Research and Clinical Trials News

Research and Clinical Trials News

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Rutgers neuroscientist sheds light on cause for 'chemo brain'

  • Monday, 25 February 2013 13:36

Study finds fog-like condition related to Chemotherapy's effect on new brain cells and rhythms

It's not unusual for Cancer patients being treated with chemotherapy to complain about not being able to think clearly, connect thoughts or concentrate on daily tasks. The complaint – often referred to as chemo-brain – is common. The scientific cause, however, has been difficult to pinpoint.

New research by Rutgers University behavioral neuroscientist Tracey Shors offers clues for this fog-like condition, medically known as chemotherapy-induced Cognitive impairment. In a featured article published in the European Journal of Neuroscience, Shors and her colleagues argue that prolonged chemotherapy decreases the development of new brain cells, a process known as neurogenesis, and disrupts ongoing brain rhythms in the part of the brain responsible for making new memories. Both, she says, are affected by learning and in some cases are necessary for learning to occur.

"One of the things that these brain rhythms do is to connect information across brain regions," says Shors, Professor II in the Department of Psychology and Center for Collaborative Neuroscience at Rutgers. "We are starting to have a better understanding of how these natural rhythms are used in the process of communication and how they change with experience."

Working in the Shors laboratory, postdoctoral fellow Miriam S. Nokia from the Department of Psychology at the University of Jyvaskyla in Finland and Rutgers neuroscience graduate student Megan Anderson treated rats with a chemotherapy drug – Temozolomide (TMZ) – used on individuals with either Malignant brain tumors or skin cancer to stop rapidly dividing cells that have gone out of control and resulted in cancer.

In this study, scientists found that the production of new healthy brain cells treated with the TMZ was reduced in the hippocampus by 34 percent after being caught in the crossfire of the drug's potency. The cell loss, coupled with the interference in brain rhythms, resulted in the animal being unable to learn difficult tasks.

Shors says the rats had great difficulty learning to associate stimulus events if there was a time gap between the activities but could learn simple task if the stimuli were not separated in time. Interestingly, she says, the drug did not disrupt the memories that were already present when the treatment began.

For cancer patients undergoing long-term chemotherapy this could mean that although they are able to do simple everyday tasks, they find it difficult to do more complicated activities like processing long strings of numbers, remembering recent conversations, following instructions and setting priorities. Studies indicate that while most cancer patients experience short-term memory loss and disordered thinking, about 15 percent of cancer patients suffer more long-lasting cognitive problems as a result of the chemotherapy treatment.

"Chemotherapy is an especially difficult time as patients are learning how to manage their treatment options while still engaging in and appreciating life. The disruptions in brain rhythms and neurogenesis during treatment may explain some of the cognitive problems that can occur during this time. The good news is that these effects are probably not long-lasting," says Shors.

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Sniffing out the side effects of radiotherapy may soon be possible

  • Friday, 22 February 2013 15:42

Researchers at the University of Warwick and The Royal Marsden NHS Foundation Trust have completed a study that may lead to clinicians being able to more accurately predict which patients will suffer from the side effects of Radiotherapy.

Gastrointestinal side effects are commonplace in radiotherapy patients and occasionally severe, yet there is no existing means of predicting which patients will suffer from them. The results of the pilot study, published in the journal Sensors, outline how the use of an electronic nose and a newer technology, FAIMS (Field Asymmetric Ion Mobility Spectrometry) might help identify those at higher risk.

Warwick Medical School, working in collaboration with the School of Engineering and The Royal Marsden NHS Foundation Trust (led by Dr J Andreyev), carried out a pilot study to look into the relationship between levels of toxicity in the gut and the likelihood of experiencing side effects.

Dr Ramesh Arasaradnam, of Warwick Medical School and Gastroenterologist at University Hospitals Coventry & Warwickshire, outlines the results of the study. "In the simplest terms, we believe that patterns in toxicity levels arise from differences in a patient's gut microflora. By using this technology we can analyse stool samples and sniff out the chemicals that are produced by these microflora to better predict the risk of side effects."

The success of the pilot study will lead to a broader investigation into the possible uses of these technologies and could be truly significant in helping clinicians inform patients receiving pelvic radiotherapy, before treatment is started.

