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OBJECTIVE Posterior cervical spine fixation is a robust strategy for stabilizing the spine for a wide range of spinal disorders. With the evolution of spinal implant technology, posterior fixation with lateral mass screws in the subaxial spine is now common. Despite interest in variable rod diameters to meet a wide range of clinical needs such as trauma, revision, and deformity surgery, indications for use of posterior cervical spine fixation are not clear. This laboratory investigation evaluates the mechanical stability and kinematic properties of lateral mass fixation with various commercially available rod diameters. METHODS The authors conducted an ex vivo experiment using 13 fresh-frozen human cervical spine specimens, instrumented from C3 to C6 with lateral mass screws, to evaluate the effects of titanium rod diameter on kinematic stability. Each intact spine was tested using a kinematic profiling machine with an optoelectrical camera and infrared sensors applying 1.5-Nm bending moments to the cranial vertebra (C2) simulating flexion-extension, lateral bending, and axial rotation anatomical motions. A compressive follower preload of 150 N was applied in flexion-extension prior to application of a bending moment. Instrumented spines were then tested with rod diameters of 3.5, 4.0, and 4.5 mm. The kinematic data between intact and surgical cases were studied using a nonparametric Wilcoxon signed-rank test. A multivariable, multilevel linear regression model was built to identify the relationship between segmental motion and rod diameter. RESULTS Instrumentation resulted in significant reduction in range of motion in all three rod constructs versus intact specimens in flexion-extension, lateral bending, and axial rotation (p < 0.05). The maximum reductions in segmental ROM versus intact spines in 3.5-, 4.0-, and 4.5-mm rod constructs were 61%, 71%, and 81% in flexion-extension; 70%, 76%, and 81% in lateral bending; and 50%, 60%, and 75% in axial rotation, respectively. Segmental motion at the adjacent segments (C2–3 and C6–7) increased significantly (p < 0.05) with increasing rod diameter. The 4.5-mm rod construct had the greatest increase in motion compared to the intact spine. CONCLUSIONS With increasing rod diameters from 3.5 to 4.0 mm, flexion-extension, lateral bending, and axial rotation across C3–6 were significantly reduced (p < 0.05). Similar trends were observed with a statistically significant reduction in motion in all anatomical planes when the rod diameter was increased to 4.5 mm. Although the increase in rod diameter resulted in a more rigid construct, it also created an increase (p < 0.05) in the kinematics of the adjacent segments (C2–3 and C6–7). Whether this increase translates into adverse long-term clinical effects in vivo requires further investigation and clinical assessment.

Breast cancer molecular features and modern therapies are not included in spine metastasis prediction algorithms.To examine molecular differences and the impact of postoperative systemic therapy to improve prognosis prediction for spinal metastases surgery and aid surgical decision making.This is a retrospective multi-institutional study of patients who underwent spine surgery for symptomatic breast cancer spine metastases from 2008 to 2021 at the Massachusetts General Hospital and Brigham and Women's Hospital. We studied overall survival, stratified by breast cancer molecular subtype, and calculated hazard ratios (HRs) adjusting for demographics, tumor characteristics, treatments, and laboratory values. We tested the performance of established models (Tokuhashi, Bauer, Skeletal Oncology Research Group, New England Spinal Metastases Score) to predict and compare all-cause.A total of 98 patients surgically treated for breast cancer spine metastases were identified (100% female sex; median age, 56 years [IQR, 36-84 years]). The 1-year probabilities of survival for hormone receptor positive, hormone receptor positive/human epidermal growth factor receptor 2+, human epidermal growth factor receptor 2+, and triple-negative breast cancer were 63% (45 of 71), 83% (10 of 12), 0% (0 of 3), and 12% (1 of 8), respectively ( P.001). Patients with triple-negative breast cancer had a higher proportion of visceral metastases, brain metastases, and poor physical activity at baseline. Postoperative chemotherapy and endocrine therapy were associated with prolonged survival. The Skeletal Oncology Research Group prognostic model had the highest discrimination (area under the receiver operating characteristic, 0.77 [95% CI, 0.73-0.81]). The performance of all prognostic scores improved when preoperative molecular data and postoperative systemic treatment plans was considered.Spine metastases risk tools were able to predict prognosis at a significantly higher degree after accounting for molecular features which guide treatment response.

OBJECTIVE Low fusion rates and cage subsidence are limitations of lumbar fixation with stand-alone interbody cages. Various approaches to interbody cage placement exist, yet the need for supplemental posterior fixation is not clear from clinical studies. Therefore, as prospective clinical studies are lacking, a comparison of segmental kinematics, cage properties, and load sharing on vertebral endplates is needed. This laboratory investigation evaluates the mechanical stability and biomechanical properties of various interbody fixation techniques by performing cadaveric and finite element (FE) modeling studies. METHODS An in vitro experiment using 7 fresh-frozen human cadavers was designed to test intact spines with 1) stand-alone lateral interbody cage constructs (lateral interbody fusion, LIF) and 2) LIF supplemented with posterior pedicle screw-rod fixation (360° constructs). FE and kinematic data were used to validate a ligamentous FE model of the lumbopelvic spine. The validated model was then used to evaluate the stability of stand-alone LIF, transforaminal lumbar interbody fusion (TLIF), and anterior lumbar interbody fusion (ALIF) cages with and without supplemental posterior fixation at the L4–5 level. The FE models of intact and instrumented cases were subjected to a 400-N compressive preload followed by an 8-Nm bending moment to simulate physiological flexion, extension, bending, and axial rotation. Segmental kinematics and load sharing at the inferior endplate were compared. RESULTS The FE kinematic predictions were consistent with cadaveric data. The range of motion (ROM) in LIF was significantly lower than intact spines for both stand-alone and 360° constructs. The calculated reduction in motion with respect to intact spines for stand-alone constructs ranged from 43% to 66% for TLIF, 67%–82% for LIF, and 69%–86% for ALIF in flexion, extension, lateral bending, and axial rotation. In flexion and extension, the maximum reduction in motion was 70% for ALIF versus 81% in LIF for stand-alone cases. When supplemented with posterior fixation, the corresponding reduction in ROM was 76%–87% for TLIF, 86%–91% for LIF, and 90%–92% for ALIF. The addition of posterior instrumentation resulted in a significant reduction in peak stress at the superior endplate of the inferior segment in all scenarios. CONCLUSIONS Stand-alone ALIF and LIF cages are most effective in providing stability in lateral bending and axial rotation and less so in flexion and extension. Supplemental posterior instrumentation improves stability for all interbody techniques. Comparative clinical data are needed to further define the indications for stand-alone cages in lumbar fusion surgery.

