Bone metastasis from glioblastoma: a systematic review.

INTRODUCTION: Glioblastoma (GBM) is a devastating disease with poor overall survival. Despite the common occurrence of GBM among primary brain tumors, metastatic disease is rare. Our goal was to perform a systematic literature review on GBM with osseous metastases and understand the rate of metastasis to the vertebral column as compared to the remainder of the skeleton, and how this histology would fit into our current paradigm of treatment for bone metastases. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant literature search was performed using the PubMed database from 1952 to 2021. Search terms included "GBM", "glioblastoma", "high-grade glioma", "bone metastasis", and "bone metastases". RESULTS: Of 659 studies initially identified, 67 articles were included in the current review. From these 67 articles, a total of 92 distinct patient case presentations of metastatic glioblastoma to bone were identified. Of these cases, 58 (63%) involved the vertebral column while the remainder involved lesions within the skull, sternum, rib cage, and appendicular skeleton. CONCLUSION: Metastatic dissemination of GBM to bone occurs. While the true incidence is unknown, workup for metastatic disease, especially involving the spinal column, is warranted in symptomatic patients. Lastly, management of patients with GBM vertebral column metastases can follow the International Spine Oncology Consortium two-step multidisciplinary algorithm for the management of spinal metastases.

Bone Metastases, Skeletal-Related Events, and Survival in Patients With Metastatic Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors.

BACKGROUND: Bone metastases and skeletal-related events (SREs) are a frequent cause of morbidity in patients with metastatic non-small cell lung cancer (mNSCLC). Data are limited on bone metastases and SREs in patients with mNSCLC treated using immune checkpoint inhibitors (ICIs), and on the efficacy of bone-modifying agents (BMAs) in this setting. Here we report the incidence, impact on survival, risk factors for bone metastases and SREs, and impact of BMAs in patients with mNSCLC treated with ICIs in a multi-institutional cohort. PATIENTS AND METHODS: We conducted a retrospective study of patients with mNSCLC treated with ICIs at 2 tertiary care centers from 2014 through 2017. Overall survival (OS) was compared between patients with and without baseline bone metastases using a log-rank test. A Cox regression model was used to evaluate the association between OS and the presence of bone metastases at ICI initiation, controlling for other confounding factors. RESULTS: We identified a cohort of 330 patients who had received ICIs for metastatic disease. Median patient age was 63 years, most patients were treated in the second line or beyond (n=259; 78%), and nivolumab was the most common ICI (n=211; 64%). Median OS was 10 months (95% CI, 8.4-12.0). In our cohort, 124 patients (38%) had baseline bone metastases, and 43 (13%) developed SREs during or after ICI treatment. Patients with bone metastases had a higher hazard of death after controlling for performance status, histology, line of therapy, and disease burden (hazard ratio, 1.57; 95% CI, 1.19-2.08; P=.001). Use of BMAs was not associated with OS or a decreased risk of SREs. CONCLUSIONS: Presence of bone metastases at baseline was associated with a worse prognosis for patients with mNSCLC treated with ICI after controlling for multiple clinical characteristics. Use of BMAs was not associated with reduced SREs or a difference in survival.

Dura promotes metastatic potential in prostate cancer through the CXCR2 pathway.

PURPOSE: Spinal metastases are common in cancer. This preferential migration/growth in the spine is not fully understood. Dura has been shown to affect the surrounding microenvironment and promote cancer growth. Here, we investigate the role of dural cytokines in promoting the metastatic potential of prostate cancer (PCa) and the involvement of the CXCR2 signaling pathway. METHODS: The role of dural conditioned media (DCM) in proliferation, migration and invasion of five PCa cell lines with various hormone sensitivities was assessed in the presence or absence of the CXCR2 inhibitor, SB225002. CXCR2 surface protein was examined by FACS. Cytokine levels were measured using a mouse cytokine array. RESULTS: We observed high levels of cytokines produced by dura and within the vertebral body bone marrow, namely CXCL1 and CXCL2, that act on the CXCR2 receptor. All prostate cell lines treated with DCM demonstrated significant increase in growth, migration and invasion regardless of androgen sensitivity, except PC3, which did not significantly increase in invasiveness. When treated with SB225002, the growth response to DCM by cells expressing the highest levels of CXCR2 as measured by FACS (LNCaP and 22Rv1) was blunted. The increase in migration was significantly decreased in all lines in the presence of SB225002. Interestingly, the invasion increase seen with DCM was unchanged when these cells were treated with the CXCR2 inhibitor, except PC3 did demonstrate a significant decrease in invasion. CONCLUSION: DCM enhances the metastatic potential of PCa with increased proliferation, migration and invasion. This phenomenon is partly mediated through the CXCR2 pathway.

