Therapeutic Opportunities for Biomarkers in Metastatic Spine Tumors.

For many spine surgeons, patients with metastatic cancer are often present in an emergent situation with rapidly progressive neurological dysfunction. Since the Patchell trial, scoring systems such as NOMS and SINS have emerged to guide the extent of surgical excision and fusion in the context of chemotherapy and radiation therapy. Yet, while multidisciplinary decision-making is the gold standard of cancer care, in the middle of the night, when a patient needs spinal surgery, the wealth of chemotherapy data, clinical trials, and other medical advances can feel overwhelming. The goal of this review is to provide an overview of the relevant molecular biomarkers and therapies driving patient survival in lung, breast, prostate, and renal cell cancer. We highlight the molecular differences between primary tumors (i.e., the patient's original lung cancer) and the subsequent spinal metastasis. This distinction is crucial, as there are limited data investigating how metastases respond to their primary tumor's targeted molecular therapies. Integrating information from primary and metastatic markers allows for a more comprehensive and personalized approach to cancer treatment.

Minimally invasive posterior cervical foraminotomy versus the anterior transcorporeal approach for cervical radiculopathy: a systematic review and meta-analysis.

OBJECTIVE: Surgical decompression is often indicated for symptomatic cases of cervical radiculopathy. In the cervical spine, minimally invasive posterior cervical foraminotomy (MIS-PCF) and the anterior transcorporeal approach (ATCA) are modern techniques available to surgeons. This systematic review and single-arm meta-analysis aimed to assess surgical and patient-reported outcomes of MIS-PCF and ATCA for cervical radiculopathy. METHODS: A systematic review of the literature was conducted using 1) Ovid; 2) Epub Ahead of Print and In-Process, In-Data-Review & Other Non-Indexed Citations; and 3) Scopus databases, which reported outcomes following cervical decompression using MIS-PCF or the ATCA. Specifically, baseline characteristics, operative outcomes, and changes in visual analog scale (VAS) neck pain score were assessed. The quality of the studies was graded using the modified Newcastle-Ottawa Scale for observational studies. RESULTS: Forty studies with 1661 patients were identified. The comparative analysis of both techniques revealed no significant differences in complication (7%, 95% CI 5%-10%, p = 0.75) or reoperation rates (5%, 95% CI 3%-7%, p = 0.41). Additionally, there were no significant differences in estimated blood loss (55.39, 95% CI 44.62-66.16 ml, p = 0.55) or operative time (85.15, 95% CI 65.38-104.92 minutes, p = 0.05). The ATCA showed significantly greater improvement (p < 0.01) in VAS neck pain scores following surgery (ATCA point reduction 6.7, 95% CI 6.0-7.5 points vs MIS-PCF 3.0, 95% CI 1.0-5.0 points). CONCLUSIONS: The ATCA and MIS-PCF are effective modern techniques for the surgical treatment of radiculopathy. Both approaches showed comparable postoperative outcomes, including complication and reoperation rates. However, the ATCA was shown to provide significantly greater improvement in VAS neck pain scores.

Enhancing Cadaver Labs for Endoscopic Spine Surgery: The Glove as the "Lesion".

OBJECTIVE: We describe a novel yet simple training exercise for residents who are being introduced to endoscopic spine surgery. METHODS: Prior to residents training on the endoscopic interlaminar approach, the course faculty performed an endoscopic transforaminal approach and inserted a small piece of a surgical glove into the ventral epidural space of a cadaveric torso. The transforaminal approach did not alter the anatomy of the interlaminar approach, so the residents were able to practice as if it were a de novo situation. Placing the small "lesion" provided an exercise to confirm the residents were able to safely access the area and provided practice for them to carefully grasp the "lesion" and remove it. Prior to resident training on the endoscopic transforaminal approach, the course faculty utilized an interlaminar approach to place the "lesion." A questionnaire with a five-point Likert scale of agreement was completed by the residents to assess their experience with the training exercise. RESULTS: Five residents attended the cadaver lab, and 100% strongly agreed that the cadaver lab provided a realistic representation of the procedure demonstrated, the "lesion" removal added to their educational experience, and they were overall satisfied with the educational session. CONCLUSIONS: One of the lessons learned with this exercise that we will consider in future courses would be to place a radiodense "lesion" that could be visualized on fluoroscopy and serve as a radiologic target to find. This can help guide the trainee in knowing where to search if the "lesion" is more difficult to find.

The impact of socioeconomic determinants on the access to care and survival in patients with spinal chordomas- a national cancer database analysis.

