Non-Invasive Brain Tumor Blaster Gets FDA Panel Support

A new non-invasive device that uses alternating electrical fields to blast brain tumors and kill cancer cells before they can multiply has received the backing of a US Food and Drug Administration (FDA) panel, although two panel members abstained from voting because of concerns that while trials showed the device was safe, it did not appear to be effective. The main argument in support of the device appears to be that it offers patients a higher quality of life, and is not necessarily about longer survival, where its effect appears to be minimal.

Brain Tumor Blaster Gets FDA Panel Support

Patients who attended the panel hearing last week urged members to recommend FDA approval. The Neurological Devices Panel of the Medical Devices Advisory Committee to the FDA held its hearing on 17 and 18 March in Gaithersburg, Maryland, to provide advice and recommendations concerning the NovoTTF-100A Treatment Kit (TTF stands for for tumor treating fields). The device, which is portable, is carried in a shoulderbag and can be worn continuously; it uses non-invasive technology and is developed by Novocure Ltd, a subsidiary of Standen Ltd with operations in Portsmouth, New Hampshire in the US and a research center in Haifa, Israel.

Briefing notes for the committee note that the pre-market application for the device describes its intended use as a monotherapy after other surgery and radiation options have been exhausted, in place of standard therapy for histologically- or radiologically- confirmed glioblastoma multiforme (GBM) in adults (21 years and above). The device deilivers very low intensity alternating electrical fields generated by special insulated electrodes applied to the surface of the skin on the scalp. Because of the unique shape of cancer cells when they are about to divide, the TTFields generate forces inside the cells that cause various cell components to pile up and become displaced in such a way that they fall apart, effectively preventing cell division and eventually causing cell death. Data from a trial suggests that the fields affect healthy brain cells much less than cancer cells because they multiply at a much slower rate, if at all.

Glioblastoma is one of the most lethal forms of brain cancer and most patients don't survive more than five years after diagnosis. It is very difficult to treat. The usual treatment is surgical removal of as much of the tumor as possible, followed by radiation and chemotherapy. Many patients also take Avastin, a drug that stops the growth of blood vessels that feed the tumor. According to a report in the Wall Street Journal, the FDA panel voted 7 to 3 in favor of a question as to whether the benefits of the device outweighed the risks, and two members abstained. The panel was split on whether the product was effective, although it agreed unanimously that it was safe. It seems likely that such a majority vote means the FDA will approve the device for use in the US; although the agency is not bound to follow the recommendation of its advisory committees, it usually does.

One panel member, Sarah Hollingsworth Lisanby, a brain-stimulation expert who chairs the psychiatry department at Duke University, abstained because she was not convinced the clinical trial report the company submitted showed the device was effective, although she said the technology "could be a real breakthrough", reported the Wall Street Journal. The FDA panel reviewed a report of a trial involving 237 patients in Europe, the US and Israel, who had advanced brain cancer and had already received standard treatments when they enrolled. Half the patients were asked to connect the device and wear it for 20 hours a day. The other half did not use the device, they received standard chemotherapy treatments. Most of the patients in both groups died within six months, a few survived a bit longer. But the FDA said the data on the US patients showed a slight trend toward longer survival. A phase II study of the device is already under way for patients with locally advanced and metastatic non-small cell lung-cancer (NSCLC) who have failed prior treatments with chemotherapy. The device has received its CE Mark and is approved for sale in six European countries as a treatment for glioblastoma. The FDA is expected to make a ruling in the next three months.

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Progression of Cancerous Tumors

A new method of examining cancerous tumors suggests that tumors may not evolve gradually, but rather in a punctuated or staccato-like bursts. The finding has shed new light on the process of tumor growth and metastasis, and may help in the development of new methods to clinically evaluate tumors.

Progression of Cancerous Tumors

The new analytic method, devised by Cold Spring Harbor Laboratory (CSHL) Professor Michael Wigler and colleagues, features a process called single cell sequencing (SNS), which enables accurate quantification of genomic copy number within a single cell nucleus. Genomic copy number refers to the amount of DNA in the nucleus. In cancer, portions of the genome are amplified or deleted, giving rise to extra or missing copies of key genes and interfering with mechanisms that normally control cell growth.

"We demonstrated that we can obtain accurate and high-resolution copy number profiles by sequencing a single cell from a cancerous tumor and that by examining multiple cells from the same cancer, we can make inferences about how the cancer evolved and spread," said Wigler. The CSHL team used two sampled tumors. Both were primary invasive breast cancer tumors of the so-called "triple-negative" type, generally regarded as the most aggressive form of breast cancer. One tumor sample was known from prior testing to be polygenomic: composed of distinct populations of tumor cells, whose number, genomic type and evolutionary history were not readily measurable using conventional techniques.

