Deep brain stimulation and frameless stereotactic radiosurgery in the treatment of bilateral parkinsonian tremor: target selection and case report of two patients

Considerable positive experience in functional radiosurgery has been reported since Leksell??s first experience in 1951, but the development of frameless radiosurgery was been limited because of the difficulty of identifying invisible functional targets. In this paper we report on two cases of bilateral parkinsonian tremor successfully treated with DBS on one side and with frameless radiosurgery on the contralateral side. We focus on the methodology developed to define the three-dimensional target coordinates for frameless radiosurgery. Two patients suffering from a disabling upper-limb parkinsonian tremor underwent frameless radiosurgical thalamotomy. To accurately identify the treatment target the CT gantry was treated as a stereotactic frame; a rototranslation between the origin of the screen and the origin of the stereotactic atlas allowed us to obtain atlas-registered 3D coordinates of each point on the CT axial brain slices. Both patients achieved complete bilateral tremor control by unilateral radiosurgery and contralateral DBS. We developed a method for determining the 3D coordinates of a known functional target to treat with frameless radiosurgery. Based on the initial experiences, frameless radiosurgery appears to be an alternative treatment for Parkinsonian upper limb tremor in the presence of increased surgical risks for DBS placement.     

Multisession radiosurgery for grade 2 (WHO), high risk meningiomas. A phase II clinical trial

Journal of Neuro-Oncology - Patients suffering from recurrent and residual grade 2 (WHO) meningiomas after subtotal excision should be considered as high-risk groups with an uncertain prognosis....     

Radiotherapy of meningioma: a treatment in need of radiobiological research

Purpose: Meningiomas account for one third of primary intracranial tumors; nevertheless information on meningioma cell lines and in vivo models is scant. Although radiotherapy is one of the most relevant therapeutic options for the treatment of patients with meningioma, radiobiological research to understand tumor response to this treatment is far from being thoroughly figured out. The aim of this report is to provide a comprehensive picture of the current literature on this field, so as to foster research in this regard.

Methods: We carried out a review of meningioma radiobiology based on a peer-reviewed PubMed search.

Results: Our findings confirm that the main limitation of radiobiological research into meningioma is the paucity of robust in vitro and in vivo models. Alternative approaches to overcome the already identified problems, and to allow better understanding of the entire histopathological spectrum of meningiomas have been explored.

Conclusions: A radiobiological perspective of meningioma may help to improve clinical results both in terms of tumor control and healthy tissue sparing. Although we are far from drawing any conclusions, this review can lead researchers to identify some clues for future areas of study.     

A new rapid bedside assay for quantitative testing of D-Dimer (Cardiac D-Dimer) in the diagnostic work-up for deep vein thrombosis

The accuracy of a new bedside, rapid and quantitative D-Dimer assay (Cardiac D-Dimer) was evaluated in outpatients with clinically suspected deep vein thrombosis (DVT); VIDAS test was used as reference method. Eighty consecutive outpatients with suspected DVT of a lower limb were included in the study. Patients were classified as DVT positive or negative according to results of objective test (serial CUS), pretest clinical probability and 3-month follow-up. DVT was diagnosed in 32/80 patients (40%). The performance of the two D-Dimer assays was comparable, as indicated by the areas under the ROC curves (0.89 and 0.88, for Cardiac D-Dimer and VIDAS, respectively) and the coefficient of correlation (r=0.91). The reproducibility of the test was acceptable (from 6.2% to 12.0%). The sensitivity and negative predictive values were 100% for both tests. The specificity (SP) and positive predictive values (PPV) were similar (SP: 50.0% and 52.0%, PPV: 57.1% and 58.2%, for Cardiac D-Dimer and VIDAS, respectively). The Cardiac D-Dimer test proved to be very accurate and produced results fully comparable to those obtained with the VIDAS test. Since the test can be directly performed in the emergency room within a few minutes, it seems to have great clinical potential. The place of this assay in the diagnostic strategy of DVT remains to be determined in prospective management studies.     