Dr Arasaradnam explains what this could mean for radiotherapy patients, "In essence, we will be able to predict those who are likely to develop severe gut related side effects by the pattern of gut fermentation that are altered as a result of radiotherapy. This will enable future directed therapy in these high risk groups."

Dr James Covington, from the Warwick School of Engineering adds, "This technology offers considerable opportunities for the future. This shows just one application of being able to inform treatment by 'sniffing' patients. We foresee a time when such technology will become as routine a diagnostic test as checking blood pressure is today."

It is further evidence of the ongoing collaboration between Warwick Medical School and School of Engineering. This technology, first developed at Warwick in the early 1990s has been in continuous development ever since, producing some of the most sophisticated chemical sensors and sensor systems available today.

In 2009, the same high tech gas sensor was taken from the automotive world and used to research into quicker diagnosis for some gastrointestinal illnesses and metabolic diseases.

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5-ALA fluorescence guides resection of recurrent glioblastoma multiforme

  • Tuesday, 19 February 2013 21:02

Charlottesville, VA, February 19, 2013. Neurosurgeons from UC San Francisco describe the use of 5-aminolevulinic acid (5-ALA) fluorescence in guiding resection of recurrent Glioblastoma Multiforme (GBM). Ingestion of 5-ALA by a patient before surgery leads to fluorescence of Tumor cells intraoperatively in response to certain wavelengths of light. This can provide information not necessarily available through magnetic resonance imaging ( MRI), the standard mode of imaging used to detect primary and recurrent GBMs. The additional information provided by 5-ALA fluorescence can guide surgeons in the treatment of individual cases.

The case of a 56-year-old man is described in the article "Subependymal spread of recurrent glioblastoma detected with the Intraoperative use of 5-aminolevulinic acid. Case report," by Tene A. Cage, M.D., Melike Pekmezci, M.D., Michael Prados, M.D., and Mitchel S. Berger, M.D., published today online, ahead of print, in the Journal of Neurosurgery. The patient presented with frequent transient visual disturbances. Seven years earlier, he had undergone gross-total (maximum) resection of a GBM located in the right Occipital Lobe. A new MRI study was performed and the images showed three distinct, new sites of tumor in the man's right Temporal Lobe. There was no evidence of recurrent tumor at the site where the original tumor had been located.

Glioblastoma multiforme (GBM) is the most common primary tumor of the brain. It is extremely aggressive and is usually treated with resection followed by Chemotherapy and Radiotherapy. Even using this treatment, patient survival is not long: on average 1 to 2 years. The authors note that the best way to lengthen survival is to remove as much tumor as possible. This holds for recurrent GBM as well as for the initial tumor.

The patient in this case was scheduled for surgery to remove the three new lesions. To aid in visualization of the lesions intraoperatively, the neurosurgical team, led by Mitchel S. Berger, M.D., Chairman of the Department of Neurological Surgery at UC San Francisco, administered 5-ALA to the patient four hours prior to surgery. During surgery, a blue light was used to activate 5-ALA fluorescence of tumor cells and thus differentiate tumor from other brain tissue. Using the blue light, the surgeons were able to detect tumor cells along the lining of the right Lateral ventricle, in the ependymal and subependymal regions. Although the appearance of the three lesions on preoperative MRI had indicated distinct sites of recurrent disease (multicentric tumor recurrence), the fluorescence of tumor cells during surgery mapped out the spread of disease from the original GBM site in the right occipital lobe to three sites in the right temporal lobe through a pathway along the wall of the right ventricle. This showed that the GBM recurrence was not multicentric at all. The fluorescence also made it possible for the surgeons to identify and resect additional tumor tissue along the pathway between the original and recurrent lesions.

According to the authors, MRI is unable to clearly delineate diffuse tumor infiltrating the ependyma and subependymal zone lining the lateral ventricle. Addition of 5-ALA fluorescence during surgery revealed the pathway of tumor spread through these regions.

With recurrent GBM, it is valuable to distinguish whether the recurrence is multicentric disease or infiltrative disease extending from the original tumor. According to Dr. Berger, "Multicentric disease can add a worse Prognosis. Finding it during surgery is important and can influence the extent of resection." Addition of 5-ALA fluorescence has been identified as substantially increasing the success of achieving maximum resection. Dr. Berger says that intraoperative use of 5-ALA "could be useful in all GBM cases."

