bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of Gamma Knife surgery for brain metastases in eloquent locations
Authors: Dea Nicolas , Borduas Martin , Kenny Brendan , Fortin David , Mathieu David 
Published: November 2018

Object
Brain metastases are the most frequently occurring cerebral tumors. Tumors that are located in eloquent cerebral parenchyma can cause considerable morbidity and may pose a significant challenge during surgery. Gamma Knife surgery (GKS) is a recognized treatment modality for brain metastases. This study was undertaken to assess the safety and efficacy of GKS, specifically for brain metastases in eloquent locations.

Methods
Charts of patients harboring brain metastases that were treated by GKS at the Centre Hospitalier Universitaire de Sherbrooke between August 2004 and April 2008 were reviewed. Planning images were assessed by an independent neurosurgeon to assess tumor location. Eloquent locations included the primary motor, somatosensory, speech, and visual cortices; the basal ganglia; the thalamus; and the brainstem. Data on survival, tumor response, and complications were analyzed and compared with data published on surgical treatment of these lesions.

Results
During the study period, 650 metastases in 295 patients were treated with GKS; of these, 164 metastases in 95 patients were located in eloquent areas. In this subgroup, the median age of patients was 59 years and women constituted 57.9% of the population. The median Karnofsky Performance Scale score was 80% (range 50%–100%). Patients were categorized according to their recursive partitioning analysis class: Class 1, 22.1%; Class 2, 70.5%; and Class 3, 7.4% of patients. Non–small cell lung cancer was the most common primary tumor (63.2% of metastases), followed by small cell lung (8.4%), breast (7.4%), colorectal (5.3%), and renal cell (4.2%) cancers, as well as melanoma (4.2%). The median dose to the tumor margin was 18 Gy (range 14–24 Gy). The median duration of survival after GKS was 8.2 months. The recursive partitioning analysis class was the most significant variable affecting survival (p < 0.0001). Immediate control was achieved in 92.9% of tumors, and 68.6% of tumors were still controlled at the last follow-up. The median time to tumor progression was 16 months. Higher margin dose (p = 0.002), the absence of edema (p = 0.009), and the non–small cell lung cancer tissue type (p = 0.035) positively affected response rates. Steroid medications were no longer used in 46% of patients after GKS. New neurological deficits occurred in 5.7% of patients and seizures in 5.7%. All these deficits were transient and patients completely recovered in response to a temporary course of steroids. Imaging studies showed that new edema occurred in 8.6% of treated metastases and biopsy-proven radiation necrosis in 1.4%.

Conclusions
Gamma Knife surgery is safe and effective for brain metastases located in eloquent areas.
Analysis of radiosurgical results in patients with brain metastases according to the number of brain lesions: is stereotactic radiosurgery effective for multiple brain metastases?
Authors: Chang Won Seok , Kim Hae Yu , Chang Jin Woo , Park Yong Gou , Chang Jong Hee 
Published: November 2018

Object
Whole-brain radiation therapy (WBRT), open resection, and stereotactic radiosurgery (SRS) are widely used for treatment of metastatic brain lesions, and many physicians recommend WBRT for multiple brain metastases. However, WBRT can be performed only once per patient, with rare exceptions. Some patients may require SRS for multiple metastatic brain lesions, particularly those patients harboring more than 10 lesions. In this paper, treatment results of SRS for brain metastasis were analyzed, and an attempt was made to determine whether SRS is effective, even in cases involving multiple metastatic brain lesions.

Methods
The authors evaluated the cases of 323 patients who underwent SRS between October 2005 and October 2008 for the treatment of metastatic brain lesions. Treatment was performed using the Gamma Knife model C or Perfexion. The patients were divided into 4 groups according to the number of lesions visible on MR images: Group 1, 1–5 lesions; Group 2, 6–10 lesions: Group 3, 11–15 lesions; and Group 4, > 15 lesions. Patient survival and progression-free survival times, taking into account both local and distant tumor recurrences, were analyzed.

Results
The patients consisted of 172 men and 151 women with a mean age at SRS of 59 years (range 30–89 years). The overall median survival time after SRS was 10 months (range 8.7–11.4 months). The median survival time of each group was as follows: Group 1, 10 months; Group 2, 10 months; Group 3, 13 months; and Group 4, 8 months. There was no statistical difference between survival times after SRS (log-rank test, p = 0.554), although the probability of development of new lesions in the brain was greater in Group 4 (p = 0.014). Local tumor control rates were not statistically different among the groups (log-rank test, p = 0.989); however, remote disease progression was more frequent in Group 4 (log-rank test, p = 0.014).