''Temozolomide induced PARP activation deregulates NAD metabolism. Additive cytotoxic effect of TMZ and NAMPT inhibitors in IDH1 mutant cancers. NAD and cell viability effects with TMZ and NAMPT inhibitors in endogenous IDH1 mutant cancers. Combination treatment with TMZ and NAMPT inhibitor in IDH1 mutant and wild-type cells. Cell death mechanisms that underlie combined TMZ and NAMPT inhibitor treatment in IDH1 mutant cells. In vivo effects of combined TMZ and NAMPT inhibitor treatment for endogenous IDH1 mutant cancer.''

'Temozolomide induced PARP activation deregulates NAD metabolism. Additive cytotoxic effect of TMZ and NAMPT inhibitors in IDH1 mutant cancers. NAD and cell viability effects with TMZ and NAMPT inhibitors in endogenous IDH1 mutant cancers. Combination treatment with TMZ and NAMPT inhibitor in IDH1 mutant and wild-type cells. Cell death mechanisms that underlie combined TMZ and NAMPT inhibitor treatment in IDH1 mutant cells. In vivo effects of combined TMZ and NAMPT inhibitor treatment for endogenous IDH1 mutant cancer.'

Purpose:Liquid biopsy offers a minimally invasive tool to diagnose and monitor the heterogeneous molecular landscape of tumors over time and therapy. Detection of TERT promoter mutations (C228T, C250T) in cfDNA has been successful for some systemic cancers but has yet to be demonstrated in gliomas, despite the high prevalence of these mutations in glioma tissue (>60% of all tumors).Experimental Design:Here, we developed a novel digital droplet PCR (ddPCR) assay that incorporates features to improve sensitivity and allows for the simultaneous detection and longitudinal monitoring of two TERT promoter mutations (C228T and C250T) in cfDNA from the plasma of patients with glioma.Results:In baseline performance in tumor tissue, the assay had perfect concordance with an independently performed clinical pathology laboratory assessment of TERT promoter mutations in the same tumor samples [95% confidence interval (CI), 94%–100%]. Extending to matched plasma samples, we detected TERT mutations in both discovery and blinded multi-institution validation cohorts with an overall sensitivity of 62.5% (95% CI, 52%–73%) and a specificity of 90% (95% CI, 80%–96%) compared with the gold-standard tumor tissue–based detection of TERT mutations. Upon longitudinal monitoring in 5 patients, we report that peripheral TERT-mutant allele frequency reflects the clinical course of the disease, with levels decreasing after surgical intervention and therapy and increasing with tumor progression.Conclusions:Our results demonstrate the feasibility of detecting circulating cfDNA TERT promoter mutations in patients with glioma with clinically relevant sensitivity and specificity.

Supplementary File Figure legends

Supplementary Figure 4. Correlations between (a) progression free survival, (b) overall survival, (c) tumor grade, (d) contrast enhancement, (e) type of TERT mutation, (f) tumor volume, (g) duration of disease, (h) age. Contingency tables are provided for (i) Discovery Sample Set 1 (j) Discovery Sample Set 2 (k) MultiInstitution Validation Cohort (l) Overall Combined Cohort. (m) 4 replicates of 4 uL of cfDNA from matched CSF samples (n=4; n=3 TERT mutant and n=1 WT) was used as input for absolute quantification of TERT mutant and wildtype copies. MAF is calculated using the formula described in Methods. Copies/mL for plasma samples are plotted against Study ID, classified by SNapSHOT/Pathology as floating bars, with line at the mean copies/mL. (n) Contingency table for matched CSF plasma.

OBJECTIVE The effectiveness of starting systemic therapies after surgery for spinal metastases from renal cell carcinoma (RCC) has not been evaluated in randomized controlled trials. Agents that target tyrosine kinases, mammalian target of rapamycin signaling, and immune checkpoints are now commonly used. Variables like sarcopenia, nutritional status, and frailty may impact recovery from spine surgery and are considered when evaluating a patient’s candidacy for such treatments. A better understanding of the significance of these variables may help improve patient selection for available treatment options after surgery. The authors used comparative effectiveness methods to study the treatment effect of postoperative systemic therapies (PSTs) on survival. METHODS Univariable and multivariable Cox regression analyses were performed to determine factors associated with overall survival (OS) in a retrospective cohort of adult patients who underwent spine surgery for metastatic RCC between 2010 and 2019. Propensity score–matched (PSM) analysis and inverse probability weighting (IPW) were performed to determine the treatment effect of PST on OS. To address confounding and minimize bias in estimations, PSM and IPW were adjusted for covariates, including age, sex, frailty, sarcopenia, nutrition, visceral metastases, International Metastatic RCC Database Consortium (IMDC) risk score, and performance status. RESULTS In total, 88 patients (73.9% male; median age 62 years, range 29–84 years) were identified; 49 patients (55.7%) had an intermediate IMDC risk, and 29 (33.0%) had a poor IMDC risk. The median follow-up was 17 months (range 1–104 months) during which 57 patients (64.7%) died. Poor IMDC risk (HR 3.2 [95% CI 1.08–9.3]), baseline performance status (Eastern Cooperative Oncology Group score 3 or 4; HR 2.7 [95% CI 1.5–4.7]), and nutrition (prognostic nutritional index [PNI] first tertile, PNI < 40.74; HR 2.69 [95% CI 1.42–5.1]) were associated with worse OS. Sarcopenia and frailty were not significantly associated with poor survival. PST was associated with prolonged OS, demonstrated by similar effects from multivariable Cox analysis (HR 0.55 [95% CI 0.30–1.00]), PSM (HR 0.53 [95% CI 0.29–0.93]), IPW (HR 0.47 [95% CI 0.24–0.94]), and comparable confidence intervals. The median survival for those receiving PST was 28 (95% CI 19–43) months versus 12 (95% CI 4–37) months for those who only had surgery (log-rank p = 0.027). CONCLUSIONS This comparative analysis demonstrated that PST is associated with improved survival in specific cohorts with metastatic spinal RCC after adjusting for frailty, sarcopenia, and malnutrition. The marked differences in survival should be taken into consideration when planning for surgery.

