Spinal Metastases Research Articles

Association between Opioid Requirement and Overall Survival in Patients with Spinal Metastases.

Clinical evidence shows that opioid administration in cancer patients is associated with shorter survival. This study explored the impact of opioid requirement on overall survival of patients with spinal metastases. We also evaluated the association between opioid requirement and tumor-related spinal instability. We retrospectively identified 428 patients who had been diagnosed with spinal metastases from February 2009 to May 2017. Those with an opioid prescription during the first 1 month after the diagnosis were included in this study. Patients given opioids were divided into two groups: the opioid requirement group [≥5 mg oral morphine equivalent (OME)/day] and the nonopioid group (<5 mg OME/day). Spinal instability due to metastases was evaluated using the Spinal Instability Neoplastic Score (SINS). Cox proportional hazards analysis was performed to evaluate the relationship between opioid use and overall survival. The most frequent primary cancer site was the lung, in 159 patients (37%), followed by the breast in 75 (18%) and the prostate in 46 (11%). Multivariate analyses showed that patients who required ≥5 mg OME/day were approximately twofold more likely to die after a spinal metastases diagnosis than those who required <5 mg OME/day (hazard ratio 2.13; 95% confidence interval 1.69-2.67; p<0.001). The SINS was significantly higher in the opioid requirement group than those in the nonopioid group (p<0.001). For patients with spinal metastases, opioid requirement was associated with shorter survival, independently of known prognostic factors. The patients were also more likely to have tumor-related spinal instability than those in the nonopioid group.

Papel de la radioterapia en el manejo de las metástasis vertebrales: últimas novedades

Spine metastases are a common cause of pain in the oncologic patient which can generate functional limitation, in addition to complications derived from spinal cord compression, radicular compression and fractures. A complex approach to these metastases is required due to the risk of permanent sequelae. With the increase in survival rates due to new emerging treatments, the possibilities of presenting vertebral metastases are increasing, therefore, the management of these lesions should be aimed at pain relief and maintenance of ambulation. Radiotherapy has a fundamental role in the management of these lesions, and technological advances in recent years have made it possible to improve the quality and intentionality of the treatments, going from having a palliative intent to proposing treatments that improve local control. In this article we describe how the stereotactic body radiotherapy (SBRT) technique, in selected patients, can improve local control and its value in oligometastatic patients and after surgery.

Introducing Radiotherapy in Metastatic Merkel Cell Carcinoma Patients with Limited Progression on Avelumab: An Effective Step against Primary and Secondary Immune Resistance?

To investigate the ability of radiotherapy (RT) to prolong progression-free survival (PFS) and to report treatment-related toxicities among oligoprogressive metastatic Merkel cell carcinoma (mMCC) patients on avelumab. We retrospectively collected clinical data on mMCC patients who underwent radiotherapy for limited progression on avelumab. Patients were categorized as primary or secondary immune refractory depending on the time of onset of resistance to immunotherapy (at the first or subsequent follow-up visits after avelumab initiation). Pre- and post-RT PFS were calculated. Overall survival (OS) from the first progression treated with RT was also reported. Radiological responses and toxicities were evaluated according to the irRECIST criteria and RTOG scoring system, respectively. Eight patients, including five females, with a median age of 75 years, met our inclusion criteria. The median gross tumor and clinical target volumes at first progression on avelumab were 29.85 cc and 236.7 cc, respectively. The treatment sites included lymph node, skin, brain, and spine metastases. Four patients received more than one course of RT. Most patients were treated with palliative radiation doses (mainly 30 Gy in 3 Gy/day fractions). Two patients were treated with stereotactic RT. Five/eight patients were primary immune refractory. The objective response rate at the first post-RT assessment was 75%, whereas no local failure was reported. The median pre-RT PFS was 3 months. The pre-RT PFS was 37.5% at 6 months and 12.5% at 1 year. The median post-RT PFS was not reached. The post-RT PFS was 60% at 6 months and 1 year. The post-RT OS was 85.7% at 1 year and 64.3% at 2 years. No relevant treatment-related toxicity was observed. After a median follow-up of 18.5 months, 6/8 patients are still alive and continuing on avelumab therapy. Adding radiotherapy to mMCC patients with limited progression on avelumab seems to be safe and effective in prolonging the successful use of immunotherapy, regardless of the type of immune refractoriness.

