Stereotactic radiosurgery for spinal metastases with or without separation surgery.

OBJECT: In patients with significant epidural spinal cord compression, initial surgical decompression and stabilization of spinal metastases, as opposed to radical oncological resection, provides a margin around the spinal cord that facilitates subsequent treatment with high-dose adjuvant stereotactic radiosurgery (SRS). If a safe margin exists between tumor and spinal cord on initial imaging, then high-dose SRS may be used as the primary therapy, eliminating the need for surgery. Selecting the appropriate approach has shown greater efficacy of tumor control, neurological outcome, and duration of response when compared with external beam radiotherapy, regardless of tumor histology. This study evaluates the efficacy of this treatment approach in a series of 57 consecutive patients. METHODS: Patients treated for spinal metastases between 2007 and 2011 using the Varian Trilogy Linear Accelerator were identified retrospectively. Each received SRS, with or without initial surgical decompression and instrumentation. Medical records were reviewed to assess neurological outcome and surgical or radiation-induced complications. Magnetic resonance images were obtained for each patient at 3-month intervals posttreatment, and radiographic response was assessed as stability/regression or progression. End points were neurological outcome and local radiographic disease control at death or latest follow-up. RESULTS: Fifty-seven patients with 69 lesions were treated with SRS for spinal metastases. Forty-eight cases (70%) were treated with SRS alone, and 21 (30%) were treated with surgery prior to SRS. A single fraction was delivered in 38 cases (55%), while a hypofractionated scheme was used in 31 (45%). The most common histological entities were renal cell, breast, and lung carcinomas. Radiographically, local disease was unchanged or regressed in 63 of 69 tumors (91.3%). Frankel score improved or remained stable in 68 of 69 cases (98.6%). CONCLUSIONS: SRS, alone or as an adjunct following surgical decompression, provides durable local radiographic disease control while preserving or improving neurological function. This less-invasive alternative to radical spinal oncological resection appears to be effective regardless of tumor histology without sacrificing durability of radiographic or clinical response.

Repeat Gamma Knife surgery for trigeminal neuralgia: long-term results.

OBJECT: The purpose of this study was to assess the long-term outcome achieved after repeat Gamma Knife surgery (GKS) for trigeminal neuralgia (TN) using a uniform treatment plan. METHODS: Between 1985 and 2010, 53 patients underwent repeat GKS for refractory TN. In the initial GKS, which involved targeting the root entry zone of the trigeminal nerve, a maximal dose of 80 Gy was used with a 4-mm collimator so that the 50% isodose line abutted the pons. In the second GKS, the treatment plan consisted of a 70-Gy dose directed at a target 4-5 mm distal to the first target on the trigeminal nerve. The mean follow-up duration in these patients was 42 months. Outcomes were defined using the Marseille scale: excellent (Class I or II, no pain with or without medications), good (Class III or IV, ≥ 50% relief), and poor (Class V, < 50% relief). RESULTS: Trigeminal neuralgia pain was controlled (≥ 50% improvement with or without medications) after repeat GKS in 70% of patients at 1 year, 50% at 3 years, 50% at 5 years, and 50% at 10 years, as defined by a Kaplan-Meier analysis. A correlation was found between facial numbness and pain relief (p = 0.047). No difference was found between patients with Type 1 TN and those with Type 2 TN, and there was no correlation between the best relief obtained and long-term durability of relief from pain. Twenty-two patients (47.8%) described their trigeminal dysfunction in the following manner: numbness (45.6%), dry eye (10.9%), taste change (8.7%), or jaw weakness (2.2%). In only 8.7% of cases did the patient experience facial numbness that was regarded as bothersome. CONCLUSIONS: Repeat GKS for TN at the doses used provides substantial long-term relief. Treatment failure occurred up to 28 months after the second GKS. Facial numbness correlated with more durable pain relief after repeat GKS in this series.

Lentiviral gene therapy with platelet-derived growth factor B sustains accelerated healing of diabetic wounds over time.

The treatment of diabetic wounds is a formidable clinical challenge. In this study, lentiviral vectors carrying the human platelet-derived growth factor B (PDGF-B) gene were used to treated diabetic mouse wounds. Full-thickness 2.0-cm x 2.0-cm excisional wounds were created on the dorsa of genetically diabetic C57BL/KsJ-m+/+Lepr(db) mice. Lentiviral vectors containing the PDGF-B gene were injected into the wound margins and base. Mice were killed at 14-, 21-, and 35-day intervals. Measurement of the residual epithelial gap showed a trend towards increased healing in lentiviral PDGF-treated wounds compared with untreated and saline-treated wounds at all time points. At 21 days, there was significantly increased healing in lentiviral PDGF-treated wounds (0.98+/-0.17 cm) compared with saline-treated wounds (1.22+/-0.30 cm; P<0.05). Immunohistochemistry for CD31 revealed significantly increased neovascularization in lentiviral PDGF-treated wounds compared with untreated and saline-treated wounds at 14 and 21 days (P<0.01). Picrosirius red staining demonstrated thicker and more highly organized collagen fibers in treated wounds compared with untreated and saline-treated wounds. Quantitative analysis of collagen content showed a 3.5-fold and 2.3-fold increase in lentiviral PDGF-treated wounds versus untreated and saline-treated wounds, respectively (P<0.01). Lentiviral gene therapy with PDGF-B can sustain diabetic wound healing over time and may possess promising potential in the clinical setting.