Reliability of the Spinal Instability Neoplastic Score (SINS) among radiation oncologists: an assessment of instability secondary to spinal metastases

BACKGROUND: The Spinal Instability Neoplastic Score (SINS) categorizes tumor related spinal instability. It has the potential to streamline the referral of patients with established or potential spinal instability to a spine surgeon. This study aims to define the inter- and intra-observer reliability and validity of SINS among radiation oncologists. METHODS: Thirty-three radiation oncologists, across ten international sites, rated 30 neoplastic spinal disease cases. For each case, the total SINS (0-18 points), three clinical categories (stable: 0-6 points, potentially unstable: 7-12 points, and unstable: 13-18 points), and a binary scale (‘stable’: 0-6 points and ‘current or possible instability’; surgical consultation recommended: 7-18 points) were recorded. Evaluation was repeated 6-8 weeks later. Inter-observer agreement and intra-observer reproducibility were calculated by means of the kappa statistic and translated into levels of agreement (slight, fair, moderate, substantial, and excellent). Validity was determined by comparing the ratings against a spinal surgeon’s consensus standard. RESULTS: Radiation oncologists demonstrated substantial (κ = 0.76) inter-observer and excellent (κ = 0.80) intra-observer reliability when using the SINS binary scale (‘stable’ versus ‘current or possible instability’). Validity of the binary scale was also excellent (κ = 0.85) compared with the gold standard. None of the unstable cases was rated as stable by the radiation oncologists ensuring all were appropriately recommended for surgical consultation. CONCLUSIONS: Among radiation oncologists SINS is a highly reliable, reproducible, and valid assessment tool to address a key question in tumor related spinal disease: Is the spine ‘stable’ or is there ‘current or possible instability’ that warrants surgical assessment

Spinal Metastases and the Evolving Role of Molecular Targeted Therapy, Chemotherapy, and Immunotherapy

Metastatic involvement of the spine is a common complication of systemic cancer progression. Surgery and external beam radiotherapy are palliative treatment modalities aiming to preserve neurological function, control pain and maintain functional status. More recently, with development of image guidance and stereotactic delivery of high doses of conformal radiation, local tumor control has improved; however recurrent or radiation refractory disease remains a significant clinical problem with limited treatment options. This manuscript represents a narrative overview of novel targeted molecular therapies, chemotherapies, and immunotherapy treatments for patients with breast, lung, melanoma, renal cell, prostate, and thyroid cancers, which resulted in improved responses compared to standard chemotherapy. We present clinical examples of excellent responses in spinal metastatic disease which have not been specifically documented in the literature, as most clinical trials evaluate treatment response based on visceral disease. This review is useful for the spine surgeons treating patients with metastatic disease as knowledge of these responses could help with timing and planning of surgical interventions, as well as promote multidisciplinary discussions, allowing development of an individualized treatment strategy to patients presenting with widespread multifocal progressive disease, where surgery could lead to suboptimal results

Prognostic Molecular Biomarkers in Chordomas: A Systematic Review and Identification of Clinically Usable Biomarker Panels

INTRODUCTION AND OBJECTIVE: Despite the improvements in management and treatment of chordomas over time, the risk of disease recurrence remains high. Consequently, there is a push to develop effective systemic therapeutics for newly diagnosed and recurrent disease. In order to tailor treatment for individual chordoma patients and develop effective surveillance strategies, suitable clinical biomarkers need to be identified. The objective of this study was to systematically review all prognostic biomarkers for chordomas reported to date in order to classify them according to localization, study design and statistical analysis. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed published studies reporting biomarkers that correlated with clinical outcomes. We included time-to-event studies that evaluated biomarkers in skull base or spine chordomas. To be included in our review, the study must have analyzed the outcomes with univariate and/or multivariate methods (log-rank test or a Cox-regression model). RESULTS: We included 68 studies, of which only 5 were prospective studies. Overall, 103 biomarkers were analyzed in 3183 patients. According to FDA classification, 85 were molecular biomarkers (82.5%) mainly located in nucleus and cytoplasm (48% and 27%, respectively). Thirty-four studies analyzed biomarkers with Cox-regression model. Within these studies, 32 biomarkers (31%) and 22 biomarkers (21%) were independent prognostic factors for PFS and OS, respectively. CONCLUSION: Our analysis identified a list of 13 biomarkers correlating with tumor control rates and survival. The future point will be gathering all these results to guide the clinical validation for a chordoma biomarker panel. Our identified biomarkers have strengths and weaknesses according to FDA\u27s guidelines, some are affordable, have a low-invasive collection method and can be easily measured in any health care setting (RDW and D-dimer), but others molecular biomarkers need specialized assay techniques (microRNAs, PD-1 pathway markers, CDKs and somatic chromosome deletions were more chordoma-specific). A focused list of biomarkers that correlate with local recurrence, metastatic spread and survival might be a cornerstone to determine the need of adjuvant therapies