A Machine Learning Algorithm for Predicting 6-Week Survival in Spinal Metastasis: An External Validation Study Using 2,768 Taiwanese Patients.

There are predictive algorithms for predicting 3-month and 1-year survival in patients with spinal metastasis. However, advance in surgical technique, immunotherapy, and advanced radiation therapy has enabled shortening of postoperative recovery, which returns dividends to the overall quality-adjusted life-year. As such, the Skeletal Oncology Research Group machine learning algorithm (SORG-MLA) was proposed to predict 6-week survival in patients with spinal metastasis, whereas its utility for patients treated with nonsurgical treatment was untested externally. This study aims to validate the survival prediction of the 6-week SORG-MLA for patients with spinal metastasis and provide the measurement of model consistency (MC). Discrimination using area under the receiver operating characteristic curve, calibration, Brier score, and decision curve analysis were conducted to assess the model's performance in the Taiwanese-based cohort. MC was also applied to detect the proportion of paradoxical predictions among 6-week, 3-month, and 1-year survival predictions. The long-term prognosis should not be better than the shorter-term prognosis in that of an individual. The 6-week survival rate was 84.2%. The SORG-MLA retained good discrimination with an area under the receiver operating characteristic curve of 0.78 (95% confidence interval, 0.75 to 0.80) and good prediction accuracy with a Brier score of 0.11 (null model Brier score 0.13). There is an underestimation of the 6-week survival rate when the predicted survival rate is less than 50%. Decision curve analysis showed that the model was suitable for use over all threshold probabilities. MC showed suboptimal consistency between 6-week and 90-day survival prediction (78%). The results of this study supported the utility of the algorithm. The online tool (https://sorg-apps.shinyapps.io/spinemetssurvival/) can be used by both clinicians and patients in informative decision-making discussion before management of spinal metastasis.

Metastasis of spine from adenoid cystic carcinoma of the parotid gland: two case reports

BackgroundSpinal metastasis from adenoid cystic carcinoma of the salivary gland is extremely rare. We present two interesting cases of spinal metastasis from adenoid cystic carcinoma of the parotid gland.Case summaryA 29-year-old Persian male and a 48-year-old Persian female presented with parotid gland mass. The two patients received parotidectomy and radiotherapy. The pathological examination result was adenoid cystic carcinoma. Because of intractable back pain, patients were referred to the hospital after 7 years and 9 months, respectively. Both cases underwent spinal surgery. Histopathology confirmed spinal metastasis from adenoid cystic carcinoma of the parotid gland (case 1: T6, T12, and L1; case 2: T12). Anterior corpectomy of T12 and lateral screw fixation at T11 and L1 were done in case 2. Posterior spinal fusions from T2 to L3 and from T10 to L2 were performed in case 1 and case 2, respectively. Both patients showed good clinical improvement. The last follow-up (case 1: 24 months; case 2: 6 months after surgery), plain radiographs and computed tomography scan showed good fusion without instrumental failure and magnetic resonance imaging revealed good decompression of the spinal cord of both cases.ConclusionAlthough spinal metastasis from adenoid cystic carcinoma of the parotid gland is extremely rare, it is necessary to be careful in the differential diagnosis.

Risk Factors for Poor Outcome after Palliative Surgery for Metastatic Spinal Tumors.

Palliative surgery is performed to improve the quality of life of patients with spinal metastases. However, it is sometimes difficult to achieve the expected results because the patient's condition, and risk factors related to poor outcomes have not been well elucidated. This study aimed to evaluate the functional outcomes and investigate the risk factors for poor outcomes after palliative surgery for spinal metastasis. We retrospectively reviewed the records of 117 consecutive patients who underwent palliative surgery for spinal metastases. Neurological and ambulatory statuses were evaluated pre- and post-operatively. Poor outcomes were defined as no improvement or deterioration in functional status or early mortality, and the related risk factors were analyzed using multivariate logistic regression analysis. The results showed neurological improvement in 48% and ambulatory improvement in 70% of the patients with preoperative impairment, whereas 18% of the patients showed poor outcomes. In the multivariate analysis, low hemoglobin levels and low revised Tokuhashi scores were identified as risk factors for poor outcomes. The present results suggest that anemia and low revised Tokuhashi scores are related not only to life expectancy but also to functional recovery after surgery. Treatment options should be carefully selected for the patients with these factors.