PURPOSE: Chordomas are rare malignant neoplasms primarily treated surgically. Disparities related to race and socioeconomic status, may affect patient outcomes. This study aims to identify prognostic factors for access to care and survival in patients with spinal chordomas. METHODS: The NCDB database was queried between the years 2004 and 2017. Kaplan-Meier curves were constructed to compare survival probabilities among different groups, based on race and socioeconomic determinents. RESULTS: 1769 patients were identified, with 87% being White, 5% Hispanic, 4% Black, and Asian each. The mean age was 61.3 years. Most patients received care at academic/research centers and lived in a large metropolitan area, with no difference between races. A significantly higher percentage of Black patients did not undergo surgery (p < 0.001), with no statistically significant difference in survival between races (p = 0.97). A higher survival probability was seen in patients with other government insurances (p < 0.0001), in higher income quartiles (p < 0.0001), in metropolitan areas (p = 0.023), and at an academic/research center (p < 0.0001). A lower survival probability was seen in patients who are uninsured, in rural areas, and at community cancer programs (p < 0.0001). CONCLUSION: This study highlights disparities in access to surgical intervention for patients with spinal chordomas, especially among Black individuals. It emphasizes the significant impact of insurance status and income on access to surgical care and highlights geographical and institutional variations in survival rates. Addressing socioeconomic differences is crucial for fostering equity in neurosurgical outcomes.

Awake Robotic Minimally Invasive Transforaminal Lumbar Interbody Fusion Under Spinal Anesthesia: A Prospective Study with 1-Year Follow-up.

BACKGROUND: We describe our protocol and outcomes of awake robotic minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) under spinal anesthesia. METHODS: We conducted a prospective study of 10 consecutive patients undergoing awake robotic single-level MIS-TLIF with the Mazor X robot. We prospectively collected patient-reported outcomes (back and leg pain visual analog scale and Oswestry Disability Index) preoperatively at 1-month and 1-year follow-ups and assessed fusion and screw placement accuracy with a 1-year computed tomography (CT) scan. RESULTS: Median age was 61 years (interquartile range [IQR] = 57.7-66). Median body mass index was 27 kg/m2. No intraoperative complications were reported. Most (9/10) patients were discharged home, and 50% discharged on the day of surgery. Median length of stay was 16.5 hours (IQR = 5-35.5). Median follow-up was 12.5 months (IQR = 12-13.5), with 9 patients having at least 12-month follow-up, with CT scans documenting good screw placement (Gertzbein-Robbins grade A) and solid bony fusion. Median preoperative back pain visual analog scale score was 7.8 (IQR = 6.9-8) versus 1.5 (IQR = 0-3.2) at 1-month post operation, P < 0.01, and 0 (IQR = 0-1) at 1-year follow-up, P < 0.01; median preoperative leg pain 8 (IQR = 7.4-8) versus 0 (IQR = 0-1.2) at 1-month post operation, P < 0.01, and 0 (IQR = 0-2) at 1-year follow-up, P < 0.01; median preoperative Oswestry Disability Index 47.5 (IQR = 27.8-57.5) versus 4 (IQR = 0-16) at 1-month postoperation, P < 0.01, and 0 (IQR = 0-7) at 1-year follow-up, P < 0.01. Median preoperative disk height of the index level was 8 mm (IQR = 2.4-9.5) versus 11.4 mm (IQR = 9.2-11.2) postoperatively,P < 0.01. Median preoperative lordosis of the index level was 5 degrees (IQR = 3.4-8.5) versus 10.1 degrees (7.3-12.2) postoperatively, P < 0.01. CONCLUSIONS: Our study showed significant improvement in patient-reported outcomes at 1-month and 1-year follow-ups after awake robotic MIS-TLIF, as well as solid bony fusion on CT scans.

Proton versus photon adjuvant radiotherapy: a multicenter comparative evaluation of recurrence following spinal chordoma resection.

OBJECTIVE: Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models. METHODS: The clinical records of all patients treated with resection followed by adjuvant proton or photon radiotherapy for chordoma at Mayo Clinic were reviewed. Patient demographics, type of surgery and radiotherapy, tumor recurrence, and other variables were extracted. Decision tree classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: Fifty-three patients with a mean ± SD age of 55.2 ± 13.4 years receiving surgery and adjuvant proton or photon therapy to treat chordoma were identified; most patients were male. Gross-total resection was achieved in 54.7% of cases. Proton therapy was the most common adjuvant radiotherapy (84.9%), followed by conventional or external-beam radiation therapy (9.4%) and stereotactic radiosurgery (5.7%). Patients receiving proton therapy exhibited a 40% likelihood of having recurrence, significantly lower than the 88% likelihood observed in those treated with nonproton therapy. This was confirmed on logistic regression analysis adjusted for extent of tumor resection and tumor location, which revealed that proton adjuvant radiotherapy was associated with a decreased risk of recurrence (OR 0.1, 95% CI 0.01-0.71; p = 0.047) compared with photon therapy. The decision tree algorithm predicted recurrence with an accuracy of 90% (95% CI 55.5%-99.8%), with the lowest risk of recurrence observed in patients receiving gross-total resection with adjuvant proton therapy (23%). CONCLUSIONS: Following resection, adjuvant proton therapy was associated with a lower risk of chordoma recurrence compared with photon therapy. The described machine learning models were able to predict tumor progression based on the extent of tumor resection and adjuvant radiotherapy modality used.

