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Impact of surgery and radiation on radicular pain and myotomic weakness in patients with metastatic spine disease

Bartolozzi, Arthur R; Barzilai, Ori; Laufer, Ilya; Sahgal, Arjun; Rhines, Laurence D; Sciubba, Daniel M; Lazary, Aron; Weber, Michael H; Schuster, James M; Boriani, Stefano; Bettegowda, Chetan; Arnold, Paul M; Clarke, Michelle J; Fehlings, Michael G; Gokaslan, Ziya L; Fisher, Charles G; Bilsky, Mark; Dea, Nicolas
OBJECTIVE:Surgery is typically indicated for mechanical pain in metastatic spine disease or severe neurological compromise, but how radicular pain responds to oncological treatment is not well described. The primary aim of this study was to describe how radicular pain responds to oncological treatment, while secondary aims included pain outcomes between patients with mechanical and tumoral pain and motor improvement in patients with weakness due to nerve root compression. METHODS:Patients treated with surgery and/or radiotherapy for spinal metastases were identified from an international multicenter prospective cohort. The primary outcome was the numeric rating scale (NRS) score for pain at 3 months posttreatment. Motor recovery from radicular compression in patients with myotomic weakness and low-grade epidural compression was also analyzed. RESULTS:Of 284 patients, 129 (45%) had radicular pain ± axial pain and 155 (55%) had axial pain alone. The two groups did not significantly differ in age, comorbidities, tumor characteristics, or treatment. Two hundred two patients (71%) underwent surgery ± radiotherapy, whereas 82 (29%) had radiotherapy alone. The NRS score of patients with radicular pain improved from 6.7 to 3.4 at 3 months, a statistically significantly higher magnitude than in patients with isolated axial pain (p = 0.021). The NRS score at 3 months was similar for both groups (p = 0.876). Patients with radicular pain experienced a larger improvement with surgery compared with radiotherapy alone (p = 0.007) but had higher pretreatment pain (mean NRS score 7.0 vs 5.6, p = 0.013). Twenty-three patients identified with radicular/myotomic weakness (mean American Spinal Injury Association score 96.3 ± 3.2) at baseline improved 2.1 ± 3.8 points at 3 months. CONCLUSIONS:The magnitude of pain improvement for patients with radicular pain following surgery and radiotherapy for metastatic spine disease is higher than for patients with axial pain alone. Surgery is associated with a larger improvement in radicular pain than radiotherapy alone. These results will allow clinicians to tailor treatment options for patients with metastatic spine disease.
PMID: 40311205
ISSN: 1092-0684
CID: 5892292

AO Spine Clinical Practice Recommendations: Current Systemic Oncological Treatments with the Largest Impact on Patients with Metastatic Spinal Disease

Czyz, Marcin; Wensink, Emerens G; Coimbra, Brian; Galgano, Michael; Patel, Shreyaskumar; Redmond, Kristin; Rutges, Joost; Tan, Jiong Hao Jonathan; Barzilai, Ori; Dea, Nicolas; Gasbarrini, Alessandro; Laufer, Ilya; Lazary, Aron; Netzer, Cordula; Reynolds, Jeremy J; Rhines, Laurence D; Sahgal, Arjun; Fisher, Charles G; Verlaan, Jorrit-Jan
Study DesignLiterature review with clinical recommendation.ObjectiveTo provide the readers with a concise curation of the latest literature in recent advances in systemic oncological therapies and their implications for decision-making in patients with metastatic spinal disease. This review aims to enhance spine specialist's understanding of modern oncological treatments to facilitate optimal timing and planning of local interventions.MethodsThe latest literature in the topic of advances in oncology was reviewed by a multidisciplinary group of experts in metastatic spinal disease and clinical recommendations were formulated. The recommendations were dichotomously graded into strong and conditional (weak) based on the integration of scientific methodology and content expert opinion. This opinion considered experience and practical issues such as risks, burdens, costs, patient values, and circumstances.ResultsFour high-impact studies were reviewed, demonstrating significant advancements in systemic treatments for metastatic cancers commonly affecting the spine. These studies showed improved survival outcomes and efficacy across breast cancer, colorectal cancer, prostate cancer, and renal cell carcinoma. The findings have important implications for surgical/radiotherapy planning, including considerations for timing of interventions, wound healing, and the potential for extended survival affecting construct durability requirements.ConclusionsRecent advances in systemic oncological treatments have important implications for managing metastatic spinal disease. Understanding these developments is crucial for spine specialists to optimize decision-making through a multidisciplinary approach, particularly regarding timing of local interventions, strategy of the surgical approach and reconstruction.[Formula: see text].
PMID: 40153520
ISSN: 2192-5682
CID: 5817582