Spine metastases: thermal ablation and augmentation.

Substantial advances in percutaneous minimally invasive musculoskeletal oncologic interventions including thermal ablation and vertebral augmentation offer a robust armamentarium for interventional radiologists for management of patients with spinal metastases. Such interventions have proved safe and effective in management of selected patients with vertebral metastases. Special attention to procedure techniques including choice of ablation modality, vertebral augmentation technique, and thermal protection is essential for improved patient outcomes. Familiarity with the described interventions and implementation of procedural safety measures will further enhance the role of radiologists in the management of patients with spinal metastases. This article provides a review of the most recent advances in thermal ablation and vertebral augmentation as well as the role of radiologists for treatment of spinal metastases.

Risk Factors for Postoperative Unfavorable Ambulatory Status After Spinal Surgery for Metastatic Spinal Tumor.

A retrospective comparative study. This study aimed to investigate factors associated with postoperative unfavorable ambulatory status following surgery for metastatic spinal tumors using a nationwide in-hospital database. Surgical treatment for metastatic spinal tumors can improve the ambulatory status and quality of life. However, some patients fail to regain the ability to walk, thereby resulting in poor quality of life. No large-scale study has previously evaluated factors associated with postoperative poor ambulatory status in this clinical context. The Diagnosis Procedure Combination database from 2018 to 2019 was used to extract data from patients who underwent surgical procedures for spinal metastasis. Postoperative unfavorable ambulatory status was defined as (1) nonambulatory at discharge or (2) a decreased mobility score of the Barthel Index between admission and discharge. Multivariable logistic regression was used to evaluate factors associated with postoperative unfavorable ambulatory status while adjusting for confounders. This study analyzed 1786 eligible patients. Of whom, 1061 (59%) patients were ambulatory on admission and 1249 (70%) on discharge. Postoperative unfavorable ambulatory status was observed in 597 (33%) patients, with a significantly lower rate of discharge to home (41%/81%, P <0.001) and a longer postoperative hospital stay (46.2 days/31.4 days, P <0.001). Multivariable regression analysis revealed male sex [odds ratio (OR): 1.43, P =0.002], laminectomy without fusion (OR: 1.55, P =0.034), Charlson Comorbidity Index of ≥7 (OR: 1.37, P =0.014), and preoperative nonambulatory status (OR: 6.61, P <0.001) as factors associated with postoperative unfavorable ambulatory status. Our large-scale database analysis revealed that 33% of patients experienced unfavorable ambulatory status following spinal metastasis surgery. Laminectomy without fusion and preoperative nonambulatory status were among several factors influencing the prospect of unfavorable ambulatory status following surgery.

Artificial Intelligence and Predictive Modeling in Spinal Oncology: A Narrative Review.

Artificial intelligence (AI) tremendously influences our daily lives and the medical field, changing the scope of medicine. One of the fields where AI, and, in particular, predictive modeling, holds great promise is spinal oncology. An accurate patient prognosis is essential to determine the optimal treatment strategy for patients with spinal metastases. Multiple studies demonstrated that the physician's survival predictions are inaccurate, which resulted in the development of numerous predictive models. However, difficulties arise when trying to interpret these models and, more importantly, assess their quality. To provide an overview of all stages and challenges in developing predictive models using the Skeletal Oncology Research Group machine learning algorithms as an example. A narrative review of all relevant articles known to the authors was conducted. Building a predictive model consists of 6 stages: preparation, development, internal validation, presentation, external validation, and implementation. During validation, the following measures are essential to assess the model's performance: calibration, discrimination, decision curve analysis, and the Brier score. The structured methodology in developing, validating, and reporting the model is vital when building predictive models. Two principal guidelines are the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis checklist and the prediction model risk of bias assessment. To date, many predictive modeling studies lack the right validation measures or improperly report their methodology. A new health care age is being ushered in by the rapid advancement of AI and its applications in spinal oncology. A myriad of predictive models are being developed; however, the subsequent stages, quality of validation, transparent reporting, and implementation still need improvement. Given the rapid rise and use of AI prediction models in patient care, it is valuable to know how to assess their quality and to understand how these models influence clinical practice. This article provides guidance on how to approach this.