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Cage TA, Pekmezci M, Prados M, Berger MS. Subependymal spread of recurrent glioblastoma detected with the intraoperative use of 5-aminolevulinic acid. Case report. Journal of Neurosurgery, published online, ahead of print, on February 19, 2013 (DOI: 10.3171/2013.1.JNS121537).

Disclosure: The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

For additional information, please contact:

Ms. Jo Ann M. Eliason, Communications Manager
Journal of Neurosurgery Publishing Group
One Morton Drive, Suite 200
Charlottesville, Virginia 22903
Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it
Telephone 434-982-1209; Fax 434-924-2702

For 68 years, the Journal of Neurosurgery has been recognized by neurosurgeons and other medical specialists the world over for its authoritative clinical articles, cutting-edge laboratory research papers, renowned case reports, expert technical notes, and more. Each article is rigorously peer reviewed. The Journal of Neurosurgery is published monthly by the JNS Publishing Group, the scholarly journal division of the American Association of Neurological Surgeons, an association dedicated to advancing the specialty of neurological surgery in order to promote the highest quality of patient care. The Journal of Neurosurgery appears in print and on the Internet.

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Genetic landscape of common brain tumors holds key to personalized treatment

  • Friday, 25 January 2013 09:25

Nearly the entire genetic landscape of the most common form of brain Tumor can be explained by abnormalities in just five genes, an international team of researchers led by Yale School of Medicine scientists report online in the Jan. 24 edition of the journal Science. Knowledge of the genomic profile of the tumors and their location in the brain make it possible for the first time to develop personalized medical therapies for meningiomas, which currently are only managed surgically.

Meningioma tumors affect about 170,000 patients in the United States. They are usually benign but can turn Malignant in about 10 percent of cases. Even non-cancerous tumors can require surgery if they affect the surrounding brain tissue and disrupt neurological functions.

Approximately half of the tumors have already been linked to a mutation or deletion of a gene called neurofibromin 2, or NF2. The origins of the rest of the meningiomas had remained a mystery.

The Yale team conducted genomic analyses of 300 meningiomas and found four new genetic suspects, each of which yields clues to the origins and treatment of the condition. Tumors mutated with each of these genes tend to be located in different areas of the brain, which can indicate how likely they are to become malignant.

"Combining knowledge of these mutations with the location of tumor growth has direct clinical relevance and opens the door for personalized therapies," said Murat Gunel, the Nixdorff-German Professor of Neurosurgery, professor of genetics and of neurobiology, and senior author of the study. Gunel is also a member of Yale Cancer Center's Genetics and Genomics Research Program.

For instance, two of the mutations identified — SMO and AKT1 — have been linked to various cancers. SMO mutations had previously been found in basal cell carcinoma and are the target of an already approved drug for that form of skin cancer. Another, KLF4, activates a suite of genes and is known for its role in inducing stem cell formation, even in cells that have fully differentiated into a specific tissue type. Mutations in a TRAF7, a gene not previously associated with cancer, were found in approximately one-fourth of tumors. Meningiomas with these mutations are found in the Skull Base and are unlikely to become cancerous. In contrast, NF2 mutant tumors that flank the brain's hemispheres are more likely to progress to malignancy, especially in males.

Doctors may be able to use targeted Chemotherapy on patients with non-NF2 mutations, especially those with recurrent or invasive meningiomas and those who are surgically at high risk. Individualized chemotherapies could also spare patients irradiation treatment, a risk factor for progression of these generally benign tumors. Gunel said it may also be possible to extend these approaches to more malignant tumors.

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Funding for the study was provided by Gregory M. Kiez and Mehmet Kutman Foundation.

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NCCN Guidelines® Recommend NovoTTF™ Therapy as a Standard Treatment Option for CNS Cancers

  • Thursday, 24 January 2013 23:26

St. Helier, Jersey – January 18, 2013 - Novocure Limited announced today that Novocure’s NovoTTF™ Therapy has been added to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers. The new NCCN Guidelines® indicate that physicians consider using NovoTTF Therapy as a new option, in addition to surgery, Chemotherapy, and radiation, for patients with glioblastoma brain tumors that recur or progress after initial treatment. The National Comprehensive Cancer Network® (NCCN®) is an alliance of 21 of the world’s leading cancer centers. The new guidelines are published online at www.nccn.org.