Objective: Adult cervical deformity (ACD) is a debilitating spinal condition that causes significant pain, neurologic dysfunction, and functional impairment. Surgery is often performed to correct cervical alignment, but the optimal amount of correction required to improve patient-reported outcomes (PROs) are not yet well-defined.Methods: A review of the literature was performed and Fisher z-transformation (Zr) was used to pool the correlation coefficients between alignment parameters and PROs. The strength of correlation was defined according to the following: poor (0 < r ≤ 0.3), fair (0.3 < r ≤ 0.5), moderate (0.5 < r ≤ 0.8), and strong (0.8 < r ≤ 1).Results: Increased C2–7 sagittal vertical axis was fairly associated with increased Neck Disability Index (NDI) (pooled Zr = 0.31; 95% confidence interval [CI], -0.03 to 0.58). Changes in T1 slope minus cervical lordosis poorly correlated with NDI (pooled Zr = -0.04; 95% CI, -0.23 to 0.30). Increased C7–S1 was poorly associated with worse EuroQoL 5-Dimension (pooled Zr = -0.22; 95% CI, -0.36 to -0.06). Correction of horizontal gaze did not correlate with legacy metrics. Modified Japanese Orthopedic Association correlated with C2-slope, C7–S1, and C2–S1.Conclusion: Spinal alignment parameters variably correlated with improved health-related quality of life and myelopathy after corrective surgery for ACD. Further studies evaluating legacy PROs, Patient-Reported Outcomes Measurement System, and ACD specific instruments are needed for further validation.

The introduction and integration of robot technology into modern spine surgery provides surgeons with millimeter accuracy for pedicle screw placement. Coupled with computer-based navigation platforms, robot-assisted spine surgery utilizes augmented reality to potentially improve the safety profile of instrumentation.In this study, the authors seek to determine the safety and efficacy of robotic-assisted pedicle screw placement compared to conventional free-hand (FH) technique.We conducted a systematic review of the electronic databases using different MeSH terms from 1980 to 2020.The present study measures pedicle screw accuracy, complication rates, proximal-facet joint violation, intraoperative radiation time, radiation dosage, and length of surgery.A total of 1,525 patients (7,379 pedicle screws) from 19 studies with 777 patients (51.0% with 3,684 pedicle screws) in the robotic-assisted group were included. Perfect pedicle screw accuracy, as categorized by Gerztbein-Robbin Grade A, was significantly superior with robotic-assisted surgery compared to FH-technique (Odds ratio [OR]: 1.68, 95% confidence interval [CI]: 1.20-2.35; p=.003). Similarly, clinically acceptable pedicle screw accuracy (Grade A+B) was significantly higher with robotic-assisted surgery versus FH-technique (OR: 1.54, 95% CI: 1.01-2.37; p=.05). Furthermore, the complication rates and proximal-facet joint violation were 69% (OR: 0.31, 95% CI: 0.20-0.48; p.00001) and 92% less likely (OR: 0.08, 95% CI: 0.03-0.20; p.00001) with robotic-assisted surgery versus FH-group. Robotic-assisted pedicle screw implantation significantly reduced intraoperative radiation time (MD: -5.30, 95% CI: -6.83-3.76; p.00001) and radiation dosage (MD: -3.70, 95% CI: -4.80-2.60; p.00001) compared to the conventional FH-group. However, the length of surgery was significantly higher with robotic-assisted surgery (MD: 22.70, 95% CI: 6.57-38.83; p=.006) compared to the FH-group.This meta-analysis corroborates the accuracy of robot-assisted pedicle screw placement.

OBJECTIVEAlthough several prognostic scores for spinal metastatic disease have been developed in the past 2 decades, the applicability and validity of these models to specific cancer types are not yet clear. Most of the data used for model formation are from small population sets and have not been updated or externally validated to assess their performance. Developing predictive models is clinically relevant as prognostic assessment is crucial to optimal decision-making, particularly the decision for or against spine surgery. In this study, the authors investigated the performance of various spinal metastatic disease risk models in predicting prognosis for spine surgery to treat metastatic renal cell carcinoma (RCC).METHODSData of patients who underwent surgery for RCC metastatic to the spine at 2 tertiary centers between 2010 and 2019 were retrospectively retrieved. The authors determined the prognostic value associated with the following scoring systems: the Tomita score, original and revised Tokuhashi scores, original and modified Bauer scores, Katagiri score, the Skeletal Oncology Research Group (SORG) classic algorithm and nomogram, and the New England Spinal Metastasis Score (NESMS). Regression analysis of patient variables in association with 1-year survival after surgery was assessed using Cox proportional hazard models. Calibration and time-dependent discrimination analysis were tested to quantify the accuracy of each scoring system at 3 months, 6 months, and 1 year.RESULTSA total of 86 metastatic RCC patients were included (median age 64 years [range 29–84 years]; 63 males [73.26%]). The 1-year survival rate was 72%. The 1-year survival group had a good performance status (Karnofsky Performance Scale [KPS] score 80%–100%) and an albumin level > 3.5 g/dL (p < 0.05). Multivariable-adjusted Cox regression analysis showed that poor performance status (KPS score < 70%), neurological deficit (Frankel grade A–D), and hypoalbuminemia (< 3.5 g/dL) were associated with a higher risk of death before 1 year (p < 0.05). The SORG nomogram, SORG classic, original Tokuhashi, and original Bauer demonstrated fair performance (0.7 < area under the curve < 0.8). The NESMS differentiates survival among the prognostic categories with the highest accuracy (area under the curve > 0.8).CONCLUSIONSThe present study shows that the most cited and commonly used scoring systems have a fair performance predicting survival for patients undergoing spine surgery for metastatic RCC. The NESMS had the best performance at predicting 1-year survival after surgery.