Advancing Metastatic Spine Tumor Research: A Review of AO Spine Knowledge Forum Tumor's Scientific Contributions Derived From the EPOSO Network, 2014-2024

Rutges, Joost Phj; Zuckerman, Scott L; Arnold, Paul M; Bettegowda, Chetan; Boriani, Stefano; Clarke, Michelle J; Fehlings, Michael G; Ziya L Gokaslan,; Lazary, Aron; Rhines, Laurence D; Sahgal, Arjun; Sciubba, Daniel M; Schuster, James M; Weber, Michael H; Laufer, Ilya; Fisher, Charles G; ,
Study DesignNarrative Review.ObjectivesTo summarize the work of the AO Spine Knowledge Forum Tumor, specifically studies from the Epidemiology, Process and Outcomes in Spine Oncology (EPOSO) study.MethodsA narrative review of all published manuscripts from the EPOSO study was undertaken. EPOSO represents a multicenter, prospective registry effort across 10 North American and European sites to enroll patients with metastatic disease of the spine.ResultsThe current review summarized all studies from the EPOSO network, divided into the following five sections: (1) quality of life and satisfaction, (2) overall survival, (3) spinal instability, (4) neurologic outcome in patients with metastatic epidural spinal cord compression or radicular pain, and (5) patient and tumor-specific factors. Several important findings were elucidated. Patient evaluation should include SINS, nutritional status, severity and duration of neurologic deficit, extent of metastatic tumor burden, and differentiation of axial from radicular pain. Moreover, SOSGOQ2.0 serves as a useful and validated instrument for patient-reported outcome instrument. Despite the palliative nature of metastatic spine surgery, clear improvement in quality-of-life is seen. Even in patients with short-survival, the remaining weeks and months of life result in improved quality-of-life. Metastatic spine surgery often improves neurologic function, potentially enhancing survival through increased performance status.ConclusionsSeveral noteworthy results have come from the EPOSO network, highlighting important trends in metastatic spine care. The AO Spine Knowledge Forum Tumor has helped advancing metastatic spine tumor research as well as ensure these new findings reach and benefit clinicians and their patients.
PMCID:11907629
PMID: 40074676
ISSN: 2192-5682
CID: 5808562

Surgical Adverse Events for Primary Tumors of the Spine and Their Impact on Outcomes: An Observational Study From the Primary Tumors Research and Outcomes Network

Laflamme, Mathieu; Gasbarrini, Alessandro; Rhines, Laurence D; Lazary, Aron; Gokaslan, Ziya L; Reynolds, Jeremy J; Luzzati, Alessandro; Disch, Alexander C; Chou, Dean; Clarke, Michelle J; Wei, Feng; Bettegowda, Chetan; Rampersaud, Y Raja; Boriani, Stefano; Shin, John H; Lord, Elizabeth; Sciubba, Daniel M; Laufer, Ilya; Sahgal, Arjun; Fisher, Charles G; Dea, Nicolas; ,
BACKGROUND AND OBJECTIVES/OBJECTIVE:Aggressive resection for primary tumors of the spine are associated with a high rate of adverse events (AEs), but the impact of AEs on patient-reported outcomes (PROs) remains unknown and is critical to the shared decision-making. Our primary objective was to assess the impact of surgical AEs on PROs using an international registry. Assessing the impact on clinical outcomes and identifying risk factors for AEs were our secondary objectives. METHODS:Patients who underwent surgery for a primary spinal tumor were selected through the Primary Tumor Research and Outcomes Network. Our primary outcome was the impact of AEs on PROs at 3 and 12 months after surgery (measured with Spinal Oncology Study Group Outcomes Questionnaire, Short-Form 36, and EuroQol 5 Dimension). We also assessed the impact on clinical outcomes (local control, surgical margins, readmission, reoperation, and mortality). We stratified our results according to severity of AEs, histology, and type of resection. RESULTS:374 patients met inclusion criteria (219 males/155 females). The mean age of the cohort was 48.7 years. The most frequent histology was chordoma (37.3%) followed by chondrosarcoma (8.8%). Sixty-seven patients (17.9%) experienced at least 1 intraoperative AE and 117 patients (31.3%) had at least 1 postoperative AE within 3 months. Overall, 159 patients (42.5%) experienced AEs. The readmission rate was significantly higher in patients who experienced AEs (Any AE: 10.1% vs no AE: 1.9% within 3 months; P = <0.001). PROs were not significantly affected by AEs in most questionnaires. Local control, risk of reoperation, mortality, and achieving preplanned margins were similar between AE groups. CONCLUSION/CONCLUSIONS:The rate of surgical AEs is considerable in this population. Surgical AEs seem to be associated with a higher number of readmissions, but do not seem to result in significant differences in PROs or in a higher risk of reoperation, mortality, and failure to achieve preplanned margins.
PMID: 39907438
ISSN: 1524-4040
CID: 5783952

