Preoperative radiosurgery for brain metastases (PREOP-1): A feasibility trial.

Purpose: Preoperative radiosurgery (SRS) of brain metastases (BM) aims to achieve cavity local control with a reduction in leptomeningeal relapse (LMD) and without additional radionecrosis compared to postoperative SRS. We present the final results of a prospective feasibility trial of linac-based stereotactic radiosurgery (SRS) prior to neurosurgical resection of a brain metastasis (PREOP-1). Methods: Eligibility criteria included a BM up to 4 cm in diameter for elective resection. The primary endpoint was the feasibility of delivering linac-based preoperative SRS in all patients prior to anticipated gross tumour resection. Secondary endpoints included rates of LMD, local control and overall survival. Exploratory endpoints were the level of expression of immunological and proliferative markers. Results: Thirteen patients of median age 65 years (range 41-77) were recruited. Twelve patients (92 %) received preoperative radiosurgery and metastasectomy and one patient went directly to surgery and received postoperative SRS, thus the primary endpoint was not met. The median time between referral and preoperative SRS was 6.5 working days (1-10) and from SRS to neurosurgery was 1 day (0-5). The median prescribed dose was 16 Gy (14-19) to a median planning target volume of 12.7 cm3 (5.9-26.1). Five patients completed 12-month follow-up after preoperative SRS without local recurrence or leptomeningeal disease. The patient who received postoperative FSRT developed LMD after six months. There was one transient toxicity (grade 2 alopecia) and nine patients have died from extracranial causes. Patients reported significant improvement in motor weakness at 6 months (P = 0.04). No pattern in changes of marker expression was observed. Conclusion: In patients with large brain metastasis without raised intracranial pressure, linac-based preoperative SRS was feasible in 12/13 patients and safe in 12/12 patients without any surgical delay or intracranial complications.

Five fraction stereotactic radiotherapy after brain metastasectomy: a single-institution experience and literature review.

PURPOSE: The outcomes of five fraction stereotactic radiotherapy (hfSRT) following brain metastasectomy were evaluated and compared with published series. METHODS: 30 Gy in 5 fractions HfSRT prescribed to the surgical cavity was reduced to 25 Gy if the volume of 'brain-GTV' receiving 20 Gy exceeded 20 cm3. Endpoints were local recurrence, nodular leptomeningeal recurrence, new brain metastases and radionecrosis. The literature was searched for reports of clinical and dosimetric outcomes following postoperative hfSRT in 3-5 fractions. RESULTS: 39 patients with 40 surgical cavities were analyzed. Cavity local control rate at 1 year was 33/40 (82.5%). 3 local failures followed 30 Gy/5 fractions and 4 with 25 Gy/5 fractions. The incidence of leptomeningeal disease (LMD) was 7/40 (17.5%). No grade 3-4 toxicities, particularly no radionecrosis, were reported. The incidence of distant brain metastases was 15/40 (37.5%). The median overall survival was 15 months. Across 13 published series, the weighted mean local control was 83.1% (adjusted for sample size), the mean incidence of LMD was 14.9% (7-34%) and the mean rate of radionecrosis was 10.3% (0-20.6%). CONCLUSION: Postoperative hfSRT can be delivered with 25-30 Gy in 5 fractions with efficacy in excess of 82% and no significant toxicity when the dose to 'brain-GTV' does not exceed 20 cm3.

Gamma Knife surgery for a hemangioma of the cavernous sinus in an adult: Case report and short review of the literature.

Cavernous sinus hemangiomas (CSH) are rare benign extra-axial vascular lesions. Both radiological and clinical aspects are important, for deciding a therapeutic modality, including medical treatment, radiation therapy or microsurgery. In the particular case of CSH, a radical removal of the tumor often cannot be achieved and is associated with a considerable risk for intraoperative uncontrollable bleeding. An alternative treatment modality is radiosurgery. Here we report the case of a 45-year-old patient, who presented with diplopia due to left abducens nerve palsy. A left-sided cavernous sinus lesion was found, initially considered to be a meningioma. However, after serial MR acquisitions, a progressive and heterogeneous enhancement was observed. In order to clarify the diagnosis between meningioma and hemangioma, a diagnostic Tc-99m labeled red blood cells (RBC) scintigraphy (Tc-99m RBC scintigraphy) was performed and showed a typical perfusion blood pool mismatch, with accumulation of the RBC at the level of the left CS, which is typical for a hemangioma. The patient underwent Gamma Knife surgery. The CSH showed a significant reduction in size starting 6 months after treatment and a full regression of the left abducens nerve palsy was observed within 1 year. These clinical and radiological results persisted over the next 3 years.

Susceptibility changes in meningiomas influence the apparent diffusion coefficient in diffusion-weighted MRI.

INTRODUCTION: Cell-dense tumors may restrict diffusivity which can be measured by diffusion-weighted MRI (DWI), and which is quantified by the apparent diffusion coefficient (ADC). Little is known about diffusivity in meningiomas. These tumors frequently show hemorrhage and calcification which can be demonstrated using susceptibility weighted MRI (SWI). Both DWI and SWI represent T2-derived MRI sequences. Here we investigated ADC variability in meningiomas and analyzed whether susceptibility changes (SWIpos) alter diffusivity. METHODS: We grouped newly diagnosed meningiomas according to the presence (SWIpos) or absence (SWIneg) of susceptibility changes. ADC values were calculated using region-of-interest analysis, and ADC values of SWIpos and SWIneg meningiomas were compared. In addition ADC histograms were created. RESULTS: We retrospectively studied 36 patients (13 WHO grade I, 8 WHO grade II, 15 suspected meningiomas). Thirteen meningiomas (36%) exhibited SWIpos. Global ADC values were higher in SWIpos (1.00 ± 0.15 × 10-3mm(2)/s) compared to SWIneg (0.82 ± 0.09 × 10-3mm(2)/s) tumors (P<0.0001). Meningiomas showing both SWIpos and SWIneg areas caused two separated histogram peaks, whereas homogeneously appearing meningiomas with either SWIposor SWIneg areas showed one peak only. ADC values did not correlate with age or gender, and showed substantial overlap between WHO grade I and II. CONCLUSION: Susceptibility changes (SWIpos) in meningiomas influence measures of diffusivity by increasing ADC values on average by 38%. This shift has to be considered when conclusions on tumor behavior are drawn from DWI. Further studies should address whether ADC changes and histogram patterns can be used to monitor treatment of meningiomas.

NMDA receptor activation limits the number of synaptic connections during hippocampal development.

Activity-dependent synaptic plasticity triggered by N-methyl-d-aspartate (NMDA) receptor activation is a fundamental property of many glutamatergic synapses and may be critical for the shaping and refinement of the structural and functional properties of neuronal circuits during early postnatal development. Using a combined morphological and electrophysiological approach, we showed that chronic blockade of NMDA receptors in hippocampal slice cultures during the first two weeks of postnatal development leads to a substantial increase in synapse number and results in a more complex dendritic arborization of CA1 pyramidal cells. Thus, the development of excitatory circuitry in the hippocampus is determined by two opposing processes: NMDA receptor-independent synapse formation and NMDA receptor-dependent attenuation of synaptogenesis.