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Treatment of intramedullary spinal cord tumors: a modified Delphi technique of the North American Spine Society Section of Spine Oncology

Hersh, Andrew M; Pennington, Zach; Lubelski, Daniel; Elsamadicy, Aladine A; Dea, Nicolas; Desai, Atman; Gokaslan, Ziya L; Goodwin, C Rory; Hsu, Wesley; Jallo, George I; Krishnaney, Ajit; Laufer, Ilya; Lo, Sheng-Fu Larry; Macki, Mohamed; Mehta, Ankit I; Ozturk, Ali; Shin, John H; Soliman, Hesham; Sciubba, Daniel M
OBJECTIVE:Intramedullary spinal cord tumors (IMSCTs) are rare tumors with heterogeneous presentations and natural histories that complicate their management. Standardized guidelines are lacking on when to surgically intervene and the appropriate aggressiveness of resection, especially given the risk of new neurological deficits following resection of infiltrative tumors. Here, the authors present the results of a modified Delphi method using input from surgeons experienced with IMSCT removal to construct a framework for the operative management of IMSCTs based on the clinical, radiographic, and tumor-specific characteristics. METHODS:A modified Delphi technique was conducted using a group of 14 neurosurgeons experienced in IMSCT resection. Three rounds of written correspondence, surveys, and videoconferencing were carried out. Participants were queried about clinical and radiographic criteria used to determine operative candidacy and guide decision-making. Members then completed a final survey indicating their choice of observation or surgery, choice of resection strategy, and decision to perform duraplasty, in response to a set of patient- and tumor-specific characteristics. Consensus was defined as ≥ 80% agreement, while responses with 70%-79% agreement were defined as agreement. RESULTS:Thirty-six total characteristics were assessed. There was consensus favoring surgical intervention for patients with new-onset myelopathy (86% agreement), chronic myelopathy (86%), or progression from mild to disabling numbness (86%), but disagreement for patients with mild numbness or chronic paraplegia. Age was not a determinant of operative candidacy except among frail patients, who were deemed more suitable for observation (93%). Well-circumscribed (93%) or posteriorly located tumors reaching the surface (86%) were consensus surgical lesions, and participants agreed that the presence of syringomyelia (71%) and peritumoral T2 signal change (79%) were favorable indications for surgery. There was consensus that complete loss of transcranial motor evoked potentials with a 50% decrease in the D-wave amplitude should halt further resection (93%). Preoperative symptoms seldom influenced choice of resection strategy, while a distinct cleavage plane (100%) or visible tumor-cord margins (100%) strongly favored gross-total resection. CONCLUSIONS:The authors present a modified Delphi technique highlighting areas of consensus and agreement regarding surgical management of IMSCTs. Although not intended as a substitute for individual clinical decision-making, the results can help guide care of these patients. Additionally, areas of controversy meriting further investigation are highlighted.
PMID: 37856379
ISSN: 1547-5646
CID: 5625762

Gender and Sex Differences in Health-related Quality of Life, Clinical Outcomes and Survival after Treatment of Metastatic Spine Disease