Association between timing of kyphoplasty and opioid prescribing risk after vertebral fracture.

OBJECTIVE: Approximately 550,000 Americans experience vertebral fracture annually, and most receive opioids to treat the resulting pain. Kyphoplasty of the fractured vertebra is a procedural alternative that may mitigate risks of even short-term opioid use. While reports of kyphoplasty's impact on pain scores are mixed, no large-scale data exist regarding opioid prescribing before and after the procedure. This study was conducted to determine whether timing of kyphoplasty following vertebral fracture is associated with duration or intensity of opioid prescribing. METHODS: This retrospective cohort study used 2001-2014 insurance claims data from a single, large private insurer in the US across multiple care settings. Patients were adults with vertebral fractures who were prescribed opioids and underwent balloon-assisted kyphoplasty within 4 months of fracture. Opioid overdose risk was stratified by prescribed average daily morphine milligram equivalents using CDC guidelines. Filled prescriptions and risk categories were evaluated at baseline and 90 days following kyphoplasty. RESULTS: Inclusion criteria were met by 7119 patients (median age 77 years, 71.7% female). Among included patients, 3505 (49.2%) were opioid naïve before fracture. Of these patients, 31.1% had new persistent opioid prescribing beyond 90 days after kyphoplasty, and multivariable logistic regression identified kyphoplasty after 8 weeks as a predictor (OR 1.34, 95% CI 1.02-1.76). For patients previously receiving opioids, kyphoplasty > 4 weeks after fracture was associated with persistently elevated prescribing risk (OR 1.84, 95% CI 1.23-2.74). CONCLUSIONS: New persistent opioid prescribing occurred in nearly one-third of patients undergoing kyphoplasty after vertebral fracture, although early treatment was associated with a reduction in this risk. For patients not naïve to opioids before fracture diagnosis, early kyphoplasty was associated with less persistent elevation of opioid overdose risk. Subsequent trials must compare opioid use by vertebral fracture patients treated via operative (kyphoplasty) and nonoperative (ongoing opioid) strategies before concluding that kyphoplasty lacks value, and early referral for kyphoplasty may be appropriate to avoid missing a window of efficacy.

The feasibility of computer-assisted 3D navigation in multiple-level lateral lumbar interbody fusion in combination with posterior instrumentation for adult spinal deformity.

OBJECTIVE: The lateral lumbar interbody fusion (LLIF) technique is used to treat many common spinal degenerative pathologies including kyphoscoliosis. The use of spinal navigation for LLIF has not been broadly adopted, especially in adult spinal deformity. The purpose of this study was to evaluate the feasibility as well as the intraoperative and navigation-related complications of computer-assisted 3D navigation (CaN) during multiple-level LLIF for spinal deformity. METHODS: Retrospective analysis of clinical and operative characteristics was performed for all patients > 18 years of age who underwent multiple-level CaN LLIF combined with posterior instrumentation for adult spinal deformity at the University of Michigan between 2014 and 2020. Intraoperative CaN-related complications, LLIF approach-related postoperative complications, and medical postoperative complications were assessed. RESULTS: Fifty-nine patients were identified. The mean age was 66.3 years (range 42-83 years) and body mass index was 27.6 kg/m2 (range 18-43 kg/m2). The average coronal Cobb angle was 26.8° (range 3.6°-67.0°) and sagittal vertical axis was 6.3 cm (range -2.3 to 14.7 cm). The average number of LLIF and posterior instrumentation levels were 2.97 cages (range 2-5 cages) and 5.78 levels (range 3-14 levels), respectively. A total of 6 intraoperative complications related to the LLIF stage occurred in 5 patients. Three of these were CaN-related and occurred in 2 patients (3.4%), including 1 misplaced lateral interbody cage (0.6% of 175 total lateral cages placed) requiring intraoperative revision. No patient required a return to the operating room for a misplaced interbody cage. A total of 12 intraoperative complications related to the posterior stage occurred in 11 patients, with 5 being CaN-related and occurring in 4 patients (6.8%). Univariate and multivariate analyses revealed no statistically significant risk factors for intraoperative and CaN-related complications. Transient hip weakness and numbness were found to be in 20.3% and 22.0% of patients, respectively. At the 1-month follow-up, weakness was observed in 3.4% and numbness in 11.9% of patients. CONCLUSIONS: Use of CaN in multiple-level LLIF in the treatment of adult spinal deformity appears to be a safe and effective technique. The incidence of approach-related complications with CaN was 3.4% and cage placement accuracy was high.