Conclusions
In this study, patients harboring more than 15 metastatic brain lesions were found to have faster development of new lesions in the brain. This may be due to the biological properties of the patients' primary lesions, for example, having a greater tendency to disseminate hematogenously, especially to the brain, or a higher probability of missed or invisible lesions (microscopic metastases) to treat on stereotactic MR images at the time of radiosurgery. However, the mean survival times after SRS were not statistically different between groups. According to the aforementioned results, SRS may be a good treatment option for local control of metastatic lesions and for improved survival in patients with multiple metastatic brain lesions, even those patients who harbor more than 15 metastatic brain lesions, who, after SRS, may have early and easily detectable new metastatic lesions.
Low-dose Gamma Knife surgery for nonfunctioning pituitary adenomas
Authors: El-Shehaby Amr M. N. , Reda Wael A. , Tawadros Sameh R. , Abdel Karim Khaled M. 
Published: November 2018

Object
The primary concern when performing Gamma Knife surgery for pituitary adenoma is preservation of vision and pituitary function while achieving tumor growth control. Higher prescribed radiation doses are typically correlated with higher incidences of postradiosurgical hormone deficiencies. The goal of the present study was to retrospectively analyze the feasibility of using a lower prescribed radiation dose in the treatment of nonfunctioning pituitary adenomas and the effect of this dose on vision, pituitary function, and tumor growth control.

Methods
The study was conducted in 38 patients with nonfunctioning pituitary adenomas, who were treated between January 2002 and July 2008. Twenty-one patients were available for follow-up (13 men and 8 women). The mean follow-up period was 44 months (range 24–90 months). Nineteen patients had previously undergone surgery. Pituitary dysfunction developed after surgery in 3 patients. One patient had an abnormal pituitary hormone profile before radiosurgery due to an attack of pituitary apoplexy. Visual field defects were present in 12 patients. The prescribed radiation dose was 12 Gy in all patients. The tumor volume ranged from 0.5 to 11.8 cm3 (mean 4.8 cm3). The maximum dose to the visual pathway was kept below 10 Gy. The mean maximum dose delivered to the visual pathway was 7.9 Gy.

Results
The patients were followed up for a period of 24 to 90 months (mean 44 months). The size of the tumor decreased in 11 patients (52%) and remained stable in 9 patients (43%). In 1 patient there was tumor growth outside the previous radiation field (on the contralateral side). Among the 12 patients with visual field defects, 9 (75%) experienced an improvement and the remaining patients' vision remained stable. In only 4 patients was the visual improvement associated with tumor shrinkage. The hormone profile remained normal in all patients except for the 4 patients who had pituitary dysfunction before radiosurgery.

Conclusions
The 12-Gy prescribed dose used in this study seems to be sufficient for producing tumor control while sparing the patient from radiation-induced pituitary dysfunction. In addition, visual improvement was reported in a number of cases. A larger series and longer follow-up are required to confirm these results.
Gamma Knife surgery for patients with brainstem metastases
Authors: Kawabe Takuya , Yamamoto Masaaki , Sato Yasunori , Barfod Bierta E. , Urakawa Yoichi , Kasuya Hidetoshi , Mineura Katsuyoshi 
Published: November 2018

Object
Because brainstem metastases are not deemed resectable, stereotactic radiosurgery (SRS) is the only treatment modality expected to achieve a radical cure. The authors describe their treatment results, focusing particularly on how long patients can survive without neurological deterioration following SRS for brainstem metastases.

Methods
This was an institutional review board–approved, retrospective cohort study in which the authors pulled from their database information on 2553 consecutive patients with brain metastases who underwent Gamma Knife surgery (GKS) at the Mito GammaHouse between July 1998 and July 2011. Among the 2553 patients, excluding cases in which there was meningeal dissemination, 200 cases of brainstem metastases (78 women and 122 men with a mean age of 64 years [range 36–86 years]) were identified and analyzed. The most common primary site was the lung (137 patients) followed by the gastrointestinal tract (24 patients), breast (17 patients), kidney (12 patients), and others (10 patients). Among the 200 patients, 15 patients (7.5%) harbored at least 2 tumors in the brainstem: 11 patients had 2 tumors, 2 patients had 3 tumors, and 1 patient each had 4 or 5 tumors. Therefore, a total of 222 tumors were irradiated. These 222 tumors were located in the pons (121 lesions), the midbrain (65 lesions), and the medulla oblongata (36 lesions). The mean and median tumor volumes were 1.3 and 0.2 cm3 (range 0.005–10.7 cm3), and the median peripheral radiation dose was 18.0 Gy (range 12.0–25.0 Gy).