Goodwin, C Rory; Price, Meghan; Goodwin, Andrea N; Dalton, Tara; Versteeg, Anne L; Sahgal, Arjun; Rhines, Laurence D; Schuster, James M; Weber, Michael H; Lazary, Aron; Boriani, Stefano; Bettegowda, Chetan; Fehlings, Michael G; Arnold, Paul M; Dea, Nicolas; Charest-Morin, Raphaele; Shin, John; Laufer, Ilya; Chou, Dean; Gokaslan, Ziya L; Clarke, Michelle J; Fisher, Charles G; Sciubba, Daniel M; ,
STUDY DESIGN/METHODS:Retrospective review of prospective, multicenter and international cohort study. OBJECTIVE:To describe the effect of gender on HRQoL, clinical outcomes and survival for patients with spinal metastases treated with either surgery and/or radiation. SUMMARY OF BACKGROUND DATA/BACKGROUND:Gender differences in health-related outcomes are demonstrated in numerous studies, with women experiencing worse outcomes and receiving lower standards of care than men, however, the influence that gender has on low health-related quality of life (HRQoL) and clinical outcomes after spine surgery remains unclear. METHODS:Patient demographic data, overall survival, treatment details, perioperative complications, and HRQoL measures including EQ-5D, pain NRS, the short form 36 version 2 (SF-36v2) and the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0) were reviewed. Patients were stratified by sex, and a separate sensitivity analysis that excluded gender-specific cancers (i.e., breast, prostate, etc.) was performed. RESULTS:The study cohort included 207 female and 183 male patients, with age, smoking status, and site of primary cancer being significantly different between the two cohorts (P<0.001). Both males and females experienced significantly improved SOSGOQ2.0, EQ-5D, and pain NRS scores at all study time points from baseline (P<0.001). Upon sensitivity analysis, (gender-specific cancers removed from analysis), the significant improvement in SOSGOQ physical, mental, and social subdomains and on SF-36 domains disappeared for females. Males experienced higher rates of postoperative complications. Kaplan-Meier survival analysis of both the overall and sensitivity analysis cohorts showed females lived longer than males after treatment (P=0.001 and 0.043, respectively). CONCLUSION/CONCLUSIONS:Both males and females experienced significantly improved HRQoL scores after treatment, but females demonstrated longer survival and a lower complication rate. This study suggests that gender may be a prognostic factor in survival and clinical outcomes for patients undergoing treatment for spine metastases and should be taken into consideration when counseling patients accordingly.
PMID: 38149519
ISSN: 1528-1159
CID: 5623572

Developing an Automated Registry (Autoregistry) of Spine Surgery Using Natural Language Processing and Health System Scale Databases

Cheung, Alexander T M; Kurland, David B; Neifert, Sean; Mandelberg, Nataniel; Nasir-Moin, Mustafa; Laufer, Ilya; Pacione, Donato; Lau, Darryl; Frempong-Boadu, Anthony K; Kondziolka, Douglas; Golfinos, John G; Oermann, Eric Karl
BACKGROUND AND OBJECTIVES/OBJECTIVE:Clinical registries are critical for modern surgery and underpin outcomes research, device monitoring, and trial development. However, existing approaches to registry construction are labor-intensive, costly, and prone to manual error. Natural language processing techniques combined with electronic health record (EHR) data sets can theoretically automate the construction and maintenance of registries. Our aim was to automate the generation of a spine surgery registry at an academic medical center using regular expression (regex) classifiers developed by neurosurgeons to combine domain expertise with interpretable algorithms. METHODS:We used a Hadoop data lake consisting of all the information generated by an academic medical center. Using this database and structured query language queries, we retrieved every operative note written in the department of neurosurgery since our transition to EHR. Notes were parsed using regex classifiers and compared with a random subset of 100 manually reviewed notes. RESULTS:A total of 31 502 operative cases were downloaded and processed using regex classifiers. The codebase required 5 days of development, 3 weeks of validation, and less than 1 hour for the software to generate the autoregistry. Regex classifiers had an average accuracy of 98.86% at identifying both spinal procedures and the relevant vertebral levels, and it correctly identified the entire list of defined surgical procedures in 89% of patients. We were able to identify patients who required additional operations within 30 days to monitor outcomes and quality metrics. CONCLUSION/CONCLUSIONS:This study demonstrates the feasibility of automatically generating a spine registry using the EHR and an interpretable, customizable natural language processing algorithm which may reduce pitfalls associated with manual registry development and facilitate rapid clinical research.
PMID: 37345933
ISSN: 1524-4040
CID: 5542832

Role of Frailty Status in Prediction of Clinical Outcomes of Traumatic Spinal Injury: A Systematic Review and Meta-Analysis