Background Preoperative prognostication of adverse events (AEs) for patients undergoing surgery for lumbar degenerative spondylolisthesis (LDS) can improve risk stratification and help guide the surgical decision-making process. The aim of this study was to develop and validate a set of predictive variables for 30-day AEs after surgery for LDS. Methods The American College of Surgeons National Surgical Quality Improvement Program was used for this study (2005–2016). Logistic regression (enter, stepwise, and forward) and LASSO (least absolute shrinkage and selection operator) methods were performed to identify and select variables for analyses, which resulted in 26 potential models. The final model was selected based on clinical criteria and numeric results. Results The overall 30-day rate of AEs for 80,610 patients who underwent surgery for LDS in this database was 4.9% (n = 3965). The median age of the cohort was 58.0 years (range, 18–89 years). The model with the following 10-predictive factors (age, gender, American Society of Anesthesiologists grade, autogenous iliac bone graft, instrumented fusion, levels of surgery, surgical approach, functional status, preoperative serum albumin [g/dL] and serum alkaline phosphatase [IU/L]) performed well on the discrimination, calibration, Brier score, and decision analyses to develop machine learning algorithms. Logistic regression showed higher areas under the curve than did LASSO methods across the different models. The predictive probability derived from the best model is uploaded on an open-access Web application, which can be found at: https://spine.massgeneral.org/drupal/Lumbar-Degenerative-AdverseEvents . Conclusions It is feasible to develop machine learning algorithms from large datasets to provide useful tools for patient counseling and surgical risk assessment.

Treatment of osteoporosis with medications like teriparatide, a parathyroid hormone, is known to improve bone density and reduce the risk of osteoporotic vertebral fractures. Anecdotal and limited surgical series have described the utility of this treatment for osteoporotic patients prior to spinal fusion surgery, but there is variability in adoption of this strategy as well as consensus regarding optimal treatment duration before and after surgery. In this study, the clinical results of the use of teriparatide for this application are reviewed and critically examined. We conducted a systematic review of electronic databases using different MeSH terms from 1980 to 2020. Pooled and subgroup analyses were performed using fixed and random effect models based upon the heterogeneity (I2). The results were reported as either mean difference (MD) or odds ratio (OR) with 95% confidence interval (CI). A total of 771 patients from 12 studies were identified. Three hundred seventy-seven patients (90.8% females) were treated with teriparatide. Lumbar spinal fusion rates were significantly higher among patients who received teriparatide compared to the non-teriparatide group (OR 2.15, 95%CI 1.56–2.97, p

Objective Interbody spacers have been successfully used in spinal fusion procedures with the aim to restore disc height, provide stability, and promote bone fusion. The authors evaluated the efficacy of structural body allograft versus polyetheretherketone (PEEK) implants in patients undergoing spinal fusion surgery. Methods A systematic review of electronic databases was conducted using different Medical Subject Headings terms from January 1970 to August 2019. Pooled and subgroup analyses were performed using random-effects and fixed-effects models based on I2 heterogeneity. Results The analysis included 6640 patients (structural allograft 64% and PEEK cage 36%) from 7 comparative studies. There were no statistically significant differences in age (P = 0.27), sex (P = 0.31), body mass index (P = 0.82), and smoking status (P = 0.27) between the 2 groups. Overall, the mean follow-up was 12.9 ± 1.5 months. Pooled meta-analysis revealed that patients with structural allograft had 2.59-fold higher likelihood of fusion compared with patients with PEEK cages (odds ratio [OR] 2.59, 95% confidence interval [CI] 1.02–6.57, P = 0.05) at last follow-up evaluation. Patients with structural allograft had 61% less likelihood of pseudarthrosis (OR 0.39, 95% CI 0.15–0.98, P = 0.05) and 74% lower incidence of reoperation compared with patients with PEEK implants (OR 0.26, 95% CI 0.09–0.79, P = 0.02). Our results suggest that patients with structural allografts had a higher subsidence rate compared with patients with PEEK implants, but this was statistically insignificant (OR 1.07, 95% CI 0.45–2.53, P = 0.89). Conclusions Our results corroborate that structural allografts are highly effective in promoting bony fusion compared with PEEK implants in patients undergoing spinal fusion surgery.

