Faculty Bibliography

PURPOSE/OBJECTIVE:We sought to characterize outcomes from a large institutional database of patients treated with 3-fraction spine stereotactic body radiation therapy (SBRT) after prior overlapping RT. MATERIALS AND METHODS/METHODS:The primary outcome of interest was local failure (LF) in the treated lesion, defined based on MRI. We also characterized toxicities such as vertebral compression fracture (VCF) and radiation myelitis (RM). RESULTS:There were 83 patients treated to 87 spinal lesions between 2014-2023. Median follow-up was 14.2 (interquartile range (IQR) 6-29.4) months and median overall survival was 20.5 (95% confidence interval (CI) 16.5-29.9) months. Most lesions were treated with 27 Gy in 3 fractions (n=78; 90%). Most lesions had been treated with prior conventionally fractionated RT (59%), and the most common histology was prostate cancer (n=15; 17%). The 1- and 2-year LF rate was 8.4% (95% CI 3.7-16%) and 15% (95% CI 8.1-24%), respectively. On univariable analysis, lower minimum dose (DMin) to the planning target volume (PTV) (HR 0.85, 95% CI 0.74-0.99, p=0.03) and colorectal, cholangio-, or hepatocellular carcinoma histology (HR 5.6, 95% CI 1.11-28.4, p=0.037) were associated with risk of LF. There was 1 case of RM (1.3%) and 5 cases (5.5%) of VCF. CONCLUSION/CONCLUSIONS:Re-irradiation with spine SBRT in 3 fractions appears safe and is associated with a 2-year local control rate of 85%. Lower PTV DMin and gastrointestinal histology were associated with increased risk of LF. Further work is needed to identify the optimal dose-fractionation regimen for re-irradiation with spine SBRT.

Study DesignLiterature review with clinical recommendations.ObjectiveProviding a clear and concise overview based on the of key literature and consensus expert opinion on spinal fusion following stabilization for spine metastases and offer actionable recommendations on when to fuse and not fuse in this patient population.MethodsKey articles from the published literature on spinal metastases treated with stabilization followed by fusion were reviewed, and clinical recommendations were formulated. The recommendations are categorized as either strong or conditional based on an assessment of methodological quality and expert opinion. This assessment considers factors such as experience, risks, burdens, costs, patient values, and circumstances.ResultsFour articles were selected by practicing spinal oncology surgeons and each was evaluated for its methodological strength and its scientific evidence.ConclusionFusion rarely influences clinical outcomes in metastatic spine surgery. Treatment should prioritize mechanical stability, pain control, functional preservation, and timely continuation of oncologic therapy rather than pursuing bony arthrodesis. Fusion should be considered exclusively in select long-surviving patients, however routine attempts to enhance fusion or delay adjuvant therapy are not justified.[Formula: see text].