Deep learning-based magnetic resonance imaging of the spine in the diagnosis and physiological evaluation of spinal metastases

Background and objectiveSpinal metastasis accounts for 70% of the bone metastases of tumors, so how to diagnose and predict spinal metastasis in time through effective methods is very important for the physiological evaluation of the therapy of patients. MethodsMRI scans of 941 patients with spinal metastases from the affiliated hospital of Guilin Medical University were collected, analyzed, and preprocessed, and the data were submitted to a deep learning model designed with our convolutional neural network. We also used the Softmax classifier to classify the results and compared them with the actual data to judge the accuracy of our model. ResultsOur research showed that the practical model method could effectively predict spinal metastases. The accuracy was up to 96.45%, which could be used to diagnose the physiological evaluation of spinal metastases. ConclusionThe model obtained in the final experiment can capture the focal signs of patients with spinal metastases more accurately and can predict the disease in time, which has a good application prospect.

Risk factors for pulmonary cement embolism after percutaneous vertebroplasty and radiofrequency ablation for spinal metastases.

Pulmonary cement embolism is a rare but underestimated complication of vertebroplasty due to the relative lack of study and examination. This study aims to investigate the incidence of pulmonary cement embolism in patients with spinal metastasis who undergo PVP with RFA and to analyze the relative risk factors. A total of 47 patients were retrospectively included and classified into pulmonary cement embolism (PCE) group and non-pulmonary cement embolism (NPCE) group by comparing pre- and postoperative pulmonary CT scan images. The demographic and clinical information of the patients was obtained. Demographic data in the two groups were compared using the chi-square test for qualitative data and the unpaired t test for quantitative data. Multiple logistic regression analysis was used to identify risk factors related to pulmonary cement embolism. Pulmonary cement embolism was detected in 11 patients (23.4%), and all patients were asymptomatic and followed up regularly. Risk analysis showed that multiple segments (≥3, p=0.022), thoracic vertebrae (p=0.0008), and unipedicular puncture approach (p=0.0059) were risk factors for pulmonary cement embolism. There was a high incidence of pulmonary cement embolism if bone cement leaked into the para vertebral venous plexus in the thoracic vertebra (p<0.0001). Vein leakage of cement was related to the integrity of the vertebral cortex. The number of involved vertebrae, lesion location, and puncture approach are independent risk factors for pulmonary cement embolism. There was a high incidence of pulmonary cement embolism if bone cement leaked into the para vertebral venous plexus in the thoracic vertebra. Surgeons should consider these factors when formulating therapeutic strategies.

Harmine loaded Au@MSNs@PEG@Asp6 nano-composites for treatment of spinal metastasis from lung adenocarcinoma by targeting ANXA9 in vivo experiment.

Annexin A9 (ANXA9) has been proved to be concerned with cancer development. However, to explore the clinical consequences of ANXA9 in lung adenocarcinoma (LUAD), especially its correlation to spinal metastasis (SM) has no in-depth study. The study was expected to elucidate the mechanism of ANXA9 in regulating SM of LUAD and create a productive nano-composites delivery system targeting this gene for treatment of SM. Harmine (HM), a β-carboline extracted from the traditional Chinese herb Peganum harmala, loaded Au@MSNs@PEG@Asp6 (NPS) nano-composites were synthesized. Bioinformatics analysis and clinical specimens' tests were used to verify the association between ANXA9 and prognosis of LUAD with SM. The immunohistochemistry (IHC) was employed to detect the expression levels of the ANXA9 protein in LUAD tissues with or without SM, and its significance in clinic was also explored. ANXA9‑siRNA was applied to investigate the molecular mechanism of ANXA9 in tumor behaviors. The HM release kinetics was detected by high performance liquid chromatography (HPLC) method. The cellular uptake efficiency of nanoparticles by A549 cells was observed by fluorescence microscope. Antitumor effects of nanoparticles were assessed in the nude mouse model of SM. The genomic amplification of ANXA9 was prevalent in LUAD tissues and closely associated with poor outcome and SM (P<0.01). The experimental result manifested that high expression of ANXA9 could lead to wretched prognosis and ANXA9 was an independent risk factor for survival (P<0.05). After impeding expression of ANXA9, the proliferation and metastatic ability of tumor cells obviously decreased, and expression of matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9) were considerably downregulated, while the expression of associated oncogene pathway were downregulated (P<0.01) as well. The synthesized HM-loaded NPS nano-composites could target to cancer and response to reactive oxygen species (ROS) to release HM slowly. Notably, in comparison to free HM, the nano-composites showed excellent targeting and anti-tumor effects in the A549 cell-bearing mouse model. ANXA9 may serve as a novel biomarker for predicting poor prognosis in LUAD, and we provided an efficient and targeting drug delivery nano-composites system for precise treatment of SM from LUAD.