Fadu Head and Neck Squamous Cell Carcinoma Induces Hyperexcitability of Primary Sensory Neurons in an In Vitro Coculture Model

Introduction: Currently, cancer pain is viewed as a process orchestrated by the release of pronociceptive molecules and the invasion of neural structures, referred to as perineural invasion (PNI). Cancer pain resulting from PNI is well-documented, but the mechanisms leading to peripheral sensitization because of tumor growth are not fully known. Methods: A retrospective study was used to examine how the use of anti-inflammatory medications affected preoperative pain in patients with oral squamous cell carcinoma cancer. We then used an in vitro coculture model in which dorsal root ganglion (DRG) neurons were incubated together with Fadu human head and neck squamous cell carcinoma cancer cells to explore how cancer cells affect the electrical membrane properties of sensory neurons. Results: We found that inflammation contributes to preoperative pain in patients with oral squamous cell carcinoma. After coculture with Fadu human head and neck squamous cell carcinoma cancer cells, we identified markers of inflammation in coculture media and found evidence of neuronal sensitization, including spontaneous activity, reduced current thresholds, depolarized resting membrane potential, and enhanced responses to current stimulation in human and rat DRG neurons. In rats, these effects were influenced by sex and age: neurons from young adult female rats were resistant to changes in neuronal activity, in contrast to neurons from older adult female rats or male rats of either age group. Conclusions: Pro-inflammatory substances released in cancer cell-DRG coculture promoted neuronal hyperexcitability and may contribute to cancer pain after PNI, and these effects may differ across age groups and sexes

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

Advances in the Management of Spinal Metastases: What the Radiologist Needs to Know

Spine is the most frequently involved site of osseous metastases. With improved disease-specific survival in patients with Stage IV cancer, durability of local disease control has become an important goal for treatment of spinal metastases. Herein, we review the multidisciplinary management of spine metastases, including conventional external beam radiation therapy, spine stereotactic radiosurgery, and minimally invasive and open surgical treatment options. We also present a simplified framework for management of spinal metastases used at The University of Texas MD Anderson Cancer Center, focusing on the important decision points where the radiologist can contribute

Multidisciplinary Management of Spinal Metastases: What the Radiologist Needs To Know

The modern management of spinal metastases requires a multidisciplinary approach that includes radiation oncologists, surgeons, medical oncologists, and diagnostic and interventional radiologists. The diagnostic radiologist can play an important role in the multidisciplinary team and help guide assessment of disease and selection of appropriate therapy. The assessment of spine metastases is best performed on MRI, but imaging from other modalities is often needed. We provide a review of the clinical and imaging features that are needed by the multidisciplinary team caring for patients with spine metastases and stress the importance of the spine radiologist taking responsibility for synthesizing imaging features across multiple modalities to provide a report that advances patient care

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

Study Design: Narrative Review. Objectives: To summarize the work of the AO Spine Knowledge Forum Tumor, specifically studies from the Epidemiology, Process and Outcomes in Spine Oncology (EPOSO) study. Methods: A 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. Results: The 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. Conclusions: Several 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.</p