituitary tumors. METHODS: Over a ten-year period, 70 operations were performed on 66 patients with intracranial meningiomas using the compact, mobile PoleStar N20 iMRI navigation system. A retrospective review was conducted examining patient demographics, surgical characteristics, and outcomes. RESULTS: 36 meningiomas were above the skull base and 30 were of the skull base. Four (5.7%) operations were done for recurrent meningiomas. 63 patients (95.5%) had WHO grade I and 3 patients (4.5%) had WHO grade III meningiomas. 9 (12.8%) patients required additional tumor resection based on iMRI findings, and in 4 patients (6%) iMRI imaging allowed for avoidance of additional dissection near critical neurovascular structures. CONCLUSIONS: Up to 15.7% of patients had surgery positively affected by intraoperative imaging either improving the resection or avoiding unnecessary additional dissection which could potentially harm critical neurologic structures. As iMRI becomes more widely available it may be valuable to use in an appropriate subset of patients with intracranial meningiomas.

Congenital Agenesis of the C6 Pedicle Leading to Misdiagnosis of a Traumatically Jumped Facet: A Case Report.

This case report discusses the rare issue of an atrophic cervical pedicle at the C6 level in a patient found unconscious with a jumped facet and an unknown mechanism of injury. A means to discern between traumatic jumped facets versus congenital anomalies is addressed, including missing pedicles, which is encountered at the C6 level in this case. A literature review revealed that the most common level where this occurs is at the C6 level. The structural anatomic pathologies and the variants relative to congenital facet atrophy are identified, including the location and the surrounding vasculature; more specifically, the vertebral arteries. This information is helpful to assist clinicians when discerning between a traumatic subluxation injury that requires instrumentation and reduction versus a congenital anomaly that can usually be managed conservatively.

Compact Intraoperative MRI: Stereotactic Accuracy and Future Directions.

BACKGROUND: Intraoperative imaging must supply data that can be used for accurate stereotactic navigation. This information should be at least as accurate as that acquired from diagnostic imagers. OBJECTIVES: The aim of this study was to compare the stereotactic accuracy of an updated compact intraoperative MRI (iMRI) device based on a 0.15-T magnet to standard surgical navigation on a 1.5-T diagnostic scan MRI and to navigation with an earlier model of the same system. METHODS: The accuracy of each system was assessed using a water-filled phantom model of the brain. Data collected with the new system were compared to those obtained in a previous study assessing the older system. The accuracy of the new iMRI was measured against standard surgical navigation on a 1.5-T MRI using T1-weighted (W) images. RESULTS: The mean error with the iMRI using T1W images was lower than that based on images from the 1.5-T scan (1.24 vs. 2.43 mm). T2W images from the newer iMRI yielded a lower navigation error than those acquired with the prior model (1.28 vs. 3.15 mm). CONCLUSIONS: Improvements in magnet design can yield progressive increases in accuracy, validating the concept of compact, low-field iMRI. Avoiding the need for registration between image and surgical space increases navigation accuracy.

Hippocampal-sparing and target volume coverage in treating 3 to 10 brain metastases: A comparison of Gamma Knife, single-isocenter VMAT, CyberKnife, and TomoTherapy stereotactic radiosurgery.

PURPOSE: Our purpose was to evaluate hippocampal doses and target volume coverage with and without hippocampal sparing when treating multiple brain metastases using various stereotactic radiosurgery (SRS) platforms. METHODS AND MATERIALS: We selected 10 consecutive patients with 14 separate treatments who had been treated in our department for 3 to 10 brain metastases and added hippocampal avoidance contours. All 14 treatments were planned with GammaPlan for Gamma Knife, Eclipse for single isocenter volumetric modulated arc therapy (VMAT), TomoTherapy Treatment Planning System (TPS) for TomoTherapy, and MultiPlan for CyberKnife. Initial planning was performed with the goal of planning target volume coverage of V100 ≥95% without hippocampal avoidance. If the maximum hippocampal point dose (Dmax) was <6.6 Gy in a single fraction and <40% of the hippocampi received ≤4.5 Gy, no second plan was performed. If either constraint was not met, replanning was performed with these constraints. RESULTS: There was a median of 6 metastases per plan, with an average total tumor volume of 7.32 mL per plan. The median hippocampal Dmax (in Gy) without sparing averaged 1.65, 9.81, 4.38, and 5.46, respectively (P < .0001). Of 14 plans, 3 Gamma Knife and CyberKnife plans required replanning, whereas 13 VMAT and 8 TomoTherapy plans required replanning. The hippocampal constraints were not achievable in 1 plan on any platform when the tumor was bordering the hippocampus. The mean volume of brain receiving 12 Gy (in mL), which has been associated with symptomatic radionecrosis, was 23.57 with Gamma Knife, 76.77 with VMAT, 40.86 with CyberKnife, and 104.06 with TomoTherapy (P = .01). The overall average conformity indices for all plans ranged from 0.36 to 0.52. CONCLUSIONS: Even with SRS, the hippocampi can receive a considerable dose; however, if the hippocampi are outlined as organs of risk, sparing these structures is feasible in nearly all situations with all 4 platforms, without detriment to target coverage, and should be considered in all patients undergoing SRS for multiple brain metastases. SUMMARY: Hippocampi play an important role in memory, and sparing of these structures in whole brain radiation can improve neurocognitive outcomes. The hippocampi are not routinely spared when using stereotactic radiosurgery. We evaluated the incidental dose to the hippocampi when treating multiple brain metastases and sought to examine if hippocampal sparing is feasible without detriment to target coverage. We found that hippocampal sparing is possible without affecting coverage or conformality in most cases across treatment platforms.