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Kidney Transplantation Not Equally Available to All

Not all racial and ethnic groups have equal access to kidney transplantation, according to a study appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN). The results indicate that the reasons for these disparities are varied and that more focused efforts are needed to address them.

Increasing patients on dialysis who need kidney transplants

For most individuals who develop kidney failure or end-stage renal disease, kidney transplantation is the best treatment option. Unfortunately, certain racial and ethnic groups are less likely to receive kidney transplants than others. Despite the increasing diversity of patients on dialysis who need kidney transplants, no prior studies had comprehensively compared the barriers to transplantation among different racial and ethnic groups.  

Yoshio Hall, MD (University of Washington, Seattle) and his colleagues investigated the rates and determinants of waitlisting and deceased-donor kidney transplantation among 503,090 non-elderly adults of different racial and ethnic groups who initiated dialysis between 1995 and 2006. They followed the patients through 2008.  The researchers found that the annual crude rates of deceased-donor transplantation from the time of dialysis initiation were lowest in American Indians/Alaska Natives (2.4%) and blacks (2.8%), intermediate in Pacific Islanders (3.1%) and Hispanics (3.2%), and highest in non-Hispanic whites (5.9%) and Asians (6.4%).  

The reasons for these differences in rates varied among racial and ethnic groups: blacks, American Indians, and Alaska Natives face continued difficulty in accessing transplant waitlists, primarily due to socioeconomic factors, while Hispanics and Pacific Islanders encounter delays from waitlists, which may be negatively influenced by regional organ availability, linguistic isolation, and perhaps cultural isolation. "Looking forward, our study suggests that interventions to address local population-specific barriers to transplantation may help to reduce overall racial, ethnic, and socioeconomic disparities in accessing kidney transplantation," said Dr. Hall.

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Patients With Hypertension Should Avoid Sugar-Sweetened Drinks

In the International Study of Macro/Micronutrients and Blood Pressure (INTERMAP), for every extra sugar-sweetened beverage drunk per day participants on average had significantly higher systolic blood pressure by 1.6 millimeters of mercury (mm Hg) and diastolic blood pressure higher by 0.8 mm Hg. This remained statistically significant even after adjusting for differences in body mass, researchers said. Researchers found higher blood pressure levels in individuals who consumed more glucose and fructose, both sweeteners that are found in high-fructose corn syrup, the most common sugar sweetener used by the beverage industry. 

Hypertension should avoid Sugar-Sweetened Drinks

Higher blood pressure was more pronounced in people who consumed high levels of both sugar and sodium. They found no consistent association between diet soda intake and blood pressure levels. Those who drank diet soda had higher mean BMI than those who did not and lower levels of physical activity. "This points to another possible intervention to lower blood pressure," said Paul Elliott, Ph.D., senior author and professor in the Department of Epidemiology and Biostatistics in the School of Public Health at Imperial College London. "These findings lend support for recommendations to reduce the intake of sugar-sweetened beverages, as well as added sugars and sodium in an effort to reduce blood pressure and improve cardiovascular health."

In INTERMAP, researchers analyzed consumption of sugar-sweetened drinks, sugars and diet beverages in 2,696 participants, 40- to 59-years-old, in eight areas of the United States and two areas of the United Kingdom. Participants reported what they ate and drank for four days via in depth interviews administered by trained observers, underwent two 24-hour urine collections, eight blood pressure readings and responded a detailed questionnaire on lifestyle, medical and social factors. The researchers found that sugar intake in the form of glucose, fructose and sucrose was highest in those consuming more than one sugar-sweetened beverage daily. They also found that individuals consuming more than one serving per day of sugar-sweetened beverages consumed more calories than those who didn't, with average energy intake of more than 397 calories per day.

Those who did not consume sugar-sweetened beverages had lower average body mass index (BMI) than those who consumed more than one of these drinks daily. "People who drink a lot of sugar-sweetened beverages appear to have less healthy diets," said Ian Brown, Ph.D., research associate at Imperial College London. "They are consuming empty calories without the nutritional benefits of real food. They consume less potassium, magnesium and calcium. "One possible mechanism for sugar-sweetened beverages and fructose increasing blood pressure levels is a resultant increase in the level of uric acid in the blood that may in turn lower the nitric oxide required to keep the blood vessels dilated. Sugar consumption also has been linked to enhanced sympathetic nervous system activity and sodium retention." The study's limitations include that it was cross-sectional and diet was self-reported. "This is a population study. It's one piece of the evidence in a jigsaw puzzle that needs to be completed," Brown said. "In the meantime, people who want to drink sugar-sweetened beverages should do so only in moderation."

The American Heart Association recommends no more than half of the discretionary calorie allowance from added sugars, which for most American women is no more than 100 calories per day and for most American men no more than 150 calories per day. Discretionary calories are the remaining calories in a person's "energy allowance" after consuming the recommended types and amounts of foods to meet all daily nutrient requirements.

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