Detection and isolation of disseminated tumor cells in bone marrow of patients with clinically localized prostate cancer.

BACKGROUND: Disseminated tumor cells (DTCs) have been reported in the bone marrow (BM) of patients with localized prostate cancer (PCa). However, the existence of these cells continues to be questioned, and few methods exist for viable DTC isolation. Therefore, we sought to develop novel approaches to identify and, if detected, analyze localized PCa patient DTCs. METHODS: We used fluorescence-activated cell sorting (FACS) to isolate a putative DTC population, which was negative for CD45, CD235a, alkaline phosphatase, and CD34, and strongly expressed EPCAM. We examined tumor cell content by bulk cell RNA sequencing (RNA-Seq) and whole-exome sequencing after whole genome amplification. We also enriched for BM DTCs with α-EPCAM immunomagnetic beads and performed quantitative reverse trancriptase polymerase chain reaction (qRT-PCR) for PCa markers. RESULTS: At a threshold of 4 cells per million BM cells, the putative DTC population was present in 10 of 58 patients (17%) with localized PCa, 4 of 8 patients with metastatic PCa of varying disease control, and 1 of 8 patients with no known cancer, and was positively correlated with patients' plasma PSA values. RNA-Seq analysis of the putative DTC population collected from samples above (3 patients) and below (5 patients) the threshold of 4 putative DTCs per million showed increased expression of PCa marker genes in 4 of 8 patients with localized PCa, but not the one normal donor who had the putative DTC population present. Whole-exome sequencing also showed the presence of single nucleotide polymorphisms and structural variants in the gene characteristics of PCa in 2 of 3 localized PCa patients. To examine the likely contaminating cell types, we used a myeloid colony formation assay, differential counts of cell smears, and analysis of the RNA-Seq data using the CIBERSORT algorithm, which most strongly suggested the presence of B-cell lineages as a contaminant. Finally, we used EPCAM enrichment and qRT-PCR for PCa markers to estimate DTC prevalence and found evidence of DTCs in 21 of 44 samples (47%). CONCLUSION: These data support the presence of DTCs in the BM of a subset of patients with localized PCa and describe a novel FACS method for isolation and analysis of viable DTCs.

Surgical Approach to Bone Metastases.

PURPOSE OF REVIEW: The purpose of this review was to examine the recent changes in the surgical treatment of bone metastases and how the treatment paradigm has shifted with the improvement of adjuvant therapies. How surgery fits into the local and systemic treatment was reviewed for bone metastases in different areas. RECENT FINDINGS: The more common use of targeted chemotherapies and focused high-dose radiation have altered the treatment paradigm of bone metastases. Overall changes in the surgical treatment of bone metastases have been driven by an increased multidisciplinary approach to metastatic cancer and the awareness that one type of surgery does not work for all patients. The individual patient treatment goals dictate the surgical procedures used to achieve these goals. Advancements in adjuvant therapy-like radiation and more targeted chemotherapies have allowed for less invasive surgical approaches and therefore faster recoveries and reduced surgical morbidity for patients.

An integrated multidisciplinary algorithm for the management of spinal metastases: an International Spine Oncology Consortium report.

Spinal metastases are becoming increasingly common because patients with metastatic disease are living longer. The close proximity of the spinal cord to the vertebral column limits many conventional therapeutic options that can otherwise be used to treat cancer. In response to this problem, an innovative multidisciplinary approach has been developed for the management of spinal metastases, leveraging the capabilities of image-guided stereotactic radiosurgery, separation surgery, vertebroplasty, and minimally invasive local ablative approaches. In this Review, we discuss the variables that should be considered during the management of these patients and review the role of each discipline and their respective management options to provide optimal care. This work is synthesised into a practical algorithm to aid clinicians in the management of patients with spinal metastasis.