Tranexamic acid (TXA) is an effective and commonly used hemostatic agent for perioperative blood loss in various surgical specialties. It is being increasingly used in spinal deformity surgery. We aimed to evaluate the safety and efficacy of topical TXA (tTXA) compared to both placebo and/or intravenous (IV) TXA in patients undergoing spinal deformity surgery. We conducted a systematic review of the electronic databases using different MeSH terms from January 1970 to August 2019. Pooled and subgroup analysis was performed using fixed and random-effect model based upon the heterogeneity (I2). A total of 609 patients (tTXA: n = 258, 42.4%) from 8 studies were included. We found that there was a statistically significant difference in terms of (i) postoperative blood loss [mean difference (MD) − 147.1, 95% CI − 189.5 to − 104.8, p

The potential of big data analytics to improve the quality of care for patients with spine tumors is significant. At this moment, the application of big data analytics to oncology and spine surgery is at a nascent stage. As such, efforts are underway to advance data-driven oncologic care, improve patient outcomes, and guide clinical decision making. This is both relevant and critical in the practice of spine oncology as clinical decision making is often made in isolation looking at select variables deemed relevant by the physician. With rapidly evolving therapeutics in surgery, radiation, interventional radiology, and oncology, there is a need to better develop decision-making algorithms utilizing the vast data available for each patient. The challenges and limitations inherent to big data analyses are presented with an eye towards future directions.

Artificial intelligence is poised to influence various aspects of patient care, and neurosurgery is one of the most uprising fields where machine learning is being applied to provide surgeons with greater insight about the pathophysiology and prognosis of neurological conditions. This chapter provides a guide for clinicians on relevant aspects of machine learning and reviews selected application of these methods in intramedullary spinal cord tumors. The potential areas of application of machine learning extend far beyond the analyses of clinical data to include several areas of artificial intelligence, such as genomics and computer vision. Integration of various sources of data and application of advanced analytical approaches could improve risk assessment for intramedullary tumors.

Artificial intelligence is poised to influence various aspects of patient care, and neurosurgery is one of the most uprising fields where machine learning is being applied to provide surgeons with greater insight about the pathophysiology and prognosis of neurological conditions. This chapter provides a guide for clinicians on relevant aspects of machine learning and reviews selected application of these methods in intramedullary spinal cord tumors. The potential areas of application of machine learning extend far beyond the analyses of clinical data to include several areas of artificial intelligence, such as genomics and computer vision. Integration of various sources of data and application of advanced analytical approaches could improve risk assessment for intramedullary tumors.

Symptomatic cervical spinal stenosis and carotid artery stenosis are common neurosurgical diseases, but little is known about the management of their concurrent presentation. We present a 62 year-old woman with a precipitous decline in bilateral lower extremity strength, dexterity, and gait, and a 2-year history of amaurosis fugax. She was found to have cervical stenosis at C5-C7 with cord compression, lumbar stenosis at L3-L5 with a right L4-L5 synovial cyst, and moderate right internal carotid artery stenosis of 50–70%. The patient underwent a staged procedure. Stage 1 was a simultaneous right carotid endarterectomy and C6 corpectomy with C5-C7 anterior fusion. Stage 2 was a C3-T1 posterior decompression and fusion and L3-L5 decompression with synovial cyst removal. The presentation of concurrent cervical stenosis and CAS is likely underappreciated. Deciding between simultaneous or staged CEA and spinal decompression should be based on a careful risk-benefit assessment and tailored to the relative severity of symptoms, patient anatomy and comorbidities.

OBJECTIVE Cancer patients with spinal metastases may undergo surgery without clear assessments of prognosis, thereby impacting the optimal palliative strategy. Because the morbidity of surgery may adversely impact recovery and initiation of adjuvant therapies, evaluation of risk factors associated with mortality risk and complications is critical. Evaluation of body composition of cancer patients as a surrogate for frailty is an emerging area of study for improving preoperative risk stratification. METHODS To examine the associations of muscle characteristics and adiposity with postoperative complications, length of stay, and mortality in patients with spinal metastases, the authors designed an observational study of 484 cancer patients who received surgical treatment for spinal metastases between 2010 and 2019. Sarcopenia, muscle radiodensity, visceral adiposity, and subcutaneous adiposity were assessed on routinely available 3-month preoperative CT images by using a validated deep learning methodology. The authors used k-means clustering analysis to identify patients with similar body composition characteristics. Regression models were used to examine the associations of sarcopenia, frailty, and clusters with the outcomes of interest. RESULTS Of 484 patients enrolled, 303 had evaluable CT data on muscle and adiposity (mean age 62.00 ± 11.91 years; 57.8% male). The authors identified 2 clusters with significantly different body composition characteristics and mortality risks after spine metastases surgery. Patients in cluster 2 (high-risk cluster) had lower muscle mass index (mean ± SD 41.16 ± 7.99 vs 50.13 ± 10.45 cm2/m2), lower subcutaneous fat area (147.62 ± 57.80 vs 289.83 ± 109.31 cm2), lower visceral fat area (82.28 ± 48.96 vs 239.26 ± 98.40 cm2), higher muscle radiodensity (35.67 ± 9.94 vs 31.13 ± 9.07 Hounsfield units [HU]), and significantly higher risk of 1-year mortality (adjusted HR 1.45, 95% CI 1.05–2.01, p = 0.02) than individuals in cluster 1 (low-risk cluster). Decreased muscle mass, muscle radiodensity, and adiposity were not associated with a higher rate of complications after surgery. Prolonged length of stay (> 7 days) was associated with low muscle radiodensity (mean 30.87 vs 35.23 HU, 95% CI 1.98–6.73, p < 0.001). CONCLUSIONS Body composition analysis shows promise for better risk stratification of patients with spinal metastases under consideration for surgery. Those with lower muscle mass and subcutaneous and visceral adiposity are at greater risk for inferior outcomes.

Recent developments in machine learning (ML) methods demonstrate unparalleled potential for application in the spine. The ability for ML to provide diagnostic faculty, produce novel insights from existing capabilities, and augment or accelerate elements of surgical planning and decision making at levels equivalent or superior to humans will tremendously benefit spine surgeons and patients alike. In this review, we aim to provide a clinically relevant outline of ML-based technology in the contexts of spinal deformity, degeneration, and trauma, as well as an overview of commercial-level and precommercial-level surgical assist systems and decisional support tools. Furthermore, we briefly discuss potential applications of generative networks before highlighting some of the limitations of ML applications. We conclude that ML in spine imaging represents a significant addition to the neurosurgeon's armamentarium-it has the capacity to directly address and manifest clinical needs and improve diagnostic and procedural quality and safety-but is yet subject to challenges that must be addressed before widespread implementation.