CXCL12 Expression is Predictive of a Shorter Time to Tumor Progression in Low-Grade Glioma: A Single-Institution Study in 50 Patients

Summary The clinical course of 50 patients with low-grade glioma (31 male, 19 female) undergoing surgery at a single Institution from 1992 to 1996 was analyzed in relationship with known prognostic factors as far as time to tumor progression (TTP) and survival time (ST) are concerned. Moreover, microvessel density (MVD) and expression of the angiogenesis-related chemokine CXCL12 were investigated in surgical specimens. Age at diagnosis ranged from 1 to 68 years (median 30). Histology revealed 11 fibrillary, 6 protoplasmatic, 5 gemistocytic astrocytoma, 18 oligoastrocytoma and 10 oligodendroglioma. Mean follow-up was 86 months. Four patients were lost to follow-up. Of the remaining 46, twenty-four have shown disease progression and 14 have died. Median overall survival was not achieved; an estimated 75% percentage of survivors was found at 78 months. Complete gross tumor removal was associated to a longer TTP (P = 0.04 logrank). Of the investigated immunohistochemical parameters, while MVD was not predictive of subsequent TTP, expression of CXCL12 was associated with a significantly shorter TTP (P = 0.01 logrank): this predictive value remained significant (P = 0.02) at multivariate analysis. The data suggest the possible prognostic value for CXCL-12 (an angiogenesis- and tumor-growth-related chemokine) on TTP in low-grade gliomas.     

<Emphasis Type="Italic">In vitro</Emphasis> effects of topotecan and ionizing radiation on TRAIL/Apo2L-mediated apoptosis in malignant glioma

The survival of patients with malignant gliomas is still unsatisfactory despite multimodality treatment, therefore new therapeutic strategies are required. Tumor necrosis factor apoptosis related ligand (TRAIL/Apo2L), a member of the tumor necrosis factor superfamily, may induce apoptotic cell death in several tumors, but not in normal cells, upon binding with specific receptors. In the present study, the expression and function of TRAIL receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5) has been investigated in five human glioma cell lines (U87, U138, U373, A172, SW1783) in ex vivo tumors and in primary cultures obtained from the tumors. Our data show that gliomas preferentially express TRAIL R2 and that treatment with topotecan, a topoisomerase I inhibitor, significantly up-regulates its expression as detected by flow cytometry and western blotting. Moreover, in most cases, treatment with topotecan resulted in an increased sensitivity to TRAIL-dependent apoptosis, although cyclohexymide had to be added to induce apoptosis. On glioma cell lines, the effects of irradiation on TRAIL receptors were also analysed. In our experimental conditions, irradiation with 2Gy had a modest additive effect on TRAIL-dependent apoptosis and was not able to modulate TRAIL receptor expression.     

Immunotherapy in association with stereotactic radiotherapy for non-small cell lung cancer brain metastases: results from a multicentric retrospective study on behalf of AIRO

BackgroundTo define efficacy and toxicity of Immunotherapy (IT) with stereotactic radiotherapy (SRT) including radiosurgery (RS) or hypofractionated SRT (HFSRT) for brain metastases (BM) from non-small cell lung cancer (NSCLC) in a multicentric retrospective study from AIRO (Italian Association of Radiotherapy and Clinical Oncology).MethodsNSCLC patients with BM receiving SRT + IT and treated in 19 Italian centers were analyzed and compared with a control group of patients treated with exclusive SRT.ResultsOne hundred patients treated with SRT + IT and 50 patients treated with SRT-alone were included. Patients receiving SRT + IT had a longer intracranial Local Progression-Free Survival (iLPFS) (propensity score-adjusted P = .007). Among patients who, at the diagnosis of BM, received IT and had also extracranial progression (n = 24), IT administration after SRT was shown to be related to a better overall survival (OS) (P = .037). A multivariate analysis, non-adenocarcinoma histology, KPS = 70 and use of HFSRT were associated with a significantly worse survival (P = .019, P = .017 and P = .007 respectively). Time interval between SRT and IT ≤7 days (n = 90) was shown to be related to a longer OS if compared to SRT-IT interval >7 days (n = 10) (propensity score-adjusted P = .008). The combined treatment was well tolerated. No significant difference in terms of radionecrosis between SRT + IT patients and SRT-alone patients was observed. The time interval between SRT and IT had no impact on the toxicity rate.ConclusionsCombined SRT + IT was a safe approach, associated with a better iLPFS if compared to exclusive SRT.