Search

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. [ABSTRACT FROM AUTHOR]

Acrylamide is a synthetic monomer with a wide scope of industrial applications, mainly as a precursor in the production of several polymers, such as polyacrylamide. The main uses of polyacrylamides are in water and wastewater treatment processes, pulp and paper processing, and mining and mineral processing. The announcement by the Swedish National Food Administration in April 2002 of the presence of acrylamide predominantly in heat-treated carbohydrate-rich foods sparked intensive investigations into acrylamide, encompassing the occurrence, chemistry, agricultural practices, and toxicology, in order to establish if there is a potential risk to human health from the presence of this contaminant in the human diet. The link of acrylamide in foods to the Maillard reaction and, in particular, to the amino acid asparagine has been a major step forward in elucidating the first feasible chemical route of formation during the preparation and processing of food. Other probably minor pathways have also been proposed, including acrolein and acrylic acid. This review addresses the analytical and mechanistic aspects of the acrylamide issue and summarizes the progress made to date by the European food industries in these key areas. Essentially, it presents experimental results generated under laboratory model conditions, as well as under actual food processing conditions covering different food categories, such as potatoes, biscuits, cereals, and coffee. Since acrylamide formation is closely linked to food composition, factors such as the presence of sugars and availability of free amino acids are also considered. Many new findings that contribute towards a better understanding of the formation and presence of acrylamide in foods are presented. Many national authorities across the world are assessing the dietary exposure of consumers to acrylamide, and scientific projects have commenced to gather new information about the toxicology of acrylamide. These are expected to provide new scientific knowledge that will help to clarify whether or not there is a risk to human health from the consumption of foods containing low amounts of acrylamide. [ABSTRACT FROM AUTHOR]

Cites a study which sought to review the progress made by the European food and drink industry on acrylamide research. Presence of acrylamide in carbohydrate-rich food; Development of methods to quantify acrylamide reliably at relatively low levels in wide variety of different foodstuffs; Discussion on the chemical and physical aspects of acrylamide formation in foods.