Faculty Bibliography

STUDY DESIGN/METHODS:Scoping review. OBJECTIVE:To identify which markers are used as surrogates for malnutrition in metastatic spine disease and which are the most studied outcomes associated with it. METHODS:A scoping review was performed by searching the PubMed/Medline, EMBASE, and Web of Science databases up to July 2022. We searched for articles exploring markers of malnutrition in spine oncology patients including but not limited to albumin, body weight, weight loss, and nutrition indices. A narrative synthesis was performed. RESULTS:A total of 61 articles reporting on 31,385 patients met inclusion criteria. There were 13 different surrogate markers of nutrition, with the most common being albumin in 67% of studies (n = 41), body weight/BMI in 34% (n = 21), and muscle mass in 28% (n = 17). The most common studied outcomes were survival in 82% (n = 50), complications in 28% (n = 17), and length of stay in 10% (n = 6) of studies. Quality of life and functional outcomes were assessed in 2% (n = 1) and 3% (n = 2) of studies, respectively. Out of 61 studies, 18% (n = 11) found no association between the examined markers and outcome. CONCLUSION/CONCLUSIONS:Assessment of nutritional status in patients with spinal metastases is fundamental. However, there is lack of a comprehensive and consistent way of assessing malnutrition in oncologic spine patients and therefore inconsistency in its relationship with outcomes. A consensus agreement on the assessment and definition of malnutrition in spine tumor patients is needed.

STUDY DESIGN/METHODS:Narrative Review. OBJECTIVE:The management of spinal tumors requires a multi-disciplinary approach including surgery, radiation, and systemic therapy. Surgical approaches typically require posterior segmental instrumentation to maintain long-term spinal stability. Carbon fiber reinforced pedicle screws (CFRP) are increasingly used in the oncologic setting due to reductions in both imaging artifacts and radiotherapy perturbations compared to titanium implants. We performed a review of the literature and highlight advantages and future areas of study for CFRP. METHODS:We performed a systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and identified 10 articles including 573 patients. Across all studies we reviewed patient demographics, tumor types treated, hardware-related features, complication rates, recurrence, survival, and follow-up. RESULTS:Across 10 studies, a total of 1371 screws placed. Surgical and non-surgical complications were reported in 18.3% of patients. Disease progression at the surgical site was detected in 7.3% of patients. There was no significant difference in clinical or hardware complications between CFRP or titanium implants. The most frequent complication attributable to implanted CFRP hardware included screw breakage in 2.4% and loosening in 1.7% of patients, respectively. CONCLUSION/CONCLUSIONS:CFRP provide a unique tool in the setting of spinal oncology. With a safety profile comparable to titanium, we review the documented advantages of CFRP posterior implants compared to titanium, while also addressing their current limitations. Additionally, we highlight several areas of future research to identify the optimal patients who will achieve the greatest benefit of CFRP.

STUDY DESIGN/METHODS:Systematic review and clinimetric analysis. OBJECTIVES/OBJECTIVE:Frailty and sarcopenia predict worse surgical outcomes among spinal degenerative and deformity-related populations; this association is less clear in the context of spinal oncology. Here, we sought to identify frailty and sarcopenia tools applied in spinal oncology and appraise their clinimetric properties. METHODS:, 2000, until June 2022. Study characteristics, frailty tools, and measures of sarcopenia were recorded. Component domains, individual items, cut-off values, and measurement techniques were collected. Clinimetric assessment was performed according to Consensus-based Standards for Health Measurement Instruments. RESULTS:). Frailty and sarcopenia measures lacked or had uncertain content and construct validity. Frailty measures were objective except the Johns-Hopkins Adjusted Clinical Groups. All tools were feasible except the Hospital Frailty Risk Score (HFRS). Positive predictive validity was observed for the HFRS and in select studies employing the mFI-5, MSTFI, and L3-TPA/VBA. All frailty tools had floor or ceiling effects. CONCLUSIONS:Existing tools for evaluating frailty and sarcopenia among patients undergoing surgery for spinal tumors have poor clinimetric properties. Here, we provide a pragmatic approach to utilizing existing frailty and sarcopenia tools, until more clinimetrically robust instruments are developed.

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.