Roohollahi, Faramarz; Farahbakhsh, Farzin; Kankam, Samuel Berchi; Mohammadi, Mohammad; Mohammadi, Aynaz; Korkorian, Rojin; Hobabi, Sepehr; Moarrefdezfouli, Azin; Molavi, Shervin; Davies, Benjamin Marshall; Zipser, Carl; Laufer, Ilya; Harrop, James Shields; Arnold, Paul; Martin, Allan R; Rahimi-Movaghar, Vafa
Although many frailty tools have been used to predict traumatic spinal injury (TSI) outcomes, identifying predictors of outcomes after TSI in the aged population is difficult. Frailty, age and TSI association are interesting topics of discussion in geriatric literature. However, the association between these variables are yet to be clearly elucidated. We conducted a systematic review to investigate the association between frailty and TSI outcomes. The authors searched Medline, EMBASE, Scopus, and Web of Science for relevant studies. Studies with observational designs that assessed baseline frailty status in individuals suffering from TSI published from inception until 26th March 2023 were included. LoS, AEs, and mortality were the outcomes of interest. Of the 2425 citations, 16 studies involving 37,640 participants were included. The modified frailty index (mFI) was the most common tool used to assess frailty. Meta-analysis was employed only in studies that used mFI for measuring frailty. Frailty was significantly associated with increased in-hospital or 30-day mortality (pooled OR: 1.93 [1.19; 3.11]), non-routine discharge (pooled OR: 2.44 [1.34; 4.44]), and AEs or complications (pooled OR: 2.00 [1.14; 3.50]). However, no significant relationship was found between frailty and LoS (pooled OR: 3.02 [0.86; 10.60]). Heterogeneity was observed across multiple factors, including age, injury level, frailty assessment tool, and spinal cord injury (SCI) characteristics. In conclusion, although there is limited data concerning using frailty scales to predict short-term outcomes after TSI, the results showed that frailty status may be a predictor of in-hospital mortality, AEs and unfavorable discharge destination.
PMID: 37432902
ISSN: 1557-9042
CID: 5537522

Health system-scale language models are all-purpose prediction engines

Jiang, Lavender Yao; Liu, Xujin Chris; Nejatian, Nima Pour; Nasir-Moin, Mustafa; Wang, Duo; Abidin, Anas; Eaton, Kevin; Riina, Howard Antony; Laufer, Ilya; Punjabi, Paawan; Miceli, Madeline; Kim, Nora C; Orillac, Cordelia; Schnurman, Zane; Livia, Christopher; Weiss, Hannah; Kurland, David; Neifert, Sean; Dastagirzada, Yosef; Kondziolka, Douglas; Cheung, Alexander T M; Yang, Grace; Cao, Ming; Flores, Mona; Costa, Anthony B; Aphinyanaphongs, Yindalon; Cho, Kyunghyun; Oermann, Eric Karl
Physicians make critical time-constrained decisions every day. Clinical predictive models can help physicians and administrators make decisions by forecasting clinical and operational events. Existing structured data-based clinical predictive models have limited use in everyday practice owing to complexity in data processing, as well as model development and deployment1-3. Here we show that unstructured clinical notes from the electronic health record can enable the training of clinical language models, which can be used as all-purpose clinical predictive engines with low-resistance development and deployment. Our approach leverages recent advances in natural language processing4,5 to train a large language model for medical language (NYUTron) and subsequently fine-tune it across a wide range of clinical and operational predictive tasks. We evaluated our approach within our health system for five such tasks: 30-day all-cause readmission prediction, in-hospital mortality prediction, comorbidity index prediction, length of stay prediction, and insurance denial prediction. We show that NYUTron has an area under the curve (AUC) of 78.7-94.9%, with an improvement of 5.36-14.7% in the AUC compared with traditional models. We additionally demonstrate the benefits of pretraining with clinical text, the potential for increasing generalizability to different sites through fine-tuning and the full deployment of our system in a prospective, single-arm trial. These results show the potential for using clinical language models in medicine to read alongside physicians and provide guidance at the point of care.
PMID: 37286606
ISSN: 1476-4687
CID: 5536672

Carbon fiber-reinforced PEEK spinal implants for primary and metastatic spine tumors: a systematic review on implant complications and radiotherapy benefits