Single-Photon Emission Computed Tomography (SPECT-CT) as a Predictor of Pain Generators in Patients Undergoing Anterior Cervical Discectomy and Fusion (ACDF) for Axial Cervical Pain.

BACKGROUND: Axial neck pain is often associated with cervical instability, and surgical options are often reserved for patients with either neurological compromise or deformity of the spine. However, cervical facet arthropathy is often implicated with instability and the location of painful generators is often difficult to ascertain. Single-photon emission computed tomography (SPECT-CT) presents an adjunct to conventional imaging in the workup of patients with suspected facetogenic pain. We aimed to report our experience with patients undergoing anterior cervical discectomy and fusion (ACDF) guided by SPECT-CT for axial cervical pain. METHODS: We retrospectively identified all cases undergoing ACDF that presented with axial neck pain where correlating SPECT-CT high metabolism areas were identified. Patients were treated at a tertiary care institution between January 2018 and January 2021. Patients with positive radiotracer uptake pre-operatively were compared with patients undergoing ACDF without uptake on SPECT-CT. The pre- and post-operative patients who reported neck pain at one year were compared. RESULTS: Thirty-five patients were included in this retrospective cohort. The median pre- and post-intervention (at one-year follow-up) visual analog score (VAS) of patients undergoing ACDF without uptake on SPECT-CT was 7 and 3 (p<0.01), while the pre- and post-VAS for patients undergoing surgery with positive uptake on SPECT-CT was 8.5 and 0 (p<0.01). Improvement was significantly larger for patients undergoing SPECT-CT-guided ACDF (p=0.02). At one year after surgery, none of the assessed patients required additional surgical intervention. CONCLUSION: This case series represents the experience of our group to date with patients undergoing SPECT-CT-guided ACDF with results suggesting potential benefit in guiding fusion.

Surgical management of malignant melanotic nerve sheath tumors: an institutional experience and systematic review of the literature.

OBJECTIVE: Malignant melanotic nerve sheath tumors are rare tumors characterized by neoplastic melanin-producing Schwann cells. In this study, the authors report their institution's experience in treating spinal and peripheral malignant melanotic nerve sheath tumors and compare their results with the literature. METHODS: Data were collected from 8 patients who underwent surgical treatment for malignant melanotic nerve sheath tumors between 1996 and 2023 at Mayo Clinic and 63 patients from the literature. Time-to-event analyses were performed for the combined group of 71 cases to evaluate the risk of recurrence, metastasis, and death based on tumor location and type of treatment received. Unpaired 2-sample t-tests and Fisher's exact tests were used to determine statistical significance between groups. RESULTS: Between 1996 and 2023, 8 patients with malignant melanotic nerve sheath tumors underwent surgery at the authors' institution, while 63 patients were identified in the literature. The authors' patients and those in the literature had the same mean age at diagnosis (43 years). At the authors' institution, 5 patients (63%) experienced metastasis, 6 patients (75%) experienced long-term recurrence, and 5 patients (62.5%) died. In the literature, most patients (60.3%) were males, with a peak incidence between the 4th and 5th decades of life. Nineteen patients (31.1%) were diagnosed with Carney complex. Nerve root tumors accounted for most presentations (n = 39, 61.9%). Moreover, 24 patients (38.1%) had intradural lesions, with 54.2% (n = 13) being intramedullary and 45.8% (n = 11) extramedullary. Most patients underwent gross-total resection (GTR) (n = 41, 66.1%), followed by subtotal resection (STR) (n = 12, 19.4%), STR with radiation therapy (9.7%), and GTR with radiation therapy (4.8%). Sixteen patients (27.6%) experienced metastasis, 23 (39.7%) experienced recurrence, and 13 (22%) died. Kaplan-Meier analyses showed no significant differences among treatment approaches in terms of recurrence-free, metastasis-free, and overall survival (p > 0.05). Similar results were obtained when looking at the differences with respect to intradural versus nerve root location of the tumor (p > 0.05). CONCLUSIONS: Malignant melanotic nerve sheath tumors are rare tumors with a high potential for malignancy. They carry a dismal prognosis, with a pooled local recurrence rate of 42%, distant metastasis rate of 27%, and mortality rate of 26%. The findings from this study suggest a trend favoring the use of GTR alone or STR with radiation therapy over STR alone. Mortality was similar regardless, which highlights the need for the development of effective treatment options to improve survival in patients with melanotic schwannomas.

General Versus Nongeneral Anesthesia for Spinal Surgery: A Comparative National Analysis of Reimbursement Trends Over 10 Years.

