Machine Learning Enhances Ability To Predict Survival From Brain Tumors

MedicalResearch.com 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

Dr. Cooper

Lee Cooper, Ph.D.
Assistant Professor of Biomedical Informatics
Assistant Professor of Biomedical Engineering
Emory University School of Medicine – Georgia Institute of Technology

MedicalResearch.com: 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. Continue reading

Can Zika Be Used To Fight Glioblastoma Brain Tumors?

MedicalResearch.com 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

Dr. Chheda

Milan G. Chheda, MD
Assistant Professor
Department of Medicine
Oncology Division
Molecular Oncology
Department of Neurology
Washington University School of Medicine in St. Louis

MedicalResearch.com: 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.

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Targeting CD44s May Make Glioblastoma More Sensitive To Clinical Treatment

MedicalResearch.com Interview with:

Chonghui Cheng, M.D., Ph.D. Associate Professor Department of Molecular & Human Genetics Lester & Sue Smith Breast Center Baylor College of Medicine Houston, TX77030

Dr. Cheng

Chonghui Cheng, M.D., Ph.D.
Associate Professor
Department of Molecular & Human Genetics
Lester & Sue Smith Breast Center
Baylor College of Medicine
Houston, TX77030

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Understanding the mechanisms that give cancer cells the ability to survive and grow opens the possibility of developing improved treatments to control or cure disease. In the case of glioblastoma multiforme, the deadliest type of brain cancer, abnormal EGFR signaling is frequently observed.

Treatment with the EGFR inhibitor erlotinib attempts to kill cancer cells. However, the clinical benefit of treatment with this and other EGFR inhibitors has been limited by the development of drug resistance.

Scientists at Baylor College of Medicine discovered that the molecule CD44s seems to give cancer cells a survival advantage. Eliminating this advantage by reducing the amount of CD44s resulted in cancer cells being more sensitive to the deadly effects of the drug erlotinib.

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Stereotactic Radiation Therapy Achieves Superior Results in Some Brain Tumors

MedicalResearch.com Interview with:

Professor Rakesh Jalali, MD Professor of Radiation Oncology President, Indian Society of Neuro-Oncology Tata Memorial Parel, Mumbai India

Dr. Jalali

Professor Rakesh Jalali, MD
Professor of Radiation Oncology
President, Indian Society of Neuro-Oncology
Tata Memorial
Parel, Mumbai India 

MedicalResearch.com: 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.

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Targeted Radiosurgery Beats Whole Brain Radiation For Brain Tumor Survival

MedicalResearch.com Interview with:

N. Scott Litofsky, M.D. Chief of the Division of Neurological Surgery University of Missouri School of Medicine

Dr. N. Scott Litofsky,

N. Scott Litofsky, M.D.
Chief of the Division of Neurological Surgery
University of Missouri School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Radiosurgery is being used more often for treatment of brain metastases to avoid potential side effects of whole-brain radiation, such as cognition and mobility impairment. After surgical resection of a brain metastases, some radiation treatment is generally needed to control brain disease. Few studies have directly compared efficacy of tumor control between surgery followed by whole-brain radiation and surgery followed by radiosurgery.

Our objective was to compare outcomes in two groups of patients – one whose brain metastasis was treated with surgery followed by whole-brain radiation and one whose surgery was followed by radiosurgery to the post-operative tumor bed.

We found that tumor control was similar for both groups, with survival actually better in the radiosurgery group. The complications of treatment were similar.

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Mibefradil Dihydrochoride with Hypofractionated Radiation for Recurrent Glioblastoma

MedicalResearch.com Interview with:

Nataniel Lester-Coll, MD Chief Resident in Radiation Oncology at Yale New Haven, Connecticut

Dr. Nataniel Lester-Coll

Nataniel Lester-Coll, MD
Chief Resident in Radiation Oncology at Yale
New Haven, Connecticut 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Recurrent Glioblastoma Multiforme (GBM) has limited treatment options and the prognosis is poor. Mibefradil diydrochloride was identified using a high-throughput compound screen for DNA double stranded break repair inhibitors. Mibefradil was found to radiosensitize GBM tumor cells in vitro and in vivo. Based on these findings, we sought to determine the maximum tolerated dose of mibefradil and radiation therapy in a Phase I recurrent GBM study. Eligible patients with recurrent  Glioblastoma Multiforme received Mibefradil over a 17 day period, with hypofractionated radiation (600 cGy x 5 fractions). There are 18 patients currently enrolled who have completed treatment. Thus far, there is no clear evidence of radionecrosis. A final dose level of 200 mg/day was reached as the maximum tolerated dose. The drug was very well tolerated at this dose. We saw intriguing evidence of enhanced local control in selected cases. Patients enrolled in a translational substudy who received Mibefradil prior to surgery were found to have adequate levels of Mibefradil in resected brain tumor tissue.

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Computer Bests Neuroradiologists in Distinguishing Tumor Recurrence From Radiation Necrosis

MedicalResearch.com Interview with:

Dr. Pallavi Tiwari PhD Assistant Professor biomedical engineering Case Western Reserve University

Dr. Pallavi Tiwari

Dr. Pallavi Tiwari PhD
Assistant Professor biomedical engineering
Case Western Reserve University

MedicalResearch.com: 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.