BACKGROUND CONTEXT The effectiveness of starting systemic therapies after surgery for spinal metastases from renal cell carcinoma (RCC) has not been evaluated in randomized clinical trials. Agents that target tyrosine kinases, mammalian target of rapamycin signaling, and immune checkpoints are now commonly used. Variables like sarcopenia, nutritional status, and frailty may impact recovery from spine surgery and are considered when evaluating a patient's candidacy for such treatments. Better understanding the significance of these variables may help improve patient selection for available treatment options after surgery. PURPOSE Study the treatment effect of postoperative systemic therapies on survival. STUDY DESIGN/SETTING Observational study using comparative effectiveness methods. PATIENT SAMPLE Adult patients who underwent spine surgery for metastatic renal cell carcinoma (RCC) between 2010-2019 at Massachusetts General Hospital. OUTCOME MEASURES The primary outcome of this study is overall survival. Methods Univariable and multivariable Cox regression analyses were performed to determine factors associated with overall survival (OS) in a retrospective cohort of adult patients who underwent spine surgery for metastatic RCC between 2010-2019. Propensity score matched (PSM) analysis and inversive probability weighting (IPW) were performed to determine the treatment effect of postoperative systemic therapy on OS. To address confounding and minimize bias in estimations, PSM and IPW were adjusted for covariates including age, gender, frailty, sarcopenia, nutrition, visceral metastases, IMDC (International Metastatic RCC Database Consortium) risk score, and performance status. Results Eighty-eight patients (73.9% male; median age, 62 [29-84] years) were identified. Forty-nine of 88 (55.7%) had intermediate IMDC risk and 29 of 88 (33.0%) had poor IMDC risk. Median follow-up was 17 months (1-104 months) during which 57 (64.7%) died. Poor IMDC risk (HR, 3.2, [1.08-9.3]), baseline performance status (ECOG 3-4; HR, 2.7 [1.5-4.7]), and nutrition (prognostic nutritional index 1st tertile; PNI Conclusions This comparative analysis demonstrates that postoperative systemic therapy is associated with improved survival in specific cohorts with metastatic spinal RCC after adjusting for frailty, sarcopenia, and malnutrition. The marked differences in survival should be taken into consideration when planning for surgery. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Purpose: Liquid biopsy offers a minimally invasive tool to diagnose and monitor the heterogeneous molecular landscape of tumors over time and therapy. Detection of TERT promoter mutations (C228T, C250T) in cfDNA has been successful for some systemic cancers but has yet to be demonstrated in gliomas, despite the high prevalence of these mutations in glioma tissue (>60% of all tumors). Experimental Design: Here, we developed a novel digital droplet PCR (ddPCR) assay that incorporates features to improve sensitivity and allows for the simultaneous detection and longitudinal monitoring of two TERT promoter mutations (C228T and C250T) in cfDNA from the plasma of patients with glioma. Results: In baseline performance in tumor tissue, the assay had perfect concordance with an independently performed clinical pathology laboratory assessment of TERT promoter mutations in the same tumor samples [95% confidence interval (CI), 94%–100%]. Extending to matched plasma samples, we detected TERT mutations in both discovery and blinded multi-institution validation cohorts with an overall sensitivity of 62.5% (95% CI, 52%–73%) and a specificity of 90% (95% CI, 80%–96%) compared with the gold-standard tumor tissue–based detection of TERT mutations. Upon longitudinal monitoring in 5 patients, we report that peripheral TERT-mutant allele frequency reflects the clinical course of the disease, with levels decreasing after surgical intervention and therapy and increasing with tumor progression. Conclusions: Our results demonstrate the feasibility of detecting circulating cfDNA TERT promoter mutations in patients with glioma with clinically relevant sensitivity and specificity.

Liquid biopsy offers a minimally invasive tool to diagnose and monitor the heterogeneous molecular landscape of tumors over time and therapy. Gliomas have been challenging to sample with blood-based liquid biopsy due to low levels of circulating tumor-derived nucleic acid, and prior efforts have shown specific point mutations in less than 5% of glioma patients. Detection of TERT promoter mutations (C228T, C250T) in cfDNA has been successful for some systemic cancers but has yet to be demonstrated in gliomas, despite the high prevalence of these mutations in glioma tissue (>60% of all tumors). Here, we developed a novel digital droplet PCR (ddPCR) assay, that incorporates features to improve sensitivity and allows for the simultaneous detection and longitudinal monitoring of two TERT promoter mutations (C228T and C250T) in cfDNA from the plasma of glioma patients. In baseline performance in tumor tissue, (n = 157 samples), the assay had perfect concordance with an independently performed clinical pathology laboratory assessment of TERT promoter mutations in the same tumor samples (95% CI 94%-100%). Extending to matched plasma samples, we detected TERT mutations in both discovery and blinded multi-institution validation cohorts with an overall sensitivity of 62.5% (95% CI 52%-73%) and a specificity of 90% (95% CI 80%-96%) compared to the gold standard tumor tissue-based detection of TERT mutations. Upon longitudinal monitoring in 5 patients, we report that peripheral TERT mutant allele frequency reflects the clinical course of the disease with levels decreasing after surgical intervention and therapy and increasing with tumor progression. Our results demonstrate the feasibility of detecting circulating cfDNA TERT promoter mutations in glioma patients with clinically relevant sensitivity and specificity using a novel, enhanced ddPCR approach. The functionality of this assay also suggests a new clinical role for plasma-based cfDNA analysis to complement tissue-based histopathologic and molecular characterization for diagnosis and spatiotemporal monitoring of brain tumors.