The impact of blood pressure management after spinal cord injury: a systematic review of the literature.

OBJECTIVE Spinal cord injury (SCI) results in significant morbidity and mortality. Improving neurological recovery by reducing secondary injury is a major principle in the management of SCI. To minimize secondary injury, blood pressure (BP) augmentation has been advocated. The objective of this study was to review the evidence behind BP management after SCI. METHODS This systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Using the PubMed database, the authors identified studies that investigated BP management after acute SCI. Information on BP goals, duration of BP management, vasopressor selection, and neurological outcomes were analyzed. RESULTS Eleven studies that met inclusion criteria were identified. Nine studies were retrospective, and 2 were single-cohort prospective investigations. Of the 9 retrospective studies, 7 reported a goal mean arterial pressure (MAP) of higher than 85 mm Hg. For the 2 prospective studies, the MAP goals were higher than 85 mm Hg and higher than 90 mm Hg. The duration of BP management varied from more than 24 hours to 7 days in 6 of the retrospective studies that reported the duration of treatment. In both prospective studies, the duration of treatment was 7 days. In the 2 prospective studies, neurological outcomes were stable to improved with BP management. The retrospective studies, however, were contradictory with regard to the correlation of BP management and outcomes. Dopamine, norepinephrine, and phenylephrine were the agents that were frequently used to augment BP. However, more complications have been associated with dopamine use than with the other vasopressors. CONCLUSIONS There are no high-quality data regarding optimal BP goals and duration in the management of acute SCI. Based on the highest level of evidence available from the 2 prospective studies, MAP goals of 85-90 mm Hg for a duration of 5-7 days should be considered. Norepinephrine for cervical and upper thoracic injuries and phenylephrine or norepinephrine for mid- to lower thoracic injuries should be considered.

Anatomic and functional imaging in the diagnosis of spine metastases and response assessment after spine radiosurgery.

Spine stereotactic radiosurgery (SSRS) has recently emerged as an increasingly effective treatment for spinal metastases. Studies performed over the past decade have examined the role of imaging in the diagnosis of metastases, as well as treatment response following SSRS. In this paper, the authors describe and review the utility of several imaging modalities in the diagnosis of spinal metastases and monitoring of their response to SSRS. Specifically, we review the role of CT, MRI, and positron emission tomography (PET) in their ability to differentiate between osteoblastic and osteolytic lesions, delineation of initial bony pathology, detection of treatment-related changes in bone density and vertebral compression fracture after SSRS, and tumor response to therapy. Validated consensus guidelines defining the imaging approach to SSRS are needed to standardize the diagnosis and treatment response assessment after SSRS. Future directions of spinal imaging, including advances in targeted tumor-specific molecular imaging markers demonstrate early promise for advancing the role of imaging in SSRS.

Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response.

Glioblastoma (GBM) is distinguished by a high degree of intratumoral heterogeneity, which extends to the pattern of expression and amplification of receptor tyrosine kinases (RTKs). Although most GBMs harbor RTK amplifications, clinical trials of small-molecule inhibitors targeting individual RTKs have been disappointing to date. Activation of multiple RTKs within individual GBMs provides a theoretical mechanism of resistance; however, the spectrum of functional RTK dependence among tumor cell subpopulations in actual tumors is unknown. We investigated the pattern of heterogeneity of RTK amplification and functional RTK dependence in GBM tumor cell subpopulations. Analysis of The Cancer Genome Atlas GBM dataset identified 34 of 463 cases showing independent focal amplification of two or more RTKs, most commonly platelet-derived growth factor receptor α (PDGFRA) and epidermal growth factor receptor (EGFR). Dual-color fluorescence in situ hybridization was performed on eight samples with EGFR and PDGFRA amplification, revealing distinct tumor cell subpopulations amplified for only one RTK; in all cases these predominated over cells amplified for both. Cell lines derived from coamplified tumors exhibited genotype selection under RTK-targeted ligand stimulation or pharmacologic inhibition in vitro. Simultaneous inhibition of both EGFR and PDGFR was necessary for abrogation of PI3 kinase pathway activity in the mixed population. DNA sequencing of isolated subpopulations establishes a common clonal origin consistent with late or ongoing divergence of RTK genotype. This phenomenon is especially common among tumors with PDGFRA amplification: overall, 43% of PDGFRA-amplified GBM were found to have amplification of EGFR or the hepatocyte growth factor receptor gene (MET) as well.

