Author Interviews, Biomarkers, Brain Cancer - Brain Tumors, Cancer Research, Genetic Research / 21.07.2018 Interview with: Arnab Chakravarti MD Professor and Chair of Radiation Oncology Arthur G. James Cancer Hospital and Richard J. Solove Research Institute The Ohio State University Comprehensive Cancer Center What is the background for this study?   Response: Historically, the treatment for grade two gliomas has been a black box without really a standard-of-care therapy. In the past, it was really dealer’s choice, where it was based upon physician and patient preference. Either radiation alone, radiation plus chemotherapy, or chemotherapy alone, there wasn't really any data to guide therapeutic decision-making. Then about three years ago the landmark study RTOG 9802 was published, which demonstrated a survival benefit with the addition of chemotherapy to radiation versus radiation alone. That became the standard of care for the treatment of grade two gliomas. One of the tricky issues with regards to these tumors is that there's a wide range of outcomes. There are patients that succumb to disease within months, others that live decades. It's very important to personalize care for the individual patient and that's why biomarkers, prognostic and predictive biomarkers are so important. The 9802 study showed us for the general population of patients that the addition of chemotherapy to radiation improved outcomes versus radiation alone. The patient population that was selected for our study were the high-risk low-grade glioma patients. Patients who are generally over the age of 40, tumor sizes that exceeded 6 cm in terms of maximum dimension, tumors that invaded the corpus callosum, astrocytic histology of patients with neurological symptoms. These are typically the patients that were included in the study. Really the main objective of this study was to determine the efficacy of treatment compared to historical controls. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Emory, PNAS, Technology / 16.03.2018 Interview with: Lee Cooper, Ph.D. Assistant Professor of Biomedical Informatics Assistant Professor of Biomedical Engineering Emory University School of Medicine - Georgia Institute of Technology What is the background for this study? What are the main findings?  Response: Gliomas are a form of brain tumor that are often ultimately fatal, but patients diagnosed with glioma may survive as few as 6 months to 10 or more years. Prognosis is an important determinant in selecting treatment, that can range from simply monitoring the disease to surgical removal followed by radiation treatment and chemotherapy. Recent genomic studies have significantly improved our ability to predict how rapidly a patient's disease will progress, however a significant part of this determination still relies on the visual microscopic evaluation of the tissues by a neuropathologist. The neuropathologist assigns a grade that is used to further refine the prognosis determined by genomic testing. We developed a predictive algorithm to perform accurate and repeatable microscopic evaluation of glioma brain tumors. This algorithm learns the relationships between visual patterns presented in the brain tumor tissue removed from a patient brain and the duration of that patient's survival beyond diagnosis. The algorithm was demonstrated to accurately predict survival, and when combining images of histology with genomics into a single predictive framework, the algorithm was slightly more accurate than models based on the predictions of human pathologists. We were also able to identify that the algorithm learns to recognize some of the same tissue features used by pathologists in evaluating brain tumors, and to appreciate their prognostic relevance. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Zika / 07.09.2017 Interview with: Milan G. Chheda, MD Assistant Professor Department of Medicine Oncology Division Molecular Oncology Department of Neurology Washington University School of Medicine in St. Louis What is the background for this study? What are the main findings? Response: Glioblastoma is an extremely aggressive brain tumor. Most patients die in less than two years. A longstanding challenge has been killing tumor cells that are inherently resistant to our current therapies (radiation and chemotherapy). These cells, called cancer stem cells, are extremely hardy. A longstanding dream of oncologists has been to devise a way to find them and kill them. The public health epidemic in 2015 made Zhe Zhu, post-doctoral fellow in Jeremy Rich’s lab, wonder whether Zika virus could work on cancer stem cells, that share properties with stem cells in fetal brain. Zika virus doesn’t cause significant problems in adults. We took a lesson from nature and tested Zika virus. (more…)
Author Interviews / 20.08.2017 Interview with: Jianping Huang, MD, PhD Associate Professor Director of Clinical Laboratory Operations UF Brain Tumor Immunotherapy Program Department of Neurosurgery, University of Florida What is the background for this study? What are the main findings? Response: Identification and validation of molecules that are involved in tumor progression and reduced survival in glioma patients is the starting point for developing active, safe and effective therapy. Unfortunately, very few target molecules have been identified for the deadly disease of glioma up until recently. Our studies have identified that the molecule CD70 is ectopically expressed on gliomas and involved in promoting glioma progression. Our research shows that CD70 leads to a “double jeopardy” scenario in Glioblastoma (GBM) patients by promoting tumor aggressiveness and inhibiting our immune response to cancer. These results provide a strong scientific rationale to target CD70 using state-of-the-art therapeutic approaches, such as chimeric antigen receptor (CAR) T cell therapy. (more…)