Computer-assisted navigation has made a major impact on spine surgery, providing surgeons with technological tools to safely place instrumentation anywhere in the spinal column. With advances in intraoperative image acquisition, registration, and processing, many surgeons are now using navigation in their practices. The incorporation of navigation into the workflow of surgeons continues to expand with the evolution of minimally invasive techniques and robotic surgery. While numerous investigators have demonstrated the benefit of navigation for improving the accuracy of instrumentation, few have reported applying this technology to other aspects of spine surgery. Surgeries to correct spinal deformities and resect spinal tumors are technically demanding, incorporating a wide range of techniques not only for instrumentation placement but also for osteotomy planning and executing the goals of surgery. Although these subspecialties vary in their objectives, they share similar challenges with potentially high complications, invasiveness, and consequences of failed execution. Herein, we highlight the utility of using spinal navigation for applications beyond screw placement: specifically, for planning and executing osteotomies and guiding the extent of tumor resection. A narrative review of the work that has been done is supplemented with illustrative cases demonstrating these applications.

With the increasing prevalence of obesity, there is a need to understand the impact of body mass index (BMI) on spine surgery outcomes. Previous literature has reported the influence of obesity in thoracolumbar surgery; however, the impact of obesity on postoperative complications after posterior cervical fusion (PCF) is unknown.Consecutive patients who underwent cervical laminectomy and multi-level instrumented fusion for degenerative spinal conditions at an academic tertiary care hospital between 2012 and 2019 were evaluated. Patients were categorized into groups with a BMI ≥30.0 kg/mA total of 275 patients were included, with 80 obese (29.1%) and 195 nonobese (70.9%) patients. At baseline, obesity was associated with worse myelopathy (mJOA score: 10.2 vs. 13.1, P = 0.04 and Nurick grading: 3.2 vs. 1.1, P = 0.05) and abnormal cervical radiographic alignment (C2-7 sagittal vertical axis: 43.9 vs. 38.1 mm, P = 0.04). The intraoperative estimated blood loss was higher among obese patients (561.1 vs. 391.2 mL, P0.001). There was no significant difference in absolute scores for neurologic outcomes and radiographic alignment at 12 months after surgery. However, obese patients had significantly more complications than nonobese patients in terms of mechanical failure (6.3% vs. 0.5%, P = 0.05) and wound infection (8.7% vs. 0.0%, P = 0.04).Our results corroborate that PCF surgery provides significant improvement in neurologic and radiographic outcomes at 12 months after surgery for degenerative cervical spinal disorders. Obesity is a factor to consider in the pre-operative risk assessment.

Although several prognostic scores for spinal metastatic disease have been developed in the past 2 decades, the applicability and validity of these models to specific cancer types are not yet clear. Most of the data used for model formation are from small population sets and have not been updated or externally validated to assess their performance. Developing predictive models is clinically relevant as prognostic assessment is crucial to optimal decision-making, particularly the decision for or against spine surgery. In this study, the authors investigated the performance of various spinal metastatic disease risk models in predicting prognosis for spine surgery to treat metastatic renal cell carcinoma (RCC).Data of patients who underwent surgery for RCC metastatic to the spine at 2 tertiary centers between 2010 and 2019 were retrospectively retrieved. The authors determined the prognostic value associated with the following scoring systems: the Tomita score, original and revised Tokuhashi scores, original and modified Bauer scores, Katagiri score, the Skeletal Oncology Research Group (SORG) classic algorithm and nomogram, and the New England Spinal Metastasis Score (NESMS). Regression analysis of patient variables in association with 1-year survival after surgery was assessed using Cox proportional hazard models. Calibration and time-dependent discrimination analysis were tested to quantify the accuracy of each scoring system at 3 months, 6 months, and 1 year.A total of 86 metastatic RCC patients were included (median age 64 years [range 29-84 years]; 63 males [73.26%]). The 1-year survival rate was 72%. The 1-year survival group had a good performance status (Karnofsky Performance Scale [KPS] score 80%-100%) and an albumin level3.5 g/dL (p0.05). Multivariable-adjusted Cox regression analysis showed that poor performance status (KPS score70%), neurological deficit (Frankel grade A-D), and hypoalbuminemia (3.5 g/dL) were associated with a higher risk of death before 1 year (p0.05). The SORG nomogram, SORG classic, original Tokuhashi, and original Bauer demonstrated fair performance (0.7area under the curve0.8). The NESMS differentiates survival among the prognostic categories with the highest accuracy (area under the curve0.8).The present study shows that the most cited and commonly used scoring systems have a fair performance predicting survival for patients undergoing spine surgery for metastatic RCC. The NESMS had the best performance at predicting 1-year survival after surgery.

Despite updated management of glioblastoma (GB), progression is virtually inevitable. Previous data suggest a survival benefit from resection at progression; however, relatively few studies have evaluated the role of surgery in the context of contemporary GB treatment and widespread use of bevacizumab and chemotherapy. As such, the purpose of this study is to evaluate outcomes following surgical resection in patients with progressive GB since 2008. The records of all patients who underwent biopsy or resection of GB between January 1, 2008, and December 31, 2015, were retrospectively reviewed to identify 368 patients with progressive GB. Median survival and 95% confidence intervals were generated with the Kaplan-Meier method. Multivariate analysis, which controlled for age, Karnofsky Performance Status (KPS), extent of resection, adjuvant chemotherapy and radiation, tumor location, and tumor multifocality, of post-progression survival was carried out using a Cox proportional hazards model. Of 368 patients with progressive disease, 77 (20.9%) underwent resection at first documented progression. The median post-progression survivals for patients who did and did not undergo resection at this time were 12.8 and 7.0 months, respectively. In multivariate analysis, KPS ≥ 70 at progression (HR 0.438), receipt of bevacizumab at first progression (HR 0.756), and receipt of chemotherapy at first progression (HR 0.644) were associated with increased post-progression survival. Thus, surgery for progressive GB may not improve post-progression survival in the context of contemporary maximal non-surgical therapy. Further investigation is necessary to elucidate what role, if any, bevacizumab has in prolonging post-progression survival in patients with progressive GB.