Quantitative assessment of intragenic receptor tyrosine kinase deletions in primary glioblastomas: their prevalence and molecular correlates.

Intragenic deletion is the most common form of activating mutation among receptor tyrosine kinases (RTK) in glioblastoma. However, these events are not detected by conventional DNA sequencing methods commonly utilized for tumor genotyping. To comprehensively assess the frequency, distribution, and expression levels of common RTK deletion mutants in glioblastoma, we analyzed RNA from a set of 192 glioblastoma samples from The Cancer Genome Atlas for the expression of EGFRvIII, EGFRvII, EGFRvV (carboxyl-terminal deletion), and PDGFRAΔ8,9. These mutations were detected in 24, 1.6, 4.7, and 1.6 % of cases, respectively. Overall, 29 % (55/189) of glioblastomas expressed at least one RTK intragenic deletion transcript in this panel. For EGFRvIII, samples were analyzed by both quantitative real-time PCR (QRT-PCR) and single mRNA molecule counting on the Nanostring nCounter platform. Nanostring proved to be highly sensitive, specific, and linear, with sensitivity comparable or exceeding that of RNA seq. We evaluated the prognostic significance and molecular correlates of RTK rearrangements. EGFRvIII was only detectable in tumors with focal amplification of the gene. Moreover, we found that EGFRvIII expression was not prognostic of poor outcome and that neither recurrent copy number alterations nor global changes in gene expression differentiate EGFRvIII-positive tumors from tumors with amplification of wild-type EGFR. The wide range of expression of mutant alleles and co-expression of multiple EGFR variants suggests that quantitative RNA-based clinical assays will be important for assessing the relative expression of intragenic deletions as therapeutic targets and/or candidate biomarkers. To this end, we demonstrate the performance of the Nanostring assay in RNA derived from routinely collected formalin-fixed paraffin-embedded tissue.

Quality of life research in neuro-oncology: a quantitative comparison.

Our understanding of the biology of neuro-oncologic disease has improved vastly over time, however overall patient survival remains relatively poor. Our goal as clinicians, therefore, should be to ensure that the quality of life (QOL) in that survival time is optimized. Here we review neuro-oncology QOL abstracts presented at major oncology conferences and the published literature to make a quantitative comparison to other common cancer subtypes. First, all abstracts presented at major oncology meetings from 2008 to 2012 were reviewed and filtered to find those related to QOL in CNS, breast, lung, and prostate cancer. Next, a Medline search was performed to identify all QOL papers published from 2003 to 2012 for the same cancer subtypes. The results were compared as absolute values and percentages. The average percentage of CNS QOL-related abstracts presented at ASCO and ASTRO over the last 5 years was 4.9 %, compared to 6.4 % for breast, 4.4 % for lung, and 6.1 % for prostate. There is a significant difference in total percentage of QOL abstracts over the time period when comparing CNS to breast and prostate, but not lung (p < 0.05). The Medline search revealed an average of 25.2 publications per year for CNS cancer, compared to 146.2 for breast, 39.3 for lung, and 64.2 for prostate. When looking at trends over time, publications in CNS cancer have not been as prolific and have not increased as rapidly as publications in breast and lung cancer, indicating that QOL is underrepresented in neuro-oncology research. We need to improve this by standardizing QOL measures and including them in every outcome study.

Post-operative diabetes insipidus after endoscopic transsphenoidal surgery.