Author Interviews, Brain Cancer - Brain Tumors, JAMA, Radiation Therapy / 01.06.2017 Interview with: Professor Rakesh Jalali, MD Professor of Radiation Oncology President, Indian Society of Neuro-Oncology Tata Memorial Parel, Mumbai India What is the background for this study? What are the main findings? Response: Randomized controlled trials to test the efficacy of radiotherapy techniques are challenging to perform. High-precision conformal techniques such as stereotactic radiosurgery/radiotherapy, intensity modulated radiotherapy (IMRT) and particle therapy, etc have been incorporated into routine clinical practice including for brain tumors without always being supported by level-1 evidence. We therefore conducted a prospective, randomized, controlled trial of stereotactic conformal radiotherapy compared to conventional radiotherapy in young patients with residual/progressive bening and low grade brain tumors requiring radiotherapy for optimal disease control. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Case Western, MRI, Radiology, Technology / 19.09.2016 Interview with: Dr. Pallavi Tiwari PhD Assistant Professor biomedical engineering Case Western Reserve University What is the background for this study? What are the main findings? Response: One of the biggest challenges in neuro-oncology currently is distinguishing radionecrosis, a side-effect of aggressive radiation, from tumor recurrence on imaging. Surgical intervention is the only means of definitive diagnosis, but suffers from considerable morbidity and mortality. The treatments for radionecrosis and cancer recurrence are very different. Early identification of the two conditions can help speed prognosis, therapy, and improve patient outcomes. The purpose of this feasibility study was to evaluate the role of machine learning algorithms along with computer extracted texture features, also known as radiomic features, in distinguishing radionecrosis and tumor recurrence on routine MRI scans (T1w, T2w, FLAIR). The radiomic algorithms were trained on 43 studies from our local collaborating institution - University Hospitals Case Medical Center, and tested on 15 studies at a collaborating institution, University of Texas Southwest Medical Center. We further compared the performance of the radiomic techniques with two expert readers. Our results demonstrated that radiomic features can identify subtle differences in quantitative measurements of tumor heterogeneity on routine MRIs, that are not visually appreciable to human readers. Of the 15 test studies, the radiomics algorithm could identify 12 of 15 correctly, while expert 1 could identify 7 of 15, and expert 2, 8 of 15. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Cancer, Cost of Health Care / 12.08.2016 Interview with: Wuyang Yang, M.D., M.S. Research Fellow Department of Neurosurgery Johns Hopkins Hospital Baltimore, MD 21287 What is the background for this study? What are the main findings? Response: The treatment for glioblastoma (GBM) patients involves a combined approach of surgery, radiation therapy and chemotherapy. Despite advancement in the therapeutic approaches for GBM, differing socioeconomic status result in disparities in health-care access, and may superimpose a significant impact on survival of glioblastoma patients. Insurance status is an indirect indicator of overall socioeconomic status of a patient, and has been shown to correlate with survival of patients with malignant tumor in other parts of the body. We conducted the first study to determine a relationship between different types of insurance and survival of GBM patients. In our study of 13,665 cases of GBM patients, we found that non-Medicaid insured patients have a significant survival benefit over uninsured and even Medicaid insured patients. This is the first time a study describes this relationship in glioblastoma patients, and also the first to compare and quantify the likelihood of poor prognosis between different insurance categories. A difference in insurance coverage was also uncovered, and patients with insurance were more likely to be older, female, white, and married. In addition, we found that younger, female, married patients with smaller tumor size survive longer than other patients, which confirmed findings in existing literature. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Pharmacology / 29.06.2016 Interview with: Dr Kieran Breen PhD Director of Research, Brain Tumour Research University of Portsmouth, UK What is the background for this study? What are the main findings? Response: There is evidence that aspirin (acetyl salicylic acid) can be toxic to brain tumour cells. However, its existing preparations cannot readily enter the brain because the drug is a suspension rather than being completely soluble. Furthermore, there can be significant side effects associated with the existing form of the drug including gastric bleeding. The object of this research was to develop a new formulation of aspirin which is truly soluble. When combined with two other compounds, the drug enters the brain and can therefore target the tumour cells. This study also showed that aspirin can kill tumour cells without causing any damage to the normal nerve cells. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Diabetes / 27.06.2016 Interview with: Dr. Judith Schwartzbaum PhD Associate professor of epidemiology Ohio State's Comprehensive Cancer Center What is the background for this study? Response: Meningioma is a slow-growing brain tumor that is associated with obesity. To further understand this risk we examined records of blood sugar levels within approximately 15 years before tumor diagnosis comparing blood sugar levels of people who developed meningioma to those in people who did not. are the main findings? Response: To our surprise we found that risk of this tumor was lower in people with high levels of blood sugar and diabetes. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research, PLoS / 13.05.2016 Interview with: Katarina Truvé PhD Swedish University of Agricultural Sciences and Kerstin Lindblad-Toh Uppsala University What is the background for this study? What are the main findings? Dr. Truvé: Gliomas are malignant brain tumors that are rarely curable. These tumors occur with similar frequencies in both dogs and humans. Gliomas in dogs are strikingly similar at the biological and imaging level to human tumor counterparts. Some dog breeds such as Boxer and Bulldog are at considerably higher risk of developing glioma. Since these breeds at high risk are recently related, they are most likely carrying shared genetic risk factors. Our goal was therefore to use the dog genome to locate genes that may be involved in the development of glioma in both dogs and humans. We found a strongly associated locus and identified three candidate genes, DENR, P2RX7 and CAMKK2 in the genomic region. We have shown that CAMKK2 is lower expressed in glioma tumors than normal tissue in both dogs and human, and it has been reported that the associated canine mutation in P2RX7 results in a decrease in receptor function. (more…)
Author Interviews, Blood Pressure - Hypertension, Brain Cancer - Brain Tumors / 22.04.2016 Interview with: Hervé Chneiweiss MD PhD Bâtiment A3 pièce 336 Case courrier 2 Plasticité Gliale et Tumeurs cérébrales Neuroscience Paris Seine (directeur) Inserm/Université Pierre et Marie Curie What is the background for this study? What are the main findings? Dr. Chneiweiss: Treatments available for glioblastoma -- malignant brain tumors -- have little effect. An international collaboration[1] led by the Laboratoire Neurosciences Paris-Seine (CNRS/ INSERM/UPMC)[2] tested active ingredients from existing medications and eventually identified one compound of interest, prazosin, on these tumors. We chose to study the most common malignant tumors that develop from brain cells, glioblastomas, which represent the fourth most frequent cause of cancer deaths among adults and the second in children. This is due to the inefficacy of current treatments. Indeed, a glioblastoma can resist treatment and reawaken from a very small number of tumor cells called glioblastoma-initiating cells (GIC). It is these cells -- whose characteristics and properties resemble those of stem cells -- that were targeted in the study. Rather than trying to discover new compounds, the team opted for repositioning existing drugs. In other words, we tested a collection of substances used for so long to treat other conditions that their patents have now fallen into the public domain[3]. This method makes it possible to develop new active ingredients cheaply and very rapidly. Twelve hundred compounds were thus tested on normal human neural stem cells and on glioblastoma-initiating cells from different aggressive tumors. Twelve of these compounds showed a toxic effect on GIC -- and none on the normal neural stem cells. The most effective was prazosin. Tested in mice carrying glioblastoma-initiating cells, prazosin significantly reduced the size of tumors and prolonged survival of the mice by more than 50%. [1] Including scientists from the Laboratoire d'Innovation Thérapeutique (CNRS/Université de Strasbourg), the Stanford University Institute for Stem Cell Biology and Regenerative Medicine (USA) and the Instituto Estadual do Cérebro Paulo Niemeyer in Rio de Janeiro (Brazil). [2] This laboratory forms part of the Institut de Biologie Paris-Seine. [3] Pharmaceutical compounds are protected by a patent for 20 years after their discovery. Because of the length of the clinical trials that are necessary before a drug can be put on the market, the duration of their patent protection does not normally exceed 10-15 years after a Marketing Authorization (MA) is granted. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Brigham & Women's - Harvard, PNAS / 06.04.2016 Interview with: Rakesh K. Jain, Ph.D. A.W.Cook Professor of Radiation Oncology (Tumor Biology) Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA    02114 What is glioblastoma and why is it difficult to treat?

Dr. Jain: Glioblastoma (GBM) is the most common malignant tumor of the brain, and remains highly lethal. The standard treatment consists of surgical removal followed by chemo-radiation and anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) antibody. Unfortunately, glioblastoma cells invade the brain far from the original tumor mass. Hence, even with the best surgical techniques it is not possible to remove all tumor cells, as they are embedded in vital parts of the brain at the time of the surgery. As a result, even after multimodal therapies, most  glioblastoma patients succumb to their disease within 2 years. New approaches are desperately needed. What is anti-angiogenic therapy and why is it used for glioblastoma?