Frontline Voice: AO Spine Member Survey Regarding Spine Oncology Knowledge Generation and Translation Needs

Goodwin, Matthew L; Loomans, Janneke I; Barzilai, Ori; Dea, Nicolas; Gasbarrini, Alessandro; Lazáry, Aron; Netzer, Cordula; Reynolds, Jeremy; Rhines, Laurence; Sahgal, Arjun; Verlaan, Jorrit-Jan; Fisher, Charles G; Laufer, Ilya; On Behalf Of Ao Spine Knowledge Forum Tumor,
STUDY DESIGN/METHODS:cross-sectional survey. OBJECTIVES/OBJECTIVE:To evaluate AO Spine members' practices and comfort in managing metastatic and primary spine tumors, explore the use of decision-support and patient assessment tools, and identify knowledge gaps and future needs in spine oncology. METHODS:An online survey was distributed to AO Spine members to query comfort levels with key decisions in spinal oncology management, utilization of decision frameworks and spine oncology-specific instruments, and educational material preferences. RESULTS:Responses were obtained from 381 members across 82 countries. Most respondents were orthopedic spine surgeons (62%) or neurosurgeons (36%), with 42% performing 100-200 spine surgeries per year. Extradural primary and metastatic tumors were managed by 84% and 95% of respondents, respectively, with survival and frailty assessment tools used for both. While most surgeons felt comfortable determining when emergency surgery was needed (81% for primary and 82% for metastatic tumors), nuanced decisions about surgical timing were more challenging. Surgeons also noted challenges in tailoring the oncologic surgical plan to what the patient could safely tolerate. There was a strong desire for guidelines on tumor-related spinal pain (85%), treatment timing (85%), stabilization (85%), and glucocorticoid use for symptomatic extradural metastatic tumors (77%). Interest was high for classification systems for spine tumor pain (65%) and stabilization decisions (80%). CONCLUSIONS:Additional support is needed in decision-making regarding surgical timing, patient selection, and tailoring treatment invasiveness to life expectancy and frailty. Surgeons seek further guidance to prevent neurologic deterioration and optimize recovery. Guidelines and classification systems were highly coveted for daily practice.
PMCID:11773503
PMID: 39868544
ISSN: 2192-5682
CID: 5780592

Augmenting Large Language Models With Automated, Bibliometrics-Powered Literature Search for Knowledge Distillation: A Pilot Study for Common Spinal Pathologies

Kurland, David B; Alber, Daniel A; Palla, Adhith; de Souza, Daniel N; Lau, Darryl; Laufer, Ilya; Frempong-Boadu, Anthony K; Kondziolka, Douglas; Oermann, Eric K
BACKGROUND AND OBJECTIVES/OBJECTIVE:Scholarly output is accelerating in medical domains, making it challenging to keep up with the latest neurosurgical literature. The emergence of large language models (LLMs) has facilitated rapid, high-quality text summarization. However, LLMs cannot autonomously conduct literature reviews and are prone to hallucinating source material. We devised a novel strategy that combines Reference Publication Year Spectroscopy-a bibliometric technique for identifying foundational articles within a corpus-with LLMs to automatically summarize and cite salient details from articles. We demonstrate our approach for four common spinal conditions in a proof of concept. METHODS:Reference Publication Year Spectroscopy identified seminal articles from the corpora of literature for cervical myelopathy, lumbar radiculopathy, lumbar stenosis, and adjacent segment disease. The article text was split into 1024-token chunks. Queries from three knowledge domains (surgical management, pathophysiology, and natural history) were constructed. The most relevant article chunks for each query were retrieved from a vector database using chain-of-thought prompting. LLMs automatically summarized the literature into a comprehensive narrative with fully referenced facts and statistics. Information was verified through manual review, and spine surgery faculty were surveyed for qualitative feedback. RESULTS:Our tandem approach cost less than $1 for each condition and ran within 5 minutes. Generative Pre-trained Transformer-4 was the best-performing model, with a near-perfect 97.5% citation accuracy. Surveys of spine faculty helped refine the prompting scheme to improve the cohesion and accessibility summaries. The final artificial intelligence-generated text provided high-fidelity summaries of each pathology's most clinically relevant information. CONCLUSION/CONCLUSIONS:We demonstrate the rapid, automated summarization of seminal articles for four common spinal pathologies, with a generalizable workflow implemented using consumer-grade hardware. Our tandem strategy fuses bibliometrics and artificial intelligence to bridge the gap toward fully automated knowledge distillation, obviating the need for manual literature review and article selection.
PMID: 40662770
ISSN: 1524-4040
CID: 5897082