Diabetes insipidus (DI) after endoscopic transsphenoidal surgery (ETSS) can lead to increased morbidity, longer hospital stays, and increased medication requirements. Predicting which patients are at high risk for developing DI can help direct services to ensure adequate care and follow-up. The objective of this study was to review our institution's experience with ETSS and determine which clinical/laboratory variables are associated with DI in this patient population. The authors wanted to see if there was an easily determined single value that would help predict which patients develop DI. This represents the largest North American series of this type. We retrospectively reviewed the charts of patients who had undergone ETSS for resection of sellar and parasellar pathology between 2006 and 2011. We examined patient and tumor characteristics and their relationship to postoperative DI. Out of 172 endoscopic transsphenoidal surgeries, there were 15 cases of transient DI (8.7%) and 14 cases of permanent DI (8.1%). Statistically significant predictors of postoperative DI (p < 0.05) included tumor volume and histopathology (Rathke's cleft cyst and craniopharyngioma). Significant indicators of development of DI were postoperative serum sodium, preoperative to postoperative change in sodium level, and urine output prior to administration of 1-deamino-8-D-arginine vasopressin. An increase in serum sodium of ≥2.5 mmol/L is a positive marker of development of DI with 80% specificity, and a postoperative serum sodium of ≥145 mmol/L is a positive indicator with 98% specificity. Identifying perioperative risk factors and objective indicators of DI after ETSS will help physicians care for patients postoperatively. In this large series, we demonstrated that there were multiple perioperative risk factors for the development of DI. These findings, which are consistent with other reports from microscopic surgical series, will help identify patients at risk for diabetes insipidus, aid in planning treatment algorithms, and increase vigilance in high risk patients.

Local Control in Patients with Metastatic Renal Cell Carcinoma to the Spine: The Experience of an Institution with a Multidisciplinary Spine Oncology Program.

BACKGROUND: The outcomes for patients with metastatic renal cell carcinoma (RCC) to the spine who underwent stereotactic body radiotherapy (SBRT) through a multidisciplinary spine oncology program are not well described. We sought to describe the clinical course and local control rates at 1 and 2 years for these patients. METHODS: A retrospective analysis of a prospectively maintained database of adult oncologic patients receiving SBRT to the spine through a multidisciplinary spine oncology program at a single institution from 2010 to 2021 was performed. Patients with a pathologic diagnosis of RCC were included. RESULTS: A total of 75 spinal sites were treated in 60 patients. Of the 60 patients, 75.0% were men, and the mean patient age was 59.2 ± 11.3 years. At 1 year after treatment, 6 of the 60 patients were lost to follow-up. Of the remaining 54 patients, 18 were censored by death and 7 treatment sites showed local recurrence, for 37 of 44 treatment sites with local control (87.8%). At 2 years, 1 additional local recurrence had developed, 15 patients were censored by death, and no additional patients had been lost to follow-up, resulting in 28 of 36 treatment sites with local control (83.2%). None of the patients who had undergone repeat SBRT had local recurrence at 1 or 2 years. For those with local recurrence, the average time from treatment to progression was 6.6 ± 6.5 months. CONCLUSIONS: In this cohort, one of the largest reported studies of spine SBRT for metastatic RCC, local control was high at 1 and 2 years. Our findings support the role of coordinated, algorithmic treatment for these patients.

Patients with progression of spinal metastases who present to the clinic have better outcomes compared to those who present to the emergency department.

BACKGROUND: As cancer therapies have improved, spinal metastases are increasingly common. Resulting complications have a significant impact on patient's quality of life. Optimal methods of surveillance and avoidance of neurologic deficits are understudied. This study compares the clinical course of patients who initially presented to the emergency department (ED) versus a multidisciplinary spine oncology clinic and who underwent stereotactic body radiation therapy (SBRT) secondary to progression/presentation of metastatic spine disease. METHODS: We performed a retrospective analysis of a prospectively maintained database of adult oncologic patients who underwent spinal SBRT at a single hospital from 2010 to 2021. Descriptive statistics and survival analyses were performed. RESULTS: We identified 498 spinal radiographic treatment sites in 390 patients. Of these patients, 118 (30.3%) presented to the ED. Patients presenting to the ED compared to the clinic had significantly more severe spinal compression (52.5% vs. 11.7%; p < 0.0001), severe pain (28.8% vs. 10.3%; p < 0.0001), weakness (24.5% vs. 4.5%; p < 0.0001), and difficulty walking (24.5% vs. 4.5%; p < 0.0001). Patients who presented to the ED compared to the clinic were significantly more likely to have surgical intervention followed by SBRT (55.4% vs. 15.3%; p < 0.0001) compared to SBRT alone. Patients who presented to the ED compared to the clinic had a significantly quicker interval to distant spine progression (5.1 ± 6.5 vs. 9.1 ± 10.2 months; p = 0.004), systemic progression (5.1 ± 7.2 vs. 9.2 ± 10.7 months; p < 0.0001), and worse overall survival (9.3 ± 10.0 vs. 14.3 ± 13.7 months; p = 0.002). CONCLUSION: The establishment of multidisciplinary spine oncology clinics is an opportunity to potentially allow for earlier, more data-driven treatment of their spinal metastatic disease.