BACKGROUND AND OBJECTIVES: Nongeneral anesthesia (non-GA) spine surgery is growing in popularity and has facilitated earlier postoperative recovery, reduced cost, and fewer complications compared with spine surgery under general anesthesia (GA). Changes in reimbursement policies have been demonstrated to correlate with clinical practice; however, they have yet to be studied for GA vs non-GA spine procedures. We aimed to investigate trends in physician reimbursement for GA vs non-GA spine surgery in the United States. METHODS: We queried the ACS-NSQIP for GA and non-GA (regional, epidural, spinal, and anesthesia care/intravenous sedation) spine surgeries during 2011-2020. Work relative value units per operative hour (wRVUs/h) were retrieved for decompression or stabilization of the cervical, thoracic, and lumbar spine. Propensity score matching (1:1) was performed using all baseline variables. RESULTS: We included 474 706 patients who underwent spine decompression or stabilization procedures. GA was used in 472 248 operations, whereas 2458 operations were non-GA. The proportion of non-GA spine operations significantly increased during the study period. Operative times ( P < .001) and length of stays ( P < .001) were shorter in non-GA when compared with GA procedures. Non-GA lumbar procedures had significantly higher wRVUs/h when compared with the same procedures performed under GA (decompression; P < .001 and stabilization; P = .039). However, the same could not be said about cervicothoracic procedures. Lumbar decompression surgeries using non-GA witnessed significant yearly increase in wRVUs/h ( P < .01) contrary to GA ( P = .72). Physician reimbursement remained stable for procedures of the cervical or thoracic spine regardless of the anesthesia. CONCLUSION: Non-GA lumbar decompressions and stabilizations are associated with higher and increasing reimbursement trends (wRVUs/h) compared with those under GA. Reimbursement for cervical and thoracic surgeries was equal regardless of the type of anesthesia and being relatively stable during the study period. The adoption of a non-GA technique relative to the GA increased significantly during the study period.

Extent of Surgical Resection as a Predictor of Tumor Progression in Skull Base Chordomas: A Multicenter Volumetric Analysis.

INTRODUCTION: Skull-base chordomas are aggressive tumors with a propensity for recurrence/progression. Even with standard of care (SoC), 5-year recurrence rates are variable (19%-54%). This high recurrence/progression rate correlates with increased morbidity and mortality. We sought to analyze a multicenter cohort of skull base chordomas to identify predictors of progression in patients receiving SoC. METHODS: The [Blinded]-Neurosurgery data registry was queried for skull base chordomas treated from 2008-2020. Patients with the histopathologic diagnosis of chordoma were included. The cohort was composed of patients with preoperative and postoperative magnetic resonance imaging. Tumor volume and radiologic characteristics were obtained from axial T2 sequences using a Digital Imaging and Communications in Medicine viewer. Survival analysis was performed using Kaplan-Meier method, and time-to-event multivariate regression was performed to identify independent predictors of progression. RESULTS: The cohort included 195 patients, of which 66 patients met inclusion criteria; median age was 44, and 28 (42%) were females. Fifty-four (82%) received SoC, 7 (11%) resection only, and 5 (8%) radiotherapy only. Median preoperative and postoperative tumor volumes were 11.55 cm3 (0.33-54.89) and 0.34 cm3 (0-42.52), respectively. Recurrence rate with SoC was 37%. Postoperative tumor volume (P = 0.010) correlated with progression. A postoperative volume of >4.9 cm3 (P = 0.044), ≤81.3% of tumor resection (P = 0.02), and lower-clivus location (P < 0.005) correlated with decreased time to progression. CONCLUSIONS: Skull base chordomas can be challenging to resect. Even though maximal resection and radiotherapy improve rate of tumor progression, many of these lesions eventually recur. We have identified a postoperative tumor volume of ≥4.9 cm3 and extent of resection of ≤81.3% in this cohort as predictors of progression in patients receiving SoC.

What Factors Predict the Development of Neurologic Deficits Following Resection of Intramedullary Spinal Cord Tumors: A Multi-Center Study.

BACKGROUND: Intramedullary spinal cord tumors are challenging to resect, and their postoperative neurological outcomes are often difficult to predict, with few studies assessing this outcome. METHODS: We reviewed the medical records of all patients surgically treated for Intramedullary spinal cord tumors at our multisite tertiary care institution (Mayo Clinic Arizona, Mayo Clinic Florida, Mayo Clinic Rochester) between June 2002 and May 2020. Variables that were significant in the univariate analyses were included in a multivariate logistic regression. "MissForest" operating on the Random Forest algorithm, was used for data imputation, and K-prototype was used for data clustering. Heatmaps were added to show correlations between postoperative neurological deficit and all other included variables. Shapley Additive exPlanations were implemented to understand each feature's importance. RESULTS: Our query resulted in 315 patients, with 160 meeting the inclusion criteria. There were 53 patients with astrocytoma, 66 with ependymoma, and 41 with hemangioblastoma. The mean age (standard deviation) was 42.3 (17.5), and 48.1% of patients were women (n = 77/160). Multivariate analysis revealed that pathologic grade >3 (OR = 1.55; CI = [0.67, 3.58], P = 0.046 predicted a new neurological deficit. Random Forest algorithm (supervised machine learning) found age, use of neuromonitoring, histology of the tumor, performing a midline myelotomy, and tumor location to be the most important predictors of new postoperative neurological deficits. CONCLUSIONS: Tumor grade/histology, age, use of neuromonitoring, and myelotomy type appeared to be most predictive of postoperative neurological deficits. These results can be used to better inform patients of perioperative risk.

