Faculty Bibliography
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123
Impact of RAS-MAPK Pathway Genetic Alterations on Radiotherapy Response in Metastatic Lung Adenocarcinoma
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.
PMCID:12695007
PMID: 41348985
ISSN: 2473-4284
CID: 6014692
Predictors of Kyphoplasty Failures Requiring Surgical Stabilization in Patients With Cancer With Pathological Vertebral Body Fractures
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.
PMID: 41217376
ISSN: 1524-4040
CID: 6014672
Robotic Resection of Spinal and Paraspinal Tumors
BACKGROUND AND OBJECTIVES/OBJECTIVE:Robotic arm surgical systems provide minimally invasive access and are commonly used in multiple surgical fields, with limited application in neurosurgery. Our institutional experience has led us to explore the benefits of a neurosurgeon trained to perform robotic surgery as part of a multidisciplinary team. The objective of this study is to evaluate the feasibility, safety, and outcomes of robotic resection for spinal nerve sheath tumors (NST). METHODS:Retrospective case series of robotic-assisted intracavitary approaches and resection of NSTs including thoracic, retroperitoneal, and transperitoneal. Surgical outcomes are compared to a historical cohort of open surgical resection of NSTs. RESULTS:Nineteen cases presented, of which 2 were combined posterior spinal followed by robotic tumor resection. One of 19 cases was converted to an open surgery. Gross total resection was achieved in all cases. There were 2 cases of postoperative Horner's syndrome, and 1 case with an intraoperative durotomy that was repaired primarily with no postoperative sequelae. Median estimated blood loss was 50 cc (range: 5-650) and median length of stay was 1 day (range: 0-6), with 9 (47.4%) patients discharged on postoperative day 1 and 3 (15.8%) patients discharged on an outpatient basis. Compared with our previously reported institutional outcomes for open resection of 25 tumors, there was a significant increase in rates of gross total resection (100 vs 60%, P = .002) and decrease in length of stay (median 1 vs 5 days, P < .0001). CONCLUSION/CONCLUSIONS:Robotic resection of complex paraspinal tumors appears safe and effective including for preservation of neurological function and may reduce surgical morbidity. Integration of robotic surgical platforms holds the potential to significantly affect neurological surgery.
PMCID:12519572
PMID: 39162431
ISSN: 2332-4260
CID: 6014602
International journal of radiation oncology biology physics. 2025:123(3):829-838.DOI: 10.1016/j.ijrobp.2025.05.078
Histologic Classifier of Radiosensitivity to Spine Stereotactic Body Radiation Therapy
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.
PMID: 40516631
ISSN: 1879-355x
CID: 6014652
Canadian journal of surgery = Journal canadien de chirurgie. 2025:68(6suppl3):S58-S132.DOI: 10.1503/cjs.020125
Canadian Spine Society: 25th Annual Scientific Conference, February 25 to 28, 2025, Fairmont Le Manoir Richelieu, La Malbaie, Charlevoix, Que., Canada
PMID: 41386990
ISSN: 1488-2310
CID: 5978112
Association Between Nutritional Status and Survival in Patients Requiring Treatment for Spinal Metastases
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.
PMID: 41196049
ISSN: 1524-4040
CID: 5960062
An International Delphi Consensus on Defining the Optimal Surgical Composite Outcome in Metastatic Spine Disease (OSCO-M)
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.
PMID: 40851377
ISSN: 1528-1159
CID: 5909872
Impact of surgery and radiation on radicular pain and myotomic weakness in patients with metastatic spine disease
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: Reducing the Surgical Footprint of Surgery for Spinal Metastases
Study DesignLiterature review with clinical recommendations.ObjectiveSpinal metastases represent a late complication of cancer and a major factor in decreased quality of life. The role of surgery for specific indications for spinal metastases is well established. Given the significant morbidity associated with spine surgery in this frail population, efforts are ongoing to decrease the surgical footprint. The objective of this study is to provide the readers with a concise curation of the latest spine literature on reducing the surgical footprint for spine metastases and clinical recommendations for how the practicing clinician should interpret and make use of this evidence.MethodsThe latest spine literature in the topic of reducing the surgical footprint for spine metastases was reviewed and clinical recommendations were formulated. The recommendations are dichotomously graded into strong and conditional based on the integration of scientific methodology and content expert opinion. This opinion considers experience and practical issues such as risks, burdens, costs, patient values, and circumstances.ResultsFour high impact studies were selected for review. The findings suggest that surgery plays a key role in improving patients' quality of life, but incidence of adverse events remains high and hence methods to decrease surgical morbidity are necessary. The integration of radiation into the treatment algorithm allows for less extensive surgical procedures and SBRT should be strongly considered after surgery for spine metastases in appropriate patient populations. Implementation of enhanced recovery after surgery (ERAS) protocols reduce perioperative morbidity for both open and minimally invasive surgeries and should be considered on an institutional level. Utilization of minimally invasive surgical stabilization should be considered as it results in fewer post operative complications, lower infection rates, less blood loss during surgery, and a shorter hospital stay compared to open stabilization of unstable pathology thoracolumbar fractures.ConclusionsThe role and benefits of surgery for metastatic spine disease are well established, yet surgery carries significant risk for adverse events which may negatively affect overall cancer care. Methods for reducing the surgical footprint include incorporation of stereotactic radiation allowing less extensive surgery, implementation of ERAS protocols and utilization of minimally invasive surgical strategies.
PMCID:12170550
PMID: 40521797
ISSN: 2192-5682
CID: 5870732
Evaluation of Adverse Events and the Impact on Health-Related Outcomes in Patients Undergoing Surgery for Metastatic Spine Tumors: Analysis of the Metastatic Tumor Research and Outcomes Network (MTRON) Registry Dataset
Study DesignThis study is part of the AO Spine Metastatic Tumor Research and Outcomes Network [MTRON], an international multicenter prospective observational registry including patients with spinal metastases.ObjectivesThis study aims to elucidate the incidence of surgical complications, their risk factors and consequent effects on survival outcomes, hospital length of stay, and overall health-related quality of life (HRQOL) parameters in a large cohort of patients affected by spinal metastases who were surgically treated.MethodsAvailable data from February 2017 to July 2023 were analyzed. The primary outcome of this study was the evaluation of the incidence of intraoperative and postoperative adverse events (AEs). The secondary outcomes included the assessment of risk factors for surgery-related AEs and the impact of AEs on survival, length of hospital stay and quality of life.ResultsAmong the 1267 patients analyzed, 6.9% experienced intraoperative AEs and 19.3% experienced at least 1 postoperative AE. Several factors resulted to be associated to the occurrence of postoperative AEs: age, smoking habit, poor Eastern Cooperative Oncology Group (ECOG) Performance status, previous radiation therapy at the index target, duration of surgery, number of instrumented levels, simultaneous anterior and posterior approach, presence of metastases at other sites, multiple spinal metastases. Postoperative AEs were associated with reduced survival rates, increased hospital length of stay and poorer HRQOL outcomes, particularly in domains such as neurological function and mental health. In general, surgery substantially improves HRQOL across multiple domains, with these benefits persisting over time despite the occurrence of AEs. However, patients with preoperative risk factors, including comorbidities, smoking, neurological impairment, and prior radiation therapy, experienced less improvement.ConclusionsThe negative impact of AEs on overall survival and HRQOL could be associated with the presence of some preoperative parameters of frailty that are detected as risk factors for AEs occurrence. This finding emphasizes the need for personalized preoperative assessments and optimized perioperative care strategies.
PMID: 40480956
ISSN: 2192-5682
CID: 5862952