OBJECTIVE:Chordomas are rare, locally aggressive primary neoplasms. Resection with negative margins is the primary recommended therapeutic approach, while adjuvant radiotherapy and chemotherapy can also play a role in their treatment in certain situations, including lesions with positive margins or those that are poorly differentiated or dedifferentiated. Cervical spine chordomas pose significant surgical challenges given their proximity to critical anatomical structures and the mechanical constraints of the cervical spine. In the current case series, authors aimed to explore the clinical and patient-reported outcomes (PROs) of the surgical treatment of cervical chordomas in a large multicenter cohort. METHODS:This multicenter case series analysis utilized data from the prospectively collected Primary Tumor Research and Outcomes Network (PTRON) registry, from its inception (May 16, 2016) to data extraction (February 29, 2024). The study population was restricted to patients with histologically confirmed cervical chordomas involving levels C0-7, who underwent surgical treatment at one of the participating centers, and for whom both the initially planned and postoperatively pathologically confirmed surgical margins were documented. Patient demographics, tumor characteristics, surgical and adjuvant treatments, local recurrence-free survival (LRFS), overall survival (OS), and perioperative adverse events were retrieved. PROs included the Spine Oncology Study Group Outcomes Questionnaire version 2.0 (SOSGOQ2.0), EQ-5D, and SF-36 version 2.0 (SF-36v2). RESULTS:Thirty-eight patients were identified, 12 of whom underwent true en bloc resection (EBR), 18 of whom underwent deliberate intralesional resection, and 8 of whom underwent EBR after intralesional surgery or in whom EBR failed. True EBR led to better LRFS (92% vs 83% vs 63%, respectively) and OS (83% vs 39% vs 50%, respectively). Surgical adverse events within 1 year were more frequent with true EBR (100% vs 39% vs 75%, respectively). EQ-5D, SOSGOQ2.0, and SF-36v2 showed improvement with true EBR, whereas the trends for PROs from the other groups were more variable. CONCLUSIONS:This multicenter case series analysis provides critical insights into the clinical outcomes and PROs in the largest cohort of surgically treated cervical spine chordomas described to date. It underscores the importance and challenges of wide resection for oncological control. It establishes the associated morbidity and provides an overview of PROs following surgery. These findings contribute valuable evidence to inform shared decision-making and optimize patient care.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Separation surgery followed by stereotactic body radiation therapy (SBRT) for solid tumor malignancies metastatic to the spine has excellent durable 2-year local control rates. Preoperative embolization (PEm) is used as an adjunct to decrease operative blood loss for known hypervascular tumor histologies. Recent studies suggest potential benefits of PEm on local control and overall survival, but they involved heterogeneous tumor populations over time periods where systemic therapy was evolving rapidly. Therefore, we set out to determine the impact of PEm for metastatic spine tumors on a 2-year local control and overall survival in a histologically homogeneous cohort of patients with hypervascular tumor histologies. METHODS:This was a single-center, retrospective chart review from 2011 to 2022 at a quaternary cancer center for all patients with renal cell carcinoma, hepatocellular carcinoma, or thyroid cancer diagnosed with spinal metastatic disease who underwent surgical treatment followed by SBRT with or without PEm. RESULTS:Overall, 161 patients were included with 71 undergoing PEm (63 successful and 8 unsuccessful) and 90 not receiving PEm. The 8 who underwent angiogram but were not embolized were considered in the no PEm cohort. Between PEm and no PEm groups, there was no significant difference in age, sex, Eastern Cooperative Oncology Group, preoperative American Spinal Injury Association score, tumor histologies, number of adjacent segments involved, Spinal Instability Neoplastic Scale score, hospital length of stay, time from surgery to SBRT, radiation treatment dose (biological effective dose and equivalent dose in 2-gray fractions), or number of fractions (P > .05 for all). The median overall survival was 18 months for both groups with no significant difference between PEm and no PEm (P = .8). There was no significant difference in 12- and 24-month local control with rates of 94.8% and 91.7% for no PEm and 96.8% and 95.2% for the PEm group, respectively (P = .7). CONCLUSION/CONCLUSIONS:PEm demonstrated no impact on local control or overall survival in patients with hypervascular spine metastases undergoing separation surgery followed by SBRT.

Study DesignNarrative Review.ObjectivesTo summarize the scientific contributions generated from the AO Spine Knowledge Forum Tumor (AOSKFT) databases, focusing on primary spine tumors, and highlight key findings, research trends, and future directions.MethodsData from the Primary Tumor Retrospective (PT-Retro) and Primary Tumor Research Outcome Network (PTRON) registries were analyzed. The nineteen studies included were peer-reviewed manuscripts focused on primary spine tumors, excluding abstracts, book chapters, systematic reviews, and metastatic studies.ResultsThe PT-Retro registry compiled data from 1495 patients across 18 primary tumor histologies, offering insights into recurrence, survival, and treatment paradigms. Key findings emphasize the importance of Enneking-appropriate (EA) resection in improving survival and reducing recurrence in tumors such as chordoma, chondrosarcoma, and osteosarcoma. Genetic markers, including hTERT promoter mutations and rs2305089 SNP, were linked to prognosis in specific histologies. Benign tumors, such as giant cell tumors and aneurysmal bone cysts, demonstrated variable outcomes with different surgical approaches and selective arterial embolization.ConclusionsThe AOSKFT registries have significantly advanced knowledge in primary spine tumor management, emphasizing preoperative staging, surgical margins, and multidisciplinary approaches. International, multicentric registries are essential for studying rare diseases like primary spine tumors, enabling robust data collection, improved statistical power, and broader applicability of findings across diverse clinical settings. Ongoing prospective data collection through PTRON will further refine evidence-based care for these rare and challenging conditions.