Extracranial-Intracranial Bypass for Moyamoya Disease: The Influence of Racial and Socioeconomic Disparities on Outcomes - A National Inpatient Sample Analysis.

BACKGROUND: Extracranial-intracranial (EC-IC) bypass is an established therapeutic option for Moyamoya disease (MMD). However, little is known about the effects of racial and ethnic disparities on outcomes. This study assessed trends in EC-IC bypass outcomes among MMD patients stratified by race and ethnicity. METHODS: Utilizing the US National Inpatient Sample, we identified MMD patients undergoing EC-IC bypass between 2002 and 2020. Demographic and hospital-level data were collected. Multivariable analysis was conducted to identify independent factors associated with outcomes. Trend analysis was performed using piecewise joinpoint regression. RESULTS: Out of 14,062 patients with MMD, 1771 underwent EC-IC bypass. Of these, 60.59% were White, 17.56% were Black, 12.36% were Asians, 8.47% were Hispanic, and 1.02% were Native Americans. Nonhome discharge was noted in 21.7% of cases, with a 6.7% death and 3.8% postoperative neurologic complications rates. EC-IC bypass was more commonly performed in Native Americans (23.38%) and Asians (17.76%). Hispanics had the longest mean length of stay (8.4 days) and lower odds of nonhome discharge compared to Whites (odds ratio: 0.64; 95% confidence interval: 0.40-1.03; P = 0.04). Patients with Medicaid, private insurance, self-payers, and insurance paid by other governments had lower odds of nonhome discharge than those with Medicare. CONCLUSION: This study highlights racial and socioeconomic disparities in EC-IC bypass for patients with MMD. Despite these disparities, we did not find any significant difference in the quality of care. Addressing these disparities is essential for optimizing MMD outcomes.

Comparative outcomes of awake spine surgery under spinal versus general anesthesia: a comprehensive systematic review and meta-analysis.

BACKGROUND: Awake surgery, under spinal anesthesia (SA), is an alternative to surgery under general anesthesia (GA), in neurological and spine surgery. In the literature, there seem to be some evidence supporting benefits associated with the use of this anesthetic modality, as compared to GA. Currently, there is a notable lack of updated and comprehensive review addressing the complications associated with both awake SA and GA in spine surgery. We hence aimed to perform a systematic review of the literature and meta-analysis on the topic. METHODS: A systematic search was conducted to identify studies that assessed SA in spine surgery from database inception to April 14, 2023, in PubMed, Medline, Embase, and Cochrane databases. Outcomes of interest included estimated blood loss, length of hospital stay, operative time, and overall complications. Meta-analysis was conducted using random effects models. RESULTS: In total, 38 studies that assessed 7820 patients were included. The majority of the operations that were treated with SA were single-level lumbar cases. Awake patients had significantly shorter lengths of hospital stay (Mean difference (MD): - 0.40 days; 95% CI - 0.64 to - 0.17) and operative time (MD: - 19.17 min; 95% CI - 29.68 to - 8.65) compared to patients under GA. The overall complication rate was significantly higher in patients under GA than SA (RR, 0.59 [95% CI 0.47-0.74]). Patients under GA had significantly higher rates of postoperative nausea/vomiting RR, 0.60 [95% CI 0.39-0.90]) and urinary retention (RR, 0.61 [95% CI 0.37-0.99]). CONCLUSIONS: Patients undergoing awake spine surgery under SA had significantly shorter operations and hospital stays, and fewer rates of postoperative nausea and urinary retention as compared to GA. In summary, awake spine surgery offers a valid alternative to GA and added benefits in terms of postsurgical complications, while being associated with relatively low morbidity.

Immunohistochemical markers predicting recurrence following resection and radiotherapy in chordoma patients: insights from a multicenter study [RETRACTED].

