Survival of melanoma patients treated with targeted therapy and immunotherapy after systematic upfront control of brain metastases by radiosurgery.

BACKGROUND: Targeted therapy (TT) and immunotherapies (ITs) have dramatically improved survival in metastatic melanoma (MM). However, their efficacy on brain metastasis (BM) remains limited and poorly documented. PATIENTS AND METHODS: Retrospective cohort of consecutive MM patients (pts) with BMs, all systematically upfront treated by Gamma-Knife (GK) at first BM and retreated in case of new BMs, from 2010 to 2015 at the time when ipilimumab BRAF ± MEK inhibitors and anti-PD1 were introduced in practice. Survival after 1st GK (OSGK1) according to prognostic factors and treatment. RESULTS: Among 179 consecutive pts treated by GK, 109 received IT and/or TT after the 1st GK. Median OSGK1 was 10.95 months and 1- and 2-year survival rates were 49.5% and 27.4%, respectively, versus a median overall survival (OS) of 2.29 months (p < .001) in those who did not receive IT or TT. In pts who initially had a single BM, median OS and 1- and 2-year survival rates were 14.46 months, 66.7% and 43.4%, respectively; in pts with 2-3 BMs: 8.85 months, 46.4% and 31%, respectively; in pts with >3 BMs: 7.25 months, 37.2% and 11.9%, respectively. Multivariate analysis for OSGK1 confirmed that IT and TT were significantly and highly protective. Best OSGK1 was observed in BRAF-wild-type pts receiving anti-PD1 or in BRAF-mutated pts receiving BRAF-inhibitors and anti-PD1 (12.26 and 14.82 months, respectively). CONCLUSION: In real-life MM pts with BMs, a strategy aiming at controlling BM with GK together with TT and/or TT seems to achieve unprecedented survival rates.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Three-dimensional rotational angiography in the assessment of the angioarchitecture of brain arteriovenous malformations.

BACKGROUND AND PURPOSE: The angioarchitecture of brain arteriovenous malformations (BAVM) still remains a complex subject of study despite advances in medical imaging techniques. For this reason, the present study aimed to assess whether or not 3D rotational angiography (3DXA) might improve the assessment of BAVM. PATIENTS AND METHODS: Included prospectively were 72 patients who had undergone conventional digital subtraction angiography (DSA) and 3DXA for pretherapeutic assessment of BAVM prior to radiosurgery. Dimensional criteria, arterial-feed patterns, venous drainage, points of weakness and vascular densities (VD) of the nidus and shunt zone were studied. RESULTS: 3DXA detected all arteriovenous shunts by revealing abnormal venous enhancement. Post-processing tools similar to CT and MRI may also be used to make complex 3D reconstructions. In addition, the technique provided significant help for volumetric estimations, extraction of arterial feeders and origins of draining veins, and analysis of the 3D conformation of the nidus. Furthermore, 3DXA detected significantly more points of weakness, such as intranidus aneurysms and venous anomalies (P<0.005). In 65% of cases, a gradient of vascular enhancement intensity was found between the arteries and draining veins surrounding or comprising the nidus. VD, or the percentages of space occupied by the enhanced vascular elements, was evaluated in both the nidus and shunt zone. VD in the shunt zone was highest in untreated patients with no history of bleeding (P<0.005). CONCLUSION: 3DXA offers a useful approach to BAVM exploration and can improve our knowledge of lesional angioarchitecture, necessary for the planning of therapeutic strategies.

Improvement of the intrinsic time resolving power of the Cologne iron-free orange type electron spectrometers.

Conversion electron spectroscopy represents an important tool for nuclear structure analysis of medium and heavy nuclei. Two iron-free magnetic electron spectrometers of the orange type have been installed at the Institute for Nuclear Physics of the University of Cologne. The very large transmission of 15% and the very good energy resolution of 1% makes the iron-free orange spectrometer a powerful instrument. By means of fast timing techniques, lifetimes of nuclear excited states can be measured with an accuracy better than 20 ps. For the first time, the energy dependent centroid position of prompt events yielding the time-walk characteristics (the prompt curve) of the orange spectrometer fast timing setup has been measured using prompt secondary δ-electrons generated in a pulsed beam experiment. The prompt curve calibrated as a function of energy allows precise lifetime determination down to a few tens of picoseconds by the use of the centroid shift method.