Metastasectomy of spinal lesions from thyroid carcinomas

Patients with differentiated thyroid carcinomas (DTCs) have a favourable long-term survival. Spinal metastases (SMs) cause a decline in performance status (PS), directly affecting mortality and indirectly preventing the use of systemic therapies. Metastasectomy is indicated, if feasible, as it yields the best local tumour control. Our study aimed to examine the long-term clinical outcomes of metastasectomy for SMs of thyroid carcinomas. We collected data on 22 patients with DTC (16 follicular and six papillary carcinomas) and one patient with medullary carcinoma who underwent complete surgical resection of SMs at our institution between July 1992 and July 2017, with a minimum postoperative follow-up of five years. The cancer-specific survival (CSS) from the first spinal metastasectomy to death or the last follow-up was determined using Kaplan-Meier analysis. Potential factors associated with survival were evaluated using the log-rank test. We analyzed the clinical parameters and outcome data, including pre- and postoperative disability (Eastern Cooperative Oncology Group PS 3), lung and non-spinal bone metastases, and history of radioiodine and kinase inhibitor therapies. Lung and other bone metastases at the time of surgery were observed in ten and eight patients, respectively. Three patients experienced local tumour recurrences at the operated site. The five- and ten-year CSS rates in the 22 patients with DTC were 77% and 52%, respectively. Pre- and postoperative disability and operative site tumour recurrence were identified as risk factors for short postoperative survival. Metastasectomy for resectable SM from DTC yielded favourable results and has the potential to improve survival.

Safety and clinical efficacy of immune checkpoint inhibition and stereotactic body radiotherapy in patients with spine metastasis.

Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the treatment of patients with many tumor histologies. Simultaneously, stereotactic body radiotherapy (SBRT) provides excellent local control (LC) and plays an important role in the management of spine metastasis. Promising preclinical work suggests the potential therapeutic benefit of combining SBRT with ICI therapy, but the safety profile of combined therapy is unclear. This study aimed to evaluate the toxicity profile associated with ICI in patients receiving SBRT and, secondarily, whether ICI administration sequence with respect to SBRT affects LC or overall survival (OS) outcomes. The authors retrospectively reviewed patients with spine metastasis treated with SBRT at an academic center. Patients who received ICI at any point during their disease course were compared to those with the same primary tumor types who did not receive ICI by using Cox proportional hazards analyses. Primary outcomes were long-term sequelae, including radiation-induced spinal cord myelopathy, esophageal stricture, and bowel obstruction. Secondarily, models were created to evaluate OS and LC in the cohort. Two hundred forty patients who received SBRT to 299 spine metastases were included in this study. The most common primary tumor types were non-small cell lung cancer (n = 59 [24.6%]) and renal cell carcinoma (n = 55 [22.9%]). One hundred eight patients received at least 1 dose of ICI, with the most common regimen being single-agent anti-PD-1 (n = 80 [74.1%]), followed by combination CTLA-4/PD-1 inhibitors (n = 19 [17.6%]). Three patients experienced long-term radiation-induced sequelae: 2 had esophageal stricture and 1 had bowel obstruction. No patients developed radiation-induced myelopathy. There was no association between receipt of ICI and development of any of these adverse events (p > 0.9). Similarly, ICI was not significantly associated with either LC (p = 0.3) or OS (p = 0.6). In the entire cohort, patients who received ICI prior to beginning SBRT had worse median survival, but ICI sequence with respect to SBRT was not significantly prognostic of either LC (p > 0.3) or OS (p > 0.07); instead, baseline performance status was most predictive of OS (HR 1.38, 95% CI 1.07-1.78, p = 0.012). Treatment regimens that combine ICIs before, concurrent with, and after SBRT for spine metastases are safe, with minimal risk for increased rates of long-term toxicity.

Stereotactic body radiotherapy for spine metastases: a review of 24 Gy in 2 daily fractions.