Results
The overall median survival time (MST) was 6.0 months. Distribution of MSTs across Recursive Partitioning Analysis (RPA) classes showed that the MSTs were 9.4 months in Class I (20 patients), 6.0 months in Class II (171 patients), and 1.9 months in Class III (9 patients). Better Karnofsky Performance Scale score, single metastasis, and well-controlled primary tumor were significant predictive factors for longer survival. The neurological and qualitative survival rates were 90.8% and 89.2%, respectively, at 24 months post-GKS. Better KPS score and smaller tumor volume tended to be associated with prolonged qualitative survival. Follow-up imaging studies were available for 129 patients (64.5%). The tumor control rate was 81.8% at 24 months post-GKS. Smaller tumor volume tended to contribute to tumor control.

Conclusions
The present results indicate that GKS is effective in the treatment of brainstem metastases, particularly from the viewpoint of maintaining a good neurological condition in the patient.
Stereotactic radiosurgery to the resection bed for intracranial metastases and risk of leptomeningeal carcinomatosis
Authors: Ojerholm Eric , Lee John Y. K. , Thawani Jayesh P. , Miller Denise , O'Rourke Donald M. , Dorsey Jay F. , Geiger Geoffrey A. , Nagda Suneel , Kolker James D. , Lustig Robert A. , Alonso-Basanta Michelle 
Published: November 2018

ObjectFollowing resection of a brain metastasis, stereotactic radiosurgery (SRS) to the cavity is an emerging alternative to postoperative whole-brain radiation therapy (WBRT). This approach attempts to achieve local control without the neurocognitive risks associated with WBRT. The authors aimed to report the outcomes of a large patient cohort treated with this strategy.MethodsA retrospective review identified 91 patients without a history of WBRT who received Gamma Knife (GK) SRS to 96 metastasis resection cavities between 2007 and 2013. Patterns of intracranial control were examined in the 86 cases with post-GK imaging. Survival, local failure, and distant failure were estimated by the Kaplan-Meier method. Prognostic factors were tested by univariate (log-rank test) and multivariate (Cox proportional hazards model) analyses.ResultsCommon primary tumors were non–small cell lung (43%), melanoma (14%), and breast (13%). The cases were predominantly recursive partitioning analysis Class I (25%) or II (70%). Median preoperative metastasis diameter was 2.8 cm, and 82% of patients underwent gross-total resection. A median dose of 16 Gy was delivered to the 50% isodose line, encompassing a median treatment volume of 9.2 cm3. Synchronous intact metastases were treated in addition to the resection bed in 43% of cases. Patients survived a median of 22.3 months from the time of GK. Local failure developed in 16 cavities, for a crude rate of 18% and 1-year actuarial local control of 81%. Preoperative metastasis diameter ≥ 3 cm and residual or recurrent tumor at the time of GK were associated with local failure (p = 0.04 and 0.008, respectively). Distant intracranial failure occurred in 55 cases (64%) at a median of 7.3 months from GK. Salvage therapies included WBRT and additional SRS in 33% and 31% of patients, respectively. Leptomeningeal carcinomatosis developed in 12 cases (14%) and was associated with breast histology and infratentorial cavities (p = 0.024 and 0.012, respectively).ConclusionsThis study bolsters the existing evidence for SRS to the resection bed. Local control rates are high, but patients with larger preoperative metastases or residual/recurrent tumor at the time of SRS are more likely to fail at the cavity. While most patients develop distant intracranial failure, an SRS approach spared or delayed WBRT in the majority of cases. The risk of leptomeningeal carcinomatosis does not appear to be elevated with this strategy.
To fractionate or not to fractionate? That is the question for the radiosurgery of hypoxic tumors
Authors: Toma-Dasu Iuliana , Sandström Helena , Barsoum Pierre , Dasu Alexandru 
Published: November 2018