Dr. Jain: One key feature ofglioblastomas is their highly abnormal, leaky and ineffective vasculature. This leads to brain swelling around the tumor and poor tumor blood perfusion, which in turn can render the tumors more aggressive. These vascular abnormalities are due to the uncontrolled overproduction in GBMs of angiogenic factors such as VEGF. Anti-angiogenic therapies using anti-VEGF agents can transiently “normalize” the GBM vasculature structure and function and reduce brain swelling, increase blood perfusion, and impact morbidity and survival. Unfortunately, even when this therapy is added to the standard therapy with surgery and chemo-radiation, GBM patients typically do not survive on average more than 1.5 years. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Dermatology, JAMA / 27.01.2016 Interview with: Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital University of Copenhagen Hellerup, Denmark   Medical Research: What is the background for this study? What are the main findings? Dr. Egeberg: There appears to be an overlap in the pathogenesis of rosacea and glioma, focused around matrix metalloproteinases. Rosacea may be associated with an increased risk of glioma, however, it is important to note that the absolute risk is still low. Whether this is a causal link is not known. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research / 10.11.2015

Dr. Priscilla Kaliopi Brastianos MD Instructor, Medicine, Harvard Medical School Assistant Physician in Medicine Hematology/Oncology, Massachusetts General Interview with: Dr. Priscilla Kaliopi Brastianos MD Instructor, Medicine, Harvard Medical School Assistant Physician in Medicine Hematology/Oncology, Massachusetts General Hospital Medical Research: What is the background for this study? What are the main findings? Response: Craniopharyngiomas are rare brain tumors that can cause serious problems because of their location near critical structures in the brain, such as optic and other cranial nerves, the pituitary gland and the hypothalamus. Not only does the growing tumor compromise neurological and hormonal functions by impinging on these structures, but treatment by surgical removal or radiation therapy can produce the same symptoms by damaging adjacent tissues. In addition, since the tumor adheres to these nearby critical structures, complete removal is difficult, which can lead rapid recurrence. Medical therapies have not been effective for craniopharyngiomas, namely because we did not understand the molecular underpinnings of these tumors. Last year, we performed genomic characterization of craniopharyngiomas, with the goal to identify potential therapeutic targets. We were surprised to find that nearly all papillary craniopharyngiomas have BRAF mutations, which are the same mutations that have been found in melanoma. We recently had the opportunity to translate our results to the clinic. A 38 year old patient presented to our institution, requiring 4 urgent neurosurgeries in 2 months for his papillary craniopharyngioma. When we presented a fifth time, we treated him with a therapy that targets his BRAF mutation. After just 4 days of therapy, his tumor had shrunk by nearly 25%. Similar to what is done in BRAF mutant melanoma, we added a MEK inhibitor to his treatment. By day 34 of therapy, his tumor was more than 80% smaller. We  also detected the BRAF mutation in this patient’s blood. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research / 02.09.2015

Roger Packer MD Senior Vice President Center for Neuroscience & Behavioral Health Children's National Medical Center Washington, D.C. Interview with: Roger Packer MD Senior Vice President Center for Neuroscience & Behavioral Health Children's National Medical Center Washington, D.C.   MedicalResearch: What is the background for this study? What are the main findings? Dr. Packer: The background is that medulloblastoma is the most common childhood malignant brain tumor. It carries with it a variable prognosis. For some subsets of patients, with current available treatment which includes surgery, radiation and chemotherapy, we see survival rates as high as 90% (and often cures) 5 years following diagnosis and treatment. However, for some subsets of patients, survival rates are much poorer, in those with higher risk characteristics as low as 40% at 5 years. Current treatment also carries with it a significant risk for long term sequelae, including intellectual loss secondary to radiation therapy and persistent, at times devastating neurologic complications such as unsteadiness. To try to improve our understanding and ultimately our therapy for medulloblastoma, an international working group has shared patient specimens and patient information to attempt to determine what the molecular predictors of outcome are for children with medulloblastoma and if such molecular genetic findings can be used to develop better, safer therapies. Children’s National is part of this international collective of institutions, which published this and other studies. The main findings of this study are that complex, integrated genetic analysis of tumor specimens can be used to better understand and set the scene for better treatment of medulloblastoma.  Medulloblastoma can be broken into relatively distinct, molecular subtypes each with its own prognosis and potential therapy. A major finding of this study was that within a given tumor, different areas showed the same molecular genetic pattern. The importance of this is that since the tumors are relatively the same in different areas, molecularly-targeted therapies have an excellent chance of working on the entire tumor, resulting in better tumor control and safer treatments. (more…)