STUDY DESIGN/METHODS:Narrative review. OBJECTIVES/OBJECTIVE:This article aims to provide a narrative review of the current state of research for liquid biopsy in spinal tumors and to discuss the potential application of liquid biopsy in the clinical management of patients with spinal tumors. METHODS:A comprehensive review of the literature was performed using PubMed, Google Scholar, Medline, Embase and Cochrane databases, and the review was limited to articles of English language. All the relevant articles which were identified to be related to liquid biomarker study in spinal tumors, were studied in full text. RESULTS:Liquid biopsy has revolutionized the field of precision medicine by guiding personalized clinical management of cancer patients based on the liquid biomarker status. In recent years, more research has been done to investigate its potential utilization in patients with tumors from the spine. Herein, we review the liquid biomarkers that have been proposed in different spine malignancies including chordoma, chondrosarcoma, Ewing sarcoma, osteosarcoma, astrocytoma and ependymoma. We also discuss the wide window of opportunity to utilize these liquid biomarkers in diagnosis, treatment response, monitoring, and detection of minimal residual disease in patients with spinal tumors. CONCLUSIONS:Liquid biomarkers, especially blood-derived circulating tumor DNA, has a promising clinical utility as they are disease-specific, minimally invasive, and the procedure is repeatable. Prospective studies with larger populations are needed to fully establish its use in the setting of spinal tumors.

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.

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.

STUDY DESIGN/METHODS:Narrative Literature review. OBJECTIVE:To provide a general overview of important molecular markers and targeted therapies for the most common neoplasms (lung, breast, prostate and melanoma) that metastasize to the spine and offer guidance on how to best incorporate them in the clinical setting. METHODS:A narrative review of the literature was performed using PubMed, Google Scholar, Medline databases, as well as the histology-specific National Comprehensive Cancer Network guidelines to identify relevant articles limited to the English language. Relevant articles were reviewed for commonly described molecular mutations or targeted therapeutics, as well as associated clinical outcomes, and surgery-related risks. RESULTS:Molecular markers and targeted therapies have dramatically improved the survival of cancer patients. The increasing importance of prognostic molecular markers and targeted therapies provides rationale for their incorporation into clinical decision-making for patients diagnosed with metastatic spine disease. In this review, we discuss the molecular markers/mutations and targeted therapies associated with the most common malignancies that metastasize to the spine and provide a framework that the surgeon can utilize when evaluating patients for potential intervention. Finally, we provide case examples that highlight the importance of molecular prognostication and therapies in surgical decision-making. CONCLUSION/CONCLUSIONS:An integrated understanding of the implications of surgery, radiation, molecular markers and targeted therapies that guide prognostication and treatment is warranted in order to achieve the most favorable outcomes for patients with metastatic spine disease.

STUDY DESIGN/METHODS:Delphi study. OBJECTIVE:The objective of this study was to identify risk factors associated with the development and/or progression of neurological deficits in patients with metastatic spinal disease. METHODS:A three-round Delphi study was conducted between January-May 2023 including AO Spine members, comprising mainly neurosurgeons and orthopedic surgeons. In round 1, participants listed radiological factors, patient characteristics, tumor characteristics, previous cancer-related treatment factors and additional factors. In round 2, participants ranked the factors on importance per category and selected a top 9 from all factors. Kendall's W coefficient of concordance was calculated as a measure of consensus. In the final round, participants provided feedback on the rankings resulting from round 2. Lastly, the highest-ranking factors were more clearly defined and operationalized by an expert panel. RESULTS:Over two hundred physicians and researchers participated in each round. The factors listed in the first round were collapsed into 12 radiological factors, 14 patient characteristics, 6 tumor characteristics and 12 previous cancer-related treatment factors. High agreement was found in round 3 on the top-half lists in each category and the overall top 9, originating from round 2. Kendall's W indicated strong agreement between the participants. 'Epidural spinal cord compression', 'aggressive tumor behavior' and 'mechanical instability' were deemed most influential for the development of neurological deficits. CONCLUSION/CONCLUSIONS:This study provides factors that may be related to the development and/or progression of neurological deficits in patients with metastatic spinal disease. This list can serve as a basis for future directions in prognostication research.

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.