What is the Optimal Management of Metastatic Spine Patients With Intermediate Spinal Instability Neoplastic Scores: To Operate or Not to Operate?

Kwan, William Chu; Zuckerman, Scott L; Fisher, Charles G; Laufer, Ilya; Chou, Dean; O'Toole, John E; Schultheiss, Markus; Weber, Michael H; Sciubba, Daniel M; Pahuta, Markian; Shin, John H; Fehlings, Michael G; Versteeg, Anne; Goodwin, Matthew L; Boriani, Stefano; Bettegowda, Chetan; Lazary, Aron; Gasbarrini, Alessandro; Reynolds, Jeremy J; Verlaan, Jorrit-Jan; Sahgal, Arjun; Gokaslan, Ziya L; Rhines, Laurence D; Dea, Nicolas
STUDY DESIGN/METHODS:Systematic review. OBJECTIVE:In patients with extradural metastatic spine disease, we sought to systematically review the outcomes and complications of patients with intermediate Spinal Instability Neoplastic Score (SINS) lesions undergoing radiation therapy, percutaneous interventions, minimally invasive surgeries, or open spinal surgeries. METHODS:Following PRISMA guidelines for systematic reviews, MEDLINE, EMBASE, Web of Science, the Cochrane Database of Systematic Reviews and the Cochrane Center Register of Controlled Trials were queried for studies that reported on SINS intermediate patients who underwent: 1) radiotherapy, 2) percutaneous intervention, 3) minimally invasive, or 4) open surgery. Dates of publication were between 2013-22. Patients with low- or high-grade SINS were excluded. Outcome measures were pain score, functional status, neurological outcome, ambulation, survival, and perioperative complications. RESULTS:Thirty-nine studies (n = 4554) were included that analyzed outcomes in the SINS intermediate cohort. Radiotherapy appeared to provide temporary improvement in pain score; however, recurrent pain led to surgery in 15%-20% of patients. Percutaneous vertebral augmentation provided improvement in pain. Minimally invasive surgery and open surgery offered improvement in pain, quality of life, neurological, and ambulatory outcomes. Open surgery may be associated with more complications. There was limited evidence for radiofrequency ablation. CONCLUSION/CONCLUSIONS:In the SINS intermediate group, radiotherapy was associated with temporary improvement of pain but may require subsequent surgery. Both minimally invasive surgery and open spinal surgery achieved improvements in pain, quality of life, and neurological outcomes for patients with spine metastases. Open surgery may be associated with more complications.
PMID: 39801116
ISSN: 2192-5682
CID: 5775922

Latest Developments in Targeted Biological Therapies in the Management of Chordoma and Chondrosarcoma

Biczo, Adam; Sahgal, Arjun; Verlaan, Jorrit-Jan; Shreyaskumar, Patel; Szoverfi, Zsolt; Schultheiss, Markus; Rhines, Laurence; Reynolds, Jeremy; Laufer, Ilya; Gasbarrini, Alessandro; Dea, Nicolas; Gokaslan, Ziya; Fisher, Charles; Bettegowda, Chetan; Boriani, Stefano; Hornicek, Francis; Goodwin, Rory; Lazary, Aron
STUDY DESIGN/METHODS:Systematic review. OBJECTIVES/OBJECTIVE:The objective of this review paper was to summarize targeted molecular therapy options for spinal chordoma and chondrosarcoma, and to provide an update on the relevant clinical trials open for recruitment. METHODS:A systematic review of the current literature was performed, according to PRISMA guidelines, to summarize the latest developments in non-surgical molecular treatment options for low grade malignant primary spinal tumours. We also summarize those actively recruiting clinical trials based on clinicaltrials.gov. RESULTS:A total of 73 studies and completed clinical trials were reviewed. Twenty actively recruiting clinical trials (eight for chordoma and twelve for chondrosarcoma) were identified. CONCLUSIONS:There is a strong need to find new therapeutic options to complement surgical resection and radiation therapy, which remain the cornerstone of management. Targeted therapies against molecular pathways show promise as compared to conventional chemotherapy.
PMID: 39801117
ISSN: 2192-5682
CID: 5775942