Fate of the Ophthalmic Artery After Treatment With the Pipeline Embolization Device.

BACKGROUND: Flow diverters have emerged as a major tool in the treatment of cerebral aneurysms. A crucial issue with the use of flow diverters is the patency of side branches covered by the device, most importantly the ophthalmic artery (OA). OBJECTIVE: To assess the patency of the OA after coverage with the pipeline embolization device (PED). METHODS: All patients who had a PED covering the OA and in whom angiographic follow-up was available were included in the study. The patency of the OA at follow-up was systematically evaluated by 2 authors who were not involved in the procedure. RESULTS: Of 95 treated patients, the OA was covered by 1 PED in 81 patients (85%) and by 2 PEDs in 14 patients (15%). Mean angiographic follow-up was 7.5 months, ranging from 3 to 24 months. At the latest follow-up, the OA remained patent in 85 patients (89%), showed diminished flow in 4 patients (4%), and was occluded in 6 patients (7%). Only 1 patient had clinical symptoms related to OA occlusion. In multivariable analysis, larger aneurysm size predicted OA occlusion (P = .04). There was also a strong trend for younger age (P = .06) and coverage by more than 1 device (P = .07). CONCLUSION: Treatment of internal carotid artery aneurysms with the PED preserves the patency of the OA in most cases. The occlusion of the OA in the few cases where it occurs is usually a clinically irrelevant event. Minimizing the number of PEDs across the OA is crucial to preserve its patency.

Mesenchymal stem cells from human fat engineered to secrete BMP4 are nononcogenic, suppress brain cancer, and prolong survival.

PURPOSE: Glioblastoma is the most common adult primary malignant intracranial cancer. It is associated with poor outcomes because of its invasiveness and resistance to multimodal therapies. Human adipose-derived mesenchymal stem cells (hAMSC) are a potential treatment because of their tumor tropism, ease of isolation, and ability to be engineered. In addition, bone morphogenetic protein 4 (BMP4) has tumor-suppressive effects on glioblastoma and glioblastoma brain tumor-initiating cells (BTIC), but is difficult to deliver to brain tumors. We sought to engineer BMP4-secreting hAMSCs (hAMSCs-BMP4) and evaluate their therapeutic potential on glioblastoma. EXPERIMENTAL DESIGN: The reciprocal effects of hAMSCs on primary human BTIC proliferation, differentiation, and migration were evaluated in vitro. The safety of hAMSC use was evaluated in vivo by intracranial coinjections of hAMSCs and BTICs in nude mice. The therapeutic effects of hAMSCs and hAMSCs-BMP4 on the proliferation and migration of glioblastoma cells as well as the differentiation of BTICs, and survival of glioblastoma-bearing mice were evaluated by intracardiac injection of these cells into an in vivo intracranial glioblastoma murine model. RESULTS: hAMSCs-BMP4 targeted both the glioblastoma tumor bulk and migratory glioblastoma cells, as well as induced differentiation of BTICs, decreased proliferation, and reduced the migratory capacity of glioblastomas in vitro and in vivo. In addition, hAMSCs-BMP4 significantly prolonged survival in a murine model of glioblastoma. We also demonstrate that the use of hAMSCs in vivo is safe. CONCLUSIONS: Both unmodified and engineered hAMSCs are nononcogenic and effective against glioblastoma, and hAMSCs-BMP4 are a promising cell-based treatment option for glioblastoma.

Functional imaging in a low-field, mobile intraoperative magnetic resonance scanner: expanded paradigms.

OBJECTIVE: We previously demonstrated the capability to obtain functional magnetic resonance imaging (MRI) scans of the motor cortex in healthy volunteers using a low-field mobile operating room-based MRI scanner with 0.12-T field strength. Using an expanded (0.15-T), but still mobile, version of this system, our goal was to acquire data showing activation of other areas of functionally important cortex. METHODS: Five healthy volunteers were scanned with the low-field scanner using finger tapping, hand touch, silent word generation, text listening, and visual stimulation paradigms. The data was analyzed offline using publicly available software. For comparison, the volunteers were then scanned with a 3-T diagnostic MRI scanner. RESULTS: Significant cortical activation was demonstrated on 16 out of 22 images obtained on the operating room-based scanner. Motor activation was most robust, followed by silent word generation, text listening, and hand touch paradigms. The correlation coefficients compared favorably with the images obtained on the 3-T scanner. The signal changes were higher for images obtained with the low-field, mobile scanner compared with those performed with the 3-T diagnostic MRI scanner. CONCLUSION: Functional MRI scans of multiple cortical areas can be acquired with a low-field strength magnet designed for intraoperative imaging. Further refinement of this technique may allow for the acquisition of true intraoperative functional MRI scans immediately, before, and even during cranial surgery in select patients.

