Faculty Bibliography

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.

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.

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.

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. 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: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.

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:Narrative review of existing literature. OBJECTIVES/OBJECTIVE:Significant technological advancements in radiotherapy planning and delivery have enabled new radiotherapy techniques for the management of spine tumors. The objective of this study was to provide a comprehensive summary of these treatment techniques for practicing spine surgeons. METHODS:A narrative review of the existing literature on stereotactic body radiation therapy (SBRT) and particle beam therapy (PBT) for the treatment of spine tumors was performed. The characteristics, implementation and evidence supporting these strategies in the management of primary spinal neoplasms were summarized. RESULTS:The clinical effectiveness of SBRT for the control and symptom palliation of metastatic spinal tumors are well demonstrated in multiple clinical trials. Risks such as fracture, radiculopathy and plexopathy exist after spine SBRT, necessitating an individualized approach in a well experienced multidisciplinary setting. SBRT should be considered a key component of a well-rounded treatment plan for metastatic spine tumors in combination with surgery, vertebral augmentation, and drug therapy, where indicated, to achieve optimal patient outcomes. Additionally, PBT and SBRT are also leading to promising results for primary spine tumors, though comparative effectiveness studies and prospective clinical trials are required to establish these modalities more formally as alternatives to conventionally fractionated photon radiotherapy. CONCLUSIONS:SBRT and PBT are emerging as effective and well tolerated treatment options for primary and metastatic spine tumors. Additional investigation is needed to personalize these treatment options and further strengthen these approaches as key components in a multidisciplinary approach to the management of spinal neoplasms.

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: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.