NovoTTFâ„¢ Therapy was studied in a randomized, controlled trial for patients with recurrent glioblastoma and the results were published in the European Journal of Cancer. The trial compared the efficacy and safety of NovoTTFâ„¢ Therapy, delivered by the NovoTTFâ„¢-100A System, to physician choice active chemotherapy. The trial results demonstrated that for recurrent glioblastoma patients, NovoTTFâ„¢ Therapy given alone produced clinically comparable efficacy outcomes with minimal toxicity and improved Quality of life compared to chemotherapy.


“We are pleased to announce that after a detailed review of the peer-reviewed literature supporting the treatment, the NCCN Guidelines Panel for CNS Cancers has recommended NovoTTF Therapy as a novel treatment modality for recurrent glioblastoma patients,” said Gabe Leung, Vice Chairman of the Board and Chair of the Global Commercialization Team for Novocure. “NCCN continues to demonstrate its leadership in establishing evidence-based standards that improve the lives of cancer patients.”


NovoTTFâ„¢ Therapy is currently available to glioblastoma patients at more than 60 leading cancer centers in the United States. Novocure will continue training physicians at additional US centers throughout 2013. Approximately 10,000 patients are diagnosed with glioblastoma each year in the United States.


“The revised NCCN Guidelines reflect the growing use of NovoTTF Therapy by neurooncologists in the United States to treat patients with recurrent glioblastoma effectively while affording them an improved quality of life compared to chemotherapy,” said Asaf Danziger, Chief Executive Officer of Novocure. “We look forward to expanding access to NovoTTF Therapy in 2013 by training physicians at additional cancer centers.”

About NovoTTFTM Therapy and the NovoTTFâ„¢-100A System

NovoTTFâ„¢ Therapy is delivered by a portable, non-invasive medical device designed for continuous use throughout the day by the patient. The device has been shown in in vitro and in vivo studies to slow and reverse Tumor growth by inhibiting mitosis, the process by which cells divide and replicate. The delivery system weighs about six pounds and creates a low intensity, alternating electric field within the tumor that exerts physical forces on electrically charged cellular components, preventing the normal mitotic process and causing cancer cell death prior to division. In patients with recurrent glioblastoma brain tumors, treatment with NovoTTFâ„¢ Therapy has been shown to provide patients with efficacy outcomes comparable to active chemotherapy with fewer side effects and a better quality of life. The NovoTTFâ„¢-100A System, a NovoTTFâ„¢ Therapy delivery system, has received marketing approval in the US and is a CE Marked device cleared for sale in the European Union and Switzerland.


The US Food and Drug Administration (FDA) approved the NovoTTF™-100A System for use as a treatment for adult patients (22 years of age or older) with histologicallyconfirmed Glioblastoma Multiforme (GBM), following histologically – or radiologicallyconfirmed recurrence in the supratentorial region of the brain after receiving chemotherapy. The device is intended to be used as monotherapy, and is intended as an alternative to standard medical therapy for GBM after surgical and radiation options have been exhausted.


Patients should only use the NovoTTFâ„¢-100A System under the supervision of a physician properly trained in use of the device. Full prescribing information is available at www.novottftherapy.com or by calling toll free 1-855-281-9301.


About Novocureâ„¢


Novocure Limited is a private Jersey Isle oncology company pioneering a novel therapy for solid tumors. Novocure’s US operations are based in New York, NY and Portsmouth, NH and the company’s research center is located in Haifa, Israel. For additional information about the company, please visit www.novocure.com.

About the National Comprehensive Cancer Network


The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 21 of the world’s leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives.


The NCCN Member Institutions are: City of Hope Comprehensive Cancer Center, Los Angeles, CA; Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA; Duke Cancer Institute, Durham, NC; Fox Chase Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Memorial Sloan-Kettering Cancer Center, New York, NY; Moffitt Cancer Center, Tampa, FL; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH; Roswell Park Cancer Institute, Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO; St. Jude Children’s Research Hospital/The University of Tennessee Health Science Center, Memphis, TN; Stanford Cancer Institute, Stanford, CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; UNMC Eppley Cancer Center at The Nebraska Medical Center, Omaha, NE; The University of Texas MD Anderson Cancer Center, Houston, TX; and Vanderbilt-Ingram Cancer Center, Nashville, TN.

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