STUDY DESIGN/METHODS:Delphi Consensus. OBJECTIVE:To define an optimal surgical composite outcome measure in patients with metastatic spine disease (OSCO-M) through international consensus among key opinion leaders. METHODS:Members of the AO Spine Knowledge Forum Tumor, an international group of dedicated spine oncology surgeons and oncologists, participated in a modified Delphi process between March 2023 and November 2024. The study was conducted in two parts. The first part aimed on identifying which outcome variables were deemed important to be included in the composite outcome. The second part focused on the definition of a successful outcome with regards to the agreed variables from Part 1. Each part consisted of a questionnaire and a consensus meeting. Consensus was achieved when a threshold of 70% agreement was reached. RESULTS:A total of 42 dedicated spine oncology surgeons and oncologists from North America, Latin America, Europe, and Asia participated. Over 87% of respondents agreed that composite measures reflect the multidimensional aspect of the surgical process more than an individual outcome variable. Most respondents (93%) agreed/strongly agreed that composite measures should be used to assess the quality of surgical care in spine oncology. Through consensus, the following three outcome variables were selected to define the OSCO-M: the absence of SAVES-V2 (Spinal Adverse Events Severity System, Version 2) Grade 3 adverse events or higher within 30 days of surgery, maintaining or improving ECOG (Eastern Cooperative Oncology Group) performance status at 90 days, and being ambulatory (with or without aid) at 90 days. CONCLUSION/CONCLUSIONS:This is the first study defining a composite outcome measure in oncologic surgery for spinal metastases derived from an international group of key opinion leaders in spine oncology. The OSCO-M may be useful for future research in spine tumor patients and serve as a benchmark to optimize outcomes.

PURPOSE/OBJECTIVE:To determine whether driver gene alterations in metastatic non-small cell lung carcinoma (NSCLC) spine metastases are associated with local tumor control after radiotherapy (RT). METHODS:Patients with NSCLC who underwent RT for spine metastasis and tumor genetic profiling were ascertained. Associations between driver gene mutations incidence of local failure were analyzed, followed by competing risk analysis for significant associations. The results were validated using in vitro clonal survival assays of CRISPR-engineered NSCLC cell lines. RESULTS:= .001). CONCLUSION/CONCLUSIONS:signaling pathway confer radioresistance in metastatic NSCLC. These genetic alterations may serve as biomarkers to personalize RT strategies or as targets to enhance radiosensitivity.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Pathological vertebral compression fractures (VCFs) cause significant morbidity in the population with cancer. Although both stabilization of fractures with kyphoplasty and pedicle screw fixation can alleviate pain and prevent neurological compromise in select patients, there are no criteria demarcating which patients can be treated with kyphoplasty alone vs pedicle screw fixation, particularly for those with intermediate spinal instability. The objective of this study was to identify predictors of kyphoplasty failure requiring subsequent surgical stabilization in patients with metastatic thoracolumbar VCFs. METHODS:Patients who underwent single or 2 level kyphoplasty for pathological VCFs between 2015 and 2020 were included in a retrospective analysis at a tertiary cancer center. The primary outcome measure was kyphoplasty failure, defined as return to the operating room for pedicle screw fixation. Hazard ratios (HR) were estimated in the competing risks setting. Thresholds for variables were identified where possible. RESULTS:Forty-two of 445 patients (9.8%) failed kyphoplasty, with an average time to failure of 318 days and a 5-year cumulative incidence of 10.3% (95% CI: 7.5%-13.6%). We found focal kyphotic angle (HR 1.09, 95% CI: 1.05-1.12, P < .0001), Spinal instability neoplastic score (HR 1.16, 95% CI: 1.05-1.28, P = .03), spinal canal compromise (HR 1.05, 95% CI: 1.03-1.07, P < .0001), and posterior element involvement (HR 1.93, 95% CI: 1.03-5.63, P = .04) to be significantly associated with increased risk of kyphoplasty failure even after mutual adjustment in the multivariable setting. There were no significant associations between kyphoplasty failure and sex, age at kyphoplasty, anatomic location, or quality of bone lesion. CONCLUSION/CONCLUSIONS:Kyphoplasty failure in metastatic VCFs is associated with specific radiographic markers of spinal instability. Patients with spinal instability neoplastic score ≥11, posterior-element involvement, canal compromise, and significant kyphosis may benefit from up-front surgical stabilization with pedicle screws, particularly for patients with anticipated long-term survival.