Stereotactic body radiotherapy (SBRT) has proven to be a highly effective treatment for selected patients with spinal metastases. Randomized evidence shows improvements in complete pain response rates and local control with lower retreatment rates favoring SBRT, compared to conventional external beam radiotherapy (cEBRT). While there are several reported dose-fractionation schemes for spine SBRT, 24 Gy in 2 fractions has emerged with Level 1 evidence providing an excellent balance between minimizing treatment toxicity while respecting patient convenience and financial strain. We provide an overview of the 24 Gy in 2 SBRT fraction regimen for spine metastases, which was developed at the University of Toronto and tested in an international Phase 2/3 randomized controlled trial. The literature summarizing global experience with 24 Gy in 2 SBRT fractions suggests 1-year local control rates ranging from 83-93.9%, and 1-year rates of vertebral compression fracture ranging from 5.4-22%. Reirradiation of spine metastases that failed prior cEBRT is also feasible with 24 Gy in 2 fractions, and 1-year local control rates range from 72-86%. Post-operative spine SBRT data are limited but do support the use of 24 Gy in 2 fractions with reported 1-year local control rates ranging from 70-84%. Typically, the rates of plexopathy, radiculopathy and myositis are under 5% in those series reporting mature follow up, with no cases of radiation myelopathy (RM) reported in the de novo setting when the spinal cord avoidance structure is limited to 17 Gy in 2 fractions. However, re-irradiation RM has been observed following 2 fraction SBRT. More recently, 2-fraction dose escalation with 28 Gy, with a higher dose constraint to the critical neural tissues, has been reported suggesting improved rates of local control. This regimen may be important in those patients with radioresistant histologies, high grade epidural disease, and/or paraspinal disease. The dose-fractionation of 24 Gy in 2 fractions is well-supported by published literature and is an ideal starting point for centers looking to establish a spine SBRT program.

Airway Management of Thyroid Malignancy with Cervical Spine Metastasis for a Two-Stage Dual Procedure; Discretion Dictates Never Burn Your Bridges

Thyroid swellings are a known cause of airway obstruction and potentially difficult intubation due to compression and deviation of the trachea. We encountered a unique challenging case of a malignant retrosternal goitre compressing the trachea, with cervical spine metastasis causing paresthesia and weakness in all four limbs, for a two-stage dual procedure, embolisation and excision of thyroid, and embolisation and fixation of the cervical spine.

A novel scoring system incorporating sarcopenia to predict postoperative survival in spinal metastasis

BACKGROUND CONTEXTAs the prevalence of spinal metastasis rises, methods to predict survival will become increasingly important for clinical decision-making. Sarcopenia may be used to predict survival in these patients. PURPOSEThe purpose of this study to develop a prediction model incorporating sarcopenia for postoperative survival in patients with spinal metastasis. DESIGNRetrospective cohort study. PATIENT SAMPLEThis study included 200 patients who underwent operative intervention for spinal metastasis in our institution, a tertiary, academic spine center. OUTCOME MEASURESThe primary outcome measure was 1-year postoperative survival. The secondary outcome measures were 3-month and 6-month postoperative survival. METHODSClinicopathological and survivorship data was collated. Sarcopenia was defined using the L3 Psoas/Vertebral Body Ratio on cross-sectional CT. Independent predictors of postoperative survival were assessed by multiple logistic regression. RESULTSOverall 1-year postoperative survival was 50%. L3/Psoas ratio ≥1.5 (OR 6.2), albumin ≥35g/l (OR 3.0) and primary tumor type were found to be independent predictors of 3 month, 6 month and 1 year postoperative survival on multivariable analysis. Age at surgery, ambulatory status and mode of presentation were not independent predictors of survival. Variables were used to generate a new scoring system, ProgMets, to predict postoperative survival. The ProgMets system had greater correlation and higher area under the curve (AUC, 0.80) for 1-year survival than other scoring systems. CONCLUSIONSThis is the first model to incorporate sarcopenia to predict survival in spinal metastasis patients and has good prediction of survival compared to previous models. This tool may be increasingly useful for informed decision making for patients and surgeons.