Khan, Hammad A; Ber, Roee; Neifert, Sean N; Kurland, David B; Laufer, Ilya; Kondziolka, Douglas; Chhabra, Arpit; Frempong-Boadu, Anthony K; Lau, Darryl
OBJECTIVE:By minimizing imaging artifact and particle scatter, carbon fiber-reinforced polyetheretherketone (CF-PEEK) spinal implants are hypothesized to enhance radiotherapy (RT) planning/dosing and improve oncological outcomes. However, robust clinical studies comparing tumor surgery outcomes between CF-PEEK and traditional metallic implants are lacking. In this paper, the authors performed a systematic review of the literature with the aim to describe clinical outcomes in patients with spine tumors who received CF-PEEK implants, focusing on implant-related complications and oncological outcomes. METHODS:A systematic review of the literature published between database inception and May 2022 was performed in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The PubMed database was queried using the terms "carbon fiber" and "spine" or "spinal." The inclusion criteria were articles that described patients with CF-PEEK pedicle screw fixation and had a minimum of 5 patients. Case reports and phantom studies were excluded. RESULTS:This review included 11 articles with 326 patients (237 with CF-PEEK-based implants and 89 with titanium-based implants). The mean follow-up period was 13.5 months, and most tumors were metastatic (67.1%). The rates of implant-related complications in the CF-PEEK and titanium groups were 7.8% and 4.7%, respectively. The rate of pedicle screw fracture was 1.7% in the CF-PEEK group and 2.4% in the titanium group. The rates of reoperation were 5.7% (with 60.0% because of implant failure or junctional kyphosis) and 4.8% (all because of implant failure or junctional kyphosis) in the CF-PEEK and titanium groups, respectively. When reported, 72.5% of patients received postoperative RT (41.0% stereotactic body RT, 30.8% fractionated RT, 25.6% proton, 2.6% carbon ion). Four articles suggested that implant artifact was reduced in the CF-PEEK group. Local recurrence occurred in 14.4% of CF-PEEK and 10.7% of titanium-implanted patients. CONCLUSIONS:While CF-PEEK harbors similar implant failure rates to traditional metallic implants with reduced imaging artifact, it remains unclear whether CF-PEEK implants improve oncological outcomes. This study highlights the need for prospective, direct comparative clinical studies.
PMID: 37382293
ISSN: 1547-5646
CID: 5540372

Cervicothoracic junction instrumentation strategies following separation surgery for spinal metastases

Chakravarthy, Vikram B; Hussain, Ibrahim; Laufer, Ilya; Goldberg, Jacob L; Reiner, Anne S; Villavieja, Jemma; Newman, William Christopher; Barzilai, Ori; Bilsky, Mark
OBJECTIVE:The cervicothoracic junction (CTJ) is a challenging region to stabilize after tumor resection for metastatic spine disease. The objective of this study was to describe the outcomes of patients who underwent posterolateral decompression and instrumented fusion (i.e., separation surgery across the CTJ for instability due to metastatic disease). METHODS:The authors performed a single-institution retrospective study of a prospectively collected cohort of patients who underwent single-approach posterior decompression and instrumented fusion across the CTJ for metastatic spine disease between 2011 and 2018. Adult patients (≥ 18 years old) who presented with mechanical instability, myelopathy, and radiculopathy secondary to metastatic epidural spinal cord compression (MESCC) of the CTJ (C7-T1) from 2011 to 2018 were included. RESULTS:Seventy-nine patients were included, with a mean age of 62.1 years. The most common primary malignancies were non-small cell lung (n = 17), renal cell (11), and prostate (8) carcinoma. The median number of levels decompressed and construct length were 3 and 7, respectively. The average operative time, blood loss, and length of stay were 179.2 minutes, 600.5 ml, and 7.7 days, respectively. Overall, 58 patients received adjuvant radiation, and median dose, fractions, and time from surgery were 27 Gy, 3 fractions, and 20 days, respectively. All patients underwent lateral mass and pedicle screw instrumentation. Forty-nine patients had tapered rods (4.0/5.5 mm or 3.5/5.5 mm), 29 had fixed-diameter rods (3.5 mm or 4.0 mm), and 1 had both. Ten patients required anterior reconstruction with poly-methyl-methacrylate. The overall complication rate was 18.8% (6 patients with wound-related complications, 7 with hardware-related complications, 1 with both, and 1 with other). For the 8 patients (10%) with hardware failure, 7 had tapered rods, all 8 had cervical screw pullout, and 1 patient also experienced rod/screw fracture. The average time to hardware failure was 146.8 days. The 2-year cumulative incidence rate of hardware failure was 11.1% (95% CI 3.7%-18.5%). There were 55 deceased patients, and the median (95% CI) overall survival period was 7.97 (5.79-12.60) months. For survivors, the median (range) follow-up was 12.94 (1.94-71.80) months. CONCLUSIONS:Instrumented fusion across the CTJ demonstrated an 18.8% rate of postoperative complications and an 11% overall 2-year rate of hardware failure in patients who underwent metastatic epidural tumor decompression and stabilization.
PMID: 36609370
ISSN: 1547-5646
CID: 5462102

