Vertebral Compression Fracture After Spine Stereotactic Body Radiotherapy: The Role of Vertebral Endplate Disruption.

BACKGROUND AND OBJECTIVES: Vertebral compression fracture (VCF) is a common, but serious toxicity of spinal stereotactic body radiotherapy (SBRT). Several variables that place patients at high risk of VCF have previously been identified, including advanced Spinal Instability Neoplastic Score (SINS), a widely adopted clinical decision criterion to assess spinal instability. We examine the role of tumoral endplate (EP) disruption in the risk of VCF and attempt to incorporate it into a simple risk stratification system. METHODS: This study was a retrospective cohort study from a single institution. Demographic and treatment information was collected for patients who received spinal SBRT between 2013 and 2019. EP disruption was noted on pre-SBRT computed tomography scan. The primary end point of 1-year cumulative incidence of VCF was assessed on follow-up MRI and computed tomography scans at 3-month intervals after treatment. RESULTS: A total of 111 patients were included. The median follow-up was 18 months. Approximately 48 patients (43%) had at least one EP disruption. Twenty patients (18%) experienced a VCF at a median of 5.2 months from SBRT. Patients with at least one EP disruption were more likely to experience VCF than those with no EP disruption (29% vs 6%, P < .001). A nomogram was created using the variables of EP disruption, a SINS of ≥7, and adverse histology. Patients were stratified into groups at low and high risk of VCF, which were associated with 2% and 38% risk of VCF ( P < .001). CONCLUSION: EP disruption is a novel risk factor for VCF in patients who will undergo spinal SBRT. A simple nomogram incorporating EP disruption, adverse histology, and SINS score is effective for quickly assessing risk of VCF. These data require validation in prospective studies and could be helpful in counseling patients regarding VCF risk and referring for prophylactic interventions in high-risk populations.

Carole A. Miller, MD: Matriarch of the Ohio State University's Department of Neurosurgery.

Carole A. Miller, M.D., was born (May 7, 1939) and raised in Kalamazoo, Michigan. She obtained her undergraduate and medical degrees at the Ohio State University. She went on to complete her neurosurgical training at the Ohio State University Medical Center. After her first faculty role at the University of Michigan (1971), she returned to the Ohio State University Medical Center (1975) where she spent nearly 4 decades. She thrived in the specialty, achieving in every facet of academic practice including scientific contributions, graduate medical education, clinical care, and leadership roles within her academic department, locally, and at the national level of organized neurosurgery. Dr. Miller passed away peacefully, on October 28, 2015, after a courageous battle with cancer. Based on her essential programmatic and specialty-related contributions, she is remembered as the 'founding mother' of neurosurgery at the Ohio State University.

Targeting neural precursors in the adult brain rescues injured dopamine neurons.

In Parkinson's disease, multiple cell types in many brain regions are afflicted. As a consequence, a therapeutic strategy that activates a general neuroprotective response may be valuable. We have previously shown that Notch ligands support neural precursor cells in vitro and in vivo. Here we show that neural precursors express the angiopoietin receptor Tie2 and that injections of angiopoietin2 activate precursors in the adult brain. Signaling downstream of Tie2 and the Notch receptor regulate blood vessel formation. In the adult brain, angiopoietin2 and the Notch ligand Dll4 activate neural precursors with opposing effects on the density of blood vessels. A model of Parkinson's disease was used to show that angiopoietin2 and Dll4 rescue injured dopamine neurons with motor behavioral improvement. A combination of growth factors with little impact on the vasculature retains the ability to stimulate neural precursors and protect dopamine neurons. The cellular and pharmacological basis of the neuroprotective effects achieved by these single treatments merits further analysis.