BACKGROUND AND OBJECTIVES/OBJECTIVE:The Patient-Generated Subjective Global Assessment (PG-SGA) is a standardized tool for assessing malnutrition in patients with cancer. The primary aim of this study was to assess the impact of preoperative nutritional status as measured by PG-SGA on survival in patients requiring surgical intervention and/or radiotherapy for spinal metastases. METHODS:Patients with spinal metastases who underwent surgery and/or radiation therapy for symptomatic spinal metastases were enrolled in the AO Spine Metastatic Tumor Research and Outcomes Network, a prospective international multicenter research registry, between September 2017 and August 2022. Using the PG-SGA, nutritional status was classified into 3 categories: A, well nourished; B, moderately malnourished; and C, severely malnourished. RESULTS:A total of 589 patients met the inclusion criteria; 362 were classified as well nourished (61%), 159 were moderately malnourished (27%), and 68 were severely malnourished (12%). The median survival was 491 days, 328 days, and 117 days for well-nourished, moderately malnourished, and severely malnourished patients, respectively. In the multivariate analyses, severe malnourishment (HR 2.5 95% CI 1.4-4.3, P < .01) and an ECOG performance status of 3 or 4 (HR 2.7 95% CI 1.2-6.0) remained associated with significantly worse survival. CONCLUSION/CONCLUSIONS:Malnutrition as measured by the PG-SGA demonstrated to be significantly and independently associated with postoperative survival. The PG-SGA is a simple and useful tool to identify spinal metastases patients at risk of early postoperative mortality, and inclusion in the preoperative evaluation of these patients should be considered.

PURPOSE/OBJECTIVE:Spine stereotactic body radiation therapy (SBRT) outperforms conventional radiation therapy in preventing local failure (LF). Data comparing dose-fractionation schemes on the likelihood of LF and vertebral compression fracture (VCF) are limited. METHODS AND MATERIALS/METHODS:This is a retrospective cohort study of 1838 patients (2702 lesions) treated between 2014 and 2023 at a single institution with de novo spine SBRT. LF was defined as progressive disease on magnetic resonance imaging. VCF was defined as progressive or new fracture on magnetic resonance imaging without LF. Death was considered a competing risk. RESULTS:Median follow-up after SBRT for surviving patients was 25 months (IQR 13-43 months). Eleven hundred ninety-seven lesions (44%) received 27 Gy in 3 fractions, 931 (34%) received 30 Gy in 3 fractions, and 574 lesions (21%) received 24 Gy in 1 fraction. Three hundred nine treatment courses involved separation surgery (11%), and 311 lesions (11%) were epidural spinal cord compression score 2 to 3. For lesions treated with 24 Gy in 1 fraction, 30 Gy in 3 fractions, and 27 Gy in 3 fractions, 2-year LF rates (95% CI) were 7% (5%-9%), 11% (9%-13%), and 17% (15%-20%), respectively (P < .001). Two-year VCF rates (95% CI) requiring stabilization were 10% (8%-13%; 24 Gy in 1 fraction), 2% (1%-3%; 27 Gy in 3 fractions), and 3% (2%-5%; 30 Gy in 3 fractions) (P < .001). For the 3-fraction regimens specifically, 30 Gy was associated with a higher overall VCF rate (P = .022) and lower LF rate (P < .001), but there was no significant difference in the risk of VCF requiring intervention (P = .15). Univariable and multivariable regression revealed histologic-based differences in LF: 2-year LF rates were 8.6% (95% CI, 6.4%-11%) for class A lesions (prostate and breast cancers), 26% (95% CI, 20%-32%) for class C lesions (cholangio-, hepatocellular, and colorectal carcinoma), and 13% (95% CI, 12%-15%) for class B lesions (other histologies) (P < .001). For class B to C, epidural spinal cord compression 2 to 3 lesions (n = 261), surgery plus SBRT reduced LF compared to SBRT alone (7.9 vs 20% at 2 years, P = .051), though this did not reach statistical significance. CONCLUSIONS:The preferred hypofractionated SBRT regimen-even for class A histologies-is 30 Gy in 3 fractions, offering superior local control with similar risk of VCF requiring intervention, compared to 27 Gy. For class B to C lesions with high-grade epidural disease, separation surgery prior to SBRT may improve local control.