Perception of frailty in spinal metastatic disease: international survey of the AO Spine community

MacLean, Mark A; Georgiopoulos, Miltiadis; Charest-Morin, Raphaële; Goodwin, C Rory; Laufer, Ilya; Dea, Nicolas; Shin, John H; Gokaslan, Ziya L; Rhines, Laurence D; O'Toole, John E; Sciubba, Daniel M; Fehlings, Michael G; Stephens, Byron F; Bettegowda, Chetan; Myrehaug, Sten; Disch, Alexander C; Netzer, Cordula; Kumar, Naresh; Sahgal, Arjun; Germscheid, Niccole M; Weber, Michael H
OBJECTIVE:Frailty has not been clearly defined in the context of spinal metastatic disease (SMD). Given this, the objective of this study was to better understand how members of the international AO Spine community conceptualize, define, and assess frailty in SMD. METHODS:The AO Spine Knowledge Forum Tumor conducted an international cross-sectional survey of the AO Spine community. The survey was developed using a modified Delphi technique and was designed to capture preoperative surrogate markers of frailty and relevant postoperative clinical outcomes in the context of SMD. Responses were ranked using weighted averages. Consensus was defined as ≥ 70% agreement among respondents. RESULTS:Results were analyzed for 359 respondents, with an 87% completion rate. Study participants represented 71 countries. In the clinical setting, most respondents informally assess frailty and cognition in patients with SMD by forming a general perception based on clinical condition and patient history. Consensus was attained among respondents regarding the association between 14 preoperative clinical variables and frailty. Severe comorbidities, extensive systemic disease burden, and poor performance status were most associated with frailty. Severe comorbidities associated with frailty included high-risk cardiopulmonary disease, renal failure, liver failure, and malnutrition. The most clinically relevant outcomes were major complications, neurological recovery, and change in performance status. CONCLUSIONS:The respondents recognized that frailty is important, but they most commonly evaluate it based on general clinical impressions rather than using existing frailty tools. The authors identified numerous preoperative surrogate markers of frailty and postoperative clinical outcomes that spine surgeons perceived as most relevant in this population.
PMID: 36883617
ISSN: 1547-5646
CID: 5432732

The Impact of Targetable Mutations on Clinical Outcomes of Metastatic Epidural Spinal Cord Compression in Patients With Non-Small-Cell Lung Cancer Treated With Hybrid Therapy (Surgery Followed by Stereotactic Body Radiation Therapy)

