Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial.

IMPORTANCE: Glioblastoma is the most devastating primary malignancy of the central nervous system in adults. Most patients die within 1 to 2 years of diagnosis. Tumor-treating fields (TTFields) are a locoregionally delivered antimitotic treatment that interferes with cell division and organelle assembly. OBJECTIVE: To evaluate the efficacy and safety of TTFields used in combination with temozolomide maintenance treatment after chemoradiation therapy for patients with glioblastoma. DESIGN, SETTING, AND PARTICIPANTS: After completion of chemoradiotherapy, patients with glioblastoma were randomized (2:1) to receive maintenance treatment with either TTFields plus temozolomide (n = 466) or temozolomide alone (n = 229) (median time from diagnosis to randomization, 3.8 months in both groups). The study enrolled 695 of the planned 700 patients between July 2009 and November 2014 at 83 centers in the United States, Canada, Europe, Israel, and South Korea. The trial was terminated based on the results of this planned interim analysis. INTERVENTIONS: Treatment with TTFields was delivered continuously (>18 hours/day) via 4 transducer arrays placed on the shaved scalp and connected to a portable medical device. Temozolomide (150-200 mg/m2/d) was given for 5 days of each 28-day cycle. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival in the intent-to-treat population (significance threshold of .01) with overall survival in the per-protocol population (n = 280) as a powered secondary end point (significance threshold of .006). This prespecified interim analysis was to be conducted on the first 315 patients after at least 18 months of follow-up. RESULTS: The interim analysis included 210 patients randomized to TTFields plus temozolomide and 105 randomized to temozolomide alone, and was conducted at a median follow-up of 38 months (range, 18-60 months). Median progression-free survival in the intent-to-treat population was 7.1 months (95% CI, 5.9-8.2 months) in the TTFields plus temozolomide group and 4.0 months (95% CI, 3.3-5.2 months) in the temozolomide alone group (hazard ratio [HR], 0.62 [98.7% CI, 0.43-0.89]; P = .001). Median overall survival in the per-protocol population was 20.5 months (95% CI, 16.7-25.0 months) in the TTFields plus temozolomide group (n = 196) and 15.6 months (95% CI, 13.3-19.1 months) in the temozolomide alone group (n = 84) (HR, 0.64 [99.4% CI, 0.42-0.98]; P = .004). CONCLUSIONS AND RELEVANCE: In this interim analysis of 315 patients with glioblastoma who had completed standard chemoradiation therapy, adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00916409

Velocity distributions of sputtered excited atoms

The first direct measurements are reported of the velocity distributions of sputtered atoms in excited states with electronic configurations completely different from the ground state. In contrast to previous work, the measured distributions for both the singlet and triplet metastable D states of Ba atoms showed no energy thresholds and had most probable energies similar to those of sputtered ground-state atoms.Peer reviewedElectrical and Computer Engineerin

Formation of excited Ag atoms in sputtering of silver

A model is presented for the formation of excited Ag* (4d 9 5s 2 ) atoms during sputtering of Ag metal by energetic Ar ϩ ions. The essential part of the formation process is the slow diffusion of 4d holes in the collision cascade from the sites of violent Ag-Ag collisions to the emitted Ag atoms. A computer simulation of Ag cascades and of the 4d-hole transport allows us to quantify the model and to describe all characteristic features of the available experimental data, in particular the fact that the sputtered Ag* atoms exhibit a narrower kinetic energy distribution than those ejected in the electronic ground state

Formation of excited Ag atoms in sputtering of silver

A model is presented for the formation of excited Ag-* (4d(9)5s(2)) atoms during sputtering of Ag metal by energetic Ar+ ions. The essential part of the formation process is the slow diffusion of 4d holes in the collision cascade from the sites of violent Ag-Ag collisions to the emitted Ag atoms. A computer simulation of Ag cascades and of the 4d-hole transport allows us to quantify the model and to describe all characteristic features of the available experimental data, in particular the fact that the sputtered Ag-* atoms exhibit a narrower kinetic energy distribution than those ejected in the electronic ground state

Imaging the internal electronic structure of a surface adsorbate with low energy ions

Time-of-flight spectra were collected for 2.5 keV Li-7(+) backscattered from Fe surfaces covered with submonolayers of iodine. Li singly scattered from the adatoms has a consistently larger neutral fraction than for scattering from the substrate, implying a region of positive charge atop the iodine. The neutral fraction decreases for off-normal exit angles, indicating a nonuniform charge distribution around the polarizable adsorbates. This demonstrates that ion scattering can image the internal electronic structure of an adatom and provides an explanation for anomalous work function changes

Internal electronic structure of adatoms on Fe(110) and Fe(100) surfaces: A low-energy Li+ scattering study

The neutralization of 400-3000 eV Li-7(+) ions scattered from clean and adsorbate-covered Fe(110) and Fe(100) surfaces was measured with time-of-flight spectroscopy. Li singly scattered from bromine, iodine, and cesium adatoms has a consistently larger neutral fraction than that for scattered from substrate sites. This suggests that the local electrostatic potential directly above these adatoms is reduced from that of the clean substrate. The neutral fraction of Li scattered from halogen adatoms is surprising in that it decreases as the emission angle moves off-normal, yet increases in the usual manner for cesium and silver adatoms. This indicates that the charge distribution associated with a halogen adsorbate is nonuniform, most likely due to internal polarization. A semiquantitative theoretical analysis shows that a nonuniform internal electron density would give rise to the observed behavior. The polarization of halogen adatoms is likely responsible for anomalous work function changes observed previously. Alkali-ion scattering is shown to be an effective tool for detecting the internal electronic structure of an adatom