Prevention and Management of Posterior Wound Complications Following Oncologic Spine Surgery: Narrative Review of Available Evidence and Proposed Clinical Decision-Making Algorithm

Leary, Owen P; Setty, Aayush; Gong, Jung Ho; Ali, Rohaid; Fridley, Jared S; Fisher, Charles G; Sahgal, Arjun; Rhines, Laurence D; Reynolds, Jeremy J; Lazáry, Áron; Laufer, Ilya; Gasbarrini, Alessandro; Dea, Nicolas; Verlaan, Jorrit-Jan; Bettegowda, Chetan; Boriani, Stefano; Mesfin, Addisu; Luzzati, Alessandro; Shin, John H; Cecchinato, Riccardo; Hornicek, Francis J; Goodwin, Matthew L; Gokaslan, Ziya L
STUDY DESIGN/METHODS:Narrative Review. OBJECTIVE:Contextualized by a narrative review of recent literature, we propose a wound complication prevention and management algorithm for spinal oncology patients. We highlight available strategies and motivate future research to identify optimal and individualized wound management for this population. METHODS:We conducted a search of recent studies (2010-2022) using relevant keywords to identify primary literature in support of current strategies for wound complication prevention and management following spine tumor surgery. When primary literature specific to spine tumor cases was not available, data were extrapolated from studies of other spine surgery populations. Results were compiled into a proposed clinical algorithm to guide practice considering available evidence. RESULTS:Based on available literature, we recommend individualized stratification of patients according to identifiable risk factors for wound complication and propose several interventions which might be employed preventatively, including intrawound antibiotic administration, negative pressure wound therapy, and primary flap closure of the surgical wound. Of these, the available evidence, weighing possible risks vs benefits, most strongly favors primary flap closure of surgical wounds, particularly for patients with multiple risk factors. A secondary algorithm to guide management of wound complications is also proposed. CONCLUSIONS:Wound complications such as SSI and dehiscence remain a significant source of morbidity following spine tumor surgery. Triaging patients on an individualized basis according to risk factors for complication may aid in selecting appropriate prophylactic strategies to prevent these complications. Future research in this area is still needed to strengthen recommendations.
PMCID:11726526
PMID: 39801119
ISSN: 2192-5682
CID: 5775982

Defining Spine Cancer Pain Syndromes: A Systematic Review and Proposed Terminology

Pahuta, Markian; Laufer, Ilya; Lo, Sheng-Fu Larry; Boriani, Stefano; Fisher, Charles; Dea, Nicolas; Weber, Michael H; Chou, Dean; Sahgal, Arjun; Rhines, Laurence; Reynolds, Jeremy; Lazary, Aron; Gasbarrinni, Alessandro; Verlaan, Jorrit-Jan; Gokaslan, Ziya; Bettegowda, Chetan; Sarraj, Mohamed; Barzilai, Ori; ,
STUDY DESIGN/METHODS:Systematic Review. OBJECTIVES/OBJECTIVE:Formalized terminology for pain experienced by spine cancer patients is lacking. The common descriptors of spine cancer pain as mechanical or non-mechanical is not exhaustive. Misdiagnosed spinal pain may lead to ineffective treatment recommendations for cancer patients. METHODS:We conducted a systematic review of pain terminology that may be relevant to spinal oncology patients. We provide a comprehensive and unbiased summary of the existing evidence, not limited to the spine surgery literature, and subsequently consolidate these data into a practical, clinically relevant nomenclature for spine oncologists. RESULTS:Our literature search identified 3515 unique citations. Through title and abstract screening, 3407 citations were excluded, resulting in 54 full-text citations for review. Pain in cancer patients is typically described as nociceptive pain (somatic vs visceral), neurologic pain and treatment related pain. CONCLUSIONS:We consolidate the terminology used in the literature and consolidated into clinically relevant nomenclature of biologic tumor pain, mechanical pain, radicular pain, neuropathic pain, and treatment related pain. This review helps standardize terminology for cancer-related pain which may help clinicians identify pain generators.
PMCID:11726517
PMID: 39801118
ISSN: 2192-5682
CID: 5775962