Chakravarthy, Vikram B; Schachner, Benjamin; Amin, Anubhav G; Reiner, Anne S; Yamada, Yoshiya; Schmitt, Adam; Higginson, Daniel S; Laufer, Ilya; Bilsky, Mark H; Barzilai, Ori
BACKGROUND:In treatment of metastatic epidural spinal cord compression (MESCC), hybrid therapy, consisting of separation surgery, followed by stereotactic body radiation therapy, has become the mainstay of treatment for radioresistant pathologies, such as non-small-cell lung cancer (NSCLC). OBJECTIVE:To evaluate clinical outcomes of MESCC secondary to NSCLC treated with hybrid therapy and to identify clinical and molecular prognostic predictors. METHODS:This is a single-center, retrospective study. Adult patients (≥18 years old) with pathologically confirmed NSCLC and spinal metastasis who were treated with hybrid therapy for high-grade MESCC or nerve root compression from 2012 to 2019 are included. Outcome variables evaluated included overall survival (OS) and progression-free survival, local tumor control in the competing risks setting, surgical and radiation complications, and clinical-genomic correlations. RESULTS:One hundred and three patients met inclusion criteria. The median OS for this cohort was 6.5 months, with progression of disease noted in 5 (5%) patients at the index tumor level requiring reoperation and/or reirradiation at a mean of 802 days after postoperative stereotactic body radiation therapy. The 2-year local control rate was 94.6% (95% CI: 89.8-99.3). Epidermal growth factor receptor (EGFR) treatment-naïve patients who initiated EGFR-targeted therapy after hybrid therapy had significantly longer OS (hazard ratio 0.47, 95% CI 0.23-0.95, P = .04) even after adjusting for smoking status. The presence of EGFR exon 21 mutation was predictive of improved progression-free survival. CONCLUSION/CONCLUSIONS:Hybrid therapy in NSCLC resulted in 95% local control at 2 years after surgery. EGFR treatment-naïve patients initiating therapy after hybrid therapy had significantly improved survival advantage. EGFR-targeted therapy initiated before hybrid therapy did not confer survival benefit.
PMID: 36477376
ISSN: 1524-4040
CID: 5383082

Long Term Clinical Outcomes of Patients with Colorectal Cancer with Metastatic Epidural Spinal Cord Compression treated with Hybrid Therapy (Surgery followed by Stereotactic Body Radiation Therapy)

Chakravarthy, Vikram B; Schachner, Ben; Amin, Anubhav; Reiner, Anne S; Yamada, Yoshiya; Schmitt, Adam; Higginson, Daniel S; Laufer, Ilya; Bilsky, Mark H; Barzilai, Ori
BACKGROUND:"Hybrid-therapy", consisting of separation-surgery followed by stereotactic body radiation therapy (SBRT) has become the mainstay treatment for radioresistant spinal metastases. Histology-specific outcomes for hybrid therapy are scarce. In clinical practice, colorectal cancer (CRC) is particularly thought to have poor outcomes regarding spinal metastases. The goal of this study is to evaluate clinical outcomes for patients treated with hybrid therapy for spinal metastases from CRC. METHODS:This is a retrospective study performed at a tertiary cancer center. Adult patients with CRC spinal metastasis who were treated with hybrid-therapy for high-grade epidural spinal cord or nerve root compression from 2005-2020 were included. Outcome variables evaluated included patient demographics, overall survival (OS) and progression-free survival (PFS), surgical and radiation complications, and clinical-genomic correlations. RESULTS:Fifty patients met inclusion criteria. Progression of disease occurred in 7 (14%) patients at the index-level requiring reoperation and/or reirradiation at a mean of 400 days after surgery. Postoperative complications occurred in 16% of patients, with 3 (6%) requiring intervention. Adenomatous polyposis coli (APC) exon 14 and 16 mutations were found in 15 of 17 patients tested and in all 3 of 7 local failures tested. Twenty patients (40%) underwent further radiation due to disease progression at another spinal levels. CONCLUSIONS:Hybrid-therapy in CRC patients resulted in 86.7% local control at two years after surgery, with limited complications. APC mutations are commonly present in CRC patients with spine metastases and may suggest worse prognosis. Patients with CRC spinal metastases commonly progress outside the index treatment level.
PMID: 36272727
ISSN: 1878-8769
CID: 5360662