ObjectThis study aimed to investigate the impact of tumor hypoxia on treatment outcome for metastases commonly treated with radiosurgery using 1 fraction of radiation and the potential gain from reoxygenation if the treatment is delivered in a few radiation fractions.MethodsIn silico metastasis-like radiosurgery targets were modeled with respect to size, density of clonogenic cells, and oxygenation. Treatment plans were produced for the targets using Leksell GammaPlan, delivering clinically relevant doses and evaluating the tumor control probability (TCP) that could be expected in each case. Fractionated schedules with 3, 4, and 5 fractions resulting in similar biological effective doses were also considered for the larger target, and TCP was determined under the assumption that local reoxygenation takes place between fractions.ResultsThe results showed that well-oxygenated small- and medium-size metastases are well controlled by radiosurgery treatments delivering 20 or 22 Gy at the periphery, with TCPs ranging from 90% to 100%. If they are moderately hypoxic, the TCP could decrease to 60%. For large metastases, the TCPs from single-fraction treatments ranged from 0% to 19%, depending on tumor oxygenation. However, for fractionated treatments, the TCP for hypoxic tumors could significantly increase up to 51%, if reoxygenation occurs between fractions.ConclusionsThis study shows that hypoxia worsens the response to single-fraction radiosurgery, especially for large tumors. However, fractionated therapy for large hypoxic tumors might considerably improve the TCP and might constitute a simple way to improve the outcome of radiosurgery for patients with hypoxic tumors.
Factors associated with venous thromboembolic events following ICU admission in patients undergoing spinal surgery: an analysis of 1269 consecutive patients
Authors: Cloney Michael Brendan , Goergen Jack , Hopkins Benjamin S. , Dhillon Ekamjeet Singh , Dahdaleh Nader S. 
Published: November 2018

OBJECTIVEVenous thromboembolic events (VTEs) are a common cause of morbidity and mortality after spine surgery. Patients admitted to the intensive care unit (ICU) following spine surgery exhibit high-risk clinical characteristics.METHODSThe authors retrospectively analyzed 1269 ICU patients who had undergone spine surgery between January 1, 2009, and May 31, 2015. Relevant demographic, procedural, and outcome variables were collected.RESULTSPatients admitted to the ICU postoperatively had a postoperative VTE rate of 10.2%, compared to 2.5% among all spine surgery patients during the study period. ICU patients had a higher comorbid disease burden (odds ratio [OR] 1.45, p < 0.001), and were more likely to have a history of a bleeding disorder (2.60% vs 0.46%, OR 2.85, p = 0.028), receive a transfusion (OR 4.81, p < 0.001), have a fracture repaired (OR 4.30, p < 0.001), have an estimated blood loss > 500 ml (OR 1.95, p = 0.009), have an osteotomy (OR 20.47, p = 0.006), or have a corpectomy (OR 3.48, p = 0.007) than patients not admitted to the ICU. There was a significant difference in time to VTE between patients undergoing osteotomy and patients undergoing scoliosis corrections without osteotomy (p = 0.0431), patients with fractures (p = 0.0113), and patients undergoing fusions for indications other than scoliosis or fracture (p = 0.0056). Patients who developed a deep vein thrombosis (DVT) during their ICU stay were more likely to have received a prophylactic inferior vena cava filter placement (OR 8.98, p < 0.001), have undergone an interbody fusion procedure (OR 2.38, p = 0.037), have a history of DVT (OR 3.25, p < 0.001), and have shorter surgery times (OR 0.30, p = 0.002). Patients who developed a pulmonary embolism (PE) during the ICU stay were more likely to have a history of PE (OR 12.68 p = 0.015), history of DVT (OR 5.11, p = 0.042), fracture diagnosis (OR 7.02, p = 0.040), and diagnosis of scoliosis (OR 7.78, p = 0.024). Patients with higher BMIs (OR 0.85, p = 0.036) and those who received anticoagulation treatment (OR 0.16, p = 0.031) were less likely to develop a PE during their ICU stay.CONCLUSIONSPatients admitted to the ICU following spine surgery have a higher rate of VTE than non-ICU patients. Time to VTE varied by pathology. Factors independently associated with VTE in the ICU are distinct from factors otherwise associated with VTE. Some factors are independently associated with VTE throughout the 30-day postoperative period, while others are associated with VTE specifically during the initial ICU stay or after leaving the ICU.
C2 neurofibromas in neurofibromatosis type 1: genetic and imaging characteristics
Authors: Waqar Mueez , Huson Susan , Evans D. Gareth , Ealing John , Karabatsou Konstantina , George K. Joshi , Soh Calvin 
Published: November 2018