OBJECTIVE: Chordomas are rare tumors that often recur regardless of surgery with negative margins and postoperative radiotherapy. The predictive accuracy of widely used immunohistochemical (IHC) markers in addressing the recurrence of skull base chordomas (SBCs) is yet to be determined. This study aimed to investigate IHC markers in the prediction of recurrence after SBC resection with adjuvant radiation therapy. METHODS: The authors reviewed the records of patients who had treatment for SBC between January 2017 and June 2021 across the Mayo Clinic in Minnesota, Florida, and Arizona. Exclusion criteria included patients who had no histopathology or recurrence as an outcome. Histopathological markers included cytokeratin A1/A3 only, epithelial membrane antigen (EMA), S100 protein, pan-cytokeratin, IN1, GATA3, CAM5.2, OSCAR, and chondroid. Information from patient records was abstracted, including treatment, clinical and radiological follow-up duration, demographics, and histopathological factors. Decision tree and random forest classifiers were trained and tested to predict the recurrence based on unseen data using an 80/20 split. RESULTS: A total of 38 patients with a diagnosis of SBC who underwent resection (gross-total resection: 42.1%; and subtotal resection: 57.9%) and radiation therapy were extracted from the medical records. The mean patient age was 48.2 (SD 19.6) years; most patients were male (n = 23; 60.5%) and White (n = 36; 94.7%). Pan-cytokeratin was associated with an increased risk of postoperative recurrence (OR 14.67, 95% CI 2.44-88.13; p = 0.00517) after resection and adjuvant radiotherapy. The decision tree analysis found pan-cytokeratin-positive tumors to have a 78% chance of being classified as a recurrence, with an accuracy of 75%. The distribution of minimal depth in the prediction of postoperative recurrence indicates that the most important variables were pan-cytokeratin, followed by cytokeratin A1/A3 and EMA. CONCLUSIONS: The authors' machine learning algorithm identified pan-cytokeratin as the largest contributor to recurrence among other IHC markers after SBC resection. Machine learning may facilitate the prediction of outcomes in rare tumors, such as chordomas.

Association between immunohistochemical markers and tumor progression following resection of spinal chordomas: a multicenter study.

OBJECTIVE: Chordomas are slow-growing tumors derived from notochord remnants. Despite margin-negative excision and postoperative radiation therapy, spinal chordomas (SCs) often progress. The potential of immunohistochemical (IHC) markers, such as epithelial membrane antigen (EMA), combined with machine learning algorithms to predict long-term (≥ 12 months) postoperative tumor progression, has been understudied. The authors aimed to identify IHC markers using trained tree-based algorithms to predict long-term (≥ 12 months) postoperative tumor progression. METHODS: The authors reviewed the records of patients who underwent resection of SCs between January 2017 and June 2021 across the Mayo Clinic enterprise. Demographics, type of treatment, histopathology, and other relevant clinical factors were abstracted from each patient's record. Low tumor progression was defined as more than a 94.3-mm3 decrease in the tumor size at the latest radiographic follow-up. Decision trees and random forest classifiers were trained and tested to predict the long-term volumetric progression after an 80/20 data split. RESULTS: Sixty-two patients diagnosed with and surgically treated for SC were identified, of whom 31 were found to have a more advanced tumor progression based on the tumor volume change cutoff of 94.3 mm3. The mean age was 54.3 ± 13.8 years, and most patients were male (62.9%) and White (98.4%). The most common treatment modality was subtotal resection with radiation therapy (35.5%), with proton beam therapy being the most common (71%). Most SCs were sacrococcygeal (41.9%), followed by cervical (32.3%). EMA-positive SCs had a postoperative progression risk of 67%. Pancytokeratin-positive SCs had a progression rate of 67%; however, patients with S100 protein-positive SCs had a 54% risk of progression. The accuracy of this model in predicting the progression of unseen test data was 66%. Pancytokeratin (mean minimal depth = 1.57), EMA (mean minimal depth = 1.58), cytokeratin A1/A3 (mean minimal depth = 1.59), and S100 protein (mean minimal depth = 1.6) predicted the long-term volumetric progression. Multiway variable importance plots show the relative importance of the top 10 variables based on three measures of varying significance and their predictive role. CONCLUSIONS: These IHC variables with tree-based machine learning tools successfully demonstrate a high capacity to identify a patient's tumor progression pattern with an accuracy of 66%. Pancytokeratin, EMA, cytokeratin A1/A3, and S100 protein were the IHC drivers of a low tumor progression. This shows the power of machine learning algorithms in analyzing and predicting outcomes of rare conditions in a small sample size.

Immunohistochemical markers predicting long-term recurrence following clival and spinal chordoma resection: a multicenter study.