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Insurance Status Affects Glioblastoma Survival

MedicalResearch.com Interview with:

Wuyang Yang, M.D., M.S. Research Fellow Department of Neurosurgery Johns Hopkins Hospital Baltimore, MD 21287

Dr. Wuyang Yang

Wuyang Yang, M.D., M.S.
Research Fellow
Department of Neurosurgery
Johns Hopkins Hospital
Baltimore, MD 21287

MedicalResearch.com: 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.

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Optune as Standard Treatment Option for Newly Diagnosed Glioblastoma

Novocure is the developer of Optune, which uses Tumor Treating Fields to treat cancer. Tumor Treating Fields, or TTFields, are low intensity, alternating electric fields within the intermediate frequency range. TTFields disrupt cell division through physical interactions with key molecules during mitosis. This non-invasive treatment targets solid tumors.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The National Comprehensive Cancer Network (NCCN) has recommended Optune as a standard treatment option for newly diagnosed glioblastoma (GBM) in its Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers. NCCN panel members designated Optune together with temozolomide as a category 2A treatment for newly diagnosed GBM for patients with good performance status, indicating uniform consensus among panel members to add Optune to the guidelines for newly diagnosed GBM. Optune has been included in the NCCN Guidelines as a category 2B treatment option for recurrent GBM since 2015. The recommendation follows the publication of Novocure’s EF-14 phase 3 pivotal trial data in The Journal of the American Medical Association (JAMA) in December, 2015. The EF-14 phase 3 pivotal trial demonstrated that adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival in newly diagnosed GBM.
Glioblastoma, also called glioblastoma multiforme, or GBM, is a type of primary brain cancer. Approximately 12,500 GBM tumors, or tumors that may transform into GBM, are diagnosed in the U.S. each year. GBM is the most common type of primary brain cancer in adults. It is more likely to appear in older adults and to affect men than women. GBM is one of the deadliest forms of cancer, with patients typically not surviving beyond 15 months after diagnosis.

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Soluble Aspirin May Be Able To Cross Blood-Brain Barrier To Attack Glioblastomas

MedicalResearch.com Interview with:

Dr Kieran Breen PhD Director of Research, Brain Tumour Research University of Portsmouth, UK

Dr. Kieran Breen

Dr Kieran Breen PhD
Director of Research, Brain Tumour Research
University of Portsmouth, UK

MedicalResearch.com: 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. Continue reading

Meningioma Risk Lower In Patients With High Blood Sugar and Diabetes

MedicalResearch.com Interview with:

Dr. Judith Schwartzbaum PhD Associate professor of epidemiology Ohio State's Comprehensive Cancer Center

Dr. Judith Schwartzbaum

Dr. Judith Schwartzbaum PhD
Associate professor of epidemiology
Ohio State’s Comprehensive Cancer Center

MedicalResearch.com: 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.

MedicalResearch.com:What 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.

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Neuroblastoma: Adding Novel Monoclonal Antibody To Chemotherapy Shrunk More Tumors

MedicalResearch.com Interview with:

Wayne L. Furman, MD Department of Oncology Jude Children's Research Hospital Memphis, TN 38105-3678

Dr. Wayne Furman

Wayne L. Furman, MD
Department of Oncology
Jude Children’s Research Hospital
Memphis, TN 38105-3678

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Furman: Despite improvement in 2-yr EFS from 46% to 66% with the inclusion of dinutuximab, a monoclonal antibody that recognizes a glycoprotein on neuroblasts called ‘GD2’ (disialoganglioside), more than one-third of children with high-risk neuroblastoma still are not cured. Therefore novel therapeutic approaches are needed for this subset of patients. The clinical evaluation of various anti-GD 2 monoclonal antibodies in children with neuroblastoma has been exclusively focused on treatment of patients after recovery from consolidation, in a state of ‘minimal residual disease’. This is because traditionally chemotherapy has been thought to be too immunosuppressive to combine with monoclonal antibodies. However recent studies suggest, even in the setting of “bulky” solid tumors, the combination of chemotherapy with monoclonal antibodies can enhance the effectiveness of the antibodies. First, chemotherapy can increase the efficacy of antibodies by depleting cells of the immune system that suppress immune function. Also chemotherapy-induced tumor cell death can trigger tumor antigen release, uptake by antigen processing cells and an enhanced antitumor immune response. There is also data that anti-GD2 monoclonal antibodies can suppress tumor cell growth independent of immune system involvement. Furthermore anti-GD2 monoclonal antibodies and chemotherapy have non-overlapping toxicities. All of these reasons were good reasons to evaluate the addition of a novel anti-GD2 monoclonal antibody, called hu14.18K322A, to chemotherapy, outside the setting of minimal residual disease, in children with newly diagnosed children with high-risk neuroblastoma.

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Dog Genome Can Be Used To Identify Human Brain Tumor Genes

MedicalResearch.com Interview with:

Katarina Truvé PhD Swedish University of Agricultural Sciences and  Kerstin Lindblad-Toh Uppsala University

Dr. Katarina Truvé

Katarina Truvé PhD
Swedish University of Agricultural Sciences and
Kerstin Lindblad-Toh
Uppsala University

MedicalResearch.com: 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.

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Anti-Hypertension Drug Prazosin May Inhibit Glioblastoma Brain Tumor Cells

MedicalResearch.com 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

Dr. Herve Chneiweiss

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

MedicalResearch.com: 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.

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Dual Treatment Strategies Can Slow Glioblastoma Tumor Growth

MedicalResearch.com 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

Dr. Rakesh Jain

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

MedicalResearch.com: 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.

MedicalResearch.com: 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.

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