OBJECTIVEC2 nerve root neurofibromas have been reported frequently in patients with neurofibromatosis type 1 (NF1), although their genetic and imaging characteristics are unexplored. The aim of this study was to characterize genetic and spinal imaging findings in a large cohort of NF1 patients with C2 neurofibromas.METHODSThe authors performed a review of national NF1 referrals between 2009 and 2016. Inclusion criteria were at least 1 C2 root neurofibroma and cervical-spine or whole-spine MRI scans available for analysis. Blinded imaging review was performed by a neuroradiologist with an interest in NF1.RESULTSFifty-four patients with 106 C2 neurofibromas were included. The median age was 32.5 years (range 15–61 years), and there were slightly more male patients (33 vs 21 female patients). Splice-site (30%) and missense (20%) variants were frequent. Spinal neurofibromas were distributed in all spine regions (65%) or in the cervical spine alone (22%). Most (93%) C2 neurofibromas were visible on MRI scans of the head. Intradural invasion and cord compression in the cervical spine included the C2 level in 95% and 80% of patients, respectively. Compared with all other cervical spine neurofibromas in these patients, C2 neurofibromas had higher rates of intraspinal extension (75% vs 32%; OR 6.20, 95% CI 3.85–9.97; p < 0.001), intradural invasion (53% vs 26%; OR 3.20, 95% CI 2.08–4.92; p < 0.001), and cord compression (25% vs 13%; OR 2.26, 95% CI 1.35–3.79; p = 0.002). However, C2 neurofibromas had lower rates of extraforaminal growth beyond the transverse process (12% vs 62%; OR 0.09, 95% CI 0.05–0.16; p < 0.001).CONCLUSIONSC2 neurofibromas are associated with an aggressive intraspinal phenotype, limited growth outside the spinal canal, and an uncommon genetic profile. These observations require future study.
Biomechanical assessment of proximal junctional semi-rigid fixation in long-segment thoracolumbar constructs
Authors: Viswanathan Vibhu K. , Ganguly Ranjit , Minnema Amy J. , DeVries Watson Nicole A. , Grosland Nicole M. , Fredericks Douglas C. , Grossbach Andrew J. , Viljoen Stephanus V. , Farhadi H. Francis 
Published: November 2018

OBJECTIVEProximal junctional kyphosis (PJK) and failure (PJF) are potentially catastrophic complications that result from abrupt changes in stress across rigid instrumented and mobile non-fused segments of the spine (transition zone) after adult spinal deformity surgery. Recently, data have indicated that extension (widening) of the transitional zone via use of proximal junctional (PJ) semi-rigid fixation can mitigate this complication. To assess the biomechanical effectiveness of 3 semi-rigid fixation constructs (compared to pedicle screw fixation alone), the authors performed cadaveric studies that measured the extent of PJ motion and intradiscal pressure changes (ΔIDP).METHODSTo measure flexibility and ΔIDP at the PJ segments, moments in flexion, extension, lateral bending (LB), and torsion were conducted in 13 fresh-frozen human cadaveric specimens. Five testing cycles were conducted, including intact (INT), T10–L2 pedicle screw-rod fixation alone (PSF), supplemental hybrid T9 Mersilene tape insertion (MT), hybrid T9 sublaminar band insertion (SLB1), and hybrid T8/T9 sublaminar band insertion (SLB2).RESULTSCompared to PSF, SLB1 significantly reduced flexibility at the level rostral to the upper-instrumented vertebral level (UIV+1) under moments in 3 directions (flexion, LB, and torsion, p ≤ 0.01). SLB2 significantly reduced motion in all directions at UIV+1 (flexion, extension, LB, torsion, p < 0.05) and at UIV+2 (LB, torsion, p ≤ 0.03). MT only reduced flexibility in extension at UIV+1 (p = 0.02). All 3 constructs revealed significant reductions in ΔIDP at UIV+1 in flexion (MT, SLB1, SLB2, p ≤ 0.02) and torsion (MT, SLB1, SLB2, p ≤ 0.05), while SLB1 and SLB2 significantly reduced ΔIDP in extension (SLB1, SLB2, p ≤ 0.02) and SLB2 reduced ΔIDP in LB (p = 0.05). At UIV+2, SLB2 similarly significantly reduced ΔIDP in extension, LB, and torsion (p ≤ 0.05).CONCLUSIONSCompared to MT, the SLB1 and SLB2 constructs significantly reduced flexibility and ΔIDP in various directions through the application of robust anteroposterior force vectors at UIV+1 and UIV+2. These findings indicate that semi-rigid sublaminar banding can most effectively expand the transition zone and mitigate stresses at the PJ levels of long-segment thoracolumbar constructs.