OBJECTIVE: Chordomas are rare tumors from notochordal remnants and account for 1%-4% of all primary bone malignancies, often arising from the clivus and sacrum. Despite margin-negative resection and postoperative radiotherapy, chordomas often recur. Further, immunohistochemical (IHC) markers have not been assessed as predictive of chordoma recurrence. The authors aimed to identify the IHC markers that are predictive of postoperative long-term (≥ 1 year) chordoma recurrence by using trained multiple tree-based machine learning (ML) algorithms. METHODS: The authors reviewed the records of patients who had undergone treatment for clival and spinal chordomas between January 2017 and June 2021 across the Mayo Clinic enterprise (Minnesota, Florida, and Arizona). Demographics, type of treatment, histopathology, and other relevant clinical factors were abstracted from each patient record. Decision tree and random forest classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: One hundred fifty-one patients diagnosed and treated for chordomas were identified: 58 chordomas of the clivus, 48 chordomas of the mobile spine, and 45 chordomas sacrococcygeal in origin. Patients diagnosed with cervical chordomas were the oldest among all groups (58 ± 14 years, p = 0.009). Most patients were male (n = 91, 60.3%) and White (n = 139, 92.1%). Most patients underwent resection with or without radiation therapy (n = 129, 85.4%). Subtotal resection followed by radiation therapy (n = 51, 33.8%) was the most common treatment modality, followed by gross-total resection then radiation therapy (n = 43, 28.5%). Multivariate analysis showed that S100 and pan-cytokeratin are more likely to predict the increase in the risk of postoperative recurrence (OR 3.67, 95% CI 1.09-12.42, p= 0.03; and OR 3.74, 95% CI 0.05-2.21, p = 0.02, respectively). In the decision tree analysis, a clinical follow-up > 1897 days was found in 37% of encounters and a 90% chance of being classified for recurrence (accuracy = 77%). Random forest analysis (n = 500 trees) showed that patient age, type of surgical treatment, location of tumor, S100, pan-cytokeratin, and EMA are the factors predicting long-term recurrence. CONCLUSIONS: The IHC and clinicopathological variables combined with tree-based ML tools successfully demonstrated a high capacity to identify recurrence patterns with an accuracy of 77%. S100, pan-cytokeratin, and EMA were the IHC drivers of recurrence. This shows the power of ML algorithms in analyzing and predicting outcomes of rare conditions of a small sample size.

Effect of race, sex, and socioeconomic factors on overall survival following the resection of intramedullary spinal cord tumors.

INTRODUCTION: Intramedullary spinal cord tumors (IMSCTs) account for 2-4% of all primary CNS tumors. Given their low prevalence and the intricacy of their diagnosis and management, it is critical to address the surrounding racial and socioeconomic factors that impact the care of patients with IMSCTs. This study aimed to investigate the association between race and socioeconomic factors with overall 5 year mortality following the resection of IMSCTs. METHODS: The study used the National Cancer Database to retrospectively analyze patients who underwent resection of IMSCTs from 2004 to 2017. Patients were divided into four cohorts by race/ethnicity, facility type, insurance, median income quartiles, and living area. The primary outcome of interest was 5 year survival, and secondary outcomes included postoperative length of stay and 30 day readmission. Descriptive and multivariable analyses were used to identify independent factors associated with mortality, with statistical significance assessed at a 2-sided p < 0.05. RESULTS: We evaluated the patient characteristics and outcomes for 8,028 patients who underwent surgical treatment for IMSCTs between 2004 and 2017. Most patients were white males (52.4%) with a mean age of 44 years where 7.17% of patients were Black, 7.6% were Hispanic, and 3% were Asian. Most were treated in an academic/research program (72.4%) and had private insurance (69.2%). Black patients had a higher odd of 5 year mortality (OR 1.4; 95% CI 1.1 to 1.77; p = 0.04) compared to white patients, while no significant differences in mortality were observed among other races. Factors associated with lower odds of mortality included being female (OR 0.89; 95% CI 0.78 to 1.02; p < 0.01), receiving treatment in an academic/research program (OR 0.51; 95% CI 0.33 to 0.79; p = 0.04), having private insurance (OR 0.65; 95% CI 0.45 to 0.93; p = 0.02), and having higher income quartiles (OR 0.77; 95% CI 0.62 to 0.96; p = 0.02). CONCLUSION: Our study sheds light on the healthcare disparities that exist in the surgical management of IMSCTs. Our findings indicate that race, sex, socioeconomic status, and treatment facility are independent predictors of 5 year mortality, with Black patients, males, those with lower socioeconomic status, and those treated at non-academic centers experiencing significantly higher mortality rates. These alarming disparities underscore the urgent need for policymakers and researchers to address the underlying factors contributing to these discrepancies and provide equal access to high-quality surgical care for patients with IMSCTs.

Flow diversion using the Pipeline embolization device for intracranial and extracranial pseudoaneurysms: a systematic review and meta-analysis of the literature.

