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Studies of experimental cervical spinal cord transection

Part I: Hemodynamic changes after acute cervical spinal cord transection

Phillip A. Tibbs, Byron Young, R. G. McAllister Jr., William H. Brooks, and Laddie Tackett

✓ Two distinct and sequential patterns of hemodynamic alteration were observed after acute cervical spinal cord transection in anesthetized dogs. Interruption of the cord initially caused a 45% increase in mean arterial pressure (p < 0.01), a 34% increase in systemic vascular resistance (p < 0.05), and a 92% increase in left ventricular dp/dt (p < 0.01), reflecting a generalized sympathetic response to trauma. Concomitant bradycardia and escape arrhythmias suggested relative parasympathetic hyperactivity. Resolution of the brief pressor response was followed by a second, more prolonged, period characterized by a fall in arterial pressure to 71% of control levels (p < 0.05), a 16% decrease in systemic vascular resistance, and a 58.5% decrease in left ventricular dp/dt (p < 0.01). These latter hemodynamic changes are consistent with sympathetic denervation and failure of regulatory mechanisms mediated by both alpha- and beta-adrenergic peripheral vascular and myocardial receptors.

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Roman O. Kowalchuk, Michael R. Waters, K. Martin Richardson, Kelly Spencer, James M. Larner, William H. McAllister, Jason P. Sheehan, and Charles R. Kersh

OBJECTIVE

This study evaluated a large cohort of patients treated with stereotactic body radiation therapy for spinal metastases and investigated predictive factors for local control, local progression-free survival (LPFS), overall survival, and pain response between the different spinal regions.

METHODS

The study was undertaken via retrospective review at a single institution. Patients with a tumor metastatic to the spine were included, while patients with benign tumors or primary spinal cord cancers were excluded. Statistical analysis involved univariate analysis, Cox proportional hazards analysis, the Kaplan-Meier method, and machine learning techniques (decision-tree analysis).

RESULTS

A total of 165 patients with 190 distinct lesions met all inclusion criteria for the study. Lesions were distributed throughout the cervical (19%), thoracic (43%), lumbar (19%), and sacral (18%) spines. The most common treatment regimen was 24 Gy in 3 fractions (44%). Via the Kaplan-Meier method, the 24-month local control was 80%. Sacral spine lesions demonstrated decreased local control (p = 0.01) and LPFS (p < 0.005) compared with those of the thoracolumbar spine. The cervical spine cases had improved local control (p < 0.005) and LPFS (p < 0.005) compared with the sacral spine and trended toward improvement relative to the thoracolumbar spine. The 36-month local control rates for cervical, thoracolumbar, and sacral tumors were 86%, 73%, and 44%, respectively. Comparably, the 36-month LPFS rates for cervical, thoracolumbar, and sacral tumors were 85%, 67%, and 35%, respectively. A planning target volume (PTV) > 50 cm3 was also predictive of local failure (p = 0.04). Fewer cervical spine cases had disease with PTV > 50 cm3 than the thoracolumbar (p = 5.87 × 10−8) and sacral (p = 3.9 × 10−3) cases. Using decision-tree analysis, the highest-fidelity models for predicting pain-free status and local failure demonstrated the first splits as being cervical and sacral location, respectively.

CONCLUSIONS

This study presents a novel risk stratification for local failure and LPFS by spinal region. Patients with metastases to the sacral spine may have decreased local control due to increased PTV, especially with a PTV of > 50 cm3. Multidisciplinary care should be emphasized in these patients, and both surgical intervention and radiotherapy should be strongly considered.