Background Modern medical management of metastatic renal cell carcinoma (RCC) includes therapies targeting tyrosine kinases, growth pathways (mammalian target of rapamycin (mTOR)), and immune checkpoints. Objective To test our hypothesis that patients with spinal metastases would benefit from postoperative systemic therapy despite presenting with disease that, in many cases, was resistant to prior systemic therapy. Methods This is an Institutional Review Board-approved clinical retrospective cohort analysis. A sample of adult patients with RCC metastatic to the spine who underwent operative intervention between January 2010 and December 2017 at 2 large academic medical centers was used in this study. Results We identified 78 patients with metastatic RCC in whom instrumented stabilization was performed in 79% and postoperative stereotactic radiosurgery was performed in 41% of patients. Of patients presenting with weakness or myelopathy, 93% noted postoperative improvement and 78% reported improvement in radicular and axial paraspinal pain severity. Increased overall survival (OS) (913 d (95% CI: 633-1975 d, n = 49) vs 222 d (95% CI: 143-1005 d, n = 29), P = .003) following surgery was noted in patients who received postoperative systemic therapy a median of 80 d (interquartile range 48-227 d) following the surgical intervention. Conclusion Postoperative outcomes and palliation of symptoms for metastatic RCC without targeted therapies in this cohort are similar to those reported in earlier series prior to the adoption of these systemic therapies. We observed a significantly longer OS among patients who received modern systemic therapies postoperatively. These findings have implications for the preoperative evaluation of patients with systemic disease who may have been deemed poor surgical candidates prior to the availability of these systemic therapies.

// Tareq A. Juratli 1, 2 , Christian Thiede 3 , Mara V.A. Koerner 1 , Shilpa S. Tummala 1 , Dirk Daubner 4 , Ganesh M. Shankar 1 , Erik A. Williams 5 , Maria Martinez-Lage 5 , Silke Soucek 2 , Katja Robel 2 , Tristan Penson 1 , Mechthild Krause 6, 7, 8 , Steffen Appold 6, 7, 8 , Matthias Meinhardt 9 , Thomas Pinzer 2 , Julie J. Miller 10 , Dietmar Krex 2, 7 , Heather A. Ely 11 , Ian M. Silverman 11 , Jason Christiansen 11 , Gabriele Schackert 2, 7 , Hiroaki Wakimoto 1 , Matthias Kirsch 2, 7, * , Priscilla K. Brastianos 12, * and Daniel P. Cahill 1, * 1 Translational Neuro-Oncology Laboratory, Department of Neurosurgery, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA 2 Department of Neurosurgery, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Dresden, Germany 3 Department of Medicine I, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Dresden, Germany 4 Institute of Neuroradiology, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Dresden, Germany 5 Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA 6 Institute of Radiooncology, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany 7 German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany 8 Department of Radiation Oncology and OncoRay, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Dresden, Germany 9 Institute of Pathology, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Dresden, Germany 10 Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA 11 Ignyta, Inc., San Diego, California, USA 12 Department of Medicine, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA * These authors have contributed equally to this work Correspondence to: Daniel P. Cahill, email: cahill@mgh.harvard.edu Priscilla K. Brastianos, email: PBRASTIANOS@mgh.harvard.edu Matthias Kirsch, email: Matthias.kirsch@uniklinikum-dresden.de Keywords: meningioma; telomere; heterogeneity; rearrangements; fusion Received: August 18, 2017 Accepted: October 30, 2017 Published: November 24, 2017 ABSTRACT Background: Recent studies have reported mutations in the telomerase reverse transcriptase promoter ( TERT p) in meningiomas. We sought to determine the frequency, clonality and clinical significance of telomere gene alterations in a cohort of patients with progressive/higher-grade meningiomas. Methods: We characterized 64 temporally- and regionally-distinct specimens from 26 WHO grade III meningioma patients. On initial diagnoses, the meningiomas spanned all WHO grades (3 grade I, 13 grade II and 10 grade III). The tumor samples were screened for TERT p and ATRX/DAXX mutations, and TERT rearrangements. Additionally, TERT p was sequenced in a separate cohort of 19 patients with radiation-associated meningiomas. We examined the impact of mutational status on patients’ progression and overall survival. Results: Somatic TERT p mutations were detected in six patients (6/26 = 23%). Regional intratumoral heterogeneity in TERT p mutation status was noted. In 4 patients, TERT p mutations were detected in recurrent specimens but not in the available specimens of the first surgery. Additionally, a TERT gene fusion ( LPCAT1-TERT ) was found in one sample. In contrary, none of the investigated samples harbored an ATRX or DAXX mutation. In the cohort of radiation-induced meningiomas, TERT p mutation was detected in two patients (10.5%). Importantly, we found that patients with emergence of TERT p mutations had a substantially shorter OS than their TERT p wild-type counterparts (2.7 years, 95% CI 0.9 – 4.5 years versus 10.8 years, 95% CI 7.8 -12.8 years, p=0.003). Conclusions: In progressive/higher-grade meningiomas, TERT p mutations are associated with poor survival, supporting a model in which selection of this alteration is a harbinger of aggressive tumor development. In addition, we observe spatial intratumoral heterogeneity of TERT p mutation status, consistent with this model of late emergence in tumor evolution. Thus, early detection of TERT p mutations may define patients with more aggressive meningiomas. Stratification for TERT alterations should be adopted in future clinical trials of progressive/higher-grade meningiomas.