Pre- and intraoperative thoracic spine localization techniques: a systematic review.

OBJECTIVE: In the era of modern medicine with an armamentarium full of state-of-the art technologies at our disposal, the incidence of wrong-level spinal surgery remains problematic. In particular, the thoracic spine presents a challenge for accurate localization due partly to body habitus, anatomical variations, and radiographic artifact from the ribs and scapula. The present review aims to assess and describe thoracic spine localization techniques. METHODS: The authors performed a literature search using the PubMed database from 1990 to 2020, compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 27 articles were included in this qualitative review. RESULTS: A number of pre- and intraoperative strategies have been devised and employed to facilitate correct-level localization. Some of the more well-described approaches include fiducial metallic markers (screw or gold), metallic coils, polymethylmethacrylate, methylene blue, marking wire, use of intraoperative neuronavigation, intraoperative localization techniques (including using a needle, temperature probe, fluoroscopy, MRI, and ultrasonography), and skin marking. CONCLUSIONS: While a number of techniques exist to accurately localize lesions in the thoracic spine, each has its advantages and disadvantages. Ultimately, the localization technique deployed by the spine surgeon will be patient-specific but often based on surgeon preference.

Differential immune landscapes in appendicular versus axial skeleton.

Roughly 400,000 people in the U.S. are living with bone metastases, the vast majority occurring in the spine. Metastases to the spine result in fractures, pain, paralysis, and significant health care costs. This predilection for cancer to metastasize to the bone is seen across most cancer histologies, with the greatest incidence seen in prostate, breast, and lung cancer. The molecular process involved in this predilection for axial versus appendicular skeleton is not fully understood, although it is likely that a combination of tumor and local micro-environmental factors plays a role. Immune cells are an important constituent of the bone marrow microenvironment and many of these cells have been shown to play a significant role in tumor growth and progression in soft tissue and bone disease. With this in mind, we sought to examine the differences in immune landscape between axial and appendicular bones in the normal noncancerous setting in order to obtain an understanding of these landscapes. To accomplish this, we utilized mass cytometry by time-of-flight (CyTOF) to examine differences in the immune cell landscapes between the long bone and vertebral body bone marrow from patient clinical samples and C57BL/6J mice. We demonstrate significant differences between immune populations in both murine and human marrow with a predominance of myeloid progenitor cells in the spine. Additionally, cytokine analysis revealed differences in concentrations favoring a more myeloid enriched population of cells in the vertebral body bone marrow. These differences could have clinical implications with respect to the distribution and permissive growth of bone metastases.

Factors impacting volumetric white matter changes following whole brain radiation therapy.

Whole brain radiation therapy (WBRT) is one of the most effective modalities for treatment of brain metastases. With increasing cancer control there is growing concern regarding the long-term effects of treatment. These effects are seen as white matter change (WMC) on brain MRI. Severity of WMC is implicated in cognitive and functional decline in many patient groups. Our objective was to identify clinical factors associated with greater accumulation of WMC following WBRT. Through retrospective review of serial MRIs obtained from 30 patients surviving greater than 1 year after WBRT, treated at a single institution between 2002 and 2007, we calculated volumetric WMC over time using segmentation software. Changes related to tumor, secondary effects, surgery or radiosurgery were excluded. Factors that influenced the rate of WMC accumulation were identified through multivariate analysis. Following WBRT, patients accumulated WMC at an average rate of 0.07% of total brain volume per month. In multivariate analyses, greater rates of accumulation were independently associated with older age (ß = 0.004, p < .0001), poor levels of glycemic control (ß = 0.048, p < .0001) and hypertension diagnosis (ß = 0.084, p < .0001). Long-term survivors of cancer allow assessment of late effects of treatment modalities. Radiation injury appears to be related to a steady rate of white matter damage over time, as indicated by progressive accumulation of WMC. Our results suggest that rate of WMC accumulation is enhanced by parameters such as hyperglycemia and hypertension. This has significant clinical impact by clearly identifying hyperglycemia, steroid-induced hyperglycemia, and other vascular risk factors as targets for intervention to decrease WMC in patients receiving WBRT.