Stereotactic accuracy of a compact intraoperative MRI system.

OBJECTIVE: To analyze the stereotactic accuracy of the PoleStar N-20, a compact intraoperative magnetic resonance imaging (iMRI) system, based on a 0.15-Tesla (T) magnet. METHODS: An MRI-compatible phantom was scanned after being positioned in both the center of the magnetic field (COF) and the periphery of the field (POF) of the PoleStar N-20 magnet. Scans were acquired at various slice thicknesses in 3 sequences: T(1) weighted, T(2) weighted and Esteady (reversed fast imaging with steady-state precession, also known as 'PSIF'). The distance between the actual location of the probe tip in space and the location of the target on the image was measured on the axial, coronal, and sagittal planes for 9 points on each image. Each measurement was repeated 3 times. We also compared the structural features of the PoleStar N-20 to those of its predecessor. RESULTS: T(1)-weighted scans yielded the most accurate measurements. There was no statistically significant difference between scans acquired at thicknesses of 2, 3, 4 and 8 mm; all were accurate for clinical purposes. Comparison of COF with POF measurements using T(1)-weighted scans did not demonstrate a statistically significant difference in accuracy. CONCLUSIONS: The PoleStar N-20 0.15-T iMRI system provides surgical navigation that is at least as accurate as the first generation model of this system, which employed a 0.12-T magnet. Further analysis of stereotactic accuracy on clinical cases using the PoleStar N-20 is needed to confirm that these results will bear out in surgical reality.

Complication avoidance: thoracolumbar and lumbar burst fractures.

Most thoracolumbar and lumbar burst fractures can be treated conservatively. Unstable fractures or fractures resulting in neurologic deficits usually require surgical treatment. Choosing an appropriate surgical approach requires a thorough understanding of the various techniques for decompression, fusion, and stabilization. Surgical options include an anterior approach, a posterior approach, or a combined anteroposterior approach. Each surgical option has unique advantages and disadvantages. Generally, the anterior approaches are best used at the thoracolumbar junction, posterior approaches are ideal for low lumbar injuries and lumbar injuries that result in complete spinal cord injuries,and anteroposterior surgeries typically are reserved for highly unstable fracture subluxations. Case illustrations show the various treatment options.

Cranial surgery with an expanded compact intraoperative magnetic resonance imager. Technical note.

In this article the authors report the implementation of an expanded compact intraoperative magnetic resonance (iMR) imager that is designed to overcome significant limitations of an earlier unit. The PoleStar N20 iMR imager has a stronger magnetic field than its predecessor (0.15 tesla compared with 0.12 tesla), a wider gap between magnet poles, and an ergonomically improved gantry design. The additional time needed in the operating room (OR) for use of iMR imaging and the number of sessions per patient were recorded. Stereotactic accuracy of the integrated navigational tool was assessed using a water-covered phantom. Of the 55 patients who have undergone surgery in the PoleStar N20 device, diagnoses included glioma in 13, meningioma in 12, pituitary adenoma in nine, other skull base lesions in seven, and miscellaneous other diagnoses. The extra time required for use of the system averaged 1.1 hours (range 0.5-2 hours). Imaging sessions averaged 2.3 per surgery (range one-six sessions). Measurement of stereotactic accuracy revealed that T1-weighted images were the most accurate. Thinner slices yielded measurably greater accuracy, although this was of questionable clinical significance (all sequences < or =4 mm had a mean error of < or = 1.8 mm). The position of the phantom in the center compared with the periphery of the magnetic field did not affect accuracy (mean error 0.9 mm for each). The PoleStar N20 appears to make intraoperative neuroimaging with a low-field-strength magnet much more practical than it was with the first-generation device. Greater ease of positioning resulted in a decrease in added time in the OR and encouraged a larger number of imaging sessions.

Imaging androgen receptor function during flutamide treatment in the LAPC9 xenograft model.

The current understanding of the response of androgen receptor to pharmacologic inhibitors in prostate cancer is derived primarily from serum prostate-specific antigen (PSA) levels. In this study, we test whether a novel androgen receptor-specific molecular imaging system is able to detect the action of the antiandrogen flutamide on androgen receptor function in xenograft models of prostate cancer. Adenoviruses bearing an optical imaging cassette containing an androgen receptor-responsive two-step transcriptional amplification system were injected into androgen-dependent and hormone-refractory tumors of animals undergoing systemic time-controlled release of the antiandrogen flutamide. Imaging of tumors with a cooled charge-coupled device camera revealed that the response of AdTSTA to flutamide is more sensitive and robust than serum PSA measurements. Flutamide inhibits the androgen signaling pathway in androgen-dependent but not refractory tumors. Analysis of androgen receptor and RNA polymerase II binding to the endogenous PSA gene by chromatin immunoprecipitation revealed that flutamide treatment and androgen withdrawal have different molecular mechanisms. The application of imaging technology to study animal models of cancer provides mechanistic insight into antiandrogen targeting of androgen receptor during disease progression.