Faculty Bibliography

BACKGROUND: Patients with small-cell lung cancer have a high likelihood of developing brain metastases. Many of these patients will have prophylactic cranial irradiation (PCI) or eventually undergo whole brain radiation therapy (WBRT). Despite these treatments, a large number of these patients will have progression of their intracranial disease and require additional local therapy. Stereotactic radiosurgery (SRS) is an important treatment option for such patients. METHODS: We retrospectively reviewed the charts of 44 patients with brain metastases from small-cell lung cancer treated with gamma knife SRS. Multivariate analysis was used to determine significant prognostic factors influencing survival. RESULTS: The median follow-up from SRS in this patient population was 9 months (1-49 months). The median overall survival (OS) was 9 months after SRS. Karnofsky performance status (KPS) and combined treatment involving WBRT and SRS within 4 weeks were the two factors identified as being significant predictors of increased OS (p = 0.033 and 0.040, respectively). When comparing all patients, patients treated with a combined approach had a median OS of 14 months compared to 6 months if SRS was delivered alone. We also compared the OS times from the first definitive radiation: WBRT, WBRT and SRS if combined therapy was used, and SRS if the patient never received WBRT. The median survival for those groups was 12, 14, and 13 months, respectively, p = 0.19. Seventy percent of patients had follow-up magnetic resonance imaging available for review. Actuarial local control at 6 months and 12 months was 90% and 86%, respectively. Only 1 patient (2.2%) had symptomatic intracranial swelling related to treatment, which responded to a short course of steroids. New brain metastases outside of the treated area developed in 61% of patients at a median time of 7 months; 81% of these patients had received previous WBRT. CONCLUSIONS: Stereotactic radiosurgery for small-cell lung carcinoma brain metastases provided safe and effective local tumor control in the majority of patients.

BACKGROUND: A significant number of patients with major depressive disorder are unresponsive to conventional therapies. For these patients, neuromodulation approaches are being investigated. OBJECTIVE: To determine whether epidural cortical stimulation at the left dorsolateral prefrontal cortex is safe and efficacious for major depressive disorder through a safety and feasibility study. METHODS: Twelve patients were recruited in this randomized, single-blind, sham-controlled study with a 104-week follow-up period. The main outcome measures were Hamilton Depression Rating Scale-28 (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Function (GAF), and Quality of Life Enjoyment and Satisfaction (QLES) questionnaire. An electrode was implanted over Brodmann area 9/46 in the left hemisphere. The electrode provided long-term stimulation to this target via its connections to an implanted neurostimulator in the chest. RESULTS: During the sham-controlled phase, there was no statistical difference between sham and active stimulation, although a trend toward efficacy was seen with the active stimulation group. In the open-label phase, we observed a significant improvement in outcome scores for the HDRS, MADRS, and GAF but not the QLES (HDRS: df = 7, F = 7.72, P < .001; MADRS: df = 7, F = 8.2, P < .001; GAF: df = 5, F = 16.87, P < .001; QLES: df = 5, F = 1.32, P > .2; repeated measures ANOVA). With regard to the HDRS, 6 patients had >/= 40% improvement, 5 patients had >/= 50% improvement, and 4 subjects achieved remission (HDRS < 10) at some point during the study. CONCLUSION: Epidural cortical stimulation of the left dorsolateral prefrontal cortex appears to be a safe and potentially efficacious neuromodulation approach for treatment-refractory major depressive disorder.

Stereotactic radiosurgery is used for many neoplastic, vascular, and functional disorders of the nervous system. The expanded use of this technique over the past two decades is based mainly on the spectrum of clinical research performed for these disorders. From case series to randomized trials, the safety and efficacy of radiosurgery is well documented. In this report, we discuss the key indications for radiosurgery and the kinds of research performed in this field.