OBJECTIVE: Pseudoaneurysms (PSAs) are complex vascular lesions. Flow diversion has been proposed as an alternative treatment to parent artery occlusion that preserves laminar flow. The authors of the present study investigated the safety and short-term (< 1 year) and long-term (≥ 1 year) aneurysm occlusion rates following the treatment of intracranial and extracranial PSAs using the Pipeline embolization device (PED). METHODS: An electronic database search for full-text English-language articles in Ovid MEDLINE and Epub Ahead of Print, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus was conducted following the PRISMA guidelines. Studies of any design including at least 4 patients with intracranial or extracranial PSAs treated using a PED were included in this analysis. The primary outcome of interest was the rate of peri- and postprocedural complications. Secondarily, the authors analyzed the incidence of complete aneurysm occlusion. RESULTS: A total of 90 patients with 96 PSAs across 9 studies were included. The mean age was 38.2 (SD 15.14) years, and 37.8% of the patients were women. The mean PSA size was 4.9 mm. Most PSAs were unruptured, and the most common etiology was trauma (n = 32, 35.5%), followed by spontaneous formation (n = 21, 23.3%) and iatrogenic injury (n = 19, 21.1%). Among the 51 (53.1%) intracranial and 45 (46.9%) extracranial PSAs were 19 (19.8%) dissecting PSAs. Sixty-six (77.6%) PSAs were in the internal carotid artery and 10 (11.8%) in the vertebral artery. Thirty-three (34.4%) PSAs were treated with ≥ 2 devices, and 8 (8.3%) underwent adjunctive coiling. The mean clinical and angiographic follow-up durations were 10.7 and 12.9 months, respectively. The short-term (< 1 year) and long-term (≥ 1 year) complete occlusion rates were 79% (95% CI 66%-88%, p = 0.82) and 84% (95% CI 70%-92%, p = 0.95), respectively. Complication rates were 8% for iatrogenic dissection (95% CI 3%-16%, p = 0.94), 10% for silent thromboembolism (95% CI 5%-21%, p = 0.77), and 12% for symptomatic thromboembolism (95% CI 6%-23%, p = 0.48). No treatment-related hemorrhage was observed. The overall mortality rate at the last follow-up was 14%. CONCLUSIONS: The complete occlusion rate for PSAs treated with the PED was high and increased over time. Although postprocedural complications and mortality were not insignificant, flow diversion represents a reasonably safe option for managing these complex lesions.

Verteporfin-loaded microparticles for radiosensitization of preclinical lung and breast metastatic spine cancer.

OBJECTIVE: The vertebral column is the most common site for skeletal metastasis, often leading to debilitating pain and weakness. Metastatic cancer has unique genetic drivers that potentiate tumorigenicity. There is an unmet need for novel targeted therapy in patients with spinal metastatic disease. METHODS: The authors assessed the effect of verteporfin-induced yes-associated protein (YAP) inhibition on spine metastatic cell tumorigenicity and radiation sensitivity in vitro. Animal studies used a subcutaneous xenograft mouse model to assess the use of systemic intraperitoneal verteporfin (IP-VP) and intratumoral verteporfin microparticles (IT-VP) to inhibit the tumorigenicity of lung and breast spinal metastatic tumors from primary patient-derived tissue. RESULTS: Verteporfin led to a dose-dependent decrease in migration, clonogenicity, and cell viability via inhibition of YAP and downstream effectors cyclin D1, CTGF, TOP2A, ANDRD1, MCL-1, FOSL2, KIF14, and KIF23. This was confirmed with knockdown of YAP. Verteporfin has an additive response when combined with radiation, and knockdown of YAP rendered cells more sensitive to radiation. The addition of verteporfin to YAP knockdown cells did not significantly alter migration, clonogenicity, or cell viability. IP-VP and IT-VP led to diminished tumor growth (p < 0.0001), especially when combined with radiation (p < 0.0001). Tissue analysis revealed diminished expression of YAP (p < 0.0001), MCL-1 (p < 0.0001), and Ki-67 (p < 0.0001) in tissue from verteporfin-treated tumors compared with vehicle-treated tumors. CONCLUSIONS: This is the first study to demonstrate that verteporfin-mediated inhibition of YAP leads to diminished tumorigenicity in lung and breast spinal metastatic cancer cells. Targeting of YAP with verteporfin offers promising results that could be translated to human clinical trials.

Utilization of Machine Learning to Model Important Features of 30-day Readmissions following Surgery for Metastatic Spinal Column Tumors: The Influence of Frailty.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of this study was to determine the relative importance and predicative power of the Hospital Frailty Risk Score (HFRS) on unplanned 30-day readmission after surgical intervention for metastatic spinal column tumors. METHODS: All adult patients undergoing surgery for metastatic spinal column tumor were identified in the Nationwide Readmission Database from the years 2016 to 2018. Patients were categorized into 3 cohorts based on the criteria of the HFRS: Low(<5), Intermediate(5-14.9), and High(≥ 15). Random Forest (RF) classification was used to construct predictive models for 30-day patient readmission. Model performance was examined using the area under the receiver operating curve (AUC), and the Mean Decrease Gini (MDG) metric was used to quantify and rank features by relative importance. RESULTS: There were 4346 patients included. The proportion of patients who required any readmission were higher among the Intermediate and High frailty cohorts when compared to the Low frailty cohort (Low:33.9% vs. Intermediate:39.3% vs. High:39.2%, P < .001). An RF classifier was trained to predict 30-day readmission on all features (AUC = .60) and architecturally equivalent model trained using only ten features with highest MDG (AUC = .59). Both models found frailty to have the highest importance in predicting risk of readmission. On multivariate regression analysis, Intermediate frailty [OR:1.32, CI(1.06,1.64), P = .012] was found to be an independent predictor of unplanned 30-day readmission. CONCLUSION: Our study utilizes machine learning approaches and predictive modeling to identify frailty as a significant risk-factor that contributes to unplanned 30-day readmission after spine surgery for metastatic spinal column metastases.