The NOMS approach to metastatic tumors: Integrating new technologies to improve outcomes

Treatment paradigms for patients with spine metastases have evolved significantly over the past two decades. The most transformative change to these paradigms has been the integration of spinal stereotactic radiosurgery (sSRS). sSRS allows for the delivery of tumoricidal radiation doses with sparing of nearby organs at risk, particularly the spinal cord. Evidence supports the safety and efficacy of radiosurgery as it currently offers durable local tumor control with low complication rates even for tumors previously considered radioresistant to conventional external beam radiation therapy. The role for surgical intervention remains consistent, but a trend has been observed toward less aggressive, often minimally invasive techniques. Using modern technologies and improved instrumentation, surgical outcomes continue to improve with reduced morbidity. Additionally, targeted agents such as biologics and checkpoint inhibitors have revolutionized cancer care by improving both local control and patient survival. These advances have brought forth a need for new prognostication tools and a more critical review of long-term outcomes. The complex nature of current treatment schemes necessitates a multidisciplinary approach including surgeons, medical oncologists, radiation oncologists, interventionalists and pain specialists. This review recapitulates the current state-of-the-art, evidence-based data on the treatment of spinal metastases and integrates these data into a decision framework, NOMS, which is based on four sentinel pillars of decision making in metastatic spine tumors: Neurological status, Oncologic tumor behavior, Mechanical stability, and Systemic disease burden and medical co-morbidities.

Predicting 30-day mortality after surgery for metastatic disease of the spine: the H2-FAILS score.

Scoring systems for metastatic spine disease focus on predicting long- to medium-term mortality or a combination of perioperative morbidity and mortality. However, accurate prediction of perioperative mortality alone may be the most important factor when considering surgical intervention. We aimed to develop and evaluate a new tool, the H2-FAILS score, to predict 30-day mortality after surgery for metastatic spine disease. Using the National Surgical Quality Improvement Program database, we identified 1195 adults who underwent surgery for metastatic spine disease from 2010 to 2018. Incidence of 30-day mortality was 8.7% (n = 104). Independent predictors of 30-day mortality were used to derive the H2-FAILS score. H2-FAILS is an acronym for: Heart failure (2 points), Functional dependence, Albumin deficiency, International normalized ratio elevation, Leukocytosis, and Smoking (1 point each). Discrimination was assessed using area under the receiver operating characteristic curve (AUC). The H2-FAILS score was compared with the American Society of Anesthesiologists Physical Status Classification (ASA Class), the 5-item modified Frailty Index (mFI-5), and the New England Spinal Metastasis Score (NESMS). Internal validation was performed using bootstrapping. Alpha = 0.05. Predicted 30-day mortality was 1.8% for an H2-FAILS score of 0 and 78% for a score of 6. AUC of the H2-FAILS was 0.77 (95% confidence interval: 0.72-0.81), which was higher than the mFI-5 (AUC 0.58, p < 0.001), ASA Class (AUC 0.63, p < 0.001), and NESMS (AUC 0.70, p = 0.004). Internal validation showed an optimism-corrected AUC of 0.76. The H2-FAILS score accurately predicts 30-day mortality after surgery for spinal metastasis. Prognostic level III.

Molecular characterization of long-term survivors of metastatic medulloblastoma treated with reduced-dose craniospinal irradiation.

Current standard treatment for metastatic medulloblastoma consists of 36 Gray (Gy) of craniospinal irradiation (CSI) supplemented with local irradiation and adjuvant chemotherapy after surgery. Although contemporary protocols have been designed to limit a radiation dose using risk-adapted CSI dosing to reduce neurocognitive morbidity, high-dose CSI remains the standard of care. Recently, the molecular classification of medulloblastoma has been emerging but its clinical significance has not been established particularly in patients with metastatic medulloblastoma treated with lower dose of CSI. We molecularly analyzed three cases of metastatic medulloblastoma treated with 24.0 Gy of CSI by DNA methylation analysis using the Illumina EPIC array. All three patients had spinal metastases at the time of diagnosis. Postoperative treatment included multiple courses of chemotherapy, 24 Gy of CSI with focal boost to primary and metastatic sites, and high-dose chemotherapy. There was no disease progression observed during the 9.0, 7.7, and 5.7 years post-diagnosis follow-up. The molecular diagnosis was Group 3/4 in all three cases. Cases 1 and 2 belonged to Subtypes 7 and 4, both of which were reported to be good prognostic subtypes among the group. Case 3 belonged to Subtype 5 with MYC amplification. The present cases suggest that the novel subtype classification in Group 3/4 medulloblastoma may be useful for risk stratification of patients with metastatic medulloblastoma who received lower dose of CSI than standard treatment.